User login
New cancer survival calculator focuses on oral cancer
This represents the first cancer survival calculator that provides “personalized estimates of the likelihood of surviving or dying from oral cancer or other causes,” according to the experts who developed the tool.
An analysis evaluating the new calculator revealed that people with oral cancer are more likely to die from other causes, compared with their peers without oral cancer, and that noncancer survival worsens with cancer stage.
With its unique design, the calculator “represents perhaps one of the most sophisticated and comprehensive tools to date by integrating multiple population-level data sources to account for general health status [and] disease exposures,” such as alcohol and tobacco, socioeconomic status, and coexisting conditions, the authors of an accompanying commentary wrote.
This calculator may just be the beginning. The broader aim of developing the tool, the study authors explained, is for this new calculator approach to be “applicable for developing future prognostic models of cancer and noncancer aspects of a person’s health in other cancers.”
The analysis was published in JAMA Otolaryngology–Head and Neck Surgery.
When assessing survival, factors such as cancer stage and tumor size are key, but comorbidities also play a crucial role. For oral cancer in particular, where alcohol and tobacco use are notorious risk factors, comorbidities occur frequently and are often serious.
To create a model that provides more “holistic and personalized” estimates and includes a host of factors that can affect the risk of death, the authors tapped into data from the Surveillance, Epidemiology, and End Results database to develop the SEER Oral Cancer Survival Calculator.
Alongside data from the SEER database, the calculator used data from the National Health Interview Survey’s Longitudinal Mortality Files to obtain estimates of general health status, life expectancy without cancer, and the probability of dying from the cancer or from other causes within 1-10 years among people with newly diagnosed oral cancer.
Overall, the data included 22,392 patients, aged 20-94, with oral squamous cell carcinoma, 60.5% of whom were male and 78% White, as well as 402,626 interviewees from the survey. The calculator did not include patients with tonsil- or tongue-based cancers, which were not considered anatomically part of the oral cavity.
The most common conditions coexisting with oral cancer were diabetes and chronic obstructive pulmonary disease among older patients. Among those with oral cancer, more than half (52.8%) had none of the major coexisting conditions, which also included peripheral and cerebrovascular disease, compared with 80% of the Medicare population.
The researchers described and validated four models – one that estimated the probability of death due to oral cancer, and then three others that estimated the probability of death from other causes, with variations based on the specific data and covariates included.
Overall, the models in the calculator estimated that patients with oral cancer have a higher risk of death from other causes, compared with the general population, and survival estimates for noncancer causes got worse with more advanced cancer stage.
For instance, for a patient diagnosed with stage 3 oral cancer after age 50, the chances of being alive at age 70 were 60% for females and 44% for males in the absence of cancer, whereas the corresponding survival estimates in the general U.S. population were 86% for females and 79% for males – an absolute difference of 26 and 35 percentage points.
One key reason for this trend is that patients with later-stage cancers likely also have more coexisting health conditions, first author Louise Davies, MD, from the Geisel School of Medicine at Dartmouth, Lebanon, N.H., explained.
Another reason: For cancers with low enough mortality rates, people might be more likely to die from causes other than their cancer. This can also occur in ductal carcinoma in situ breast cancer or papillary thyroid cancer, noted Dr. Davies, also from the Department of Veterans Affairs Medical Center, White River Junction, Vt.
Commenting on the study, Eric Moore, MD, a head and neck surgeon with the Mayo Clinic in Rochester, Minn., said that while such prediction tools are important, they also come with caveats.
“I think these calculators are helpful and certainly having them widely available to people gives them another piece of knowledge that can be powerful,” he told this news organization. “But you want to make sure you don’t interpret them as the end-all, be-all message, because there are an infinite number of variables that could influence survival that aren’t available in some of these datasets.”
Neil D. Gross, MD, a professor of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston, agreed. Although this new calculator uses a large dataset, such tools “can be imperfect” and some factors simply can’t be calculated, such as a person’s priorities, Dr. Gross said.
That’s why there’s no substitute for having a “very personal discussion between a patient and a physician to decide what’s best.” And this calculator is just one tool to help with that process, Dr. Gross said.
The commentary authors echoed these sentiments. “This calculator can potentially bridge the gaps between the survival estimates in the literature, life tables, clinical gestalt, and physician attempts to contextualize the inherent limitations of applying survival curves and averages to the one patient with the diagnosis,” wrote Leila J. Mady, MD, PhD, MPH, Wayne M. Koch, MD, and Carole Fakhry, MD, MPH, all from Johns Hopkins School of Medicine, Baltimore.
But a caveat in providing such predictions is the possible psychological effect the news can have.
“Potential risks of revealing personalized prognostic survival estimates to patients include increased anxiety and distress surrounding competing causes of death [and] misinterpretation of data,” the commentary authors cautioned, adding that “we must present such information with grace and sensitivity.”
Dr. Davies recommends that clinicians ask patients what they want to know because that will vary by patient and potentially over time for the same patient.
“People are more than their cancer diagnosis,” said Dr. Davies. “Giving them the opportunity to consider their life as a whole is the aim.”
The oral cancer calculator can be publicly accessed through the National Cancer Institute. The study was supported by the Department of Veterans Affairs and the National Cancer Institute as part of an interagency agreement. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
This represents the first cancer survival calculator that provides “personalized estimates of the likelihood of surviving or dying from oral cancer or other causes,” according to the experts who developed the tool.
An analysis evaluating the new calculator revealed that people with oral cancer are more likely to die from other causes, compared with their peers without oral cancer, and that noncancer survival worsens with cancer stage.
With its unique design, the calculator “represents perhaps one of the most sophisticated and comprehensive tools to date by integrating multiple population-level data sources to account for general health status [and] disease exposures,” such as alcohol and tobacco, socioeconomic status, and coexisting conditions, the authors of an accompanying commentary wrote.
This calculator may just be the beginning. The broader aim of developing the tool, the study authors explained, is for this new calculator approach to be “applicable for developing future prognostic models of cancer and noncancer aspects of a person’s health in other cancers.”
The analysis was published in JAMA Otolaryngology–Head and Neck Surgery.
When assessing survival, factors such as cancer stage and tumor size are key, but comorbidities also play a crucial role. For oral cancer in particular, where alcohol and tobacco use are notorious risk factors, comorbidities occur frequently and are often serious.
To create a model that provides more “holistic and personalized” estimates and includes a host of factors that can affect the risk of death, the authors tapped into data from the Surveillance, Epidemiology, and End Results database to develop the SEER Oral Cancer Survival Calculator.
Alongside data from the SEER database, the calculator used data from the National Health Interview Survey’s Longitudinal Mortality Files to obtain estimates of general health status, life expectancy without cancer, and the probability of dying from the cancer or from other causes within 1-10 years among people with newly diagnosed oral cancer.
Overall, the data included 22,392 patients, aged 20-94, with oral squamous cell carcinoma, 60.5% of whom were male and 78% White, as well as 402,626 interviewees from the survey. The calculator did not include patients with tonsil- or tongue-based cancers, which were not considered anatomically part of the oral cavity.
The most common conditions coexisting with oral cancer were diabetes and chronic obstructive pulmonary disease among older patients. Among those with oral cancer, more than half (52.8%) had none of the major coexisting conditions, which also included peripheral and cerebrovascular disease, compared with 80% of the Medicare population.
The researchers described and validated four models – one that estimated the probability of death due to oral cancer, and then three others that estimated the probability of death from other causes, with variations based on the specific data and covariates included.
Overall, the models in the calculator estimated that patients with oral cancer have a higher risk of death from other causes, compared with the general population, and survival estimates for noncancer causes got worse with more advanced cancer stage.
For instance, for a patient diagnosed with stage 3 oral cancer after age 50, the chances of being alive at age 70 were 60% for females and 44% for males in the absence of cancer, whereas the corresponding survival estimates in the general U.S. population were 86% for females and 79% for males – an absolute difference of 26 and 35 percentage points.
One key reason for this trend is that patients with later-stage cancers likely also have more coexisting health conditions, first author Louise Davies, MD, from the Geisel School of Medicine at Dartmouth, Lebanon, N.H., explained.
Another reason: For cancers with low enough mortality rates, people might be more likely to die from causes other than their cancer. This can also occur in ductal carcinoma in situ breast cancer or papillary thyroid cancer, noted Dr. Davies, also from the Department of Veterans Affairs Medical Center, White River Junction, Vt.
Commenting on the study, Eric Moore, MD, a head and neck surgeon with the Mayo Clinic in Rochester, Minn., said that while such prediction tools are important, they also come with caveats.
“I think these calculators are helpful and certainly having them widely available to people gives them another piece of knowledge that can be powerful,” he told this news organization. “But you want to make sure you don’t interpret them as the end-all, be-all message, because there are an infinite number of variables that could influence survival that aren’t available in some of these datasets.”
Neil D. Gross, MD, a professor of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston, agreed. Although this new calculator uses a large dataset, such tools “can be imperfect” and some factors simply can’t be calculated, such as a person’s priorities, Dr. Gross said.
That’s why there’s no substitute for having a “very personal discussion between a patient and a physician to decide what’s best.” And this calculator is just one tool to help with that process, Dr. Gross said.
The commentary authors echoed these sentiments. “This calculator can potentially bridge the gaps between the survival estimates in the literature, life tables, clinical gestalt, and physician attempts to contextualize the inherent limitations of applying survival curves and averages to the one patient with the diagnosis,” wrote Leila J. Mady, MD, PhD, MPH, Wayne M. Koch, MD, and Carole Fakhry, MD, MPH, all from Johns Hopkins School of Medicine, Baltimore.
But a caveat in providing such predictions is the possible psychological effect the news can have.
“Potential risks of revealing personalized prognostic survival estimates to patients include increased anxiety and distress surrounding competing causes of death [and] misinterpretation of data,” the commentary authors cautioned, adding that “we must present such information with grace and sensitivity.”
Dr. Davies recommends that clinicians ask patients what they want to know because that will vary by patient and potentially over time for the same patient.
“People are more than their cancer diagnosis,” said Dr. Davies. “Giving them the opportunity to consider their life as a whole is the aim.”
The oral cancer calculator can be publicly accessed through the National Cancer Institute. The study was supported by the Department of Veterans Affairs and the National Cancer Institute as part of an interagency agreement. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
This represents the first cancer survival calculator that provides “personalized estimates of the likelihood of surviving or dying from oral cancer or other causes,” according to the experts who developed the tool.
An analysis evaluating the new calculator revealed that people with oral cancer are more likely to die from other causes, compared with their peers without oral cancer, and that noncancer survival worsens with cancer stage.
With its unique design, the calculator “represents perhaps one of the most sophisticated and comprehensive tools to date by integrating multiple population-level data sources to account for general health status [and] disease exposures,” such as alcohol and tobacco, socioeconomic status, and coexisting conditions, the authors of an accompanying commentary wrote.
This calculator may just be the beginning. The broader aim of developing the tool, the study authors explained, is for this new calculator approach to be “applicable for developing future prognostic models of cancer and noncancer aspects of a person’s health in other cancers.”
The analysis was published in JAMA Otolaryngology–Head and Neck Surgery.
When assessing survival, factors such as cancer stage and tumor size are key, but comorbidities also play a crucial role. For oral cancer in particular, where alcohol and tobacco use are notorious risk factors, comorbidities occur frequently and are often serious.
To create a model that provides more “holistic and personalized” estimates and includes a host of factors that can affect the risk of death, the authors tapped into data from the Surveillance, Epidemiology, and End Results database to develop the SEER Oral Cancer Survival Calculator.
Alongside data from the SEER database, the calculator used data from the National Health Interview Survey’s Longitudinal Mortality Files to obtain estimates of general health status, life expectancy without cancer, and the probability of dying from the cancer or from other causes within 1-10 years among people with newly diagnosed oral cancer.
Overall, the data included 22,392 patients, aged 20-94, with oral squamous cell carcinoma, 60.5% of whom were male and 78% White, as well as 402,626 interviewees from the survey. The calculator did not include patients with tonsil- or tongue-based cancers, which were not considered anatomically part of the oral cavity.
The most common conditions coexisting with oral cancer were diabetes and chronic obstructive pulmonary disease among older patients. Among those with oral cancer, more than half (52.8%) had none of the major coexisting conditions, which also included peripheral and cerebrovascular disease, compared with 80% of the Medicare population.
The researchers described and validated four models – one that estimated the probability of death due to oral cancer, and then three others that estimated the probability of death from other causes, with variations based on the specific data and covariates included.
Overall, the models in the calculator estimated that patients with oral cancer have a higher risk of death from other causes, compared with the general population, and survival estimates for noncancer causes got worse with more advanced cancer stage.
For instance, for a patient diagnosed with stage 3 oral cancer after age 50, the chances of being alive at age 70 were 60% for females and 44% for males in the absence of cancer, whereas the corresponding survival estimates in the general U.S. population were 86% for females and 79% for males – an absolute difference of 26 and 35 percentage points.
One key reason for this trend is that patients with later-stage cancers likely also have more coexisting health conditions, first author Louise Davies, MD, from the Geisel School of Medicine at Dartmouth, Lebanon, N.H., explained.
Another reason: For cancers with low enough mortality rates, people might be more likely to die from causes other than their cancer. This can also occur in ductal carcinoma in situ breast cancer or papillary thyroid cancer, noted Dr. Davies, also from the Department of Veterans Affairs Medical Center, White River Junction, Vt.
Commenting on the study, Eric Moore, MD, a head and neck surgeon with the Mayo Clinic in Rochester, Minn., said that while such prediction tools are important, they also come with caveats.
“I think these calculators are helpful and certainly having them widely available to people gives them another piece of knowledge that can be powerful,” he told this news organization. “But you want to make sure you don’t interpret them as the end-all, be-all message, because there are an infinite number of variables that could influence survival that aren’t available in some of these datasets.”
Neil D. Gross, MD, a professor of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston, agreed. Although this new calculator uses a large dataset, such tools “can be imperfect” and some factors simply can’t be calculated, such as a person’s priorities, Dr. Gross said.
That’s why there’s no substitute for having a “very personal discussion between a patient and a physician to decide what’s best.” And this calculator is just one tool to help with that process, Dr. Gross said.
The commentary authors echoed these sentiments. “This calculator can potentially bridge the gaps between the survival estimates in the literature, life tables, clinical gestalt, and physician attempts to contextualize the inherent limitations of applying survival curves and averages to the one patient with the diagnosis,” wrote Leila J. Mady, MD, PhD, MPH, Wayne M. Koch, MD, and Carole Fakhry, MD, MPH, all from Johns Hopkins School of Medicine, Baltimore.
But a caveat in providing such predictions is the possible psychological effect the news can have.
“Potential risks of revealing personalized prognostic survival estimates to patients include increased anxiety and distress surrounding competing causes of death [and] misinterpretation of data,” the commentary authors cautioned, adding that “we must present such information with grace and sensitivity.”
Dr. Davies recommends that clinicians ask patients what they want to know because that will vary by patient and potentially over time for the same patient.
“People are more than their cancer diagnosis,” said Dr. Davies. “Giving them the opportunity to consider their life as a whole is the aim.”
The oral cancer calculator can be publicly accessed through the National Cancer Institute. The study was supported by the Department of Veterans Affairs and the National Cancer Institute as part of an interagency agreement. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM JAMA OTOLARYNGOLOGY–HEAD AND NECK SURGERY
Radiation approach improves swallowing in head, neck cancer
Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.
A team of British investigators are now reporting a new strategy to help lessen this problem.
In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.
Overall, said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”
The team reported the results of their phase 3 trial in The Lancet Oncology.
Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.
Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.
In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.
Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.
At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.
The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.
DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.
At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.
The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).
Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.
In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.
Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”
The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.
For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.
The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.
A team of British investigators are now reporting a new strategy to help lessen this problem.
In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.
Overall, said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”
The team reported the results of their phase 3 trial in The Lancet Oncology.
Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.
Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.
In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.
Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.
At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.
The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.
DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.
At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.
The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).
Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.
In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.
Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”
The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.
For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.
The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.
A team of British investigators are now reporting a new strategy to help lessen this problem.
In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.
Overall, said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”
The team reported the results of their phase 3 trial in The Lancet Oncology.
Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.
Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.
In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.
Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.
At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.
The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.
DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.
At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.
The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).
Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.
In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.
Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”
The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.
For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.
The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Liquid biopsy shows big promise in oropharyngeal cancer
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA OTOLARYNGOLOGY–HEAD AND NECK SURGERY
No benefit to adding limited radiation in advanced cancer
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
In head and neck cancer, better outcomes seen in patients with overweight
The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.
While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
Methods and results
For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.
The researchers found that overweight BMI (25-29.9 kg/m2) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.
Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.
Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.
The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”
It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.
“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”
Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.”
The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
Importance of nutritional support during treatment highlighted
In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.
“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”
Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.
While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
Methods and results
For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.
The researchers found that overweight BMI (25-29.9 kg/m2) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.
Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.
Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.
The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”
It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.
“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”
Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.”
The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
Importance of nutritional support during treatment highlighted
In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.
“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”
Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.
While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
Methods and results
For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.
The researchers found that overweight BMI (25-29.9 kg/m2) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.
Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.
Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.
The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”
It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.
“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”
Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.”
The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
Importance of nutritional support during treatment highlighted
In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.
“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”
Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
FROM JAMA NETWORK OPEN
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
A 65-year-old African American man presented to an Otolaryngology Head and Neck Surgery clinic at a tertiary Veterans Health Administration (VHA) facility for evaluation. The patient recalled a past diagnosis of oropharyngeal cancer (OPC), possibly associated with the human papillomavirus (HPV). After receiving the diagnosis at another VHA facility, the patient opted to seek care at a local, non-VHA facility and received approximately 7 weeks of daily radiation and weekly infusions of chemotherapy.
Six years after his initial diagnosis and treatment, the patient said he had a persistent cough with any meaningful attempts to eat or drink. He also noted he lost at least 10 lbs in the last 3 months and had been hospitalized twice during the past winter. During his second hospitalization he spent 4 days on a ventilator in the intensive care unit.
On examination, the patient appeared frail and cachectic, with significant fibrosis of the neck skin and moderate trismus. His dentition was in poor health, and an in-clinic flexible endoscopy demonstrated clear silent aspiration of oral secretions. Given his failure to thrive, the patient was urgently admitted to the hospital. A modified barium swallow study performed by the head and neck Speech Pathology team demonstrated gross aspiration with all consistencies. After extensive counseling, the patient agreed to the placement of a gastrostomy tube. He was discharged in stable condition with adequate supplies and self-care training. He was advised to continue follow-up in the Head and Neck Cancer Survivorship clinic.
Two years later, in the early phase of the COVID-19 pandemic, the patient was admitted to the hospital with COVID pneumonia. Given the damage to his lungs over the previous decade from recurrent episodes of aspiration pneumonia, the patient succumbed.
An Unexpected, Unrelenting Epidemic
Shifting population dynamics and behaviors have led to an explosion in the incidence of cancers associated with infection by oncogenic subtypes of HPV, among which cancer of the oropharynx represents the most common malignancy.1,2 OPC now afflicts more than 30,000 new patients in the United States each year.3 Given current vaccination rates against oncogenic HPV, the overall trend of increasing incidence is not expected to stabilize until the 2040s.3 Traditional cancers of the head and neck region were previously fatal after 5 years in more than 60% of cases; however, today patients with HPV-associated OPC can expect a more than 80% chance of being alive 5 years after treatment.4-7 Combining the increasing incidence of OPC with a high chance of oncologic cure has led to an ever-expanding cohort of OPC survivors.
Enthusiasm about a high rate of survival after an HPV-associated OPC diagnosis is now partially dampened by an increasing realization that neither oncologists nor healthcare systems are remotely prepared for this rapidly expanding cohort of OPC survivors. Their unique needs and problems have yet to be objectively defined and quantified.
Relationship Between Survival and Long-Term Toxicity in HPV-Associated OPC
Survivorship care after OPC treatment is a growing challenge in terms of the number of patients affected, the negative impact on quality of life (QOL), and the potential burden on the healthcare system. The rapidly growing number of OPC survivors who are living long enough to develop delayed adverse effects related to their past OPC treatment1,2,8 includes many patients in whom toxicities can be truly debilitating,9,10 generating significant unmet needs.
Tumor and Treatment Toxicity
Although HPV-associated OPC demonstrates an excellent response to conventional chemoradiotherapy (CRT), this finding cannot be interpreted to mean that reducing treatment intensity is safe for patients with this disease. Prospective trials have now demonstrated that neither replacing or eliminating conventional chemotherapy, nor significantly reducing radiation doses, can be considered safe at this time.11-15 As a result, a patient with newly diagnosed HPV-associated OPC in 2025, and potentially even 2030, is likely to receive the same treatment as patients who were treated in the late 2010s.14
Three decades ago, the chronic effects of tumor and treatment were largely limited to a small cohort of survivors; however, today they affect more patients.1,2,7 Chronic xerostomia, dysphagia, trismus, radiation fibrosis, and osteoradionecrosis (ORN) now confront tens of thousands of OPC survivors; over the coming decades, these treatment effects have the potential to affect millions of patients.16-22
While most acute toxicities resolve within several months of completing CRT, late CRT sequelae tend to be dynamic and can progress silently over many years.16,23 Adverse effects vary widely, with many toxicities (eg, dysphagia, ORN) being particularly debilitating. Many of these effects occur in a radiation dose–dependent fashion, but radiation dose does not fully predict late toxicities, pointing to a role for other, yet unidentified contributing factors.24,25
Dysphagia in Survivors of OPC
About two-thirds of survivors of head and neck cancer (HNC) who seek follow-up care 5 years after treatment report dysphagia and at least partial dependence on a feeding tube.26 The incidence of dysphagia increases proportionately with higher radiation doses delivered to the pharyngeal constrictors and supraglottic larynx.18 Dysphagia can severely reduce QOL years after treatment, necessitating substantial changes in diet and social behavior among OPC survivors. Often, patients are forced to choose between chronic malnutrition or starvation and feeding tube dependence.27 Loss of a normal oral diet is frequently one of the most affected QOL measures for OPC survivors.28
In addition to effects on QOL, dysphagia can have life-threatening consequences. In a recent systematic review and meta-analysis, life-threatening aspiration occurred after > 24 months at a reported incidence ranging from 3% to nearly 35%. Although a reduction in radiation dose to the pharyngeal constrictors can reduce chronic dysphagia,27 whether this can be done safely in most OPC patients, particularly those with bulky primary tumors, remains unclear.
Osteoradionecrosis (ORN) in Survivors of OPC
ORN is one of the most potentially serious complications of CRT and may not manifest for years after treatment. Its median time of onset after radiotherapy is 8 years in patients with OPC.24 Bone injury and impaired healing of the alveolar mucosa are signs of ORN, which occurs in ~7% of patients receiving intensity-modulated radiation therapy for OPC.17 ORN is accompanied by pain, difficulties with chewing, exacerbation of concomitant dysphagia and, in the advanced stage—gross cosmetic deformity secondary to mandibular or maxillary fracture and/or decay.29 Despite the severity of this complication, we are just beginning to understand why ORN develops in a subset of patients. Although ORN is generally more common in patients with advanced-stage OPC who receive higher doses of radiation to a larger overall bone volume,17,19,24,30 comprehensive translational research efforts focused on ORN (as well as other late toxicities of OPC treatment) are still in their infancy.
Unmet Needs in Predicting and Evaluating Late Toxicities
Predicting which patients will experience long-term treatment toxicities or which types of late toxicities they may develop is not yet possible. Whereas increased data collection and prognostic models can help inform healthcare systems as to the expected frequencies of toxicity, they are unlikely to be prognostic at the individual patient level. As such, there is a critical need for individualized biomarker strategies that can predict one’s risk of toxicity and identify normal tissue shifts in biology and function early in the process to initiate interventions before significant deterioration. Adding to the complexity of predicting late toxicities is the lack of standardization in instruments used to categorize them. Examples of tools that may be used to categorize dysphagia include the Common Terminology Criteria for Adverse Events v4.0 grading scale, the Radiation Therapy Oncology Group grading system, and the European Organization for Research and Treatment of Cancer Performance Status Scale for Head and Neck Cancer.20 The MD Anderson Symptom Inventory for head and neck cancer may also be used to catalog dysphagia and other common symptoms of HNC, as well as treatment-related concerns.31 Magnetic resonance imaging-based techniques coupled with machine learning approaches represent emerging tools that may have a role in identifying early radiation-induced bone changes that can facilitate early detection of ORN.32,33 Although conventional and newer tools can be used to generate objective metrics of treatment-related toxicity, consistent and appropriate deployment across the entire cohort of OPC survivors in the United States remains a distant goal.
Calibrating Treatment Intensity to Disease Intensity
Given the risk of severe and potentially life-threatening consequences of radiation-based treatment, there is a large unmet need to better calibrate treatment intensity to the intensity of HPV-associated OPC.14,34 In light of the good prognosis of the disease in most patients, recent efforts have focused on identifying ways to de-escalate treatment intensity while preserving the good outcomes known to be possible for patients with HPV-associated OPC. Improving tolerability and limiting the risk of late effects of radiation-based treatment is especially important with the aging population of HPV-associated OPC survivors, who would also be expected to have unrelated comorbidities.1
Various modes of de-escalation have been studied, including adding surgery to CRT, reducing radiation dose, and modifying systemic therapy regimens. Most of these efforts have largely failed to identify a safe regimen for treatment de-escalation that applies to a majority or even a significant plurality of patients with OPC.14,35,36 Although CheckMate 141 and KEYNOTE-048 garnered excitement when immune checkpoint inhibitors (ICIs) significantly prolonged overall survival and had a more favorable safety profile than standard systemic therapy in recurrent and metastatic OPC,11,37,38 adding definitive frontline avelumab to CRT failed to prolong progression-free survival versus CRT alone in the phase 3 JAVELIN Head and Neck 100 trial.13 Combined with additional recent trial data, these findings make it unlikely that an ICI-based regimen will provide previously unavailable de-escalation options for patients with OPC in the near future.
Considering continued de-escalation efforts, it is important to remember that survival is not uniform among all patients with HPV-associated OPC. For example, patients with HPV-associated OPC and a history of current or prior heavy tobacco use have not experienced the same dramatic prolongation in overall survival as their nonsmoking counterparts.36 Patients with recurrent disease also face a dismal prognosis, with failure rates of about 70% with salvage treatment with surgery, re-irradiation, or systemic therapy.38-41 Therefore, de-escalation may not be appropriate in all patients, but identifying which patients are at risk of overtreatment is not straightforward. Better risk stratification of patients may provide part of the solution but will require rigorous testing and long-term follow-up to establish.
Discussion
There is an urgent need to carefully consider how to manage long-term survivors of HPV-associated OPC. With ever-increasing numbers of patients who are living years beyond their OPC treatment, continual reevaluation of treatment strategies in certain subsets of patients and making concerted efforts to identify and manage late toxicities early is paramount. Yet there remains a critical gap in knowledge due to insufficient metrics for both toxicity intensity and the frequency of debilitating, life-threatening toxicity. Unfortunately, the lack of tools available combined with the mismatch in disease intensity with treatment intensity likely results in excessive treatment-induced toxicity for many patients.
In the absence of clear evidence about which treatment strategy to use for individual patients, clinicians are tasked with making therapeutic choices without being fully able to predict outcomes. Patient preference is important to consider, but these conversations can be complicated. How does one talk to a patient about their willingness to risk a cancer recurrence and potentially risk late toxicities when the clinician does not know whether that individual patient will develop late toxicities, or know how severe they will be? It is a tradeoff between QOL (ie, possible feeding tube dependence) and survival—yet the magnitude of the effect on QOL remains impossible to predict at present for the individual patient.
Moreover, the needs of individual OPC survivors vary. A cross-sectional study performed at Princess Margaret Cancer Centre found that 61% of the 158 participants had unmet needs related to their cancer survivorship.42 Meeting the needs of survivors may require the development of better screening instruments that can manage various complications early and effectively. Continuing to follow OPC survivors with a multidisciplinary team would most certainly be beneficial and has been reported to improve QOL.43 Continual Speech Pathology management and therapy from the time of diagnosis into the survivorship phase of care has been suggested as one way to improve functional outcomes.44 Given that coordinating long-term care teams is logistically challenging, well-planned research is warranted to equip these teams to provide OPC survivors with the care they need. These efforts will be particularly important considering the large number of survivors who will need this type of care in the coming decades. The time to start is now well past.
- Tota JE, Best AF, Zumsteg ZS, Gillison ML, Rosenberg PS, Chaturvedi AK. Evolution of the oropharynx cancer epidemic in the United States: moderation of increasing incidence in younger individuals and shift in the burden to older individuals. J Clin Oncol. 2019;37(18):1538-1546. doi:10.1200/JCO.19.00370
- Liao CI, Francoeur AA, Kapp DS, Caesar MAP, Huh WK, Chan JK. Trends in human papillomavirus-associated cancers, demographic characteristics, and vaccinations in the US, 2001-2017. JAMA Netw Open. 2022;5(3):e222530. doi:10.1001/jamanetworkopen.2022.2530
- Zhang Y, Fakhry C, D’Souza G. Projected association of human papillomavirus vaccination with oropharynx cancer incidence in the US, 2020-2045. JAMA Oncol. 2021;7(10):e212907. doi:10.1001/jamaoncol.2021.2907
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217
- Li H, Torabi SJ, Yarbrough WG, Mehra S, Osborn HA, Judson B. Association of human papillomavirus status at head and neck carcinoma subsites with overall survival. JAMA Otolaryngol Head Neck Surg. 2018;144(6):519-525. doi:10.1001/jamaoto.2018.0395
- Lill C, Bachtiary B, Selzer E, Mittlboeck M, Thurnher D. A 5-year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria. Wien Klin Wochenschr. 2017;129(11-12):398-403. doi:10.1007/s00508-017-1171-5
- Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001. doi:10.1634/theoncologist.2009-0289
- Goepfert RP, Fuller CD, Gunn GB, et al. Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors. Head Neck. 2017;39(11):2151-2158. doi:10.1002/hed.24879
- MD Anderson Head and Neck Cancer Symptom Working Group. Dose-volume correlates of mandibular osteoradionecrosis in oropharynx cancer patients receiving intensity-modulated radiotherapy: results from a case-matched comparison. Radiother Oncol. 2017;124(2):232-239. doi:10.1016/j.radonc.2017.06.026
- Goepfert RP, Lewin JS, Barrow MP, et al. Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma. Laryngoscope. 2017;127(4):842-848. doi:10.1002/lary.26153
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018;81:45-51. doi:10.1016/j.oraloncology.2018.04.008
- Burtness B, Harrington KJ, Greil R, et al; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7
- Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3
- Strohl MP, Wai KC, Ha PK. De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma–a narrative review. Ann Transl Med. 2020;8(23):1601. doi:10.21037/atm-20-2984
- Economopoulou P, Kotsantis I, Psyrri A. De-escalating strategies in HPV-associated head and neck squamous cell carcinoma. Viruses. 2021;13(9):1787. doi:10.3390/v13091787
- Buchberger AMS, Strzelczyk EA, Wollenberg B, Combs SE, Pickhard A, Pigorsch SU. Report on late toxicity in head-and-neck tumor patients with long term survival after radiochemotherapy. Cancers (Basel). 2021;13(17):4292. doi:10.3390/cancers13174292
- Caparrotti F, Huang SH, Lu L, et al. Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy. Cancer. 2017;123(19):3691-3700. doi:10.1002/cncr.30803
- Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439.
doi:10.1016/j.ijrobp.2004.05.050 - Notani KI, Yamazaki Y, Kitada H, et al. Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck. 2003;25(3):181-186. doi:10.1002/hed.10171
- Servagi-Vernat S, Ali D, Roubieu C, Durdux C, Laccourreye O, Giraud P. Dysphagia after radiotherapy: state of the art and prevention. Eur Ann Otorhinolaryngol Head Neck Dis. 2015;132(1):25-29. doi:10.1016/j.anorl.2013.09.006
- Wijers OB, Levendag PC, Braaksma MMJ, Boonzaaijer M, Visch LL, Schmitz PIM. Patients with head and neck cancer cured by radiation therapy: A survey of the dry mouth syndrome in long-term survivors. Head Neck. 2002;24(8):737-747. doi:10.1002/hed.10129
- Sroussi HY, Epstein JB, Bensadoun RJ, et al. Common oral complications of head and
neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory
dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med.
2017;6(12):2918-2931. doi:10.1002/cam4.1221 - Bentzen SM, Trotti A. Evaluation of early and late toxicities in chemoradiation trials. J Clin Oncol. 2007;25(26):4096-4103. doi:10.1200/JCO.2007.13.3983
- Sapienza LG, Thomas JJ, Mai W, et al. Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible. Rep Pract Oncol Radiother. 2022;27(3):519-526. doi:10.5603/RPOR.a2022.0057
- Togni L, Mascitti M, Vignigni A, et al. Treatment-related dysgeusia in oral and oropharyngeal cancer: a comprehensive review. Nutrients. 2021;13(10):3325. doi:10.3390/nu13103325
- Hutcheson KA, Lewin JS, Barringer DA, et al. Late dysphagia after radiotherapy-based treatment of head and neck cancer. Cancer. 2012;118(23):5793-5799. doi:10.1002/cncr.27631
- Charters EK, Bogaardt H, Freeman-Sanderson AL, Ballard KJ. Systematic review and meta-analysis of the impact of dosimetry to dysphagia and aspiration related structures. Head Neck. 2019;41(6):1984-1998. doi:10.1002/hed.25631
- Terrell JE, Ronis DL, Fowler KE, et al. Clinical predictors of quality of life in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(4):401-408.
doi:10.1001/archotol.130.4.401 - Rogers SN, D’Souza JJ, Lowe D, Kanatas A. Longitudinal evaluation of health-related quality of life after osteoradionecrosis of the mandible. Br J Oral Maxillofac Surg. 2015;53(9):854-857. doi:10.1016/j.bjoms.2015.07.008
- Kubota H, Miyawaki D, Mukumoto N, et al. Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma. Radiat Oncol. 2021;16(1):1. doi:10.1186/s13014-020-01701-5
- Rosenthal DI, Mendoza TR, Chambers MS, et al. Measuring head and neck cancer symptom burden: the development and validation of the MD Anderson symptom inventory, head and neck module. Head Neck. 2007;29(10):923-931. doi:10.1002/hed.20602
- Barua S, Elhalawani H, Volpe S, et al. Computed tomography radiomics kinetics as early imaging correlates of osteoradionecrosis in oropharyngeal cancer patients. Front Artif Intell. 2021;4:618469. doi:10.3389/frai.2021.618469
- Joint Head and Neck Radiation Therapy-MRI Development Cooperative; Mohamed ASR, He R, Ding Y, et al. Quantitative dynamic contrast-enhanced MRI identifies radiation-induced vascular damage in patients with advanced osteoradionecrosis: results of a prospective study. Int J Radiat Oncol Biol Phys. 2020;108(5):1319-1328. doi:10.1016/j.ijrobp.2020.07.029
- Lydiatt WM, Patel SG, O’Sullivan B, et al. Head and neck cancers—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122-137. doi:10.3322/caac.21389
- Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X
- Sandulache VC, Wilde DC, Sturgis EM, Chiao EY, Sikora AG. A hidden epidemic of “intermediate risk” oropharynx cancer. Laryngoscope Investig Otolaryngol. 2019;4(6):617-623. doi:10.1002/lio2.316
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/
NEJMoa1602252 - Wilde DC, Castro PD, Bera K, et al. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration. Mod Pathol. 2022;35(8):1045-1054. doi:10.1038/s41379-022-01024-8
- Sandulache VC, Michikawa C, Kataria P, et al. High-risk TP53 mutations are associated with extranodal extension in oral cavity squamous cell carcinoma. Clin Cancer Res. 2018;24(7):1727-1733. doi:10.1158/1078-0432.CCR-17-0721
- Sandulache VC, Vandelaar LJ, Skinner HD, et al. Salvage total laryngectomy after external-beam radiotherapy: a 20-year experience. Head Neck. 2016;38(suppl 1):E1962-E1968. doi:10.1002/hed.24355
- Sandulache VC, Kubik MW, Skinner HD, Malsky JA, Gelbard AH, Zevallos JP. Impact of race/ethnicity on laryngeal cancer in patients treated at a Veterans Affairs Medical Center. Laryngoscope. 2013;123(9):2170-2175. doi:10.1002/lary.24058
- Hodgkinson K, Butow P, Hobbs KM, Hunt GE, Lo SK, Wain G. Assessing unmet supportive care needs in partners of cancer survivors: the development and evaluation of the Cancer Survivors’ Partners Unmet Needs measure (CaSPUN). Psychooncology. 2007;16(9):805-813. doi:10.1002/pon.1138
- Passchier E, Stuiver MM, van der Molen L, Kerkhof SI, van den Brekel MWM, Hilgers FJM. Feasibility and impact of a dedicated multidisciplinary rehabilitation program on health-related quality of life in advanced head and neck cancer patients. Eur Arch Otorhinolaryngol. 2016;273:1577-1587. doi:10.1007/s00405-015-3648-z
- Starmer H, Edwards J. Clinical decision making with head and neck cancer patients with dysphagia. Semin Speech Lang. 2019;40(3):213-226. doi:10.1055/s-0039-1688979
A 65-year-old African American man presented to an Otolaryngology Head and Neck Surgery clinic at a tertiary Veterans Health Administration (VHA) facility for evaluation. The patient recalled a past diagnosis of oropharyngeal cancer (OPC), possibly associated with the human papillomavirus (HPV). After receiving the diagnosis at another VHA facility, the patient opted to seek care at a local, non-VHA facility and received approximately 7 weeks of daily radiation and weekly infusions of chemotherapy.
Six years after his initial diagnosis and treatment, the patient said he had a persistent cough with any meaningful attempts to eat or drink. He also noted he lost at least 10 lbs in the last 3 months and had been hospitalized twice during the past winter. During his second hospitalization he spent 4 days on a ventilator in the intensive care unit.
On examination, the patient appeared frail and cachectic, with significant fibrosis of the neck skin and moderate trismus. His dentition was in poor health, and an in-clinic flexible endoscopy demonstrated clear silent aspiration of oral secretions. Given his failure to thrive, the patient was urgently admitted to the hospital. A modified barium swallow study performed by the head and neck Speech Pathology team demonstrated gross aspiration with all consistencies. After extensive counseling, the patient agreed to the placement of a gastrostomy tube. He was discharged in stable condition with adequate supplies and self-care training. He was advised to continue follow-up in the Head and Neck Cancer Survivorship clinic.
Two years later, in the early phase of the COVID-19 pandemic, the patient was admitted to the hospital with COVID pneumonia. Given the damage to his lungs over the previous decade from recurrent episodes of aspiration pneumonia, the patient succumbed.
An Unexpected, Unrelenting Epidemic
Shifting population dynamics and behaviors have led to an explosion in the incidence of cancers associated with infection by oncogenic subtypes of HPV, among which cancer of the oropharynx represents the most common malignancy.1,2 OPC now afflicts more than 30,000 new patients in the United States each year.3 Given current vaccination rates against oncogenic HPV, the overall trend of increasing incidence is not expected to stabilize until the 2040s.3 Traditional cancers of the head and neck region were previously fatal after 5 years in more than 60% of cases; however, today patients with HPV-associated OPC can expect a more than 80% chance of being alive 5 years after treatment.4-7 Combining the increasing incidence of OPC with a high chance of oncologic cure has led to an ever-expanding cohort of OPC survivors.
Enthusiasm about a high rate of survival after an HPV-associated OPC diagnosis is now partially dampened by an increasing realization that neither oncologists nor healthcare systems are remotely prepared for this rapidly expanding cohort of OPC survivors. Their unique needs and problems have yet to be objectively defined and quantified.
Relationship Between Survival and Long-Term Toxicity in HPV-Associated OPC
Survivorship care after OPC treatment is a growing challenge in terms of the number of patients affected, the negative impact on quality of life (QOL), and the potential burden on the healthcare system. The rapidly growing number of OPC survivors who are living long enough to develop delayed adverse effects related to their past OPC treatment1,2,8 includes many patients in whom toxicities can be truly debilitating,9,10 generating significant unmet needs.
Tumor and Treatment Toxicity
Although HPV-associated OPC demonstrates an excellent response to conventional chemoradiotherapy (CRT), this finding cannot be interpreted to mean that reducing treatment intensity is safe for patients with this disease. Prospective trials have now demonstrated that neither replacing or eliminating conventional chemotherapy, nor significantly reducing radiation doses, can be considered safe at this time.11-15 As a result, a patient with newly diagnosed HPV-associated OPC in 2025, and potentially even 2030, is likely to receive the same treatment as patients who were treated in the late 2010s.14
Three decades ago, the chronic effects of tumor and treatment were largely limited to a small cohort of survivors; however, today they affect more patients.1,2,7 Chronic xerostomia, dysphagia, trismus, radiation fibrosis, and osteoradionecrosis (ORN) now confront tens of thousands of OPC survivors; over the coming decades, these treatment effects have the potential to affect millions of patients.16-22
While most acute toxicities resolve within several months of completing CRT, late CRT sequelae tend to be dynamic and can progress silently over many years.16,23 Adverse effects vary widely, with many toxicities (eg, dysphagia, ORN) being particularly debilitating. Many of these effects occur in a radiation dose–dependent fashion, but radiation dose does not fully predict late toxicities, pointing to a role for other, yet unidentified contributing factors.24,25
Dysphagia in Survivors of OPC
About two-thirds of survivors of head and neck cancer (HNC) who seek follow-up care 5 years after treatment report dysphagia and at least partial dependence on a feeding tube.26 The incidence of dysphagia increases proportionately with higher radiation doses delivered to the pharyngeal constrictors and supraglottic larynx.18 Dysphagia can severely reduce QOL years after treatment, necessitating substantial changes in diet and social behavior among OPC survivors. Often, patients are forced to choose between chronic malnutrition or starvation and feeding tube dependence.27 Loss of a normal oral diet is frequently one of the most affected QOL measures for OPC survivors.28
In addition to effects on QOL, dysphagia can have life-threatening consequences. In a recent systematic review and meta-analysis, life-threatening aspiration occurred after > 24 months at a reported incidence ranging from 3% to nearly 35%. Although a reduction in radiation dose to the pharyngeal constrictors can reduce chronic dysphagia,27 whether this can be done safely in most OPC patients, particularly those with bulky primary tumors, remains unclear.
Osteoradionecrosis (ORN) in Survivors of OPC
ORN is one of the most potentially serious complications of CRT and may not manifest for years after treatment. Its median time of onset after radiotherapy is 8 years in patients with OPC.24 Bone injury and impaired healing of the alveolar mucosa are signs of ORN, which occurs in ~7% of patients receiving intensity-modulated radiation therapy for OPC.17 ORN is accompanied by pain, difficulties with chewing, exacerbation of concomitant dysphagia and, in the advanced stage—gross cosmetic deformity secondary to mandibular or maxillary fracture and/or decay.29 Despite the severity of this complication, we are just beginning to understand why ORN develops in a subset of patients. Although ORN is generally more common in patients with advanced-stage OPC who receive higher doses of radiation to a larger overall bone volume,17,19,24,30 comprehensive translational research efforts focused on ORN (as well as other late toxicities of OPC treatment) are still in their infancy.
Unmet Needs in Predicting and Evaluating Late Toxicities
Predicting which patients will experience long-term treatment toxicities or which types of late toxicities they may develop is not yet possible. Whereas increased data collection and prognostic models can help inform healthcare systems as to the expected frequencies of toxicity, they are unlikely to be prognostic at the individual patient level. As such, there is a critical need for individualized biomarker strategies that can predict one’s risk of toxicity and identify normal tissue shifts in biology and function early in the process to initiate interventions before significant deterioration. Adding to the complexity of predicting late toxicities is the lack of standardization in instruments used to categorize them. Examples of tools that may be used to categorize dysphagia include the Common Terminology Criteria for Adverse Events v4.0 grading scale, the Radiation Therapy Oncology Group grading system, and the European Organization for Research and Treatment of Cancer Performance Status Scale for Head and Neck Cancer.20 The MD Anderson Symptom Inventory for head and neck cancer may also be used to catalog dysphagia and other common symptoms of HNC, as well as treatment-related concerns.31 Magnetic resonance imaging-based techniques coupled with machine learning approaches represent emerging tools that may have a role in identifying early radiation-induced bone changes that can facilitate early detection of ORN.32,33 Although conventional and newer tools can be used to generate objective metrics of treatment-related toxicity, consistent and appropriate deployment across the entire cohort of OPC survivors in the United States remains a distant goal.
Calibrating Treatment Intensity to Disease Intensity
Given the risk of severe and potentially life-threatening consequences of radiation-based treatment, there is a large unmet need to better calibrate treatment intensity to the intensity of HPV-associated OPC.14,34 In light of the good prognosis of the disease in most patients, recent efforts have focused on identifying ways to de-escalate treatment intensity while preserving the good outcomes known to be possible for patients with HPV-associated OPC. Improving tolerability and limiting the risk of late effects of radiation-based treatment is especially important with the aging population of HPV-associated OPC survivors, who would also be expected to have unrelated comorbidities.1
Various modes of de-escalation have been studied, including adding surgery to CRT, reducing radiation dose, and modifying systemic therapy regimens. Most of these efforts have largely failed to identify a safe regimen for treatment de-escalation that applies to a majority or even a significant plurality of patients with OPC.14,35,36 Although CheckMate 141 and KEYNOTE-048 garnered excitement when immune checkpoint inhibitors (ICIs) significantly prolonged overall survival and had a more favorable safety profile than standard systemic therapy in recurrent and metastatic OPC,11,37,38 adding definitive frontline avelumab to CRT failed to prolong progression-free survival versus CRT alone in the phase 3 JAVELIN Head and Neck 100 trial.13 Combined with additional recent trial data, these findings make it unlikely that an ICI-based regimen will provide previously unavailable de-escalation options for patients with OPC in the near future.
Considering continued de-escalation efforts, it is important to remember that survival is not uniform among all patients with HPV-associated OPC. For example, patients with HPV-associated OPC and a history of current or prior heavy tobacco use have not experienced the same dramatic prolongation in overall survival as their nonsmoking counterparts.36 Patients with recurrent disease also face a dismal prognosis, with failure rates of about 70% with salvage treatment with surgery, re-irradiation, or systemic therapy.38-41 Therefore, de-escalation may not be appropriate in all patients, but identifying which patients are at risk of overtreatment is not straightforward. Better risk stratification of patients may provide part of the solution but will require rigorous testing and long-term follow-up to establish.
Discussion
There is an urgent need to carefully consider how to manage long-term survivors of HPV-associated OPC. With ever-increasing numbers of patients who are living years beyond their OPC treatment, continual reevaluation of treatment strategies in certain subsets of patients and making concerted efforts to identify and manage late toxicities early is paramount. Yet there remains a critical gap in knowledge due to insufficient metrics for both toxicity intensity and the frequency of debilitating, life-threatening toxicity. Unfortunately, the lack of tools available combined with the mismatch in disease intensity with treatment intensity likely results in excessive treatment-induced toxicity for many patients.
In the absence of clear evidence about which treatment strategy to use for individual patients, clinicians are tasked with making therapeutic choices without being fully able to predict outcomes. Patient preference is important to consider, but these conversations can be complicated. How does one talk to a patient about their willingness to risk a cancer recurrence and potentially risk late toxicities when the clinician does not know whether that individual patient will develop late toxicities, or know how severe they will be? It is a tradeoff between QOL (ie, possible feeding tube dependence) and survival—yet the magnitude of the effect on QOL remains impossible to predict at present for the individual patient.
Moreover, the needs of individual OPC survivors vary. A cross-sectional study performed at Princess Margaret Cancer Centre found that 61% of the 158 participants had unmet needs related to their cancer survivorship.42 Meeting the needs of survivors may require the development of better screening instruments that can manage various complications early and effectively. Continuing to follow OPC survivors with a multidisciplinary team would most certainly be beneficial and has been reported to improve QOL.43 Continual Speech Pathology management and therapy from the time of diagnosis into the survivorship phase of care has been suggested as one way to improve functional outcomes.44 Given that coordinating long-term care teams is logistically challenging, well-planned research is warranted to equip these teams to provide OPC survivors with the care they need. These efforts will be particularly important considering the large number of survivors who will need this type of care in the coming decades. The time to start is now well past.
A 65-year-old African American man presented to an Otolaryngology Head and Neck Surgery clinic at a tertiary Veterans Health Administration (VHA) facility for evaluation. The patient recalled a past diagnosis of oropharyngeal cancer (OPC), possibly associated with the human papillomavirus (HPV). After receiving the diagnosis at another VHA facility, the patient opted to seek care at a local, non-VHA facility and received approximately 7 weeks of daily radiation and weekly infusions of chemotherapy.
Six years after his initial diagnosis and treatment, the patient said he had a persistent cough with any meaningful attempts to eat or drink. He also noted he lost at least 10 lbs in the last 3 months and had been hospitalized twice during the past winter. During his second hospitalization he spent 4 days on a ventilator in the intensive care unit.
On examination, the patient appeared frail and cachectic, with significant fibrosis of the neck skin and moderate trismus. His dentition was in poor health, and an in-clinic flexible endoscopy demonstrated clear silent aspiration of oral secretions. Given his failure to thrive, the patient was urgently admitted to the hospital. A modified barium swallow study performed by the head and neck Speech Pathology team demonstrated gross aspiration with all consistencies. After extensive counseling, the patient agreed to the placement of a gastrostomy tube. He was discharged in stable condition with adequate supplies and self-care training. He was advised to continue follow-up in the Head and Neck Cancer Survivorship clinic.
Two years later, in the early phase of the COVID-19 pandemic, the patient was admitted to the hospital with COVID pneumonia. Given the damage to his lungs over the previous decade from recurrent episodes of aspiration pneumonia, the patient succumbed.
An Unexpected, Unrelenting Epidemic
Shifting population dynamics and behaviors have led to an explosion in the incidence of cancers associated with infection by oncogenic subtypes of HPV, among which cancer of the oropharynx represents the most common malignancy.1,2 OPC now afflicts more than 30,000 new patients in the United States each year.3 Given current vaccination rates against oncogenic HPV, the overall trend of increasing incidence is not expected to stabilize until the 2040s.3 Traditional cancers of the head and neck region were previously fatal after 5 years in more than 60% of cases; however, today patients with HPV-associated OPC can expect a more than 80% chance of being alive 5 years after treatment.4-7 Combining the increasing incidence of OPC with a high chance of oncologic cure has led to an ever-expanding cohort of OPC survivors.
Enthusiasm about a high rate of survival after an HPV-associated OPC diagnosis is now partially dampened by an increasing realization that neither oncologists nor healthcare systems are remotely prepared for this rapidly expanding cohort of OPC survivors. Their unique needs and problems have yet to be objectively defined and quantified.
Relationship Between Survival and Long-Term Toxicity in HPV-Associated OPC
Survivorship care after OPC treatment is a growing challenge in terms of the number of patients affected, the negative impact on quality of life (QOL), and the potential burden on the healthcare system. The rapidly growing number of OPC survivors who are living long enough to develop delayed adverse effects related to their past OPC treatment1,2,8 includes many patients in whom toxicities can be truly debilitating,9,10 generating significant unmet needs.
Tumor and Treatment Toxicity
Although HPV-associated OPC demonstrates an excellent response to conventional chemoradiotherapy (CRT), this finding cannot be interpreted to mean that reducing treatment intensity is safe for patients with this disease. Prospective trials have now demonstrated that neither replacing or eliminating conventional chemotherapy, nor significantly reducing radiation doses, can be considered safe at this time.11-15 As a result, a patient with newly diagnosed HPV-associated OPC in 2025, and potentially even 2030, is likely to receive the same treatment as patients who were treated in the late 2010s.14
Three decades ago, the chronic effects of tumor and treatment were largely limited to a small cohort of survivors; however, today they affect more patients.1,2,7 Chronic xerostomia, dysphagia, trismus, radiation fibrosis, and osteoradionecrosis (ORN) now confront tens of thousands of OPC survivors; over the coming decades, these treatment effects have the potential to affect millions of patients.16-22
While most acute toxicities resolve within several months of completing CRT, late CRT sequelae tend to be dynamic and can progress silently over many years.16,23 Adverse effects vary widely, with many toxicities (eg, dysphagia, ORN) being particularly debilitating. Many of these effects occur in a radiation dose–dependent fashion, but radiation dose does not fully predict late toxicities, pointing to a role for other, yet unidentified contributing factors.24,25
Dysphagia in Survivors of OPC
About two-thirds of survivors of head and neck cancer (HNC) who seek follow-up care 5 years after treatment report dysphagia and at least partial dependence on a feeding tube.26 The incidence of dysphagia increases proportionately with higher radiation doses delivered to the pharyngeal constrictors and supraglottic larynx.18 Dysphagia can severely reduce QOL years after treatment, necessitating substantial changes in diet and social behavior among OPC survivors. Often, patients are forced to choose between chronic malnutrition or starvation and feeding tube dependence.27 Loss of a normal oral diet is frequently one of the most affected QOL measures for OPC survivors.28
In addition to effects on QOL, dysphagia can have life-threatening consequences. In a recent systematic review and meta-analysis, life-threatening aspiration occurred after > 24 months at a reported incidence ranging from 3% to nearly 35%. Although a reduction in radiation dose to the pharyngeal constrictors can reduce chronic dysphagia,27 whether this can be done safely in most OPC patients, particularly those with bulky primary tumors, remains unclear.
Osteoradionecrosis (ORN) in Survivors of OPC
ORN is one of the most potentially serious complications of CRT and may not manifest for years after treatment. Its median time of onset after radiotherapy is 8 years in patients with OPC.24 Bone injury and impaired healing of the alveolar mucosa are signs of ORN, which occurs in ~7% of patients receiving intensity-modulated radiation therapy for OPC.17 ORN is accompanied by pain, difficulties with chewing, exacerbation of concomitant dysphagia and, in the advanced stage—gross cosmetic deformity secondary to mandibular or maxillary fracture and/or decay.29 Despite the severity of this complication, we are just beginning to understand why ORN develops in a subset of patients. Although ORN is generally more common in patients with advanced-stage OPC who receive higher doses of radiation to a larger overall bone volume,17,19,24,30 comprehensive translational research efforts focused on ORN (as well as other late toxicities of OPC treatment) are still in their infancy.
Unmet Needs in Predicting and Evaluating Late Toxicities
Predicting which patients will experience long-term treatment toxicities or which types of late toxicities they may develop is not yet possible. Whereas increased data collection and prognostic models can help inform healthcare systems as to the expected frequencies of toxicity, they are unlikely to be prognostic at the individual patient level. As such, there is a critical need for individualized biomarker strategies that can predict one’s risk of toxicity and identify normal tissue shifts in biology and function early in the process to initiate interventions before significant deterioration. Adding to the complexity of predicting late toxicities is the lack of standardization in instruments used to categorize them. Examples of tools that may be used to categorize dysphagia include the Common Terminology Criteria for Adverse Events v4.0 grading scale, the Radiation Therapy Oncology Group grading system, and the European Organization for Research and Treatment of Cancer Performance Status Scale for Head and Neck Cancer.20 The MD Anderson Symptom Inventory for head and neck cancer may also be used to catalog dysphagia and other common symptoms of HNC, as well as treatment-related concerns.31 Magnetic resonance imaging-based techniques coupled with machine learning approaches represent emerging tools that may have a role in identifying early radiation-induced bone changes that can facilitate early detection of ORN.32,33 Although conventional and newer tools can be used to generate objective metrics of treatment-related toxicity, consistent and appropriate deployment across the entire cohort of OPC survivors in the United States remains a distant goal.
Calibrating Treatment Intensity to Disease Intensity
Given the risk of severe and potentially life-threatening consequences of radiation-based treatment, there is a large unmet need to better calibrate treatment intensity to the intensity of HPV-associated OPC.14,34 In light of the good prognosis of the disease in most patients, recent efforts have focused on identifying ways to de-escalate treatment intensity while preserving the good outcomes known to be possible for patients with HPV-associated OPC. Improving tolerability and limiting the risk of late effects of radiation-based treatment is especially important with the aging population of HPV-associated OPC survivors, who would also be expected to have unrelated comorbidities.1
Various modes of de-escalation have been studied, including adding surgery to CRT, reducing radiation dose, and modifying systemic therapy regimens. Most of these efforts have largely failed to identify a safe regimen for treatment de-escalation that applies to a majority or even a significant plurality of patients with OPC.14,35,36 Although CheckMate 141 and KEYNOTE-048 garnered excitement when immune checkpoint inhibitors (ICIs) significantly prolonged overall survival and had a more favorable safety profile than standard systemic therapy in recurrent and metastatic OPC,11,37,38 adding definitive frontline avelumab to CRT failed to prolong progression-free survival versus CRT alone in the phase 3 JAVELIN Head and Neck 100 trial.13 Combined with additional recent trial data, these findings make it unlikely that an ICI-based regimen will provide previously unavailable de-escalation options for patients with OPC in the near future.
Considering continued de-escalation efforts, it is important to remember that survival is not uniform among all patients with HPV-associated OPC. For example, patients with HPV-associated OPC and a history of current or prior heavy tobacco use have not experienced the same dramatic prolongation in overall survival as their nonsmoking counterparts.36 Patients with recurrent disease also face a dismal prognosis, with failure rates of about 70% with salvage treatment with surgery, re-irradiation, or systemic therapy.38-41 Therefore, de-escalation may not be appropriate in all patients, but identifying which patients are at risk of overtreatment is not straightforward. Better risk stratification of patients may provide part of the solution but will require rigorous testing and long-term follow-up to establish.
Discussion
There is an urgent need to carefully consider how to manage long-term survivors of HPV-associated OPC. With ever-increasing numbers of patients who are living years beyond their OPC treatment, continual reevaluation of treatment strategies in certain subsets of patients and making concerted efforts to identify and manage late toxicities early is paramount. Yet there remains a critical gap in knowledge due to insufficient metrics for both toxicity intensity and the frequency of debilitating, life-threatening toxicity. Unfortunately, the lack of tools available combined with the mismatch in disease intensity with treatment intensity likely results in excessive treatment-induced toxicity for many patients.
In the absence of clear evidence about which treatment strategy to use for individual patients, clinicians are tasked with making therapeutic choices without being fully able to predict outcomes. Patient preference is important to consider, but these conversations can be complicated. How does one talk to a patient about their willingness to risk a cancer recurrence and potentially risk late toxicities when the clinician does not know whether that individual patient will develop late toxicities, or know how severe they will be? It is a tradeoff between QOL (ie, possible feeding tube dependence) and survival—yet the magnitude of the effect on QOL remains impossible to predict at present for the individual patient.
Moreover, the needs of individual OPC survivors vary. A cross-sectional study performed at Princess Margaret Cancer Centre found that 61% of the 158 participants had unmet needs related to their cancer survivorship.42 Meeting the needs of survivors may require the development of better screening instruments that can manage various complications early and effectively. Continuing to follow OPC survivors with a multidisciplinary team would most certainly be beneficial and has been reported to improve QOL.43 Continual Speech Pathology management and therapy from the time of diagnosis into the survivorship phase of care has been suggested as one way to improve functional outcomes.44 Given that coordinating long-term care teams is logistically challenging, well-planned research is warranted to equip these teams to provide OPC survivors with the care they need. These efforts will be particularly important considering the large number of survivors who will need this type of care in the coming decades. The time to start is now well past.
- Tota JE, Best AF, Zumsteg ZS, Gillison ML, Rosenberg PS, Chaturvedi AK. Evolution of the oropharynx cancer epidemic in the United States: moderation of increasing incidence in younger individuals and shift in the burden to older individuals. J Clin Oncol. 2019;37(18):1538-1546. doi:10.1200/JCO.19.00370
- Liao CI, Francoeur AA, Kapp DS, Caesar MAP, Huh WK, Chan JK. Trends in human papillomavirus-associated cancers, demographic characteristics, and vaccinations in the US, 2001-2017. JAMA Netw Open. 2022;5(3):e222530. doi:10.1001/jamanetworkopen.2022.2530
- Zhang Y, Fakhry C, D’Souza G. Projected association of human papillomavirus vaccination with oropharynx cancer incidence in the US, 2020-2045. JAMA Oncol. 2021;7(10):e212907. doi:10.1001/jamaoncol.2021.2907
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217
- Li H, Torabi SJ, Yarbrough WG, Mehra S, Osborn HA, Judson B. Association of human papillomavirus status at head and neck carcinoma subsites with overall survival. JAMA Otolaryngol Head Neck Surg. 2018;144(6):519-525. doi:10.1001/jamaoto.2018.0395
- Lill C, Bachtiary B, Selzer E, Mittlboeck M, Thurnher D. A 5-year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria. Wien Klin Wochenschr. 2017;129(11-12):398-403. doi:10.1007/s00508-017-1171-5
- Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001. doi:10.1634/theoncologist.2009-0289
- Goepfert RP, Fuller CD, Gunn GB, et al. Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors. Head Neck. 2017;39(11):2151-2158. doi:10.1002/hed.24879
- MD Anderson Head and Neck Cancer Symptom Working Group. Dose-volume correlates of mandibular osteoradionecrosis in oropharynx cancer patients receiving intensity-modulated radiotherapy: results from a case-matched comparison. Radiother Oncol. 2017;124(2):232-239. doi:10.1016/j.radonc.2017.06.026
- Goepfert RP, Lewin JS, Barrow MP, et al. Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma. Laryngoscope. 2017;127(4):842-848. doi:10.1002/lary.26153
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018;81:45-51. doi:10.1016/j.oraloncology.2018.04.008
- Burtness B, Harrington KJ, Greil R, et al; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7
- Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3
- Strohl MP, Wai KC, Ha PK. De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma–a narrative review. Ann Transl Med. 2020;8(23):1601. doi:10.21037/atm-20-2984
- Economopoulou P, Kotsantis I, Psyrri A. De-escalating strategies in HPV-associated head and neck squamous cell carcinoma. Viruses. 2021;13(9):1787. doi:10.3390/v13091787
- Buchberger AMS, Strzelczyk EA, Wollenberg B, Combs SE, Pickhard A, Pigorsch SU. Report on late toxicity in head-and-neck tumor patients with long term survival after radiochemotherapy. Cancers (Basel). 2021;13(17):4292. doi:10.3390/cancers13174292
- Caparrotti F, Huang SH, Lu L, et al. Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy. Cancer. 2017;123(19):3691-3700. doi:10.1002/cncr.30803
- Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439.
doi:10.1016/j.ijrobp.2004.05.050 - Notani KI, Yamazaki Y, Kitada H, et al. Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck. 2003;25(3):181-186. doi:10.1002/hed.10171
- Servagi-Vernat S, Ali D, Roubieu C, Durdux C, Laccourreye O, Giraud P. Dysphagia after radiotherapy: state of the art and prevention. Eur Ann Otorhinolaryngol Head Neck Dis. 2015;132(1):25-29. doi:10.1016/j.anorl.2013.09.006
- Wijers OB, Levendag PC, Braaksma MMJ, Boonzaaijer M, Visch LL, Schmitz PIM. Patients with head and neck cancer cured by radiation therapy: A survey of the dry mouth syndrome in long-term survivors. Head Neck. 2002;24(8):737-747. doi:10.1002/hed.10129
- Sroussi HY, Epstein JB, Bensadoun RJ, et al. Common oral complications of head and
neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory
dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med.
2017;6(12):2918-2931. doi:10.1002/cam4.1221 - Bentzen SM, Trotti A. Evaluation of early and late toxicities in chemoradiation trials. J Clin Oncol. 2007;25(26):4096-4103. doi:10.1200/JCO.2007.13.3983
- Sapienza LG, Thomas JJ, Mai W, et al. Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible. Rep Pract Oncol Radiother. 2022;27(3):519-526. doi:10.5603/RPOR.a2022.0057
- Togni L, Mascitti M, Vignigni A, et al. Treatment-related dysgeusia in oral and oropharyngeal cancer: a comprehensive review. Nutrients. 2021;13(10):3325. doi:10.3390/nu13103325
- Hutcheson KA, Lewin JS, Barringer DA, et al. Late dysphagia after radiotherapy-based treatment of head and neck cancer. Cancer. 2012;118(23):5793-5799. doi:10.1002/cncr.27631
- Charters EK, Bogaardt H, Freeman-Sanderson AL, Ballard KJ. Systematic review and meta-analysis of the impact of dosimetry to dysphagia and aspiration related structures. Head Neck. 2019;41(6):1984-1998. doi:10.1002/hed.25631
- Terrell JE, Ronis DL, Fowler KE, et al. Clinical predictors of quality of life in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(4):401-408.
doi:10.1001/archotol.130.4.401 - Rogers SN, D’Souza JJ, Lowe D, Kanatas A. Longitudinal evaluation of health-related quality of life after osteoradionecrosis of the mandible. Br J Oral Maxillofac Surg. 2015;53(9):854-857. doi:10.1016/j.bjoms.2015.07.008
- Kubota H, Miyawaki D, Mukumoto N, et al. Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma. Radiat Oncol. 2021;16(1):1. doi:10.1186/s13014-020-01701-5
- Rosenthal DI, Mendoza TR, Chambers MS, et al. Measuring head and neck cancer symptom burden: the development and validation of the MD Anderson symptom inventory, head and neck module. Head Neck. 2007;29(10):923-931. doi:10.1002/hed.20602
- Barua S, Elhalawani H, Volpe S, et al. Computed tomography radiomics kinetics as early imaging correlates of osteoradionecrosis in oropharyngeal cancer patients. Front Artif Intell. 2021;4:618469. doi:10.3389/frai.2021.618469
- Joint Head and Neck Radiation Therapy-MRI Development Cooperative; Mohamed ASR, He R, Ding Y, et al. Quantitative dynamic contrast-enhanced MRI identifies radiation-induced vascular damage in patients with advanced osteoradionecrosis: results of a prospective study. Int J Radiat Oncol Biol Phys. 2020;108(5):1319-1328. doi:10.1016/j.ijrobp.2020.07.029
- Lydiatt WM, Patel SG, O’Sullivan B, et al. Head and neck cancers—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122-137. doi:10.3322/caac.21389
- Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X
- Sandulache VC, Wilde DC, Sturgis EM, Chiao EY, Sikora AG. A hidden epidemic of “intermediate risk” oropharynx cancer. Laryngoscope Investig Otolaryngol. 2019;4(6):617-623. doi:10.1002/lio2.316
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/
NEJMoa1602252 - Wilde DC, Castro PD, Bera K, et al. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration. Mod Pathol. 2022;35(8):1045-1054. doi:10.1038/s41379-022-01024-8
- Sandulache VC, Michikawa C, Kataria P, et al. High-risk TP53 mutations are associated with extranodal extension in oral cavity squamous cell carcinoma. Clin Cancer Res. 2018;24(7):1727-1733. doi:10.1158/1078-0432.CCR-17-0721
- Sandulache VC, Vandelaar LJ, Skinner HD, et al. Salvage total laryngectomy after external-beam radiotherapy: a 20-year experience. Head Neck. 2016;38(suppl 1):E1962-E1968. doi:10.1002/hed.24355
- Sandulache VC, Kubik MW, Skinner HD, Malsky JA, Gelbard AH, Zevallos JP. Impact of race/ethnicity on laryngeal cancer in patients treated at a Veterans Affairs Medical Center. Laryngoscope. 2013;123(9):2170-2175. doi:10.1002/lary.24058
- Hodgkinson K, Butow P, Hobbs KM, Hunt GE, Lo SK, Wain G. Assessing unmet supportive care needs in partners of cancer survivors: the development and evaluation of the Cancer Survivors’ Partners Unmet Needs measure (CaSPUN). Psychooncology. 2007;16(9):805-813. doi:10.1002/pon.1138
- Passchier E, Stuiver MM, van der Molen L, Kerkhof SI, van den Brekel MWM, Hilgers FJM. Feasibility and impact of a dedicated multidisciplinary rehabilitation program on health-related quality of life in advanced head and neck cancer patients. Eur Arch Otorhinolaryngol. 2016;273:1577-1587. doi:10.1007/s00405-015-3648-z
- Starmer H, Edwards J. Clinical decision making with head and neck cancer patients with dysphagia. Semin Speech Lang. 2019;40(3):213-226. doi:10.1055/s-0039-1688979
- Tota JE, Best AF, Zumsteg ZS, Gillison ML, Rosenberg PS, Chaturvedi AK. Evolution of the oropharynx cancer epidemic in the United States: moderation of increasing incidence in younger individuals and shift in the burden to older individuals. J Clin Oncol. 2019;37(18):1538-1546. doi:10.1200/JCO.19.00370
- Liao CI, Francoeur AA, Kapp DS, Caesar MAP, Huh WK, Chan JK. Trends in human papillomavirus-associated cancers, demographic characteristics, and vaccinations in the US, 2001-2017. JAMA Netw Open. 2022;5(3):e222530. doi:10.1001/jamanetworkopen.2022.2530
- Zhang Y, Fakhry C, D’Souza G. Projected association of human papillomavirus vaccination with oropharynx cancer incidence in the US, 2020-2045. JAMA Oncol. 2021;7(10):e212907. doi:10.1001/jamaoncol.2021.2907
- Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217
- Li H, Torabi SJ, Yarbrough WG, Mehra S, Osborn HA, Judson B. Association of human papillomavirus status at head and neck carcinoma subsites with overall survival. JAMA Otolaryngol Head Neck Surg. 2018;144(6):519-525. doi:10.1001/jamaoto.2018.0395
- Lill C, Bachtiary B, Selzer E, Mittlboeck M, Thurnher D. A 5-year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria. Wien Klin Wochenschr. 2017;129(11-12):398-403. doi:10.1007/s00508-017-1171-5
- Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001. doi:10.1634/theoncologist.2009-0289
- Goepfert RP, Fuller CD, Gunn GB, et al. Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors. Head Neck. 2017;39(11):2151-2158. doi:10.1002/hed.24879
- MD Anderson Head and Neck Cancer Symptom Working Group. Dose-volume correlates of mandibular osteoradionecrosis in oropharynx cancer patients receiving intensity-modulated radiotherapy: results from a case-matched comparison. Radiother Oncol. 2017;124(2):232-239. doi:10.1016/j.radonc.2017.06.026
- Goepfert RP, Lewin JS, Barrow MP, et al. Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma. Laryngoscope. 2017;127(4):842-848. doi:10.1002/lary.26153
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018;81:45-51. doi:10.1016/j.oraloncology.2018.04.008
- Burtness B, Harrington KJ, Greil R, et al; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7
- Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3
- Strohl MP, Wai KC, Ha PK. De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma–a narrative review. Ann Transl Med. 2020;8(23):1601. doi:10.21037/atm-20-2984
- Economopoulou P, Kotsantis I, Psyrri A. De-escalating strategies in HPV-associated head and neck squamous cell carcinoma. Viruses. 2021;13(9):1787. doi:10.3390/v13091787
- Buchberger AMS, Strzelczyk EA, Wollenberg B, Combs SE, Pickhard A, Pigorsch SU. Report on late toxicity in head-and-neck tumor patients with long term survival after radiochemotherapy. Cancers (Basel). 2021;13(17):4292. doi:10.3390/cancers13174292
- Caparrotti F, Huang SH, Lu L, et al. Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy. Cancer. 2017;123(19):3691-3700. doi:10.1002/cncr.30803
- Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439.
doi:10.1016/j.ijrobp.2004.05.050 - Notani KI, Yamazaki Y, Kitada H, et al. Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck. 2003;25(3):181-186. doi:10.1002/hed.10171
- Servagi-Vernat S, Ali D, Roubieu C, Durdux C, Laccourreye O, Giraud P. Dysphagia after radiotherapy: state of the art and prevention. Eur Ann Otorhinolaryngol Head Neck Dis. 2015;132(1):25-29. doi:10.1016/j.anorl.2013.09.006
- Wijers OB, Levendag PC, Braaksma MMJ, Boonzaaijer M, Visch LL, Schmitz PIM. Patients with head and neck cancer cured by radiation therapy: A survey of the dry mouth syndrome in long-term survivors. Head Neck. 2002;24(8):737-747. doi:10.1002/hed.10129
- Sroussi HY, Epstein JB, Bensadoun RJ, et al. Common oral complications of head and
neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory
dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med.
2017;6(12):2918-2931. doi:10.1002/cam4.1221 - Bentzen SM, Trotti A. Evaluation of early and late toxicities in chemoradiation trials. J Clin Oncol. 2007;25(26):4096-4103. doi:10.1200/JCO.2007.13.3983
- Sapienza LG, Thomas JJ, Mai W, et al. Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible. Rep Pract Oncol Radiother. 2022;27(3):519-526. doi:10.5603/RPOR.a2022.0057
- Togni L, Mascitti M, Vignigni A, et al. Treatment-related dysgeusia in oral and oropharyngeal cancer: a comprehensive review. Nutrients. 2021;13(10):3325. doi:10.3390/nu13103325
- Hutcheson KA, Lewin JS, Barringer DA, et al. Late dysphagia after radiotherapy-based treatment of head and neck cancer. Cancer. 2012;118(23):5793-5799. doi:10.1002/cncr.27631
- Charters EK, Bogaardt H, Freeman-Sanderson AL, Ballard KJ. Systematic review and meta-analysis of the impact of dosimetry to dysphagia and aspiration related structures. Head Neck. 2019;41(6):1984-1998. doi:10.1002/hed.25631
- Terrell JE, Ronis DL, Fowler KE, et al. Clinical predictors of quality of life in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(4):401-408.
doi:10.1001/archotol.130.4.401 - Rogers SN, D’Souza JJ, Lowe D, Kanatas A. Longitudinal evaluation of health-related quality of life after osteoradionecrosis of the mandible. Br J Oral Maxillofac Surg. 2015;53(9):854-857. doi:10.1016/j.bjoms.2015.07.008
- Kubota H, Miyawaki D, Mukumoto N, et al. Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma. Radiat Oncol. 2021;16(1):1. doi:10.1186/s13014-020-01701-5
- Rosenthal DI, Mendoza TR, Chambers MS, et al. Measuring head and neck cancer symptom burden: the development and validation of the MD Anderson symptom inventory, head and neck module. Head Neck. 2007;29(10):923-931. doi:10.1002/hed.20602
- Barua S, Elhalawani H, Volpe S, et al. Computed tomography radiomics kinetics as early imaging correlates of osteoradionecrosis in oropharyngeal cancer patients. Front Artif Intell. 2021;4:618469. doi:10.3389/frai.2021.618469
- Joint Head and Neck Radiation Therapy-MRI Development Cooperative; Mohamed ASR, He R, Ding Y, et al. Quantitative dynamic contrast-enhanced MRI identifies radiation-induced vascular damage in patients with advanced osteoradionecrosis: results of a prospective study. Int J Radiat Oncol Biol Phys. 2020;108(5):1319-1328. doi:10.1016/j.ijrobp.2020.07.029
- Lydiatt WM, Patel SG, O’Sullivan B, et al. Head and neck cancers—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122-137. doi:10.3322/caac.21389
- Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X
- Sandulache VC, Wilde DC, Sturgis EM, Chiao EY, Sikora AG. A hidden epidemic of “intermediate risk” oropharynx cancer. Laryngoscope Investig Otolaryngol. 2019;4(6):617-623. doi:10.1002/lio2.316
- Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/
NEJMoa1602252 - Wilde DC, Castro PD, Bera K, et al. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration. Mod Pathol. 2022;35(8):1045-1054. doi:10.1038/s41379-022-01024-8
- Sandulache VC, Michikawa C, Kataria P, et al. High-risk TP53 mutations are associated with extranodal extension in oral cavity squamous cell carcinoma. Clin Cancer Res. 2018;24(7):1727-1733. doi:10.1158/1078-0432.CCR-17-0721
- Sandulache VC, Vandelaar LJ, Skinner HD, et al. Salvage total laryngectomy after external-beam radiotherapy: a 20-year experience. Head Neck. 2016;38(suppl 1):E1962-E1968. doi:10.1002/hed.24355
- Sandulache VC, Kubik MW, Skinner HD, Malsky JA, Gelbard AH, Zevallos JP. Impact of race/ethnicity on laryngeal cancer in patients treated at a Veterans Affairs Medical Center. Laryngoscope. 2013;123(9):2170-2175. doi:10.1002/lary.24058
- Hodgkinson K, Butow P, Hobbs KM, Hunt GE, Lo SK, Wain G. Assessing unmet supportive care needs in partners of cancer survivors: the development and evaluation of the Cancer Survivors’ Partners Unmet Needs measure (CaSPUN). Psychooncology. 2007;16(9):805-813. doi:10.1002/pon.1138
- Passchier E, Stuiver MM, van der Molen L, Kerkhof SI, van den Brekel MWM, Hilgers FJM. Feasibility and impact of a dedicated multidisciplinary rehabilitation program on health-related quality of life in advanced head and neck cancer patients. Eur Arch Otorhinolaryngol. 2016;273:1577-1587. doi:10.1007/s00405-015-3648-z
- Starmer H, Edwards J. Clinical decision making with head and neck cancer patients with dysphagia. Semin Speech Lang. 2019;40(3):213-226. doi:10.1055/s-0039-1688979
NORD: Making Progress Through Collaboration
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
2023 Rare Diseases Report: Cancers
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
CBSM phone app eases anxiety, depression in cancer patients
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023