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USPSTF final recommendation on CRC screening: 45 is the new 50
Screening for colorectal cancer (CRC) should now begin at the age of 45 and not 50 for average-risk individuals in the United States, notes the final recommendation from the U.S. Preventive Services Task Force.
The recommendation finalizes draft guidelines issued in October 2020 and mandates insurance coverage to ensure equal access to CRC screening regardless of a patient’s insurance status.
The USPSTF’s final recommendations also now align with those of the American Cancer Society, which lowered the age for initiation of CRC screening to 45 years in 2018.
“New statistics project an alarming rise in the incidence of young-onset colorectal cancer, projected to be the leading cause of cancer death in patients aged 20-49 by 2040,” commented Kimmie Ng, MD, MPH, director, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Boston, and lead author of a JAMA editorial about the new guideline.
“We must take bold steps to translate the lowered age of beginning screening into meaningful decreases in CRC incidence and mortality,” she emphasized.
The USPSTF recommendations and substantial evidence supporting them were published online May 18, 2021, in JAMA.
Risk factors for CRC
As the USPSTF authors noted, age is one of the most important risk factors for CRC, with nearly 94% of all new cases of CRC occurring in adults 45 years of age and older. Justification for the lower age of CRC screening initiation was based on simulation models showing that initiation of screening at the age of 45 was associated with an estimated additional 22-27 life-years gained, compared with starting at the age of 50.
The USPSTF continues to recommend screening for CRC in all adults aged between 50 and 75 years, lowering the age for screening to 45 years in recognition of the fact that, in 2020, 11% of colon cancers and 15% of rectal cancers occurred in patients under the age of 50.
The USPSTF also continues to conclude that there is a “small net benefit” of screening for CRC in adults aged between 76 and 85 years who have been previously screened.
However, the decision to screen patients in this age group should be based on individual risk factors for CRC, a patient’s overall health status, and personal preference. Perhaps self-evidently, adults in this age group who have never been screened for CRC are more likely to benefit from CRC screening than those who have been previously screened.
Similar to the previous guidelines released in 2016, the updated USPSTF recommendations continue to offer a menu of screening strategies, although the frequency of screening for each of the screening strategies varies. Recommended screening strategies include:
- High-sensitivity guaiac fecal occult blood test or fecal immunochemical test (FIT) every year
- Stool DNA-FIT every 1-3 years
- CT colonography every 5 years
- every 5 years
- Flexible sigmoidoscopy every 10 years plus annual FIT
- screening every 10 years
“Based on the evidence, there are many tests available that can effectively screen for colorectal cancer and the right test is the one that gets done,” USPSTF member Martha Kubik, PhD, RN, said in a statement.
“To encourage screening and help patients select the best test for them, we urge primary care clinicians to talk about the pros and cons of the various recommended options with their patients,” she added.
An accompanying review of the effectiveness, accuracy, and potential harms of CRC screening methods underscores how different screening tests have different levels of evidence demonstrating their ability to detect cancer, precursor lesions, or both, as well as their ability to reduce mortality from cancer.
Eligible patients
Currently, fewer than 70% of eligible patients in the United States undergo CRC screening, Dr. Ng pointed out in the editorial. In addition, CRC disproportionately affects African American patients, who are about 20% more likely to get CRC and about 40% more likely to die from it, compared with other patient groups. Modeling studies published along with the USPSTF recommendations showed equal benefit for screening regardless of race and gender, underscoring the importance of screening adherence, especially in patient populations disproportionately affected by CRC.
“Far too many people in the U.S. are not receiving this lifesaving preventive service,” USPSTF vice chair Michael Barry, MD, said in a statement.
“We hope that this new recommendation to screen people ages 45-49, coupled with our long-standing recommendation to screen people 50-75, will prevent more people from dying from colorectal cancer,” he added.
Dr. Ng echoed this sentiment in her editorial: “The USPSTF recommendation for beginning colorectal cancer screening for average-risk adults at age 45 years has moved the field one step forward and indicates that ‘45 is the new 50,’ ” she observed.
“Lowering the recommended age to initiate screening will make colorectal cancer screening available to millions more people in the United States and, hopefully, many more lives will be saved by catching colorectal cancer earlier as well as by preventing colorectal cancer,” Dr. Ng affirmed.
All members of the USPSTF received travel reimbursement and an honorarium for participating in USPSTF meetings.
Dr. Ng reported receiving nonfinancial support from Pharmavite as well as grants from the Evergrande Group, Janssen, Revolution Medicines, Genentech, and Gilead Sciences. She has also reported receiving personal fees from Seattle Genetics, Array Biopharma, BiomX, and X-Biotix Therapeutics.
A version of this article first appeared on Medscape.com.
Screening for colorectal cancer (CRC) should now begin at the age of 45 and not 50 for average-risk individuals in the United States, notes the final recommendation from the U.S. Preventive Services Task Force.
The recommendation finalizes draft guidelines issued in October 2020 and mandates insurance coverage to ensure equal access to CRC screening regardless of a patient’s insurance status.
The USPSTF’s final recommendations also now align with those of the American Cancer Society, which lowered the age for initiation of CRC screening to 45 years in 2018.
“New statistics project an alarming rise in the incidence of young-onset colorectal cancer, projected to be the leading cause of cancer death in patients aged 20-49 by 2040,” commented Kimmie Ng, MD, MPH, director, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Boston, and lead author of a JAMA editorial about the new guideline.
“We must take bold steps to translate the lowered age of beginning screening into meaningful decreases in CRC incidence and mortality,” she emphasized.
The USPSTF recommendations and substantial evidence supporting them were published online May 18, 2021, in JAMA.
Risk factors for CRC
As the USPSTF authors noted, age is one of the most important risk factors for CRC, with nearly 94% of all new cases of CRC occurring in adults 45 years of age and older. Justification for the lower age of CRC screening initiation was based on simulation models showing that initiation of screening at the age of 45 was associated with an estimated additional 22-27 life-years gained, compared with starting at the age of 50.
The USPSTF continues to recommend screening for CRC in all adults aged between 50 and 75 years, lowering the age for screening to 45 years in recognition of the fact that, in 2020, 11% of colon cancers and 15% of rectal cancers occurred in patients under the age of 50.
The USPSTF also continues to conclude that there is a “small net benefit” of screening for CRC in adults aged between 76 and 85 years who have been previously screened.
However, the decision to screen patients in this age group should be based on individual risk factors for CRC, a patient’s overall health status, and personal preference. Perhaps self-evidently, adults in this age group who have never been screened for CRC are more likely to benefit from CRC screening than those who have been previously screened.
Similar to the previous guidelines released in 2016, the updated USPSTF recommendations continue to offer a menu of screening strategies, although the frequency of screening for each of the screening strategies varies. Recommended screening strategies include:
- High-sensitivity guaiac fecal occult blood test or fecal immunochemical test (FIT) every year
- Stool DNA-FIT every 1-3 years
- CT colonography every 5 years
- every 5 years
- Flexible sigmoidoscopy every 10 years plus annual FIT
- screening every 10 years
“Based on the evidence, there are many tests available that can effectively screen for colorectal cancer and the right test is the one that gets done,” USPSTF member Martha Kubik, PhD, RN, said in a statement.
“To encourage screening and help patients select the best test for them, we urge primary care clinicians to talk about the pros and cons of the various recommended options with their patients,” she added.
An accompanying review of the effectiveness, accuracy, and potential harms of CRC screening methods underscores how different screening tests have different levels of evidence demonstrating their ability to detect cancer, precursor lesions, or both, as well as their ability to reduce mortality from cancer.
Eligible patients
Currently, fewer than 70% of eligible patients in the United States undergo CRC screening, Dr. Ng pointed out in the editorial. In addition, CRC disproportionately affects African American patients, who are about 20% more likely to get CRC and about 40% more likely to die from it, compared with other patient groups. Modeling studies published along with the USPSTF recommendations showed equal benefit for screening regardless of race and gender, underscoring the importance of screening adherence, especially in patient populations disproportionately affected by CRC.
“Far too many people in the U.S. are not receiving this lifesaving preventive service,” USPSTF vice chair Michael Barry, MD, said in a statement.
“We hope that this new recommendation to screen people ages 45-49, coupled with our long-standing recommendation to screen people 50-75, will prevent more people from dying from colorectal cancer,” he added.
Dr. Ng echoed this sentiment in her editorial: “The USPSTF recommendation for beginning colorectal cancer screening for average-risk adults at age 45 years has moved the field one step forward and indicates that ‘45 is the new 50,’ ” she observed.
“Lowering the recommended age to initiate screening will make colorectal cancer screening available to millions more people in the United States and, hopefully, many more lives will be saved by catching colorectal cancer earlier as well as by preventing colorectal cancer,” Dr. Ng affirmed.
All members of the USPSTF received travel reimbursement and an honorarium for participating in USPSTF meetings.
Dr. Ng reported receiving nonfinancial support from Pharmavite as well as grants from the Evergrande Group, Janssen, Revolution Medicines, Genentech, and Gilead Sciences. She has also reported receiving personal fees from Seattle Genetics, Array Biopharma, BiomX, and X-Biotix Therapeutics.
A version of this article first appeared on Medscape.com.
Screening for colorectal cancer (CRC) should now begin at the age of 45 and not 50 for average-risk individuals in the United States, notes the final recommendation from the U.S. Preventive Services Task Force.
The recommendation finalizes draft guidelines issued in October 2020 and mandates insurance coverage to ensure equal access to CRC screening regardless of a patient’s insurance status.
The USPSTF’s final recommendations also now align with those of the American Cancer Society, which lowered the age for initiation of CRC screening to 45 years in 2018.
“New statistics project an alarming rise in the incidence of young-onset colorectal cancer, projected to be the leading cause of cancer death in patients aged 20-49 by 2040,” commented Kimmie Ng, MD, MPH, director, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Boston, and lead author of a JAMA editorial about the new guideline.
“We must take bold steps to translate the lowered age of beginning screening into meaningful decreases in CRC incidence and mortality,” she emphasized.
The USPSTF recommendations and substantial evidence supporting them were published online May 18, 2021, in JAMA.
Risk factors for CRC
As the USPSTF authors noted, age is one of the most important risk factors for CRC, with nearly 94% of all new cases of CRC occurring in adults 45 years of age and older. Justification for the lower age of CRC screening initiation was based on simulation models showing that initiation of screening at the age of 45 was associated with an estimated additional 22-27 life-years gained, compared with starting at the age of 50.
The USPSTF continues to recommend screening for CRC in all adults aged between 50 and 75 years, lowering the age for screening to 45 years in recognition of the fact that, in 2020, 11% of colon cancers and 15% of rectal cancers occurred in patients under the age of 50.
The USPSTF also continues to conclude that there is a “small net benefit” of screening for CRC in adults aged between 76 and 85 years who have been previously screened.
However, the decision to screen patients in this age group should be based on individual risk factors for CRC, a patient’s overall health status, and personal preference. Perhaps self-evidently, adults in this age group who have never been screened for CRC are more likely to benefit from CRC screening than those who have been previously screened.
Similar to the previous guidelines released in 2016, the updated USPSTF recommendations continue to offer a menu of screening strategies, although the frequency of screening for each of the screening strategies varies. Recommended screening strategies include:
- High-sensitivity guaiac fecal occult blood test or fecal immunochemical test (FIT) every year
- Stool DNA-FIT every 1-3 years
- CT colonography every 5 years
- every 5 years
- Flexible sigmoidoscopy every 10 years plus annual FIT
- screening every 10 years
“Based on the evidence, there are many tests available that can effectively screen for colorectal cancer and the right test is the one that gets done,” USPSTF member Martha Kubik, PhD, RN, said in a statement.
“To encourage screening and help patients select the best test for them, we urge primary care clinicians to talk about the pros and cons of the various recommended options with their patients,” she added.
An accompanying review of the effectiveness, accuracy, and potential harms of CRC screening methods underscores how different screening tests have different levels of evidence demonstrating their ability to detect cancer, precursor lesions, or both, as well as their ability to reduce mortality from cancer.
Eligible patients
Currently, fewer than 70% of eligible patients in the United States undergo CRC screening, Dr. Ng pointed out in the editorial. In addition, CRC disproportionately affects African American patients, who are about 20% more likely to get CRC and about 40% more likely to die from it, compared with other patient groups. Modeling studies published along with the USPSTF recommendations showed equal benefit for screening regardless of race and gender, underscoring the importance of screening adherence, especially in patient populations disproportionately affected by CRC.
“Far too many people in the U.S. are not receiving this lifesaving preventive service,” USPSTF vice chair Michael Barry, MD, said in a statement.
“We hope that this new recommendation to screen people ages 45-49, coupled with our long-standing recommendation to screen people 50-75, will prevent more people from dying from colorectal cancer,” he added.
Dr. Ng echoed this sentiment in her editorial: “The USPSTF recommendation for beginning colorectal cancer screening for average-risk adults at age 45 years has moved the field one step forward and indicates that ‘45 is the new 50,’ ” she observed.
“Lowering the recommended age to initiate screening will make colorectal cancer screening available to millions more people in the United States and, hopefully, many more lives will be saved by catching colorectal cancer earlier as well as by preventing colorectal cancer,” Dr. Ng affirmed.
All members of the USPSTF received travel reimbursement and an honorarium for participating in USPSTF meetings.
Dr. Ng reported receiving nonfinancial support from Pharmavite as well as grants from the Evergrande Group, Janssen, Revolution Medicines, Genentech, and Gilead Sciences. She has also reported receiving personal fees from Seattle Genetics, Array Biopharma, BiomX, and X-Biotix Therapeutics.
A version of this article first appeared on Medscape.com.
‘Inflammasomes’ may play a role in obesity-related CRC
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
COVID-19 impact on breast cancer: Upfront endocrine Rx increased
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Novel BRAF-inhibitor cream ameliorates rash from EGFR inhibitors
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
Pregnancy increases risk for symptomatic kidney stones
Pregnancy increases the risk for first-time symptomatic kidney stone formation which peaks close to the time of delivery but can persist even a year later, a population-based, case-controlled study suggests.
“We suspected the risk of a kidney stone event would be high during pregnancy, but we were surprised that the risk remained high for up to a year after delivery,” senior author Andrew Rule, MD, a nephrologist at Mayo Clinic, Rochester, Minn, said in a statement from his institution.
“[So] while most kidney stones that form during pregnancy are detected early by painful passage, some may remain stable in the kidney undetected for a longer period before dislodging and [again] resulting in a painful passage,” he added.
The study was published online April 15, 2021, in the American Journal of Kidney Diseases by Charat Thongprayoon, MD, also of the Mayo Clinic, and colleagues.
“The results of this study indicate that prenatal counseling regarding kidney stones may be warranted, especially for women with other risk factors for kidney stones, such as obesity,” he noted.
First-time stone formers
The observational study included 945 first-time symptomatic kidney stone formers aged between 15 and 45 years who were compared with 1,890 age-matched female controls from the Rochester Epidemiology Project. The latter is a medical record linkage system for almost all medical care administered in Olmsted County in Minnesota.
Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in a pregnant woman was similar in the first trimester (odds ratio, 0.92; P = .8), began to increase during the second trimester (OR, 2.00; P = .007), further increased during the third trimester (OR, 2.69; P = .001), and peaked at 0-3 months after delivery (OR, 3.53; P < .001). The risk returned to baseline by 1 year after delivery.
These associations persisted after adjustment for age and race or for diabetes, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies.
The risk of a pregnant woman developing a symptomatic kidney stone was higher in women with obesity, compared with those of normal weight (P = .01).
And compared with women who had not been pregnant before, one prior pregnancy also increased the risk of having a symptomatic kidney stone by approximately 30% (OR, 1.29; P = .03), although two or more prior pregnancies did not significantly increase symptomatic kidney stone risk.
Thus, “it can be inferred that the odds of a symptomatic kidney stone peak around the time of delivery,” the authors emphasized. “The odds of a first-time symptomatic kidney stone then decreased over time and were fully attenuated and no longer statistically significant by 12 months after delivery.”
Dr. Thongprayoon said there are several physiologic reasons why pregnancy might contribute to kidney stone formation.
During pregnancy, ureteral compression and ureteral relaxation caused by elevated progesterone levels can cause urinary stasis.
Furthermore, increased urinary calcium excretion and elevated urine pH during pregnancy can promote calcium phosphate stone formation. It is noteworthy that almost all pregnant, first-time stone formers had calcium phosphate stones.
“During pregnancy, a kidney stone may contribute to serious complications,” Dr. Thongprayoon explained.
General dietary recommendations for preventing kidney stones include drinking abundant fluids and consuming a low-salt diet.
The study was supported by the Mayo Clinic O’Brien Urology Research Center and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pregnancy increases the risk for first-time symptomatic kidney stone formation which peaks close to the time of delivery but can persist even a year later, a population-based, case-controlled study suggests.
“We suspected the risk of a kidney stone event would be high during pregnancy, but we were surprised that the risk remained high for up to a year after delivery,” senior author Andrew Rule, MD, a nephrologist at Mayo Clinic, Rochester, Minn, said in a statement from his institution.
“[So] while most kidney stones that form during pregnancy are detected early by painful passage, some may remain stable in the kidney undetected for a longer period before dislodging and [again] resulting in a painful passage,” he added.
The study was published online April 15, 2021, in the American Journal of Kidney Diseases by Charat Thongprayoon, MD, also of the Mayo Clinic, and colleagues.
“The results of this study indicate that prenatal counseling regarding kidney stones may be warranted, especially for women with other risk factors for kidney stones, such as obesity,” he noted.
First-time stone formers
The observational study included 945 first-time symptomatic kidney stone formers aged between 15 and 45 years who were compared with 1,890 age-matched female controls from the Rochester Epidemiology Project. The latter is a medical record linkage system for almost all medical care administered in Olmsted County in Minnesota.
Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in a pregnant woman was similar in the first trimester (odds ratio, 0.92; P = .8), began to increase during the second trimester (OR, 2.00; P = .007), further increased during the third trimester (OR, 2.69; P = .001), and peaked at 0-3 months after delivery (OR, 3.53; P < .001). The risk returned to baseline by 1 year after delivery.
These associations persisted after adjustment for age and race or for diabetes, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies.
The risk of a pregnant woman developing a symptomatic kidney stone was higher in women with obesity, compared with those of normal weight (P = .01).
And compared with women who had not been pregnant before, one prior pregnancy also increased the risk of having a symptomatic kidney stone by approximately 30% (OR, 1.29; P = .03), although two or more prior pregnancies did not significantly increase symptomatic kidney stone risk.
Thus, “it can be inferred that the odds of a symptomatic kidney stone peak around the time of delivery,” the authors emphasized. “The odds of a first-time symptomatic kidney stone then decreased over time and were fully attenuated and no longer statistically significant by 12 months after delivery.”
Dr. Thongprayoon said there are several physiologic reasons why pregnancy might contribute to kidney stone formation.
During pregnancy, ureteral compression and ureteral relaxation caused by elevated progesterone levels can cause urinary stasis.
Furthermore, increased urinary calcium excretion and elevated urine pH during pregnancy can promote calcium phosphate stone formation. It is noteworthy that almost all pregnant, first-time stone formers had calcium phosphate stones.
“During pregnancy, a kidney stone may contribute to serious complications,” Dr. Thongprayoon explained.
General dietary recommendations for preventing kidney stones include drinking abundant fluids and consuming a low-salt diet.
The study was supported by the Mayo Clinic O’Brien Urology Research Center and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pregnancy increases the risk for first-time symptomatic kidney stone formation which peaks close to the time of delivery but can persist even a year later, a population-based, case-controlled study suggests.
“We suspected the risk of a kidney stone event would be high during pregnancy, but we were surprised that the risk remained high for up to a year after delivery,” senior author Andrew Rule, MD, a nephrologist at Mayo Clinic, Rochester, Minn, said in a statement from his institution.
“[So] while most kidney stones that form during pregnancy are detected early by painful passage, some may remain stable in the kidney undetected for a longer period before dislodging and [again] resulting in a painful passage,” he added.
The study was published online April 15, 2021, in the American Journal of Kidney Diseases by Charat Thongprayoon, MD, also of the Mayo Clinic, and colleagues.
“The results of this study indicate that prenatal counseling regarding kidney stones may be warranted, especially for women with other risk factors for kidney stones, such as obesity,” he noted.
First-time stone formers
The observational study included 945 first-time symptomatic kidney stone formers aged between 15 and 45 years who were compared with 1,890 age-matched female controls from the Rochester Epidemiology Project. The latter is a medical record linkage system for almost all medical care administered in Olmsted County in Minnesota.
Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in a pregnant woman was similar in the first trimester (odds ratio, 0.92; P = .8), began to increase during the second trimester (OR, 2.00; P = .007), further increased during the third trimester (OR, 2.69; P = .001), and peaked at 0-3 months after delivery (OR, 3.53; P < .001). The risk returned to baseline by 1 year after delivery.
These associations persisted after adjustment for age and race or for diabetes, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies.
The risk of a pregnant woman developing a symptomatic kidney stone was higher in women with obesity, compared with those of normal weight (P = .01).
And compared with women who had not been pregnant before, one prior pregnancy also increased the risk of having a symptomatic kidney stone by approximately 30% (OR, 1.29; P = .03), although two or more prior pregnancies did not significantly increase symptomatic kidney stone risk.
Thus, “it can be inferred that the odds of a symptomatic kidney stone peak around the time of delivery,” the authors emphasized. “The odds of a first-time symptomatic kidney stone then decreased over time and were fully attenuated and no longer statistically significant by 12 months after delivery.”
Dr. Thongprayoon said there are several physiologic reasons why pregnancy might contribute to kidney stone formation.
During pregnancy, ureteral compression and ureteral relaxation caused by elevated progesterone levels can cause urinary stasis.
Furthermore, increased urinary calcium excretion and elevated urine pH during pregnancy can promote calcium phosphate stone formation. It is noteworthy that almost all pregnant, first-time stone formers had calcium phosphate stones.
“During pregnancy, a kidney stone may contribute to serious complications,” Dr. Thongprayoon explained.
General dietary recommendations for preventing kidney stones include drinking abundant fluids and consuming a low-salt diet.
The study was supported by the Mayo Clinic O’Brien Urology Research Center and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patient benefits justify price of new lupus nephritis drugs
The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.
“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.
“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.
The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.
The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.
The report was published by ICER in April 2021.
Large unmet need for treatment of lupus nephritis
In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).
Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.
Voclosporin was approved for the treatment of lupus nephritis in January 2021.
In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.
Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.
Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.
“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.
“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.
The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.
On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.
For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.
“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.
“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.
Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.
Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.
“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
Black patients underrepresented in trials
The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.
“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.
This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.
However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.
This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.
The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.
This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.
“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.
“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.
Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.
“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.
“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.
The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.
The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.
The report was published by ICER in April 2021.
Large unmet need for treatment of lupus nephritis
In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).
Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.
Voclosporin was approved for the treatment of lupus nephritis in January 2021.
In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.
Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.
Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.
“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.
“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.
The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.
On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.
For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.
“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.
“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.
Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.
Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.
“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
Black patients underrepresented in trials
The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.
“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.
This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.
However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.
This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.
The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.
This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.
“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.
“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.
Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.
“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.
“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.
The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.
The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.
The report was published by ICER in April 2021.
Large unmet need for treatment of lupus nephritis
In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).
Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.
Voclosporin was approved for the treatment of lupus nephritis in January 2021.
In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.
Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.
Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.
“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.
“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.
The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.
On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.
For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.
“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.
“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.
Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.
Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.
“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
Black patients underrepresented in trials
The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.
“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.
This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”
The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.
However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.
This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.
The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.
This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.
“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.
“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.
Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
First AI device for colonoscopy: Extra set of expert ‘eyes’
The GI Genius module is the first and only commercially available computer-aided detection system that uses AI to identify colorectal polyps during routine colonoscopy.
The technology is compatible with most standard video endoscopy systems and has been “trained” to identify colonic lesions that are possibly cancerous, according to Medtronic, the distributor of the device.
“I think that anything we can do within a reasonable cost that enhances quality and patient outcomes during colonoscopy warrants very close consideration,” David Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview.
He was not involved with the development of the GI Genius system but has worked with a similar AI device that is used in conjunction with colonoscopy.
“The whole development of the technology for AI is done by inputting repetitive images into the computer, where it develops what is called the ‘neural network,’ ” he explained.
The computer then draws upon the “education” of this neural network to identify different types of colonic lesions, “and the more inputs that are put into the computer to enhance the neural network, the more capable the program becomes in the identification of variants and lesion size and characteristics,” Dr. Johnson added.
During routine colonoscopy, the GI Genius system generates visual markers – essentially, small green squares – and a low-volume sound whenever the software detects a region of interest.
These squares are superimposed on the video generated by the endoscope camera to alert the colonoscopist to regions that may require closer assessment, either visually, by tissue sampling, or by removal of the lesion itself.
“Colonoscopy is a durable screening and surveillance strategy, but it’s not perfect [because] it depends on a physician’s skill and their ability to pick up polyps in the colon,” Jeremy Glissen Brown, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. He has also worked with an AI device.
Studies of adenoma detection during “all-comer” colonoscopies show that the rate of missed lesions ranges from a low of 6% to 40%, “so polyps are still missed during colonoscopy, and any technology that can solve parts of that problem is welcome,” Dr. Glissen Brown commented.
Clinical trial data that led to approval
The recent FDA approval of the GI Genius device was based on a prospective, randomized trial that was published in Gastroenterology in 2020. That trial involved 700 patients who were being screened or followed with colonoscopy every 3 years or longer. Participants underwent either white-light standard colonoscopy with the assistance of the GI Genius technology or standard white-light colonoscopy alone.
Results showed that the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% of patients, compared with 40.4% of patients who underwent colonoscopy alone.
In the Gastroenterology article, the authors wrote that the “14% absolute increase in adenoma detection rate obtained by computer-aided detection (CADe) in our study indicates that failure in polyp recognition is a clinically relevant cause of miss rate. Of note, the efficacy of CADe in reversing such miss rate also indicates that the same operator who missed the lesion in the first place was able to correctly diagnose it when the lesion was presented by the CADe. This underlines that the main cognitive challenge in polyp recognition is the discrimination between the candidate lesion and the surrounding healthy mucosa, whereas its correct characterization as neoplastic tissue that occurs after CADe detection is apparently a much easier task.”
The authors also noted that they did “not assess the actual number of false-positive activations by the system, as this would have altered the routine setting of our study,” but they refer to a study published in Gut in 2020 in which false-positive frames were seen in fewer than 1% of frames from the whole colonoscopy.
Because the new device improves on the ability of colonoscopy to detect lesions overall, it may reduce the risk of interval cancers between colonoscopies, Medtronic suggests.
Previous research has shown that every 1% increase in the adenoma detection rate results in a 3% decrease in the risk for colorectal cancer.
“More than 19 million screening colonoscopies are performed in the United State each year. ... Detection of adenomas during colonoscopy is an important quality metric,” James Weber, MD, a gastroenterologist affiliated with Texas Digestive Disease Consultants, Southlake, commented in a Medtronic press release.
“The addition of AI can increase the quality of colonoscopies, potentially improving diagnosis and outcomes for colon cancer patients,” he added.
Dr. Weber is also the CEO of GI Alliance, a physician-led national health care platform of independent GI practices in six states in the United States.
Computer-aided detection
Unlike other computer-aided detection technologies, GI Genius does not characterize or “diagnose” a lesion, nor does it replace laboratory sampling as a means of confirming a cancer diagnosis.
The technology acts essentially as an extra set of expert “eyes” to detect suspicious lesions during colonoscopy, which should prove helpful, Dr. Johnson and Dr. Glissen Brown both commented.
“When a gastroenterologist looks at the video image, typically, our eyes are focused in the center of that image – that’s where our 20/20 vision is,” Dr. Johnson explained.
The computer has 20/20 vision over the whole image, including the periphery, “so the technology really gives an extremely expanded acuity of vision and highlights areas that we may need to investigate further,” he added.
Dr. Glissen Brown was involved in a trial of another AI device – the real-time automatic polyp detection system (Shanghai Wision AI). That study showed an increase in colonoscopic polyp and adenoma detection rates, but this was mainly because of a higher number of diminutive adenomas detected by the automatic detection system, Dr. Gliseen Brown said. There was no important difference in the number of larger adenomas detected with the device and the number detected without it.
However, there was a significant increase in the detection of hyperplastic polyps when the automatic detection system was used. “We definitely want to look at the false positive rate – both the false positive rate under the camera when we are doing colonoscopy and under the microscope when we do biopsies,” Dr. Glissen Brown acknowledged.
In numerous prospective studies of various computer-aided detection technologies such as the GI Genius system, the false positive rate resulting in the performance of biopsy of insignificant lesions is relatively low, he said.
“Ultimately, the decision to remove or biopsy a lesion is with the physician, because the GI Genius technology just points the provider to the area of concern, and then it’s up to them to look at it and decide whether it needs to be biopsied or not,” Dr. Glissen Brown said.
“So the technology serves more as a digital safety net and points the physician in the right direction, so it shouldn’t lead to much in the way of histologic false positives,” he noted.
The only potential disadvantage to using an AI system such as the GI Genius module is the time it might take for endoscopists to learn how to use it and how much the technology might increase the time required to perform the procedure, he added.
For about 18 months, Dr. Johnson has been running a clinical trial with a similar type of AI technology during colonoscopy. He has found that the learning curve for using these systems is “inordinately short.” Dr. Glissen Brown agreed and suggested that, if physicians are already performing colonoscopies regularly, they could probably learn to use an AI system such as GI Genius in about a week.
In his experience, Dr. Johnson has found that the delay caused by use of an AI system during colonoscopy is “minimal.”
If there is any delay at all, “we know that time in the colon on withdrawal increases the detection of polyps, so more time during withdrawal may be a good thing,” he added. It should be noted that endoscopy societies recommend a withdrawal time of at least 6 minutes, which is one of the metrics used to ensure the quality of a colonoscopy, Dr. Glissen Brown explained.
Indeed, the pivotal study upon which the FDA approved the GI Genius module required a minimum withdrawal time of 6 minutes. Participants said they did not find that using the GI Genius increased withdrawal time, he added.
“I think there is enough prospective evidence at this point to suggest that this technology may really be of benefit to clinicians with a lot of different skill levels, so I would be eager to know how clinicians interact with it in the clinical setting,” Dr. Glissen Brown commented.
Dr. Johnson agreed, noting that “even the good can get better.”
Dr. Johnson disclosed relationships with this news organization, CRH Medical, the American College of Gastroenterology Research Institute, and HyGIeaCare. Dr. Glissen Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Article updated April 21, 2021.
The GI Genius module is the first and only commercially available computer-aided detection system that uses AI to identify colorectal polyps during routine colonoscopy.
The technology is compatible with most standard video endoscopy systems and has been “trained” to identify colonic lesions that are possibly cancerous, according to Medtronic, the distributor of the device.
“I think that anything we can do within a reasonable cost that enhances quality and patient outcomes during colonoscopy warrants very close consideration,” David Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview.
He was not involved with the development of the GI Genius system but has worked with a similar AI device that is used in conjunction with colonoscopy.
“The whole development of the technology for AI is done by inputting repetitive images into the computer, where it develops what is called the ‘neural network,’ ” he explained.
The computer then draws upon the “education” of this neural network to identify different types of colonic lesions, “and the more inputs that are put into the computer to enhance the neural network, the more capable the program becomes in the identification of variants and lesion size and characteristics,” Dr. Johnson added.
During routine colonoscopy, the GI Genius system generates visual markers – essentially, small green squares – and a low-volume sound whenever the software detects a region of interest.
These squares are superimposed on the video generated by the endoscope camera to alert the colonoscopist to regions that may require closer assessment, either visually, by tissue sampling, or by removal of the lesion itself.
“Colonoscopy is a durable screening and surveillance strategy, but it’s not perfect [because] it depends on a physician’s skill and their ability to pick up polyps in the colon,” Jeremy Glissen Brown, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. He has also worked with an AI device.
Studies of adenoma detection during “all-comer” colonoscopies show that the rate of missed lesions ranges from a low of 6% to 40%, “so polyps are still missed during colonoscopy, and any technology that can solve parts of that problem is welcome,” Dr. Glissen Brown commented.
Clinical trial data that led to approval
The recent FDA approval of the GI Genius device was based on a prospective, randomized trial that was published in Gastroenterology in 2020. That trial involved 700 patients who were being screened or followed with colonoscopy every 3 years or longer. Participants underwent either white-light standard colonoscopy with the assistance of the GI Genius technology or standard white-light colonoscopy alone.
Results showed that the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% of patients, compared with 40.4% of patients who underwent colonoscopy alone.
In the Gastroenterology article, the authors wrote that the “14% absolute increase in adenoma detection rate obtained by computer-aided detection (CADe) in our study indicates that failure in polyp recognition is a clinically relevant cause of miss rate. Of note, the efficacy of CADe in reversing such miss rate also indicates that the same operator who missed the lesion in the first place was able to correctly diagnose it when the lesion was presented by the CADe. This underlines that the main cognitive challenge in polyp recognition is the discrimination between the candidate lesion and the surrounding healthy mucosa, whereas its correct characterization as neoplastic tissue that occurs after CADe detection is apparently a much easier task.”
The authors also noted that they did “not assess the actual number of false-positive activations by the system, as this would have altered the routine setting of our study,” but they refer to a study published in Gut in 2020 in which false-positive frames were seen in fewer than 1% of frames from the whole colonoscopy.
Because the new device improves on the ability of colonoscopy to detect lesions overall, it may reduce the risk of interval cancers between colonoscopies, Medtronic suggests.
Previous research has shown that every 1% increase in the adenoma detection rate results in a 3% decrease in the risk for colorectal cancer.
“More than 19 million screening colonoscopies are performed in the United State each year. ... Detection of adenomas during colonoscopy is an important quality metric,” James Weber, MD, a gastroenterologist affiliated with Texas Digestive Disease Consultants, Southlake, commented in a Medtronic press release.
“The addition of AI can increase the quality of colonoscopies, potentially improving diagnosis and outcomes for colon cancer patients,” he added.
Dr. Weber is also the CEO of GI Alliance, a physician-led national health care platform of independent GI practices in six states in the United States.
Computer-aided detection
Unlike other computer-aided detection technologies, GI Genius does not characterize or “diagnose” a lesion, nor does it replace laboratory sampling as a means of confirming a cancer diagnosis.
The technology acts essentially as an extra set of expert “eyes” to detect suspicious lesions during colonoscopy, which should prove helpful, Dr. Johnson and Dr. Glissen Brown both commented.
“When a gastroenterologist looks at the video image, typically, our eyes are focused in the center of that image – that’s where our 20/20 vision is,” Dr. Johnson explained.
The computer has 20/20 vision over the whole image, including the periphery, “so the technology really gives an extremely expanded acuity of vision and highlights areas that we may need to investigate further,” he added.
Dr. Glissen Brown was involved in a trial of another AI device – the real-time automatic polyp detection system (Shanghai Wision AI). That study showed an increase in colonoscopic polyp and adenoma detection rates, but this was mainly because of a higher number of diminutive adenomas detected by the automatic detection system, Dr. Gliseen Brown said. There was no important difference in the number of larger adenomas detected with the device and the number detected without it.
However, there was a significant increase in the detection of hyperplastic polyps when the automatic detection system was used. “We definitely want to look at the false positive rate – both the false positive rate under the camera when we are doing colonoscopy and under the microscope when we do biopsies,” Dr. Glissen Brown acknowledged.
In numerous prospective studies of various computer-aided detection technologies such as the GI Genius system, the false positive rate resulting in the performance of biopsy of insignificant lesions is relatively low, he said.
“Ultimately, the decision to remove or biopsy a lesion is with the physician, because the GI Genius technology just points the provider to the area of concern, and then it’s up to them to look at it and decide whether it needs to be biopsied or not,” Dr. Glissen Brown said.
“So the technology serves more as a digital safety net and points the physician in the right direction, so it shouldn’t lead to much in the way of histologic false positives,” he noted.
The only potential disadvantage to using an AI system such as the GI Genius module is the time it might take for endoscopists to learn how to use it and how much the technology might increase the time required to perform the procedure, he added.
For about 18 months, Dr. Johnson has been running a clinical trial with a similar type of AI technology during colonoscopy. He has found that the learning curve for using these systems is “inordinately short.” Dr. Glissen Brown agreed and suggested that, if physicians are already performing colonoscopies regularly, they could probably learn to use an AI system such as GI Genius in about a week.
In his experience, Dr. Johnson has found that the delay caused by use of an AI system during colonoscopy is “minimal.”
If there is any delay at all, “we know that time in the colon on withdrawal increases the detection of polyps, so more time during withdrawal may be a good thing,” he added. It should be noted that endoscopy societies recommend a withdrawal time of at least 6 minutes, which is one of the metrics used to ensure the quality of a colonoscopy, Dr. Glissen Brown explained.
Indeed, the pivotal study upon which the FDA approved the GI Genius module required a minimum withdrawal time of 6 minutes. Participants said they did not find that using the GI Genius increased withdrawal time, he added.
“I think there is enough prospective evidence at this point to suggest that this technology may really be of benefit to clinicians with a lot of different skill levels, so I would be eager to know how clinicians interact with it in the clinical setting,” Dr. Glissen Brown commented.
Dr. Johnson agreed, noting that “even the good can get better.”
Dr. Johnson disclosed relationships with this news organization, CRH Medical, the American College of Gastroenterology Research Institute, and HyGIeaCare. Dr. Glissen Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Article updated April 21, 2021.
The GI Genius module is the first and only commercially available computer-aided detection system that uses AI to identify colorectal polyps during routine colonoscopy.
The technology is compatible with most standard video endoscopy systems and has been “trained” to identify colonic lesions that are possibly cancerous, according to Medtronic, the distributor of the device.
“I think that anything we can do within a reasonable cost that enhances quality and patient outcomes during colonoscopy warrants very close consideration,” David Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview.
He was not involved with the development of the GI Genius system but has worked with a similar AI device that is used in conjunction with colonoscopy.
“The whole development of the technology for AI is done by inputting repetitive images into the computer, where it develops what is called the ‘neural network,’ ” he explained.
The computer then draws upon the “education” of this neural network to identify different types of colonic lesions, “and the more inputs that are put into the computer to enhance the neural network, the more capable the program becomes in the identification of variants and lesion size and characteristics,” Dr. Johnson added.
During routine colonoscopy, the GI Genius system generates visual markers – essentially, small green squares – and a low-volume sound whenever the software detects a region of interest.
These squares are superimposed on the video generated by the endoscope camera to alert the colonoscopist to regions that may require closer assessment, either visually, by tissue sampling, or by removal of the lesion itself.
“Colonoscopy is a durable screening and surveillance strategy, but it’s not perfect [because] it depends on a physician’s skill and their ability to pick up polyps in the colon,” Jeremy Glissen Brown, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. He has also worked with an AI device.
Studies of adenoma detection during “all-comer” colonoscopies show that the rate of missed lesions ranges from a low of 6% to 40%, “so polyps are still missed during colonoscopy, and any technology that can solve parts of that problem is welcome,” Dr. Glissen Brown commented.
Clinical trial data that led to approval
The recent FDA approval of the GI Genius device was based on a prospective, randomized trial that was published in Gastroenterology in 2020. That trial involved 700 patients who were being screened or followed with colonoscopy every 3 years or longer. Participants underwent either white-light standard colonoscopy with the assistance of the GI Genius technology or standard white-light colonoscopy alone.
Results showed that the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% of patients, compared with 40.4% of patients who underwent colonoscopy alone.
In the Gastroenterology article, the authors wrote that the “14% absolute increase in adenoma detection rate obtained by computer-aided detection (CADe) in our study indicates that failure in polyp recognition is a clinically relevant cause of miss rate. Of note, the efficacy of CADe in reversing such miss rate also indicates that the same operator who missed the lesion in the first place was able to correctly diagnose it when the lesion was presented by the CADe. This underlines that the main cognitive challenge in polyp recognition is the discrimination between the candidate lesion and the surrounding healthy mucosa, whereas its correct characterization as neoplastic tissue that occurs after CADe detection is apparently a much easier task.”
The authors also noted that they did “not assess the actual number of false-positive activations by the system, as this would have altered the routine setting of our study,” but they refer to a study published in Gut in 2020 in which false-positive frames were seen in fewer than 1% of frames from the whole colonoscopy.
Because the new device improves on the ability of colonoscopy to detect lesions overall, it may reduce the risk of interval cancers between colonoscopies, Medtronic suggests.
Previous research has shown that every 1% increase in the adenoma detection rate results in a 3% decrease in the risk for colorectal cancer.
“More than 19 million screening colonoscopies are performed in the United State each year. ... Detection of adenomas during colonoscopy is an important quality metric,” James Weber, MD, a gastroenterologist affiliated with Texas Digestive Disease Consultants, Southlake, commented in a Medtronic press release.
“The addition of AI can increase the quality of colonoscopies, potentially improving diagnosis and outcomes for colon cancer patients,” he added.
Dr. Weber is also the CEO of GI Alliance, a physician-led national health care platform of independent GI practices in six states in the United States.
Computer-aided detection
Unlike other computer-aided detection technologies, GI Genius does not characterize or “diagnose” a lesion, nor does it replace laboratory sampling as a means of confirming a cancer diagnosis.
The technology acts essentially as an extra set of expert “eyes” to detect suspicious lesions during colonoscopy, which should prove helpful, Dr. Johnson and Dr. Glissen Brown both commented.
“When a gastroenterologist looks at the video image, typically, our eyes are focused in the center of that image – that’s where our 20/20 vision is,” Dr. Johnson explained.
The computer has 20/20 vision over the whole image, including the periphery, “so the technology really gives an extremely expanded acuity of vision and highlights areas that we may need to investigate further,” he added.
Dr. Glissen Brown was involved in a trial of another AI device – the real-time automatic polyp detection system (Shanghai Wision AI). That study showed an increase in colonoscopic polyp and adenoma detection rates, but this was mainly because of a higher number of diminutive adenomas detected by the automatic detection system, Dr. Gliseen Brown said. There was no important difference in the number of larger adenomas detected with the device and the number detected without it.
However, there was a significant increase in the detection of hyperplastic polyps when the automatic detection system was used. “We definitely want to look at the false positive rate – both the false positive rate under the camera when we are doing colonoscopy and under the microscope when we do biopsies,” Dr. Glissen Brown acknowledged.
In numerous prospective studies of various computer-aided detection technologies such as the GI Genius system, the false positive rate resulting in the performance of biopsy of insignificant lesions is relatively low, he said.
“Ultimately, the decision to remove or biopsy a lesion is with the physician, because the GI Genius technology just points the provider to the area of concern, and then it’s up to them to look at it and decide whether it needs to be biopsied or not,” Dr. Glissen Brown said.
“So the technology serves more as a digital safety net and points the physician in the right direction, so it shouldn’t lead to much in the way of histologic false positives,” he noted.
The only potential disadvantage to using an AI system such as the GI Genius module is the time it might take for endoscopists to learn how to use it and how much the technology might increase the time required to perform the procedure, he added.
For about 18 months, Dr. Johnson has been running a clinical trial with a similar type of AI technology during colonoscopy. He has found that the learning curve for using these systems is “inordinately short.” Dr. Glissen Brown agreed and suggested that, if physicians are already performing colonoscopies regularly, they could probably learn to use an AI system such as GI Genius in about a week.
In his experience, Dr. Johnson has found that the delay caused by use of an AI system during colonoscopy is “minimal.”
If there is any delay at all, “we know that time in the colon on withdrawal increases the detection of polyps, so more time during withdrawal may be a good thing,” he added. It should be noted that endoscopy societies recommend a withdrawal time of at least 6 minutes, which is one of the metrics used to ensure the quality of a colonoscopy, Dr. Glissen Brown explained.
Indeed, the pivotal study upon which the FDA approved the GI Genius module required a minimum withdrawal time of 6 minutes. Participants said they did not find that using the GI Genius increased withdrawal time, he added.
“I think there is enough prospective evidence at this point to suggest that this technology may really be of benefit to clinicians with a lot of different skill levels, so I would be eager to know how clinicians interact with it in the clinical setting,” Dr. Glissen Brown commented.
Dr. Johnson agreed, noting that “even the good can get better.”
Dr. Johnson disclosed relationships with this news organization, CRH Medical, the American College of Gastroenterology Research Institute, and HyGIeaCare. Dr. Glissen Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Article updated April 21, 2021.
COVID-19 vaccine response lower in kidney dialysis patients
the first study of its kind shows.
“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.
“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.
Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.
In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.
Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
Study compared dialysis patients with health care workers
The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.
“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.
A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.
The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.
The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.
The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).
Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).
Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.
For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.
Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.
Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.
The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
Some suggestion COVID-19 vaccines also elicit T-cell responses
Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.
“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.
Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.
“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.
The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the first study of its kind shows.
“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.
“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.
Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.
In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.
Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
Study compared dialysis patients with health care workers
The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.
“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.
A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.
The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.
The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.
The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).
Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).
Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.
For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.
Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.
Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.
The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
Some suggestion COVID-19 vaccines also elicit T-cell responses
Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.
“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.
Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.
“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.
The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the first study of its kind shows.
“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.
“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.
Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.
In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.
Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
Study compared dialysis patients with health care workers
The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.
“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.
A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.
The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.
The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.
The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).
Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).
Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.
For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.
Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.
Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.
The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
Some suggestion COVID-19 vaccines also elicit T-cell responses
Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.
“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.
Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.
“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.
The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 vaccine failure in patients with blood cancers
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Call to eradicate all types of HPV cancers, not just cervical
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.