Head & Neck/Thyroid Cancers

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Comprehensive evaluation, multidisciplinary care, individualized treatment, and ongoing follow-up are all key to the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC), according to the first European guidelines for this rare disease.

The guidelines were recently published in the European Thyroid Journal.

Lead author Chantal A. Lebbink told this news organization one of the key takeaways for clinicians is that management of pediatric thyroid nodules and DTC is «challenging and cannot be captured in a one-size-fits-all model.”

She also underlined the need for a “multidisciplinary approach in pediatric thyroid cancer expertise centers.”

Above all, Ms. Lebbink, who is a PhD student in the department of pediatric endocrinology, Wilhelmina Children’s Hospital, Utrecht, the Netherlands, said that pediatric DTC “is not adult DTC in a small person; it has different genetics and a different clinical behavior.”

The authors noted that DTC may be a rare disease, but its worldwide incidence is rising. It has several histologic subtypes, although the “vast majority” of cases are papillary thyroid carcinoma.

Crucially, there are “important differences” between adult and pediatric DTC in terms of their clinical, molecular, and pathologic characteristics, with pediatric patients commonly presenting with more advanced disease with greater lymph node involvement, distant metastases, and multifocal disease.

“However, despite the aggressive presentation, the overall survival rates are excellent,” Ms. Lebbink said.

There are also differences in genetic alterations between adult and pediatric patients. RET-PTC and NTRK fusions are more common in pediatric patients, while mutations in BRAF V600E and RAS point mutations are less frequent.
 

First European guidelines on thyroid cancer, thyroid nodules in children

Despite these differences, and the existence of U.S. guidelines, until now there have been no European recommendations on the management of pediatric thyroid nodules and DTC.

The European Thyroid Association therefore convened a panel of experts in pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology, and tasked them with looking at diagnostics and staging, treatment, and follow-up.

The 2015 American Thyroid Association pediatric guideline was used as framework for the European guideline, with the expert panel identifying areas of discordance and outstanding clinical questions (Thyroid. 2015 Jul;25[7]:716-59).

To answer these questions, they searched PubMed and identified 3,251 studies, of which 45 studies met the inclusion criteria. From this they developed a comprehensive set of recommendations. These include that a child with suspected or proven cancer be referred to an experienced multidisciplinary team and their likely benefit from higher- versus lower-intensity treatment be established.

In addition, children should undergo a preoperative evaluation, with neck palpation, comprehensive neck ultrasonography, and laboratory work-up as a minimum, with further testing suggested in case of a family history or extensive disease.

Total thyroidectomy is the recommended treatment, although the authors call for further studies to assess the impact of limited surgery, and they suggest that prophylactic central lymph node dissection be reserved for advanced cases.

Crucially, all children “should be operated on by high-volume pediatric thyroid cancer surgeons with experience in pediatric thyroid cancer and who are embedded in a center with expertise in the management of DTC,” they wrote.
 

RAI therapy recommended for all children, in contrast to ATA guidelines

Radioactive iodine (I-131) therapy is recommended for all children following total thyroidectomy, with treatment following an individual patient-based approach.

This differs slightly from the ATA guidelines, which recommend against radioactive iodine (RAI) therapy for children with low-risk differentiated thyroid cancer that is mostly confined to the thyroid (N0 or minimal N1a disease). A study presented at the recent 2022 annual meeting of the ATA found that such children who were spared RAI showed no increases in risk of remission compared with those who did receive it.

The ETA guidelines then go on to recommend that children should be followed up with thyroid-stimulating hormone monitoring and suppression to low-normal levels, as well as serum thyroglobulin measurement and neck ultrasound, although other imaging modalities are not recommended.

In children with persistent or recurrent cervical disease, “surgery or I-131 therapy are indicated depending on the size, tumor load, and degree of progression,” and the authors said that cases of radioactive refractory disease should be “thoroughly investigated.”

Patients should also be counseled on the risk of the late effects of treatment for DTC and undergo monitoring, with follow-up continued for at least 10 years. Any subsequent follow-up should be “the result of shared decision-making between the physician and the patient.”
 

Evidence for molecular testing is scarce

Ms. Lebbink said that developing the guidelines nevertheless revealed a series of gaps in current knowledge, notably that the evidence for molecular testing “and the clinical implications in the preoperative stage are scarce.”

Specifically, the “positive and negative predictive value of molecular testing in fine needle biopsy specimen for the presence of DTC in a thyroid nodule must be further investigated.»

She also said that there has been a shift towards less aggressive treatment, due to a reluctance to performed prophylactic central neck dissection, and to offer I-131 therapy after surgery.

“However, before less aggressive treatment could be recommended,” Ms. Lebbink said, “it first must be investigated if there are differences in outcomes,” such as recurrence rates, disease-free survival rates, and survival rates between patients who do and do not receive the treatments.

No funding was declared. One author has reported relationships with Sanofi, AstraZeneca, Bayer, and GE. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

Comprehensive evaluation, multidisciplinary care, individualized treatment, and ongoing follow-up are all key to the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC), according to the first European guidelines for this rare disease.

The guidelines were recently published in the European Thyroid Journal.

Lead author Chantal A. Lebbink told this news organization one of the key takeaways for clinicians is that management of pediatric thyroid nodules and DTC is «challenging and cannot be captured in a one-size-fits-all model.”

She also underlined the need for a “multidisciplinary approach in pediatric thyroid cancer expertise centers.”

Above all, Ms. Lebbink, who is a PhD student in the department of pediatric endocrinology, Wilhelmina Children’s Hospital, Utrecht, the Netherlands, said that pediatric DTC “is not adult DTC in a small person; it has different genetics and a different clinical behavior.”

The authors noted that DTC may be a rare disease, but its worldwide incidence is rising. It has several histologic subtypes, although the “vast majority” of cases are papillary thyroid carcinoma.

Crucially, there are “important differences” between adult and pediatric DTC in terms of their clinical, molecular, and pathologic characteristics, with pediatric patients commonly presenting with more advanced disease with greater lymph node involvement, distant metastases, and multifocal disease.

“However, despite the aggressive presentation, the overall survival rates are excellent,” Ms. Lebbink said.

There are also differences in genetic alterations between adult and pediatric patients. RET-PTC and NTRK fusions are more common in pediatric patients, while mutations in BRAF V600E and RAS point mutations are less frequent.
 

First European guidelines on thyroid cancer, thyroid nodules in children

Despite these differences, and the existence of U.S. guidelines, until now there have been no European recommendations on the management of pediatric thyroid nodules and DTC.

The European Thyroid Association therefore convened a panel of experts in pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology, and tasked them with looking at diagnostics and staging, treatment, and follow-up.

The 2015 American Thyroid Association pediatric guideline was used as framework for the European guideline, with the expert panel identifying areas of discordance and outstanding clinical questions (Thyroid. 2015 Jul;25[7]:716-59).

To answer these questions, they searched PubMed and identified 3,251 studies, of which 45 studies met the inclusion criteria. From this they developed a comprehensive set of recommendations. These include that a child with suspected or proven cancer be referred to an experienced multidisciplinary team and their likely benefit from higher- versus lower-intensity treatment be established.

In addition, children should undergo a preoperative evaluation, with neck palpation, comprehensive neck ultrasonography, and laboratory work-up as a minimum, with further testing suggested in case of a family history or extensive disease.

Total thyroidectomy is the recommended treatment, although the authors call for further studies to assess the impact of limited surgery, and they suggest that prophylactic central lymph node dissection be reserved for advanced cases.

Crucially, all children “should be operated on by high-volume pediatric thyroid cancer surgeons with experience in pediatric thyroid cancer and who are embedded in a center with expertise in the management of DTC,” they wrote.
 

RAI therapy recommended for all children, in contrast to ATA guidelines

Radioactive iodine (I-131) therapy is recommended for all children following total thyroidectomy, with treatment following an individual patient-based approach.

This differs slightly from the ATA guidelines, which recommend against radioactive iodine (RAI) therapy for children with low-risk differentiated thyroid cancer that is mostly confined to the thyroid (N0 or minimal N1a disease). A study presented at the recent 2022 annual meeting of the ATA found that such children who were spared RAI showed no increases in risk of remission compared with those who did receive it.

The ETA guidelines then go on to recommend that children should be followed up with thyroid-stimulating hormone monitoring and suppression to low-normal levels, as well as serum thyroglobulin measurement and neck ultrasound, although other imaging modalities are not recommended.

In children with persistent or recurrent cervical disease, “surgery or I-131 therapy are indicated depending on the size, tumor load, and degree of progression,” and the authors said that cases of radioactive refractory disease should be “thoroughly investigated.”

Patients should also be counseled on the risk of the late effects of treatment for DTC and undergo monitoring, with follow-up continued for at least 10 years. Any subsequent follow-up should be “the result of shared decision-making between the physician and the patient.”
 

Evidence for molecular testing is scarce

Ms. Lebbink said that developing the guidelines nevertheless revealed a series of gaps in current knowledge, notably that the evidence for molecular testing “and the clinical implications in the preoperative stage are scarce.”

Specifically, the “positive and negative predictive value of molecular testing in fine needle biopsy specimen for the presence of DTC in a thyroid nodule must be further investigated.»

She also said that there has been a shift towards less aggressive treatment, due to a reluctance to performed prophylactic central neck dissection, and to offer I-131 therapy after surgery.

“However, before less aggressive treatment could be recommended,” Ms. Lebbink said, “it first must be investigated if there are differences in outcomes,” such as recurrence rates, disease-free survival rates, and survival rates between patients who do and do not receive the treatments.

No funding was declared. One author has reported relationships with Sanofi, AstraZeneca, Bayer, and GE. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

Comprehensive evaluation, multidisciplinary care, individualized treatment, and ongoing follow-up are all key to the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC), according to the first European guidelines for this rare disease.

The guidelines were recently published in the European Thyroid Journal.

Lead author Chantal A. Lebbink told this news organization one of the key takeaways for clinicians is that management of pediatric thyroid nodules and DTC is «challenging and cannot be captured in a one-size-fits-all model.”

She also underlined the need for a “multidisciplinary approach in pediatric thyroid cancer expertise centers.”

Above all, Ms. Lebbink, who is a PhD student in the department of pediatric endocrinology, Wilhelmina Children’s Hospital, Utrecht, the Netherlands, said that pediatric DTC “is not adult DTC in a small person; it has different genetics and a different clinical behavior.”

The authors noted that DTC may be a rare disease, but its worldwide incidence is rising. It has several histologic subtypes, although the “vast majority” of cases are papillary thyroid carcinoma.

Crucially, there are “important differences” between adult and pediatric DTC in terms of their clinical, molecular, and pathologic characteristics, with pediatric patients commonly presenting with more advanced disease with greater lymph node involvement, distant metastases, and multifocal disease.

“However, despite the aggressive presentation, the overall survival rates are excellent,” Ms. Lebbink said.

There are also differences in genetic alterations between adult and pediatric patients. RET-PTC and NTRK fusions are more common in pediatric patients, while mutations in BRAF V600E and RAS point mutations are less frequent.
 

First European guidelines on thyroid cancer, thyroid nodules in children

Despite these differences, and the existence of U.S. guidelines, until now there have been no European recommendations on the management of pediatric thyroid nodules and DTC.

The European Thyroid Association therefore convened a panel of experts in pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology, and tasked them with looking at diagnostics and staging, treatment, and follow-up.

The 2015 American Thyroid Association pediatric guideline was used as framework for the European guideline, with the expert panel identifying areas of discordance and outstanding clinical questions (Thyroid. 2015 Jul;25[7]:716-59).

To answer these questions, they searched PubMed and identified 3,251 studies, of which 45 studies met the inclusion criteria. From this they developed a comprehensive set of recommendations. These include that a child with suspected or proven cancer be referred to an experienced multidisciplinary team and their likely benefit from higher- versus lower-intensity treatment be established.

In addition, children should undergo a preoperative evaluation, with neck palpation, comprehensive neck ultrasonography, and laboratory work-up as a minimum, with further testing suggested in case of a family history or extensive disease.

Total thyroidectomy is the recommended treatment, although the authors call for further studies to assess the impact of limited surgery, and they suggest that prophylactic central lymph node dissection be reserved for advanced cases.

Crucially, all children “should be operated on by high-volume pediatric thyroid cancer surgeons with experience in pediatric thyroid cancer and who are embedded in a center with expertise in the management of DTC,” they wrote.
 

RAI therapy recommended for all children, in contrast to ATA guidelines

Radioactive iodine (I-131) therapy is recommended for all children following total thyroidectomy, with treatment following an individual patient-based approach.

This differs slightly from the ATA guidelines, which recommend against radioactive iodine (RAI) therapy for children with low-risk differentiated thyroid cancer that is mostly confined to the thyroid (N0 or minimal N1a disease). A study presented at the recent 2022 annual meeting of the ATA found that such children who were spared RAI showed no increases in risk of remission compared with those who did receive it.

The ETA guidelines then go on to recommend that children should be followed up with thyroid-stimulating hormone monitoring and suppression to low-normal levels, as well as serum thyroglobulin measurement and neck ultrasound, although other imaging modalities are not recommended.

In children with persistent or recurrent cervical disease, “surgery or I-131 therapy are indicated depending on the size, tumor load, and degree of progression,” and the authors said that cases of radioactive refractory disease should be “thoroughly investigated.”

Patients should also be counseled on the risk of the late effects of treatment for DTC and undergo monitoring, with follow-up continued for at least 10 years. Any subsequent follow-up should be “the result of shared decision-making between the physician and the patient.”
 

Evidence for molecular testing is scarce

Ms. Lebbink said that developing the guidelines nevertheless revealed a series of gaps in current knowledge, notably that the evidence for molecular testing “and the clinical implications in the preoperative stage are scarce.”

Specifically, the “positive and negative predictive value of molecular testing in fine needle biopsy specimen for the presence of DTC in a thyroid nodule must be further investigated.»

She also said that there has been a shift towards less aggressive treatment, due to a reluctance to performed prophylactic central neck dissection, and to offer I-131 therapy after surgery.

“However, before less aggressive treatment could be recommended,” Ms. Lebbink said, “it first must be investigated if there are differences in outcomes,” such as recurrence rates, disease-free survival rates, and survival rates between patients who do and do not receive the treatments.

No funding was declared. One author has reported relationships with Sanofi, AstraZeneca, Bayer, and GE. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Uptake of the approved extended-interval dosing regimen for pembrolizumab has been poor, according to a review of Veterans Health Administration data.

In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.

The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.

Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.

However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.

Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.

Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.

Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.

And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.

The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.

Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.

“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.

“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.

In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.

It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.

If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.

“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.

To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”

Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.

Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”

Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.

The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.

A version of this article first appeared on Medscape.com.

Uptake of the approved extended-interval dosing regimen for pembrolizumab has been poor, according to a review of Veterans Health Administration data.

In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.

The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.

Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.

However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.

Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.

Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.

Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.

And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.

The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.

Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.

“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.

“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.

In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.

It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.

If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.

“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.

To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”

Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.

Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”

Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.

The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.

A version of this article first appeared on Medscape.com.

Uptake of the approved extended-interval dosing regimen for pembrolizumab has been poor, according to a review of Veterans Health Administration data.

In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.

The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.

Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.

However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.

Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.

Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.

Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.

And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.

The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.

Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.

“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.

“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.

In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.

It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.

If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.

“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.

To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”

Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.

Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”

Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.

The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.

A version of this article first appeared on Medscape.com.