Head & Neck/Thyroid Cancers

CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.

Sharon Worcester/MDedge News

Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.

The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.

“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.

The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).

Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.

The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.

In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .

Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.

Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.

“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.

Sharon Worcester/MDedge News

Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.

Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.

While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.

For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.

“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.

Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.

SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.

CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.

Sharon Worcester/MDedge News

Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.

The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.

“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.

The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).

Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.

The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.

In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .

Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.

Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.

“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.

Sharon Worcester/MDedge News

Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.

Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.

While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.

For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.

“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.

Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.

SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.

CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.

Sharon Worcester/MDedge News

Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.

The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.

“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.

The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).

Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.

The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.

In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .

Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.

Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.

“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.

Sharon Worcester/MDedge News

Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.

Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.

While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.

For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.

“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.

Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.

SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

In patients with clinically node-negative oral cavity cancers, the rate of skip metastasis to neck level IV is extremely low, according to authors of a recent meta-analysis.

The rate of level IV involvement was about 2.5%, and the rate of skip metastasis was 0.5% in the analysis, which comprised 11 retrospective studies and 2 randomized clinical trials including a total of 1,359 patients with clinically node-negative oral cavity squamous cell carcinomas.

Encountering a suspected positive lymph node during neck dissection does not appear to be an indicator of high rates of level IV involvement, according to Anton Warshavsky, MD, and colleagues in the department of otolaryngology–head and neck surgery and maxillofacial surgery at Tel Aviv Sourasky Medical Center, Israel.

“Supraomohyoid neck dissection [SOHND] is adequate for this subset of patients,” Dr. Warshavsky and coauthors wrote in a report on the study that appears in JAMA Otolaryngology–Head & Neck Surgery.

SOHND, a type of selective neck dissection, refers to removal of lymph nodes in levels I-III. This approach is now frequently used in managing clinically node-negative oral cavity squamous cell carcinoma and provides control rates similar to those associated with more extensive neck dissections, Dr. Warshavsky and colleagues wrote.

However, concern regarding the risk of skip metastases, or involvement of neck level IV without involvement of lower levels, has stirred controversy. SOHND might not be adequate in these patients because of the possibility of occult metastasis to neck level IV.

Accordingly, Dr. Warshavsky and colleagues combed the available medical literature to find relevant articles for a meta-analysis to better characterize the rate of skip metastasis to level IV in patients who had undergone neck dissection.

Level IV involvement rates in clinically node-negative patients ranged from 0% to 11.4% in the 13 included studies. Based on fixed-effects modeling, the rate of involvement was 2.53% (95% CI, 1.64-3.55%), according to the published report.

The rate of skip metastasis was “extremely low,” wrote Dr. Warshavsky and coauthors. Rates ranged from 0% to 5.50%, with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%).

Cases involving higher levels of the neck did not impact the rate of level IV metastasis, results of a subgroup analysis found. Likewise, an analysis based on T stage showed that rates of level 4 involvement were comparable and low for T stages I-II and III-IV.

These findings are limited, however, not only by the retrospective nature of this study, but also by the fact that many studies reported limited data, hampering the investigators’ ability to run statistics and perform subgroup analyses.

“Unfortunately, data in almost all of the analyzed articles failed to report the relations between the primary tumor site and the neck levels involved by metastatic tumor,” they wrote. “Only primary lesions of the tongue could be accurately assessed.”

Dr. Warshavsky and coauthors reported no conflicts of interest related to the research.

SOURCE: Warshavsky A et al. JAMA Otolaryngol Head Neck Surg. 2019 May 9. doi: 10.1001/jamaoto.2019.0784.

In patients with clinically node-negative oral cavity cancers, the rate of skip metastasis to neck level IV is extremely low, according to authors of a recent meta-analysis.

The rate of level IV involvement was about 2.5%, and the rate of skip metastasis was 0.5% in the analysis, which comprised 11 retrospective studies and 2 randomized clinical trials including a total of 1,359 patients with clinically node-negative oral cavity squamous cell carcinomas.

Encountering a suspected positive lymph node during neck dissection does not appear to be an indicator of high rates of level IV involvement, according to Anton Warshavsky, MD, and colleagues in the department of otolaryngology–head and neck surgery and maxillofacial surgery at Tel Aviv Sourasky Medical Center, Israel.

“Supraomohyoid neck dissection [SOHND] is adequate for this subset of patients,” Dr. Warshavsky and coauthors wrote in a report on the study that appears in JAMA Otolaryngology–Head & Neck Surgery.

SOHND, a type of selective neck dissection, refers to removal of lymph nodes in levels I-III. This approach is now frequently used in managing clinically node-negative oral cavity squamous cell carcinoma and provides control rates similar to those associated with more extensive neck dissections, Dr. Warshavsky and colleagues wrote.

However, concern regarding the risk of skip metastases, or involvement of neck level IV without involvement of lower levels, has stirred controversy. SOHND might not be adequate in these patients because of the possibility of occult metastasis to neck level IV.

Accordingly, Dr. Warshavsky and colleagues combed the available medical literature to find relevant articles for a meta-analysis to better characterize the rate of skip metastasis to level IV in patients who had undergone neck dissection.

Level IV involvement rates in clinically node-negative patients ranged from 0% to 11.4% in the 13 included studies. Based on fixed-effects modeling, the rate of involvement was 2.53% (95% CI, 1.64-3.55%), according to the published report.

The rate of skip metastasis was “extremely low,” wrote Dr. Warshavsky and coauthors. Rates ranged from 0% to 5.50%, with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%).

Cases involving higher levels of the neck did not impact the rate of level IV metastasis, results of a subgroup analysis found. Likewise, an analysis based on T stage showed that rates of level 4 involvement were comparable and low for T stages I-II and III-IV.

These findings are limited, however, not only by the retrospective nature of this study, but also by the fact that many studies reported limited data, hampering the investigators’ ability to run statistics and perform subgroup analyses.

“Unfortunately, data in almost all of the analyzed articles failed to report the relations between the primary tumor site and the neck levels involved by metastatic tumor,” they wrote. “Only primary lesions of the tongue could be accurately assessed.”

Dr. Warshavsky and coauthors reported no conflicts of interest related to the research.

SOURCE: Warshavsky A et al. JAMA Otolaryngol Head Neck Surg. 2019 May 9. doi: 10.1001/jamaoto.2019.0784.

In patients with clinically node-negative oral cavity cancers, the rate of skip metastasis to neck level IV is extremely low, according to authors of a recent meta-analysis.

The rate of level IV involvement was about 2.5%, and the rate of skip metastasis was 0.5% in the analysis, which comprised 11 retrospective studies and 2 randomized clinical trials including a total of 1,359 patients with clinically node-negative oral cavity squamous cell carcinomas.

Encountering a suspected positive lymph node during neck dissection does not appear to be an indicator of high rates of level IV involvement, according to Anton Warshavsky, MD, and colleagues in the department of otolaryngology–head and neck surgery and maxillofacial surgery at Tel Aviv Sourasky Medical Center, Israel.

“Supraomohyoid neck dissection [SOHND] is adequate for this subset of patients,” Dr. Warshavsky and coauthors wrote in a report on the study that appears in JAMA Otolaryngology–Head & Neck Surgery.

SOHND, a type of selective neck dissection, refers to removal of lymph nodes in levels I-III. This approach is now frequently used in managing clinically node-negative oral cavity squamous cell carcinoma and provides control rates similar to those associated with more extensive neck dissections, Dr. Warshavsky and colleagues wrote.

However, concern regarding the risk of skip metastases, or involvement of neck level IV without involvement of lower levels, has stirred controversy. SOHND might not be adequate in these patients because of the possibility of occult metastasis to neck level IV.

Accordingly, Dr. Warshavsky and colleagues combed the available medical literature to find relevant articles for a meta-analysis to better characterize the rate of skip metastasis to level IV in patients who had undergone neck dissection.

Level IV involvement rates in clinically node-negative patients ranged from 0% to 11.4% in the 13 included studies. Based on fixed-effects modeling, the rate of involvement was 2.53% (95% CI, 1.64-3.55%), according to the published report.

The rate of skip metastasis was “extremely low,” wrote Dr. Warshavsky and coauthors. Rates ranged from 0% to 5.50%, with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%).

Cases involving higher levels of the neck did not impact the rate of level IV metastasis, results of a subgroup analysis found. Likewise, an analysis based on T stage showed that rates of level 4 involvement were comparable and low for T stages I-II and III-IV.

These findings are limited, however, not only by the retrospective nature of this study, but also by the fact that many studies reported limited data, hampering the investigators’ ability to run statistics and perform subgroup analyses.

“Unfortunately, data in almost all of the analyzed articles failed to report the relations between the primary tumor site and the neck levels involved by metastatic tumor,” they wrote. “Only primary lesions of the tongue could be accurately assessed.”

Dr. Warshavsky and coauthors reported no conflicts of interest related to the research.

SOURCE: Warshavsky A et al. JAMA Otolaryngol Head Neck Surg. 2019 May 9. doi: 10.1001/jamaoto.2019.0784.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.

For patients with oropharyngeal squamous cell carcinoma (OPSCC), initial staging with PET is associated with better cancer-specific survival (CSS) than staging with other imaging modalities, based on a retrospective analysis of more than 1,700 patients.

PET was associated with a better 3-year overall survival rate than either MRI without PET or CT alone, reported lead author Rustain L. Morgan, MD, of the University of Colorado at Denver, Aurora, and colleagues.

“To our knowledge, there have been no prospective, randomized, controlled trials to date to evaluate the effect of different imaging modalities at the time of initial staging on cancer-specific survival,” the investigators wrote in Cancer. “A population-based data source such as the Surveillance, Epidemiology, and End Results [SEER]–Medicare database provides an excellent opportunity to compare the impact of imaging modality differences on survival in patients with OPSCC.”

Using SEER data, the investigators identified more than 3,704 patients with oropharyngeal cancer; following exclusions, 1,765 patients were involved in the final analysis based on various factors, including survival beyond 2 months after diagnosis and squamous cell carcinoma histology. A Cox proportional hazards model was used to assess relationships between the primary outcome and 3-year CSS rate and imaging, sex, age, region, race, and education.

Results showed that most patients had PET imaging upon diagnosis (83.3%), while fewer had CT alone (11.4%) or MRI without PET (5.2%). Several underlying trends were found: Patients in the West were more likely to undergo PET than patients in the Midwest, South, or East; patients younger than 75 years were more likely to have PET than older patients; and men were more likely to be staged with PET than women. The 3-year CSS was longest for patients who underwent PET (56.8%), followed by MRI without PET (50.1%) and CT alone (47.3%). Controlling for treatment and stage of disease, multivariate analysis also suggested that PET is associated with better CSS; patients staged with MRI without PET had a hazard ratio of 1.748 (P = .0036) and those imaged with CT alone had an HR of 1.337 (P = .0491). Although the Cox proportional hazards model for overall survival revealed numerical trends, these lacked statistical significance for MRI without PET (HR, 1.365; P =.0683) and CT alone (HR, 1.213; P = .114).

“The current study demonstrated a significant difference in CSS based on initial imaging,” the investigators wrote. “These findings are consistent with a prior study that reported that PET imaging can improve the staging of patients with head and neck cancers, particularly as it relates to radiotherapy planning.

“The data from the current study suggest the need for further prospective research to evaluate whether CT or MRI should be considered adequate for the initial staging of patients with OPSCC,” the investigators concluded.

The study was funded by the University of Colorado Cancer Center. One coauthor reported relationships with the American Heart Association and the National Heart, Lung, and Blood Institute.

SOURCE: Morgan RL et al. Cancer. 2019 May 1. doi:10.1002/cncr.32148.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.

Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.

Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.

Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).

Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).

Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.

“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.

The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”

Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.

SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.

The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.

Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.

Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.

Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).

Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).

Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.

“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.

The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”

Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.

SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.

The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.

Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.

Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.

Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).

Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).

Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.

“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.

The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”

Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.

SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.

Treatment deintensification for patients with p16+ oropharyngeal cancer (OPC) should occur only in the context of a clinical trial, according to a provisional clinical opinion released by the American Society of Clinical Oncology (ASCO).

“The hypothesis that deescalation of treatment intensity for patients with p16+ OPC can reduce long-term toxicity without compromising survival is compelling and necessitates careful study and the analysis of well-designed clinical trials before changing current treatment standards, wrote David J. Adelstein, MD, of Case Western Reserve University, Cleveland, along with his associates on the expert panel. Their report is in the Journal of Clinical Oncology.

The panel undertook a review of the literature for evidence pertaining to the treatment of patients with HPV-mediated p16+ OPC with radiation, transoral surgery, concomitant chemoradiotherapy, and chemotherapy, in addition to immunotherapy and targeted therapy. Both randomized and nonrandomized studies were included in the review, and expert consensus opinion was taken into consideration.

After the review, the panelists concluded that the presumption that deintensified treatment in patients with p16+ OPC can lower long-term adverse effects without impacting survival is still a hypothesis that warrants further testing. While early findings of deintensified treatment techniques show promise, current treatment recommendations have not changed, they said.

“The standard of care for the definitive nonoperative management of cisplatin-eligible patients with advanced disease is concurrent chemoradiation with high-dose cisplatin given every 3 weeks,” the panel wrote. “For patients undergoing initial surgical resection, adjuvant chemoradiation with concurrent high-dose cisplatin given every 3 weeks is recommended for patients with positive margins and/or extranodal tumor extension,” they added.

At present, they recommend that deintensified treatment for patients with p16+ OPC should occur only in the context of a clinical trial.

The panel acknowledged that establishing definitive recommendations for all possible clinical scenarios is challenging because of restrictive exclusion criteria in key clinical trials. As a result, the accuracy of outcome data may be limited to specific patient populations.

More information on the provisional clinical opinion is available on the ASCO website.

ASCO funded the study. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, PDS Biotechnology, and several others.

SOURCE: Adelstein DJ et al. J Clin Oncol. 2019 Apr 25. doi: 10.1200/JCO.19.00441.

Treatment deintensification for patients with p16+ oropharyngeal cancer (OPC) should occur only in the context of a clinical trial, according to a provisional clinical opinion released by the American Society of Clinical Oncology (ASCO).

“The hypothesis that deescalation of treatment intensity for patients with p16+ OPC can reduce long-term toxicity without compromising survival is compelling and necessitates careful study and the analysis of well-designed clinical trials before changing current treatment standards, wrote David J. Adelstein, MD, of Case Western Reserve University, Cleveland, along with his associates on the expert panel. Their report is in the Journal of Clinical Oncology.

The panel undertook a review of the literature for evidence pertaining to the treatment of patients with HPV-mediated p16+ OPC with radiation, transoral surgery, concomitant chemoradiotherapy, and chemotherapy, in addition to immunotherapy and targeted therapy. Both randomized and nonrandomized studies were included in the review, and expert consensus opinion was taken into consideration.

After the review, the panelists concluded that the presumption that deintensified treatment in patients with p16+ OPC can lower long-term adverse effects without impacting survival is still a hypothesis that warrants further testing. While early findings of deintensified treatment techniques show promise, current treatment recommendations have not changed, they said.

“The standard of care for the definitive nonoperative management of cisplatin-eligible patients with advanced disease is concurrent chemoradiation with high-dose cisplatin given every 3 weeks,” the panel wrote. “For patients undergoing initial surgical resection, adjuvant chemoradiation with concurrent high-dose cisplatin given every 3 weeks is recommended for patients with positive margins and/or extranodal tumor extension,” they added.

At present, they recommend that deintensified treatment for patients with p16+ OPC should occur only in the context of a clinical trial.

The panel acknowledged that establishing definitive recommendations for all possible clinical scenarios is challenging because of restrictive exclusion criteria in key clinical trials. As a result, the accuracy of outcome data may be limited to specific patient populations.

More information on the provisional clinical opinion is available on the ASCO website.

ASCO funded the study. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, PDS Biotechnology, and several others.

SOURCE: Adelstein DJ et al. J Clin Oncol. 2019 Apr 25. doi: 10.1200/JCO.19.00441.

Treatment deintensification for patients with p16+ oropharyngeal cancer (OPC) should occur only in the context of a clinical trial, according to a provisional clinical opinion released by the American Society of Clinical Oncology (ASCO).

“The hypothesis that deescalation of treatment intensity for patients with p16+ OPC can reduce long-term toxicity without compromising survival is compelling and necessitates careful study and the analysis of well-designed clinical trials before changing current treatment standards, wrote David J. Adelstein, MD, of Case Western Reserve University, Cleveland, along with his associates on the expert panel. Their report is in the Journal of Clinical Oncology.

The panel undertook a review of the literature for evidence pertaining to the treatment of patients with HPV-mediated p16+ OPC with radiation, transoral surgery, concomitant chemoradiotherapy, and chemotherapy, in addition to immunotherapy and targeted therapy. Both randomized and nonrandomized studies were included in the review, and expert consensus opinion was taken into consideration.

After the review, the panelists concluded that the presumption that deintensified treatment in patients with p16+ OPC can lower long-term adverse effects without impacting survival is still a hypothesis that warrants further testing. While early findings of deintensified treatment techniques show promise, current treatment recommendations have not changed, they said.

“The standard of care for the definitive nonoperative management of cisplatin-eligible patients with advanced disease is concurrent chemoradiation with high-dose cisplatin given every 3 weeks,” the panel wrote. “For patients undergoing initial surgical resection, adjuvant chemoradiation with concurrent high-dose cisplatin given every 3 weeks is recommended for patients with positive margins and/or extranodal tumor extension,” they added.

At present, they recommend that deintensified treatment for patients with p16+ OPC should occur only in the context of a clinical trial.

The panel acknowledged that establishing definitive recommendations for all possible clinical scenarios is challenging because of restrictive exclusion criteria in key clinical trials. As a result, the accuracy of outcome data may be limited to specific patient populations.

More information on the provisional clinical opinion is available on the ASCO website.

ASCO funded the study. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, PDS Biotechnology, and several others.

SOURCE: Adelstein DJ et al. J Clin Oncol. 2019 Apr 25. doi: 10.1200/JCO.19.00441.

Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.

However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.

Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”

“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.

A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”

“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.

Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.

“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
 

New data in pediatric patients

Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.

“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.

To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.

The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.

Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.

Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.

Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
 

Overdiagnosis vs. environmental factors and lifestyle changes

If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.

“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.

Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.

“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”

The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.

SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.

Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.

However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.

Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”

“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.

A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”

“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.

Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.

“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
 

New data in pediatric patients

Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.

“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.

To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.

The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.

Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.

Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.

Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
 

Overdiagnosis vs. environmental factors and lifestyle changes

If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.

“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.

Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.

“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”

The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.

SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.

Thyroid cancer rates are on the rise in U.S. pediatric patients, a large epidemiologic study shows, and researchers say the trend can’t be explained away purely as overdiagnosis.

However, the extent of a real increase in clinically significant cancers and what might be causing that increase remains unclear, according to authors of the study and two related editorials appearing in the journal Cancer.

Cases of pediatric differentiated thyroid cancer (DTC) cases increased by 4.43% per year in the study, which was based on data from 39 U.S. cancer registries. Increases were seen in both smaller early-stage and larger late-stage tumors, leading study authors to assert that the trend was “unlikely to be explained solely by increased medical surveillance or improved detection.”

“Environmental and individual factors may also have affected rising trends,” said Meredith S. Shiels, PhD, of the National Cancer Institute and coauthors in a report on the study.

A true increase in pediatric thyroid cancer incidence is a possibility, authors of a related editorial said; however, they also expressed concern that inferences drawn from this U.S. cancer epidemiology data may be “artifactual.”

“We believe that first it is most important to closely examine the reasons for the increase that could be attributable to overdiagnosis, given this appears to be a likely explanation,” said authors of one editorial, including Amy Y. Chen, MD, MPH, of Emory University, Atlanta, and Louise Davies, MD, MS, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.

Overdiagnosis does occur, but the “real component” of the rise in thyroid cancer incidence cannot be ignored, according to a second editorial by David Goldenberg, MD, of Penn State University, Hershey.

“Although many authors are quick to explain the rise in thyroid cancer as an artifact of the overdiagnosis of clinically insignificant thyroid cancers, multiple groups all over the world have shown that this is not sufficient to explain the rise in thyroid cancer,” Dr. Goldenberg said in his editorial.
 

New data in pediatric patients

Pediatric DTCs are rare, representing just 2%-4% of pediatric malignancies, and they’re particularly rare in relation to adult cases, comprising about 2.3% of thyroid cancer diagnoses overall, according to Dr. Shiels and coauthors of the current study.

“The rarity of pediatric DTC, the lack of information on histologic features, or both have prevented prior studies from analyzing trends by tumor size or cancer stage at diagnosis,” they said.

To address this knowledge gap, Dr. Shiels and colleagues analyzed a total of 7,296 primary DTCs in children aged 0-19 years in data obtained from the North American Association of Central Cancer Registries. Ninety-one percent of these pediatric patients had papillary thyroid cancer, 83% were female, and 76% were between the ages of 15 to 19 years.

The rate of pediatric DTCs increased from 4.77 per million in 1998 to 8.82 per million in 2013, representing an increase of 4.43% per year, they found.

Both localized and more aggressive tumors increased in incidence over that time period, they also found. The annual increase was 4.06% for local stage at diagnosis, 5.68% for regional, and 8.55% for distant disease.

Similarly, increases were seen in small and large tumors alike. The annual percentage increase was 9.46% for tumors smaller than 1 cm, and 4.69% for tumors greater than 2 cm, according to the report.

Looking at age, investigators found that the increases in incidence were significant only for 10- to 19-year-olds, while significant increases were consistently observed for both sexes and for all races and ethnicities.
 

Overdiagnosis vs. environmental factors and lifestyle changes

If further investigations point to detection of subclinical disease as the cause of the increases in pediatric DTC incidence then initiatives may be needed to curtail use of CT scans, ultrasound, and needle biopsies, as has been done in adults, Dr. Chen and Dr. Davies said in their editorial.

“When the American Thyroid Association modified their guidelines for needle biopsy of nodules to discourage sampling of small lesions, a corresponding decrease in incidence rates was observed, suggesting that, indeed, overdiagnosis was the culprit,” they said.

Although it’s not clear what environmental factors or lifestyle changes are driving an increase, obesity has been consistently linked to increases in thyroid cancer, Dr. Goldenberg said. Conversely, smoking has been linked to reduced thyroid cancer risk, which means reduced prevalence of smoking in the community could potentially contribute to increased thyroid cancer incidence.

“It is our role as physicians to protect our patients from complacency and undertreatment,” he concluded in his editorial. “Explaining away thyroid cancers as being subclinical or clinically insignificant is reminiscent of days past when we told our patients: ‘Don’t worry, it’s good cancer.’ ”

The research by Dr. Shiels and colleagues was supported by the Intramural Research Program of the National Cancer Institute. Dr. Shiels and coauthors made no conflict of interest disclosures related to their report.

SOURCE: Shiels MO et al. Cancer. 2019 Apr 23. doi: 10.1002/cncr.32125.