Head & Neck/Thyroid Cancers

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

[email protected]

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

[email protected]

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

[email protected]

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

CHICAGO – Patients who had elective neck dissection at the time of primary surgery for oral cancers had a 12.5% better overall survival rate than did patients who had therapeutic neck dissections at the time of recurrence.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil D’Cruz of the head and neck service of Tata Memorial Centre, Mumbai, India.

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study,” he said at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Patients who had elective neck dissection at the time of primary surgery for oral cancers had a 12.5% better overall survival rate than did patients who had therapeutic neck dissections at the time of recurrence.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil D’Cruz of the head and neck service of Tata Memorial Centre, Mumbai, India.

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study,” he said at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Patients who had elective neck dissection at the time of primary surgery for oral cancers had a 12.5% better overall survival rate than did patients who had therapeutic neck dissections at the time of recurrence.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil D’Cruz of the head and neck service of Tata Memorial Centre, Mumbai, India.

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study,” he said at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.

Neil Osterweil/Frontline Medical News

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.

“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.

Dr. Patel moderated the briefing, but was not involved in the study.

Results of the study are also published online in the New England Journal of Medicine.

Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.

Neil Osterweil/Frontline Medical News

Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.

In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.

The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.

At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.

The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.

For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).

The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.

Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.

The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.

CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.

Neil Osterweil/Frontline Medical News

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.

“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.

Dr. Patel moderated the briefing, but was not involved in the study.

Results of the study are also published online in the New England Journal of Medicine.

Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.

Neil Osterweil/Frontline Medical News

Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.

In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.

The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.

At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.

The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.

For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).

The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.

Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.

The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.

CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.

The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.

Neil Osterweil/Frontline Medical News

“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.

“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.

Dr. Patel moderated the briefing, but was not involved in the study.

Results of the study are also published online in the New England Journal of Medicine.

Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.

Neil Osterweil/Frontline Medical News

Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.

In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.

The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.

At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.

The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.

For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).

The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.

Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.

The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.

CHICAGO – One in four patients with recurrent or metastatic head and neck cancer respond to anti-PD-1 immunotherapy with pembrolizumab, according to preliminary expanded cohort results from KEYNOTE-012.

Among 117 evaluable patients, the objective response rate with pembrolizumab (Keytruda) was 24.8%, including 1 complete response and 28 partial responses.

Pembrolizumab was active in both human papillomavirus-negative and HPV-positive tumors, with response rates of 27.2% and 20.6%.

The efficacy is remarkable in this setting and when measured by response, pembrolizumab seems to be roughly twice as effective as cetuximab, our only targeted therapy, study author Dr. Tanguy Seiwert said during a press briefing in advance of his presentation at the annual meeting of the American Society of Clinical Oncology.

In the pivotal EXTREME trial leading to cetuximab’s approval, 36% of patients responded to cetuximab (Erbitux), when the epidermal growth factor receptor inhibitor was added to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) . Only 10%-13% of patients, however, respond to single-agent cetuximab. Also, several recent studies, with the exception of a retrospective EXTREME analysis, suggest cetuximab efficacy varies with HPV status, Dr. Seiwert, from the University of Chicago, said in an interview.

Pembrolizumab was the first anti-programmed death (PD)-1 therapy to reach the market, following its September 2014 approval for use in metastatic melanoma.

The phase Ib, multi-cohort KEYNOTE-012 enrolled patients with advanced solid tumors and previously reported a 20% response rate with pembrolizumab 10 mg/kg every 2 weeks in recurrent or metastatic SCCHN enriched for PD-L1-positive tumors.

For the expansion cohort, 132 patients with recurrent or metastatic SCCHN were enrolled, irrespective of PD-L1 expression or HPV status, and pembrolizumab was given at a fixed dose of 200 mg every 3 weeks. Their mean age was 59 years and nearly 60% had received two or more prior lines of therapy. The primary end point was objective response rate per investigator assessment using RECIST v1.1.

Overall, 56% of patents experienced some tumor shrinkage. The median time to response was 9 weeks (range, 7.6-18 weeks).

Responses were durable, with 86% of responding patients remaining in response, Dr. Seiwert said. Overall, 40 patients are still on therapy, Dr. Seiwert said.

Data reported in a separate study at the meeting suggest that a novel interferon-gamma expression signature may be useful in predicting which patients are likely to benefit from therapy, with a negative predictive value of 95% and positive predictive value of 40%, he said.

Adverse events were reported in 60% of all 132 patients, most commonly fatigue, hypothyroidism, and decreased appetite. Serious grade 3-4 drug-related events were reported in 13 patients and included pneumonitis in 2 and facial swelling in 2.

ASCO expert Dr. Gregory Masters, of Christiana Care Health System in Newark, DE., commented in a statement that, “This is yet another example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects. The diversity of patients who responded is greater than in any previous trials.”

Dr. Masters added that larger studies and longer follow-up are needed to assess the impact of treatment on patient survival.

Pembrolizumab is being evaluated against standard therapy in recurrent or metastatic head and neck cancer in two phase III trials, KEYNOTE-040 and KEYNOTE-048.

CHICAGO – One in four patients with recurrent or metastatic head and neck cancer respond to anti-PD-1 immunotherapy with pembrolizumab, according to preliminary expanded cohort results from KEYNOTE-012.

Among 117 evaluable patients, the objective response rate with pembrolizumab (Keytruda) was 24.8%, including 1 complete response and 28 partial responses.

Pembrolizumab was active in both human papillomavirus-negative and HPV-positive tumors, with response rates of 27.2% and 20.6%.

The efficacy is remarkable in this setting and when measured by response, pembrolizumab seems to be roughly twice as effective as cetuximab, our only targeted therapy, study author Dr. Tanguy Seiwert said during a press briefing in advance of his presentation at the annual meeting of the American Society of Clinical Oncology.

In the pivotal EXTREME trial leading to cetuximab’s approval, 36% of patients responded to cetuximab (Erbitux), when the epidermal growth factor receptor inhibitor was added to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) . Only 10%-13% of patients, however, respond to single-agent cetuximab. Also, several recent studies, with the exception of a retrospective EXTREME analysis, suggest cetuximab efficacy varies with HPV status, Dr. Seiwert, from the University of Chicago, said in an interview.

Pembrolizumab was the first anti-programmed death (PD)-1 therapy to reach the market, following its September 2014 approval for use in metastatic melanoma.

The phase Ib, multi-cohort KEYNOTE-012 enrolled patients with advanced solid tumors and previously reported a 20% response rate with pembrolizumab 10 mg/kg every 2 weeks in recurrent or metastatic SCCHN enriched for PD-L1-positive tumors.

For the expansion cohort, 132 patients with recurrent or metastatic SCCHN were enrolled, irrespective of PD-L1 expression or HPV status, and pembrolizumab was given at a fixed dose of 200 mg every 3 weeks. Their mean age was 59 years and nearly 60% had received two or more prior lines of therapy. The primary end point was objective response rate per investigator assessment using RECIST v1.1.

Overall, 56% of patents experienced some tumor shrinkage. The median time to response was 9 weeks (range, 7.6-18 weeks).

Responses were durable, with 86% of responding patients remaining in response, Dr. Seiwert said. Overall, 40 patients are still on therapy, Dr. Seiwert said.

Data reported in a separate study at the meeting suggest that a novel interferon-gamma expression signature may be useful in predicting which patients are likely to benefit from therapy, with a negative predictive value of 95% and positive predictive value of 40%, he said.

Adverse events were reported in 60% of all 132 patients, most commonly fatigue, hypothyroidism, and decreased appetite. Serious grade 3-4 drug-related events were reported in 13 patients and included pneumonitis in 2 and facial swelling in 2.

ASCO expert Dr. Gregory Masters, of Christiana Care Health System in Newark, DE., commented in a statement that, “This is yet another example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects. The diversity of patients who responded is greater than in any previous trials.”

Dr. Masters added that larger studies and longer follow-up are needed to assess the impact of treatment on patient survival.

Pembrolizumab is being evaluated against standard therapy in recurrent or metastatic head and neck cancer in two phase III trials, KEYNOTE-040 and KEYNOTE-048.

CHICAGO – One in four patients with recurrent or metastatic head and neck cancer respond to anti-PD-1 immunotherapy with pembrolizumab, according to preliminary expanded cohort results from KEYNOTE-012.

Among 117 evaluable patients, the objective response rate with pembrolizumab (Keytruda) was 24.8%, including 1 complete response and 28 partial responses.

Pembrolizumab was active in both human papillomavirus-negative and HPV-positive tumors, with response rates of 27.2% and 20.6%.

The efficacy is remarkable in this setting and when measured by response, pembrolizumab seems to be roughly twice as effective as cetuximab, our only targeted therapy, study author Dr. Tanguy Seiwert said during a press briefing in advance of his presentation at the annual meeting of the American Society of Clinical Oncology.

In the pivotal EXTREME trial leading to cetuximab’s approval, 36% of patients responded to cetuximab (Erbitux), when the epidermal growth factor receptor inhibitor was added to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) . Only 10%-13% of patients, however, respond to single-agent cetuximab. Also, several recent studies, with the exception of a retrospective EXTREME analysis, suggest cetuximab efficacy varies with HPV status, Dr. Seiwert, from the University of Chicago, said in an interview.

Pembrolizumab was the first anti-programmed death (PD)-1 therapy to reach the market, following its September 2014 approval for use in metastatic melanoma.

The phase Ib, multi-cohort KEYNOTE-012 enrolled patients with advanced solid tumors and previously reported a 20% response rate with pembrolizumab 10 mg/kg every 2 weeks in recurrent or metastatic SCCHN enriched for PD-L1-positive tumors.

For the expansion cohort, 132 patients with recurrent or metastatic SCCHN were enrolled, irrespective of PD-L1 expression or HPV status, and pembrolizumab was given at a fixed dose of 200 mg every 3 weeks. Their mean age was 59 years and nearly 60% had received two or more prior lines of therapy. The primary end point was objective response rate per investigator assessment using RECIST v1.1.

Overall, 56% of patents experienced some tumor shrinkage. The median time to response was 9 weeks (range, 7.6-18 weeks).

Responses were durable, with 86% of responding patients remaining in response, Dr. Seiwert said. Overall, 40 patients are still on therapy, Dr. Seiwert said.

Data reported in a separate study at the meeting suggest that a novel interferon-gamma expression signature may be useful in predicting which patients are likely to benefit from therapy, with a negative predictive value of 95% and positive predictive value of 40%, he said.

Adverse events were reported in 60% of all 132 patients, most commonly fatigue, hypothyroidism, and decreased appetite. Serious grade 3-4 drug-related events were reported in 13 patients and included pneumonitis in 2 and facial swelling in 2.

ASCO expert Dr. Gregory Masters, of Christiana Care Health System in Newark, DE., commented in a statement that, “This is yet another example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects. The diversity of patients who responded is greater than in any previous trials.”

Dr. Masters added that larger studies and longer follow-up are needed to assess the impact of treatment on patient survival.

Pembrolizumab is being evaluated against standard therapy in recurrent or metastatic head and neck cancer in two phase III trials, KEYNOTE-040 and KEYNOTE-048.

Several single nucleotide polymorphisms were found to be significantly associated with salivary gland carcinoma in a genomewide association study, Li Xu, Ph.D., and associates at the University of Texas MD Anderson Cancer Center, Houston, reported online in Cancer.

The results of what they believe is the first such study conducted to identify common genetic variants associated with salivary gland carcinoma (SGC) need to be confirmed, but indicate that these single nucleotide polymorphisms (SNPs) could be further evaluated as possible screening tools for the rare cancer, they wrote (Cancer 2015 March 30 [doi:10.1002/cncr.29381]).

©Jana Blaskova/thinkstockphotos.com

The study involved genotyping analyses of 309 cases of SGC in patients (mean age, 54 years) who had been treated at MD Anderson from September 2001 through February 2014; and 535 controls (mean age, 51 years), patients with no cancer.

Five SNPs were found to be associated with SGC risk. “The finding that the five novel SNPs associated with SGC risk are coding SNPs with functional potential, the finding that the genetic effects were considerable,” and the finding that the two SNPs with the strongest SGC risk were relatively rare among controls, “support that these five SNPs may be good candidate SNPs for SGC screening and prevention,” the authors concluded. “These findings support the existence of genetic heterogeneity between histological subtypes of SGC and provide a set of candidate SNPs and genes worthy of in-depth evaluation in future studies,” they added.

The small size of the study was among the limitations, and the results need to be confirmed in another study that also analyzes the function of the SNPs identified in the study, they noted.

In the United States, salivary gland carcinomas are rare, and account for about 0.3% of all malignancies, with an annual incidence of about 1 case per 100,000 people, Dr. Xu and associates said. A small proportion of SGCs are associated with high-dose ionizing radiation, the only well-documented environmental factor associated with the cancer, “suggesting a genetic role in the development of SGC,” they pointed out.

The authors had no disclosures. The study was partly supported by funds from the University of Texas MD Anderson Cancer Center, tge National Institutes of Health grants, and a Cancer Center Support grant.

[email protected]

Several single nucleotide polymorphisms were found to be significantly associated with salivary gland carcinoma in a genomewide association study, Li Xu, Ph.D., and associates at the University of Texas MD Anderson Cancer Center, Houston, reported online in Cancer.

The results of what they believe is the first such study conducted to identify common genetic variants associated with salivary gland carcinoma (SGC) need to be confirmed, but indicate that these single nucleotide polymorphisms (SNPs) could be further evaluated as possible screening tools for the rare cancer, they wrote (Cancer 2015 March 30 [doi:10.1002/cncr.29381]).

©Jana Blaskova/thinkstockphotos.com

The study involved genotyping analyses of 309 cases of SGC in patients (mean age, 54 years) who had been treated at MD Anderson from September 2001 through February 2014; and 535 controls (mean age, 51 years), patients with no cancer.

Five SNPs were found to be associated with SGC risk. “The finding that the five novel SNPs associated with SGC risk are coding SNPs with functional potential, the finding that the genetic effects were considerable,” and the finding that the two SNPs with the strongest SGC risk were relatively rare among controls, “support that these five SNPs may be good candidate SNPs for SGC screening and prevention,” the authors concluded. “These findings support the existence of genetic heterogeneity between histological subtypes of SGC and provide a set of candidate SNPs and genes worthy of in-depth evaluation in future studies,” they added.

The small size of the study was among the limitations, and the results need to be confirmed in another study that also analyzes the function of the SNPs identified in the study, they noted.

In the United States, salivary gland carcinomas are rare, and account for about 0.3% of all malignancies, with an annual incidence of about 1 case per 100,000 people, Dr. Xu and associates said. A small proportion of SGCs are associated with high-dose ionizing radiation, the only well-documented environmental factor associated with the cancer, “suggesting a genetic role in the development of SGC,” they pointed out.

The authors had no disclosures. The study was partly supported by funds from the University of Texas MD Anderson Cancer Center, tge National Institutes of Health grants, and a Cancer Center Support grant.

[email protected]

Several single nucleotide polymorphisms were found to be significantly associated with salivary gland carcinoma in a genomewide association study, Li Xu, Ph.D., and associates at the University of Texas MD Anderson Cancer Center, Houston, reported online in Cancer.

The results of what they believe is the first such study conducted to identify common genetic variants associated with salivary gland carcinoma (SGC) need to be confirmed, but indicate that these single nucleotide polymorphisms (SNPs) could be further evaluated as possible screening tools for the rare cancer, they wrote (Cancer 2015 March 30 [doi:10.1002/cncr.29381]).

©Jana Blaskova/thinkstockphotos.com

The study involved genotyping analyses of 309 cases of SGC in patients (mean age, 54 years) who had been treated at MD Anderson from September 2001 through February 2014; and 535 controls (mean age, 51 years), patients with no cancer.

Five SNPs were found to be associated with SGC risk. “The finding that the five novel SNPs associated with SGC risk are coding SNPs with functional potential, the finding that the genetic effects were considerable,” and the finding that the two SNPs with the strongest SGC risk were relatively rare among controls, “support that these five SNPs may be good candidate SNPs for SGC screening and prevention,” the authors concluded. “These findings support the existence of genetic heterogeneity between histological subtypes of SGC and provide a set of candidate SNPs and genes worthy of in-depth evaluation in future studies,” they added.

The small size of the study was among the limitations, and the results need to be confirmed in another study that also analyzes the function of the SNPs identified in the study, they noted.

In the United States, salivary gland carcinomas are rare, and account for about 0.3% of all malignancies, with an annual incidence of about 1 case per 100,000 people, Dr. Xu and associates said. A small proportion of SGCs are associated with high-dose ionizing radiation, the only well-documented environmental factor associated with the cancer, “suggesting a genetic role in the development of SGC,” they pointed out.

The authors had no disclosures. The study was partly supported by funds from the University of Texas MD Anderson Cancer Center, tge National Institutes of Health grants, and a Cancer Center Support grant.

[email protected]