Head & Neck/Thyroid Cancers

The Food and Drug Administration has approved the immune checkpoint inhibitor nivolumab for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

The FDA based its approval on an improvement in overall survival demonstrated in CheckMate-141, a randomized trial comparing nivolumab with the investigator’s choice of standard therapy, the FDA said in a written statement.

Earlier this year, the FDA granted accelerated approval to another checkpoint inhibitor targeting the PD-1/PD-L1 pathway, pembrolizumab, for the same indication, based on an objective response rate of 16% in the nonrandomized KEYNOTE-012 trial. Merck Sharp & Dohme, maker of pembrolizumab, is looking to demonstrate an improvement in overall survival with the ongoing KEYNOTE-040 study.

Checkmate-141 enrolled 361 patients with recurrent or metastatic SCCHN with disease progression on or within 6 months of receiving platinum-based chemotherapy and randomized (2:1) to nivolumab 3 mg/kg every 2 weeks intravenously or the investigator’s choice of cetuximab 400 mg/m² IV once, then 250 mg/m² IV weekly; methotrexate 40 mg/m² IV weekly; or docetaxel 30 mg/m² IV weekly until disease progression or unacceptable toxicity.

As reported at the European Society of Medical Oncology Congress and in the New England Journal of Medicine (2016;375:1856-67), the median overall survival was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard chemotherapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively.

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.

The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than with standard therapy were cough and dyspnea. The most common laboratory abnormalities occurring in 10% or more nivolumab-treated patients and at a higher incidence than with standard therapy were increased alkaline phosphatase level, increased amylase level, hypercalcemia, hyperkalemia, and increased thyroid-stimulating hormone level, the FDA said.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and previously has been approved to treat classical Hodgkin’s lymphoma, advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved the immune checkpoint inhibitor nivolumab for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

The FDA based its approval on an improvement in overall survival demonstrated in CheckMate-141, a randomized trial comparing nivolumab with the investigator’s choice of standard therapy, the FDA said in a written statement.

Earlier this year, the FDA granted accelerated approval to another checkpoint inhibitor targeting the PD-1/PD-L1 pathway, pembrolizumab, for the same indication, based on an objective response rate of 16% in the nonrandomized KEYNOTE-012 trial. Merck Sharp & Dohme, maker of pembrolizumab, is looking to demonstrate an improvement in overall survival with the ongoing KEYNOTE-040 study.

Checkmate-141 enrolled 361 patients with recurrent or metastatic SCCHN with disease progression on or within 6 months of receiving platinum-based chemotherapy and randomized (2:1) to nivolumab 3 mg/kg every 2 weeks intravenously or the investigator’s choice of cetuximab 400 mg/m² IV once, then 250 mg/m² IV weekly; methotrexate 40 mg/m² IV weekly; or docetaxel 30 mg/m² IV weekly until disease progression or unacceptable toxicity.

As reported at the European Society of Medical Oncology Congress and in the New England Journal of Medicine (2016;375:1856-67), the median overall survival was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard chemotherapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively.

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.

The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than with standard therapy were cough and dyspnea. The most common laboratory abnormalities occurring in 10% or more nivolumab-treated patients and at a higher incidence than with standard therapy were increased alkaline phosphatase level, increased amylase level, hypercalcemia, hyperkalemia, and increased thyroid-stimulating hormone level, the FDA said.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and previously has been approved to treat classical Hodgkin’s lymphoma, advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has approved the immune checkpoint inhibitor nivolumab for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

The FDA based its approval on an improvement in overall survival demonstrated in CheckMate-141, a randomized trial comparing nivolumab with the investigator’s choice of standard therapy, the FDA said in a written statement.

Earlier this year, the FDA granted accelerated approval to another checkpoint inhibitor targeting the PD-1/PD-L1 pathway, pembrolizumab, for the same indication, based on an objective response rate of 16% in the nonrandomized KEYNOTE-012 trial. Merck Sharp & Dohme, maker of pembrolizumab, is looking to demonstrate an improvement in overall survival with the ongoing KEYNOTE-040 study.

Checkmate-141 enrolled 361 patients with recurrent or metastatic SCCHN with disease progression on or within 6 months of receiving platinum-based chemotherapy and randomized (2:1) to nivolumab 3 mg/kg every 2 weeks intravenously or the investigator’s choice of cetuximab 400 mg/m² IV once, then 250 mg/m² IV weekly; methotrexate 40 mg/m² IV weekly; or docetaxel 30 mg/m² IV weekly until disease progression or unacceptable toxicity.

As reported at the European Society of Medical Oncology Congress and in the New England Journal of Medicine (2016;375:1856-67), the median overall survival was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard chemotherapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively.

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.

The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than with standard therapy were cough and dyspnea. The most common laboratory abnormalities occurring in 10% or more nivolumab-treated patients and at a higher incidence than with standard therapy were increased alkaline phosphatase level, increased amylase level, hypercalcemia, hyperkalemia, and increased thyroid-stimulating hormone level, the FDA said.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and previously has been approved to treat classical Hodgkin’s lymphoma, advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

COPENHAGEN – Among patients with recurrent or metastatic squamous cell carcinoma of the head and neck, those treated with the programmed death ligand–1 checkpoint inhibitor nivolumab reported consistently better quality of life than patients treated with a standard second-line agent of the investigator’s choice.

In a substudy of the randomized phase III Checkmate 141 trial, patients treated with nivolumab (Opdivo) had consistently stable outcomes across three separate, validated quality of life (QoL) instruments, reported Kevin Harrington, MBBS, of Royal Marsden Hospital in London.

“Nivolumab is the first PD-L1 [programmed death ligand–1] inhibitor to demonstrate a significant improvement in overall survival, with greater tolerability and a quality of life benefit, compared with standard of care therapy,” he said at the European Society of Medical Oncology Congress.

The overall trial results were reported at the 2016 annual meeting of the American Association for Cancer Research, and published online in the New England Journal of Medicine to coincide with Dr. Harrington’s presentation.

In this open-label trial, 361 patients with squamous cell carcinoma of the head and neck (HNSCC) that recurred or progressed within 6 months of completion of platinum-based chemotherapy were randomly assigned on a 2:1 basis to receive either nivolumab 3 mg/kg every 2 weeks, or standard, single-agent systemic chemotherapy with either methotrexate, docetaxel, or cetuximab.

After a median follow-up of 5.1 months (range, 0-16.8 months), the median overall survival, the primary endpoint, was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard therapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively. The median progression-free survival was similar between the groups, at 2 months and 2.3 months, respectively (a nonsignificant finding).

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy.
 

Patient-reported outcomes

Dr. Harrington reviewed changes from baseline in symptoms and function for three different patient-reported instruments:

• The cancer-specific EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30.

• The head and neck cancer–specific QLQ-H&N35.

• The generic health status EQ-5D-3L.

Patients were assessed on day 1 of the first treatment cycle, at week 9 and every 6 weeks thereafter of the study, at the first and second follow-up visits, and at survival follow-up visits (with the EQ-5D-3L only).

For the QLQ-C30 domains of physical, role, and social functioning, patients on nivolumab had either slight improvements from baseline or stayed the same, whereas patients on standard therapies had significant declines at both 9 and 15 weeks for all three domains.

There were no differences in functional domains on this instrument according to expression of PD-L1 (on either 1% or more of tumor cells or less than 1%).

For the EORTC QLQ-C30 symptom burden scale, patients assigned to the investigator’s choice had significantly and clinically meaningful worse symptoms, compared with patients on nivolumab at 9 and 15 weeks, and the median time to deterioration of function favored nivolumab on all subscales except for emotional functioning.

Similar differences in favor of nivolumab were seen in the EORTC QLQ-H&N35 instrument domains of pain, sensory problems, and social contact problems.

Lastly, on the EQ-5D-3L instrument, nivolumab-treated patients had stable health status, compared with worsening health status, with the difference statistically significant at week 15 (P = .037).

Anthony T.C. Chan, MD, professor of clinical oncology at the Chinese University of Hong Kong, the invited discussant, said that some of the differences in QoL noted in the study may have been due to differences between the therapies.

“The kinetics of adverse events with checkpoint blockade is now well described, and it’s quite different from systemic chemotherapy, where you get the side effects immediately. Quite often with checkpoint inhibitors, you can get adverse events up to 6-8 weeks or even longer after the start of therapy,” he said.

Nonetheless, “I think from [Checkmate 141] with the very positive results we’ve just seen with nivolumab, both in improving overall survival as well as improving patient-reported outcomes, after patients have failed platinum-based chemotherapy, nivolumab should be considered standard second-line therapy in this setting,” he said.

The trial was supported by Bristol-Myers Squibb. Dr. Harrington and Dr. Chan disclosed receiving research funding, serving as an adviser, and/or receiving travel, accommodations, and other expenses from the company.

[email protected]

COPENHAGEN – Among patients with recurrent or metastatic squamous cell carcinoma of the head and neck, those treated with the programmed death ligand–1 checkpoint inhibitor nivolumab reported consistently better quality of life than patients treated with a standard second-line agent of the investigator’s choice.

In a substudy of the randomized phase III Checkmate 141 trial, patients treated with nivolumab (Opdivo) had consistently stable outcomes across three separate, validated quality of life (QoL) instruments, reported Kevin Harrington, MBBS, of Royal Marsden Hospital in London.

“Nivolumab is the first PD-L1 [programmed death ligand–1] inhibitor to demonstrate a significant improvement in overall survival, with greater tolerability and a quality of life benefit, compared with standard of care therapy,” he said at the European Society of Medical Oncology Congress.

The overall trial results were reported at the 2016 annual meeting of the American Association for Cancer Research, and published online in the New England Journal of Medicine to coincide with Dr. Harrington’s presentation.

In this open-label trial, 361 patients with squamous cell carcinoma of the head and neck (HNSCC) that recurred or progressed within 6 months of completion of platinum-based chemotherapy were randomly assigned on a 2:1 basis to receive either nivolumab 3 mg/kg every 2 weeks, or standard, single-agent systemic chemotherapy with either methotrexate, docetaxel, or cetuximab.

After a median follow-up of 5.1 months (range, 0-16.8 months), the median overall survival, the primary endpoint, was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard therapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively. The median progression-free survival was similar between the groups, at 2 months and 2.3 months, respectively (a nonsignificant finding).

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy.
 

Patient-reported outcomes

Dr. Harrington reviewed changes from baseline in symptoms and function for three different patient-reported instruments:

• The cancer-specific EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30.

• The head and neck cancer–specific QLQ-H&N35.

• The generic health status EQ-5D-3L.

Patients were assessed on day 1 of the first treatment cycle, at week 9 and every 6 weeks thereafter of the study, at the first and second follow-up visits, and at survival follow-up visits (with the EQ-5D-3L only).

For the QLQ-C30 domains of physical, role, and social functioning, patients on nivolumab had either slight improvements from baseline or stayed the same, whereas patients on standard therapies had significant declines at both 9 and 15 weeks for all three domains.

There were no differences in functional domains on this instrument according to expression of PD-L1 (on either 1% or more of tumor cells or less than 1%).

For the EORTC QLQ-C30 symptom burden scale, patients assigned to the investigator’s choice had significantly and clinically meaningful worse symptoms, compared with patients on nivolumab at 9 and 15 weeks, and the median time to deterioration of function favored nivolumab on all subscales except for emotional functioning.

Similar differences in favor of nivolumab were seen in the EORTC QLQ-H&N35 instrument domains of pain, sensory problems, and social contact problems.

Lastly, on the EQ-5D-3L instrument, nivolumab-treated patients had stable health status, compared with worsening health status, with the difference statistically significant at week 15 (P = .037).

Anthony T.C. Chan, MD, professor of clinical oncology at the Chinese University of Hong Kong, the invited discussant, said that some of the differences in QoL noted in the study may have been due to differences between the therapies.

“The kinetics of adverse events with checkpoint blockade is now well described, and it’s quite different from systemic chemotherapy, where you get the side effects immediately. Quite often with checkpoint inhibitors, you can get adverse events up to 6-8 weeks or even longer after the start of therapy,” he said.

Nonetheless, “I think from [Checkmate 141] with the very positive results we’ve just seen with nivolumab, both in improving overall survival as well as improving patient-reported outcomes, after patients have failed platinum-based chemotherapy, nivolumab should be considered standard second-line therapy in this setting,” he said.

The trial was supported by Bristol-Myers Squibb. Dr. Harrington and Dr. Chan disclosed receiving research funding, serving as an adviser, and/or receiving travel, accommodations, and other expenses from the company.

[email protected]

COPENHAGEN – Among patients with recurrent or metastatic squamous cell carcinoma of the head and neck, those treated with the programmed death ligand–1 checkpoint inhibitor nivolumab reported consistently better quality of life than patients treated with a standard second-line agent of the investigator’s choice.

In a substudy of the randomized phase III Checkmate 141 trial, patients treated with nivolumab (Opdivo) had consistently stable outcomes across three separate, validated quality of life (QoL) instruments, reported Kevin Harrington, MBBS, of Royal Marsden Hospital in London.

“Nivolumab is the first PD-L1 [programmed death ligand–1] inhibitor to demonstrate a significant improvement in overall survival, with greater tolerability and a quality of life benefit, compared with standard of care therapy,” he said at the European Society of Medical Oncology Congress.

The overall trial results were reported at the 2016 annual meeting of the American Association for Cancer Research, and published online in the New England Journal of Medicine to coincide with Dr. Harrington’s presentation.

In this open-label trial, 361 patients with squamous cell carcinoma of the head and neck (HNSCC) that recurred or progressed within 6 months of completion of platinum-based chemotherapy were randomly assigned on a 2:1 basis to receive either nivolumab 3 mg/kg every 2 weeks, or standard, single-agent systemic chemotherapy with either methotrexate, docetaxel, or cetuximab.

After a median follow-up of 5.1 months (range, 0-16.8 months), the median overall survival, the primary endpoint, was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard therapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively. The median progression-free survival was similar between the groups, at 2 months and 2.3 months, respectively (a nonsignificant finding).

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy.
 

Patient-reported outcomes

Dr. Harrington reviewed changes from baseline in symptoms and function for three different patient-reported instruments:

• The cancer-specific EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30.

• The head and neck cancer–specific QLQ-H&N35.

• The generic health status EQ-5D-3L.

Patients were assessed on day 1 of the first treatment cycle, at week 9 and every 6 weeks thereafter of the study, at the first and second follow-up visits, and at survival follow-up visits (with the EQ-5D-3L only).

For the QLQ-C30 domains of physical, role, and social functioning, patients on nivolumab had either slight improvements from baseline or stayed the same, whereas patients on standard therapies had significant declines at both 9 and 15 weeks for all three domains.

There were no differences in functional domains on this instrument according to expression of PD-L1 (on either 1% or more of tumor cells or less than 1%).

For the EORTC QLQ-C30 symptom burden scale, patients assigned to the investigator’s choice had significantly and clinically meaningful worse symptoms, compared with patients on nivolumab at 9 and 15 weeks, and the median time to deterioration of function favored nivolumab on all subscales except for emotional functioning.

Similar differences in favor of nivolumab were seen in the EORTC QLQ-H&N35 instrument domains of pain, sensory problems, and social contact problems.

Lastly, on the EQ-5D-3L instrument, nivolumab-treated patients had stable health status, compared with worsening health status, with the difference statistically significant at week 15 (P = .037).

Anthony T.C. Chan, MD, professor of clinical oncology at the Chinese University of Hong Kong, the invited discussant, said that some of the differences in QoL noted in the study may have been due to differences between the therapies.

“The kinetics of adverse events with checkpoint blockade is now well described, and it’s quite different from systemic chemotherapy, where you get the side effects immediately. Quite often with checkpoint inhibitors, you can get adverse events up to 6-8 weeks or even longer after the start of therapy,” he said.

Nonetheless, “I think from [Checkmate 141] with the very positive results we’ve just seen with nivolumab, both in improving overall survival as well as improving patient-reported outcomes, after patients have failed platinum-based chemotherapy, nivolumab should be considered standard second-line therapy in this setting,” he said.

The trial was supported by Bristol-Myers Squibb. Dr. Harrington and Dr. Chan disclosed receiving research funding, serving as an adviser, and/or receiving travel, accommodations, and other expenses from the company.

[email protected]

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

The dentition of head and neck cancer patients is of utmost importance when they receive radiation therapy, especially because patients are living longer after a course of head and neck radiation. Good communication among the oncology team members (the radiation and medical oncologists, the maxillofacial prosthodontist/dental oncologist, otolaryngologist, reconstructive surgeon, nursing support) and the patient is essential initially, and subsequently including the general dentist as well. The aim of this primer for all those caring for patients with head and neck cancer is to underscore the important role of the dental oncologist during all phases of radiation therapy, and to provide guidelines to minimize and prevent dental complications such as radiation-induced caries and ORN.

Click on the PDF icon at the top of this introduction to read the full article.

The dentition of head and neck cancer patients is of utmost importance when they receive radiation therapy, especially because patients are living longer after a course of head and neck radiation. Good communication among the oncology team members (the radiation and medical oncologists, the maxillofacial prosthodontist/dental oncologist, otolaryngologist, reconstructive surgeon, nursing support) and the patient is essential initially, and subsequently including the general dentist as well. The aim of this primer for all those caring for patients with head and neck cancer is to underscore the important role of the dental oncologist during all phases of radiation therapy, and to provide guidelines to minimize and prevent dental complications such as radiation-induced caries and ORN.

Click on the PDF icon at the top of this introduction to read the full article.

The dentition of head and neck cancer patients is of utmost importance when they receive radiation therapy, especially because patients are living longer after a course of head and neck radiation. Good communication among the oncology team members (the radiation and medical oncologists, the maxillofacial prosthodontist/dental oncologist, otolaryngologist, reconstructive surgeon, nursing support) and the patient is essential initially, and subsequently including the general dentist as well. The aim of this primer for all those caring for patients with head and neck cancer is to underscore the important role of the dental oncologist during all phases of radiation therapy, and to provide guidelines to minimize and prevent dental complications such as radiation-induced caries and ORN.

Click on the PDF icon at the top of this introduction to read the full article.

SEATTLE – A longer course of dexamethasone was a bit better than the usual single intraoperative dose for controlling pain and dysphagia after transoral robotic surgery in a randomized trial from the Oregon Health and Science University, Portland.

Thirty-five subjects were randomized to the standard 10-mg intraoperative dexamethasone dose plus 8 mg every 8 hours for up to 4 days; 33 others were randomized to the intraoperative dose plus placebo. All the subjects had transoral robotic surgery (TORS) resection for T1 or T2 oropharyngeal squamous cell carcinoma, either partial pharyngectomy/radical tonsillectomy, base of tongue resection, or both.

The dexamethasone group had significantly less pain on postop day 3 (about 1.5 points less on the 10-point visual analogue scale) and were discharged, on average, a day earlier. They also advanced more quickly toward solid food at 1- and 3-weeks’ follow-up. “They were much more likely to be on a full-soft diet, while the placebo group was mostly still on purees, and just starting into soft foods,” said lead investigator Daniel Clayburgh, MD, a head and neck cancer specialist at the university.

Otherwise, however, the extra dexamethasone wasn’t much help; pain scores were the same in both groups for the first couple days after surgery and at follow-up, and both groups used the same amount of post-op opioids. Other than food tolerance, dysphagia metrics were pretty much the same.

“I was actually anticipating a little bit more of a benefit, but there are potentially some benefits to extended corticosteroid courses after TORS. It’s safe, and well tolerated so long as you screen out diabetes and other problems with hyperglycemia,” as was done in the study, he said. “It does decrease post-op length of stay and may provide a modest decrease in post-op pain, and may slightly accelerate advancement of dietary consistency,” Dr. Clayburgh said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Although he and his colleagues are mulling over what to do with the findings in light of other initiatives to reduce post-TORS pain, they are now likely to extend dexamethasone courses when significant post-op pain seems likely, and doing so is not otherwise contraindicated, he said.

Intraoperative corticosteroids are now routine for TORS, based on the strength of benefit in the tonsillectomy literature. The team decided to try an extended course because “being rather simple minded surgeons, we thought that if one dose is good, more should be better,” Dr. Clayburgh said.

The dexamethasone group was slightly younger than the placebo group (56 vs. 61 years) but otherwise similar; most were men. In addition to patients with hyperglycemia issues, those with confounders for post-op speech and swallowing recovery were among those excluded from the trial. Subjects required nasogastric feeding tubes for a median of 6.5 days postoperatively, lost a mean of 10 pounds in the first 2 post-op weeks, and were hospitalized for a mean of about 5 days. Dexamethasone was delivered orally or by nasogastric tube.

There was no external funding for the study, and Dr. Clayburgh had no relevant financial disclosures.

[email protected]

SEATTLE – A longer course of dexamethasone was a bit better than the usual single intraoperative dose for controlling pain and dysphagia after transoral robotic surgery in a randomized trial from the Oregon Health and Science University, Portland.

Thirty-five subjects were randomized to the standard 10-mg intraoperative dexamethasone dose plus 8 mg every 8 hours for up to 4 days; 33 others were randomized to the intraoperative dose plus placebo. All the subjects had transoral robotic surgery (TORS) resection for T1 or T2 oropharyngeal squamous cell carcinoma, either partial pharyngectomy/radical tonsillectomy, base of tongue resection, or both.

The dexamethasone group had significantly less pain on postop day 3 (about 1.5 points less on the 10-point visual analogue scale) and were discharged, on average, a day earlier. They also advanced more quickly toward solid food at 1- and 3-weeks’ follow-up. “They were much more likely to be on a full-soft diet, while the placebo group was mostly still on purees, and just starting into soft foods,” said lead investigator Daniel Clayburgh, MD, a head and neck cancer specialist at the university.

Otherwise, however, the extra dexamethasone wasn’t much help; pain scores were the same in both groups for the first couple days after surgery and at follow-up, and both groups used the same amount of post-op opioids. Other than food tolerance, dysphagia metrics were pretty much the same.

“I was actually anticipating a little bit more of a benefit, but there are potentially some benefits to extended corticosteroid courses after TORS. It’s safe, and well tolerated so long as you screen out diabetes and other problems with hyperglycemia,” as was done in the study, he said. “It does decrease post-op length of stay and may provide a modest decrease in post-op pain, and may slightly accelerate advancement of dietary consistency,” Dr. Clayburgh said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Although he and his colleagues are mulling over what to do with the findings in light of other initiatives to reduce post-TORS pain, they are now likely to extend dexamethasone courses when significant post-op pain seems likely, and doing so is not otherwise contraindicated, he said.

Intraoperative corticosteroids are now routine for TORS, based on the strength of benefit in the tonsillectomy literature. The team decided to try an extended course because “being rather simple minded surgeons, we thought that if one dose is good, more should be better,” Dr. Clayburgh said.

The dexamethasone group was slightly younger than the placebo group (56 vs. 61 years) but otherwise similar; most were men. In addition to patients with hyperglycemia issues, those with confounders for post-op speech and swallowing recovery were among those excluded from the trial. Subjects required nasogastric feeding tubes for a median of 6.5 days postoperatively, lost a mean of 10 pounds in the first 2 post-op weeks, and were hospitalized for a mean of about 5 days. Dexamethasone was delivered orally or by nasogastric tube.

There was no external funding for the study, and Dr. Clayburgh had no relevant financial disclosures.

[email protected]

SEATTLE – A longer course of dexamethasone was a bit better than the usual single intraoperative dose for controlling pain and dysphagia after transoral robotic surgery in a randomized trial from the Oregon Health and Science University, Portland.

Thirty-five subjects were randomized to the standard 10-mg intraoperative dexamethasone dose plus 8 mg every 8 hours for up to 4 days; 33 others were randomized to the intraoperative dose plus placebo. All the subjects had transoral robotic surgery (TORS) resection for T1 or T2 oropharyngeal squamous cell carcinoma, either partial pharyngectomy/radical tonsillectomy, base of tongue resection, or both.

The dexamethasone group had significantly less pain on postop day 3 (about 1.5 points less on the 10-point visual analogue scale) and were discharged, on average, a day earlier. They also advanced more quickly toward solid food at 1- and 3-weeks’ follow-up. “They were much more likely to be on a full-soft diet, while the placebo group was mostly still on purees, and just starting into soft foods,” said lead investigator Daniel Clayburgh, MD, a head and neck cancer specialist at the university.

Otherwise, however, the extra dexamethasone wasn’t much help; pain scores were the same in both groups for the first couple days after surgery and at follow-up, and both groups used the same amount of post-op opioids. Other than food tolerance, dysphagia metrics were pretty much the same.

“I was actually anticipating a little bit more of a benefit, but there are potentially some benefits to extended corticosteroid courses after TORS. It’s safe, and well tolerated so long as you screen out diabetes and other problems with hyperglycemia,” as was done in the study, he said. “It does decrease post-op length of stay and may provide a modest decrease in post-op pain, and may slightly accelerate advancement of dietary consistency,” Dr. Clayburgh said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Although he and his colleagues are mulling over what to do with the findings in light of other initiatives to reduce post-TORS pain, they are now likely to extend dexamethasone courses when significant post-op pain seems likely, and doing so is not otherwise contraindicated, he said.

Intraoperative corticosteroids are now routine for TORS, based on the strength of benefit in the tonsillectomy literature. The team decided to try an extended course because “being rather simple minded surgeons, we thought that if one dose is good, more should be better,” Dr. Clayburgh said.

The dexamethasone group was slightly younger than the placebo group (56 vs. 61 years) but otherwise similar; most were men. In addition to patients with hyperglycemia issues, those with confounders for post-op speech and swallowing recovery were among those excluded from the trial. Subjects required nasogastric feeding tubes for a median of 6.5 days postoperatively, lost a mean of 10 pounds in the first 2 post-op weeks, and were hospitalized for a mean of about 5 days. Dexamethasone was delivered orally or by nasogastric tube.

There was no external funding for the study, and Dr. Clayburgh had no relevant financial disclosures.

[email protected]

SEATTLE – Additional resection to clear positive frozen tumor bed margins in oral cavity squamous cell carcinoma – a common practice in head and neck surgery – does not improve outcomes, investigators report.

In a retrospective review of 406 patients treated with oral cavity squamous cell carcinoma resection, the difference in local recurrence between patients with positive intraoperative frozen tumor bed margins cleared by additional resection (local recurrence in 27%) and those with positive frozen margins that were not cleared (local recurrence in 34%) was not statistically significant.

The team assessed local recurrence rates after dividing their review subjects – 61 years old on average and over half men – into those with negative tumor and tumor bed margins; patients with one positive and the other negative; and patients with both margins positive. Tumor beds were cleared to negative when possible.

The various configurations mattered for prognosis. Local recurrence ranged from 7% when both margins were negative to 65% when both were positive. Cancer recurred in 19% of patients with negative tumor but positive bed margins, and 35% of patients with positive tumor but negative bed margins. “Combining margin groups provides additional prognostic information, [but] the main specimen margin was the strongest predictor of recurrence. Positive margins on the main specimen carry a poor prognosis,” said lead investigator Marisa Buchakjian, MD, at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The study “should influence the use and interpretation of margin data in oral cavity squamous cell carcinoma surgery,” she said, since the majority of head and neck surgeons rely on tumor bed margins for prognosis, and consider positive tumor beds resected to clear pretty much the same as ones that are initially negative.

That approach is probably too simple. Intraoperative frozen tumor bed margins “were unreliable tests of main specimen margins, and would in fact be expected to miss approximately 50%” that are positive, said Dr. Buchakjian of University of Iowa Hospitals and Clinics, Iowa City.

She and her associates concluded that “the concordance between tumor bed and tumor specimen margins is not good ... Cases of main specimen margin involvement with no corresponding findings in tumor bed frozen sections are common; conversely, frozen sections may show involvement, while the main specimen margins are negative. Prognostic information is contained within findings from both the frozen and specimen margins,” and neither should be considered the “true” margin. The tumor margin is an important predictor, even if margins are taken from the tumor bed.

However, “we do not believe that this provides evidence that a known positive margin should not be pursued with additional excision. We emphasize that this study highlights the prognostic importance of margin status and that an involved margin, either on the initial tumor bed frozen sections or the tumor specimen, is associated with worse outcomes regardless of the final margin result,” they said.

The authors had no conflicts of interest, and didn’t report external funding.

[email protected]

SEATTLE – Additional resection to clear positive frozen tumor bed margins in oral cavity squamous cell carcinoma – a common practice in head and neck surgery – does not improve outcomes, investigators report.

In a retrospective review of 406 patients treated with oral cavity squamous cell carcinoma resection, the difference in local recurrence between patients with positive intraoperative frozen tumor bed margins cleared by additional resection (local recurrence in 27%) and those with positive frozen margins that were not cleared (local recurrence in 34%) was not statistically significant.

The team assessed local recurrence rates after dividing their review subjects – 61 years old on average and over half men – into those with negative tumor and tumor bed margins; patients with one positive and the other negative; and patients with both margins positive. Tumor beds were cleared to negative when possible.

The various configurations mattered for prognosis. Local recurrence ranged from 7% when both margins were negative to 65% when both were positive. Cancer recurred in 19% of patients with negative tumor but positive bed margins, and 35% of patients with positive tumor but negative bed margins. “Combining margin groups provides additional prognostic information, [but] the main specimen margin was the strongest predictor of recurrence. Positive margins on the main specimen carry a poor prognosis,” said lead investigator Marisa Buchakjian, MD, at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The study “should influence the use and interpretation of margin data in oral cavity squamous cell carcinoma surgery,” she said, since the majority of head and neck surgeons rely on tumor bed margins for prognosis, and consider positive tumor beds resected to clear pretty much the same as ones that are initially negative.

That approach is probably too simple. Intraoperative frozen tumor bed margins “were unreliable tests of main specimen margins, and would in fact be expected to miss approximately 50%” that are positive, said Dr. Buchakjian of University of Iowa Hospitals and Clinics, Iowa City.

She and her associates concluded that “the concordance between tumor bed and tumor specimen margins is not good ... Cases of main specimen margin involvement with no corresponding findings in tumor bed frozen sections are common; conversely, frozen sections may show involvement, while the main specimen margins are negative. Prognostic information is contained within findings from both the frozen and specimen margins,” and neither should be considered the “true” margin. The tumor margin is an important predictor, even if margins are taken from the tumor bed.

However, “we do not believe that this provides evidence that a known positive margin should not be pursued with additional excision. We emphasize that this study highlights the prognostic importance of margin status and that an involved margin, either on the initial tumor bed frozen sections or the tumor specimen, is associated with worse outcomes regardless of the final margin result,” they said.

The authors had no conflicts of interest, and didn’t report external funding.

[email protected]

SEATTLE – Additional resection to clear positive frozen tumor bed margins in oral cavity squamous cell carcinoma – a common practice in head and neck surgery – does not improve outcomes, investigators report.

In a retrospective review of 406 patients treated with oral cavity squamous cell carcinoma resection, the difference in local recurrence between patients with positive intraoperative frozen tumor bed margins cleared by additional resection (local recurrence in 27%) and those with positive frozen margins that were not cleared (local recurrence in 34%) was not statistically significant.

The team assessed local recurrence rates after dividing their review subjects – 61 years old on average and over half men – into those with negative tumor and tumor bed margins; patients with one positive and the other negative; and patients with both margins positive. Tumor beds were cleared to negative when possible.

The various configurations mattered for prognosis. Local recurrence ranged from 7% when both margins were negative to 65% when both were positive. Cancer recurred in 19% of patients with negative tumor but positive bed margins, and 35% of patients with positive tumor but negative bed margins. “Combining margin groups provides additional prognostic information, [but] the main specimen margin was the strongest predictor of recurrence. Positive margins on the main specimen carry a poor prognosis,” said lead investigator Marisa Buchakjian, MD, at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The study “should influence the use and interpretation of margin data in oral cavity squamous cell carcinoma surgery,” she said, since the majority of head and neck surgeons rely on tumor bed margins for prognosis, and consider positive tumor beds resected to clear pretty much the same as ones that are initially negative.

That approach is probably too simple. Intraoperative frozen tumor bed margins “were unreliable tests of main specimen margins, and would in fact be expected to miss approximately 50%” that are positive, said Dr. Buchakjian of University of Iowa Hospitals and Clinics, Iowa City.

She and her associates concluded that “the concordance between tumor bed and tumor specimen margins is not good ... Cases of main specimen margin involvement with no corresponding findings in tumor bed frozen sections are common; conversely, frozen sections may show involvement, while the main specimen margins are negative. Prognostic information is contained within findings from both the frozen and specimen margins,” and neither should be considered the “true” margin. The tumor margin is an important predictor, even if margins are taken from the tumor bed.

However, “we do not believe that this provides evidence that a known positive margin should not be pursued with additional excision. We emphasize that this study highlights the prognostic importance of margin status and that an involved margin, either on the initial tumor bed frozen sections or the tumor specimen, is associated with worse outcomes regardless of the final margin result,” they said.

The authors had no conflicts of interest, and didn’t report external funding.

[email protected]

SEATTLE – Oncologic transoral robotic surgery patients spend less time in the hospital if they have neck dissections at the same time, instead of later, according to a review of 441 patients by Stony Brook (N.Y.) University.

The average hospital length of stay (LOS) was 6 days for the 349 patients (79.1%) who had lymphadenectomy neck dissections at the same time as transoral robotic surgery (TORS). The 92 patients (20.9%) who had staged procedures - neck dissections and TORS about a month apart, with TORS usually done first - stayed in the hospital an average of 8 days (P less than .0001). After risk adjustment, LOS was 43% shorter for concurrent dissections.

Cardiac arrhythmias were also more common in staged patients, perhaps because they had general anesthesia twice in a short period or maybe because staged patients were more likely to be obese (18.5% vs. 7.5%; P less than .01).

However, there were no statistically significant outcome differences otherwise, and the investigators concluded that “concurrent and staged procedures are equally safe. It is therefore reasonable to allow operator preference and patient factors to determine surgical logistics.”

Neck dissection timing has been controversial since the advent of TORS several years ago, when surgeons and administrators realized they could fit more cases into the schedule by doing neck dissections, which can take a few hours, at a different time.

Proponents of the staged approach argue, among other things, that it reduces the risk of fistulas and tracheotomies, and allows surgeons a second go at positive margins. Advocates of concurrent procedures counter that fistulas, if found, can be repaired right away, and that same-time surgery saves money, allows for earlier adjuvant therapy, and cuts anesthesia risks.

There hasn’t been much data to settle the debate, and no one has compared LOS before, so it was “important” to look into the matter, lead investigator Catherine Frenkel, MD, a Stony Brook general surgery resident, said at the American Head and Neck Society International Conference on Head and Neck Cancer.

German investigators also recently concluded that it’s pretty much a draw between concurrent and staged dissections. In a study of 41 TORS cases, “the timing of neck dissection did not make a significant difference in the outcomes. We suggest, therefore, that aspiring and established TORS teams do not restrict their appropriate indications due to robotic slot and theatre time constraints, but perform each indicated TORS case as soon as possible within their given systems, even if the neck dissections cannot be done on the same day,” they said (Eur J Surg Oncol. 2015 Jun;41[6]:773-8).

In addition to obese patients, those who had tongue or tonsil lesions were more likely to be staged in the Stony Brook analysis. About half of the surgeons in the study stuck solely to concurrent procedures, while a handful opted for the staged approach, and the rest did both. Perhaps not surprisingly, high-volume surgeons – those who did five or more TORS cases per year – were more likely to stage.

Almost two-thirds of patients had at least one complication, most commonly renal failure, heart problems, extended ventilation, and surgical errors, which included accidental punctures, postop fistulas, hemorrhages, and wound complications. A total of 13% of patients had at least one postop readmission. Apart from arrhythmias, there were no statistically significant differences in complication or 30-day readmission rates between concurrent and staged patients. High-volume surgeons were less likely to have complications.

Postop bleeding was another common problem, and more likely with staged surgeries (12% vs. 7%). Concurrent procedures had a slightly higher rate of new tracheotomies and gastrostomies, but again the differences were not statistically significant, even with pedicle and free-flap reconstruction. There was no outside funding for the work, and the investigators had no relevant conflicts of interest.

[email protected]

SEATTLE – Oncologic transoral robotic surgery patients spend less time in the hospital if they have neck dissections at the same time, instead of later, according to a review of 441 patients by Stony Brook (N.Y.) University.

The average hospital length of stay (LOS) was 6 days for the 349 patients (79.1%) who had lymphadenectomy neck dissections at the same time as transoral robotic surgery (TORS). The 92 patients (20.9%) who had staged procedures - neck dissections and TORS about a month apart, with TORS usually done first - stayed in the hospital an average of 8 days (P less than .0001). After risk adjustment, LOS was 43% shorter for concurrent dissections.

Cardiac arrhythmias were also more common in staged patients, perhaps because they had general anesthesia twice in a short period or maybe because staged patients were more likely to be obese (18.5% vs. 7.5%; P less than .01).

However, there were no statistically significant outcome differences otherwise, and the investigators concluded that “concurrent and staged procedures are equally safe. It is therefore reasonable to allow operator preference and patient factors to determine surgical logistics.”

Neck dissection timing has been controversial since the advent of TORS several years ago, when surgeons and administrators realized they could fit more cases into the schedule by doing neck dissections, which can take a few hours, at a different time.

Proponents of the staged approach argue, among other things, that it reduces the risk of fistulas and tracheotomies, and allows surgeons a second go at positive margins. Advocates of concurrent procedures counter that fistulas, if found, can be repaired right away, and that same-time surgery saves money, allows for earlier adjuvant therapy, and cuts anesthesia risks.

There hasn’t been much data to settle the debate, and no one has compared LOS before, so it was “important” to look into the matter, lead investigator Catherine Frenkel, MD, a Stony Brook general surgery resident, said at the American Head and Neck Society International Conference on Head and Neck Cancer.

German investigators also recently concluded that it’s pretty much a draw between concurrent and staged dissections. In a study of 41 TORS cases, “the timing of neck dissection did not make a significant difference in the outcomes. We suggest, therefore, that aspiring and established TORS teams do not restrict their appropriate indications due to robotic slot and theatre time constraints, but perform each indicated TORS case as soon as possible within their given systems, even if the neck dissections cannot be done on the same day,” they said (Eur J Surg Oncol. 2015 Jun;41[6]:773-8).

In addition to obese patients, those who had tongue or tonsil lesions were more likely to be staged in the Stony Brook analysis. About half of the surgeons in the study stuck solely to concurrent procedures, while a handful opted for the staged approach, and the rest did both. Perhaps not surprisingly, high-volume surgeons – those who did five or more TORS cases per year – were more likely to stage.

Almost two-thirds of patients had at least one complication, most commonly renal failure, heart problems, extended ventilation, and surgical errors, which included accidental punctures, postop fistulas, hemorrhages, and wound complications. A total of 13% of patients had at least one postop readmission. Apart from arrhythmias, there were no statistically significant differences in complication or 30-day readmission rates between concurrent and staged patients. High-volume surgeons were less likely to have complications.

Postop bleeding was another common problem, and more likely with staged surgeries (12% vs. 7%). Concurrent procedures had a slightly higher rate of new tracheotomies and gastrostomies, but again the differences were not statistically significant, even with pedicle and free-flap reconstruction. There was no outside funding for the work, and the investigators had no relevant conflicts of interest.

[email protected]

SEATTLE – Oncologic transoral robotic surgery patients spend less time in the hospital if they have neck dissections at the same time, instead of later, according to a review of 441 patients by Stony Brook (N.Y.) University.

The average hospital length of stay (LOS) was 6 days for the 349 patients (79.1%) who had lymphadenectomy neck dissections at the same time as transoral robotic surgery (TORS). The 92 patients (20.9%) who had staged procedures - neck dissections and TORS about a month apart, with TORS usually done first - stayed in the hospital an average of 8 days (P less than .0001). After risk adjustment, LOS was 43% shorter for concurrent dissections.

Cardiac arrhythmias were also more common in staged patients, perhaps because they had general anesthesia twice in a short period or maybe because staged patients were more likely to be obese (18.5% vs. 7.5%; P less than .01).

However, there were no statistically significant outcome differences otherwise, and the investigators concluded that “concurrent and staged procedures are equally safe. It is therefore reasonable to allow operator preference and patient factors to determine surgical logistics.”

Neck dissection timing has been controversial since the advent of TORS several years ago, when surgeons and administrators realized they could fit more cases into the schedule by doing neck dissections, which can take a few hours, at a different time.

Proponents of the staged approach argue, among other things, that it reduces the risk of fistulas and tracheotomies, and allows surgeons a second go at positive margins. Advocates of concurrent procedures counter that fistulas, if found, can be repaired right away, and that same-time surgery saves money, allows for earlier adjuvant therapy, and cuts anesthesia risks.

There hasn’t been much data to settle the debate, and no one has compared LOS before, so it was “important” to look into the matter, lead investigator Catherine Frenkel, MD, a Stony Brook general surgery resident, said at the American Head and Neck Society International Conference on Head and Neck Cancer.

German investigators also recently concluded that it’s pretty much a draw between concurrent and staged dissections. In a study of 41 TORS cases, “the timing of neck dissection did not make a significant difference in the outcomes. We suggest, therefore, that aspiring and established TORS teams do not restrict their appropriate indications due to robotic slot and theatre time constraints, but perform each indicated TORS case as soon as possible within their given systems, even if the neck dissections cannot be done on the same day,” they said (Eur J Surg Oncol. 2015 Jun;41[6]:773-8).

In addition to obese patients, those who had tongue or tonsil lesions were more likely to be staged in the Stony Brook analysis. About half of the surgeons in the study stuck solely to concurrent procedures, while a handful opted for the staged approach, and the rest did both. Perhaps not surprisingly, high-volume surgeons – those who did five or more TORS cases per year – were more likely to stage.

Almost two-thirds of patients had at least one complication, most commonly renal failure, heart problems, extended ventilation, and surgical errors, which included accidental punctures, postop fistulas, hemorrhages, and wound complications. A total of 13% of patients had at least one postop readmission. Apart from arrhythmias, there were no statistically significant differences in complication or 30-day readmission rates between concurrent and staged patients. High-volume surgeons were less likely to have complications.

Postop bleeding was another common problem, and more likely with staged surgeries (12% vs. 7%). Concurrent procedures had a slightly higher rate of new tracheotomies and gastrostomies, but again the differences were not statistically significant, even with pedicle and free-flap reconstruction. There was no outside funding for the work, and the investigators had no relevant conflicts of interest.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]

SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.

Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.

After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.

At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.

The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.

Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.

The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.

There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.

[email protected]

SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.

Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.

After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.

At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.

The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.

Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.

The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.

There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.

[email protected]

SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.

Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.

After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.

At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.

The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.

Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.

The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.

There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.

[email protected]

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura