User login
Calcitonin-to-CEA ratio predicts medullary thyroid cancer survival
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
[email protected]
On Twitter @mitchelzoler
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
[email protected]
On Twitter @mitchelzoler
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: Presurgery, a calcitonin-to-CEA ratio below 18 was linked with superior survival in patients whose CEA was at least 25 ng/Ml.
Data source: A single-center, retrospective study with 164 patients assessed before thyroidectomy and 187 assessed after surgery.
Disclosures: Dr. Jaber had no disclosures.
AML risk is doubled in low-risk thyroid cancer patients unnecessarily given radioactive iodine therapy
MADRID – Radioactive iodine treatment is associated with nearly twice the risk of developing acute myeloid leukemia (AML) in patients with well-differentiated thyroid cancer, based on data from the Surveillance Epidemiology and End Results (SEER) registry.
Up to 40% of patients in Europe and North America with well-differentiated thyroid cancer still receive radioactive iodine treatment “even though RAI has no proven benefit in this population,” Remco Molenaar, MD, PhD, of the University of Amsterdam reported at the European Society of Medical Oncology Congress.
Of 148,215 patients treated for well-differentiated thyroid cancer between 1973 and 2014, 55% had surgery only and 45% received surgery plus radioactive iodine treatment. After a median 4.3 years of follow-up, 44 patients developed AML. When cases in those exposed to RAI were cross-referenced to those who were not, the relative risk was increased more than fivefold. When the analysis controlled for an extensive list of potentially confounding variables, the hazard ratio of 1.79 remained statistically significant (P = .03).
“There is a nearly twofold increased risk even though radioactive iodine treatment is not indicated in this population,” Dr. Molenaar said. Moreover, AML following treatment for well-differentiated thyroid cancer was associated with a substantial reduction in expected overall survival, falling from a median 24.4 years to 7.5 years.
Compared with other AML patients, “those who develop AML after RAI also have a worse prognosis,” added Dr. Molenaar, noting the difference in overall survival is highly statistically significant (1.2 vs. 3.5 years; P = .004).
The ESMO-invited discussant, Tim Somervaille, MD, senior group leader of the Leukemia Biology Laboratory at the Cancer Research UK Manchester Institute, called this analysis “a more thorough and detailed study” than previous retrospective analyses, but he added a note of caution: Despite the almost twofold increase in risk, AML remains a rare iatrogenic event in thyroid cancer patients even if it is avoidable by withholding RAI therapy.
“These data do suggest that the risk is measurable and will further provide some downward pressure on the numbers of patients having unnecessary RAI therapy for well-differentiated thyroid cancer,” he said.
In the discussion that followed the presentation, one audience member suggested that telling patients they have a twofold increased risk of AML after RAI therapy is misleading. It was emphasized that a twofold increase of a very small number is still a very small number, but Dr. Molenaar suggested that this misses the point.
“I don’t think this is something that you need to discuss with patients, because you should not be giving RAI therapy to thyroid cancer patients with low- or intermediate-risk disease,” he said. Any AML case caused “by a therapy with no proven benefit is one too many,” especially since unnecessary RAI adds inconvenience and cost to treatment.
MADRID – Radioactive iodine treatment is associated with nearly twice the risk of developing acute myeloid leukemia (AML) in patients with well-differentiated thyroid cancer, based on data from the Surveillance Epidemiology and End Results (SEER) registry.
Up to 40% of patients in Europe and North America with well-differentiated thyroid cancer still receive radioactive iodine treatment “even though RAI has no proven benefit in this population,” Remco Molenaar, MD, PhD, of the University of Amsterdam reported at the European Society of Medical Oncology Congress.
Of 148,215 patients treated for well-differentiated thyroid cancer between 1973 and 2014, 55% had surgery only and 45% received surgery plus radioactive iodine treatment. After a median 4.3 years of follow-up, 44 patients developed AML. When cases in those exposed to RAI were cross-referenced to those who were not, the relative risk was increased more than fivefold. When the analysis controlled for an extensive list of potentially confounding variables, the hazard ratio of 1.79 remained statistically significant (P = .03).
“There is a nearly twofold increased risk even though radioactive iodine treatment is not indicated in this population,” Dr. Molenaar said. Moreover, AML following treatment for well-differentiated thyroid cancer was associated with a substantial reduction in expected overall survival, falling from a median 24.4 years to 7.5 years.
Compared with other AML patients, “those who develop AML after RAI also have a worse prognosis,” added Dr. Molenaar, noting the difference in overall survival is highly statistically significant (1.2 vs. 3.5 years; P = .004).
The ESMO-invited discussant, Tim Somervaille, MD, senior group leader of the Leukemia Biology Laboratory at the Cancer Research UK Manchester Institute, called this analysis “a more thorough and detailed study” than previous retrospective analyses, but he added a note of caution: Despite the almost twofold increase in risk, AML remains a rare iatrogenic event in thyroid cancer patients even if it is avoidable by withholding RAI therapy.
“These data do suggest that the risk is measurable and will further provide some downward pressure on the numbers of patients having unnecessary RAI therapy for well-differentiated thyroid cancer,” he said.
In the discussion that followed the presentation, one audience member suggested that telling patients they have a twofold increased risk of AML after RAI therapy is misleading. It was emphasized that a twofold increase of a very small number is still a very small number, but Dr. Molenaar suggested that this misses the point.
“I don’t think this is something that you need to discuss with patients, because you should not be giving RAI therapy to thyroid cancer patients with low- or intermediate-risk disease,” he said. Any AML case caused “by a therapy with no proven benefit is one too many,” especially since unnecessary RAI adds inconvenience and cost to treatment.
MADRID – Radioactive iodine treatment is associated with nearly twice the risk of developing acute myeloid leukemia (AML) in patients with well-differentiated thyroid cancer, based on data from the Surveillance Epidemiology and End Results (SEER) registry.
Up to 40% of patients in Europe and North America with well-differentiated thyroid cancer still receive radioactive iodine treatment “even though RAI has no proven benefit in this population,” Remco Molenaar, MD, PhD, of the University of Amsterdam reported at the European Society of Medical Oncology Congress.
Of 148,215 patients treated for well-differentiated thyroid cancer between 1973 and 2014, 55% had surgery only and 45% received surgery plus radioactive iodine treatment. After a median 4.3 years of follow-up, 44 patients developed AML. When cases in those exposed to RAI were cross-referenced to those who were not, the relative risk was increased more than fivefold. When the analysis controlled for an extensive list of potentially confounding variables, the hazard ratio of 1.79 remained statistically significant (P = .03).
“There is a nearly twofold increased risk even though radioactive iodine treatment is not indicated in this population,” Dr. Molenaar said. Moreover, AML following treatment for well-differentiated thyroid cancer was associated with a substantial reduction in expected overall survival, falling from a median 24.4 years to 7.5 years.
Compared with other AML patients, “those who develop AML after RAI also have a worse prognosis,” added Dr. Molenaar, noting the difference in overall survival is highly statistically significant (1.2 vs. 3.5 years; P = .004).
The ESMO-invited discussant, Tim Somervaille, MD, senior group leader of the Leukemia Biology Laboratory at the Cancer Research UK Manchester Institute, called this analysis “a more thorough and detailed study” than previous retrospective analyses, but he added a note of caution: Despite the almost twofold increase in risk, AML remains a rare iatrogenic event in thyroid cancer patients even if it is avoidable by withholding RAI therapy.
“These data do suggest that the risk is measurable and will further provide some downward pressure on the numbers of patients having unnecessary RAI therapy for well-differentiated thyroid cancer,” he said.
In the discussion that followed the presentation, one audience member suggested that telling patients they have a twofold increased risk of AML after RAI therapy is misleading. It was emphasized that a twofold increase of a very small number is still a very small number, but Dr. Molenaar suggested that this misses the point.
“I don’t think this is something that you need to discuss with patients, because you should not be giving RAI therapy to thyroid cancer patients with low- or intermediate-risk disease,” he said. Any AML case caused “by a therapy with no proven benefit is one too many,” especially since unnecessary RAI adds inconvenience and cost to treatment.
AT ESMO 2017
Key clinical point:
Major finding: The hazard ratio for AML after RAI therapy in well-differentiated thyroid cancer patients is almost doubled (HR = 1.79).
Data source: Population-based, retrospective study of 148,215 patients treated for well-differentiated thyroid cancer between 1973 and 2014.
Disclosures: Dr. Molenaar reported that he had no relevant financial relationships to disclose.
Pembrolizumab, nivolumab linked to 3% rate of neurologic events
Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.
These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.
Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).
Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.
If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.
The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.
Neurologic symptoms have been and continue to be one of the most common reasons for admission to a cancer center. Neurotoxic chemotherapy, direct invasion of cancer, and other neurologic complications of treatment contribute to the substantial cross talk between oncologists and neurologists. Over the past 5 years, oncology has witnessed an explosion of new immunotherapeutics that are revolutionizing drug development and patient care in oncology today. In contrast to traditional chemotherapy, which targets rapidly dividing cancer cells and can lead to adverse effects in other organs with rapid cell turnover, immunotherapies target and activate the immune system, potentially leading to a wide range of inflammatory and immune-mediated adverse events, including those in the nervous system.
Only 5 of the 10 patients described by Kao et al. experienced nonneurologic immune-related adverse events, suggesting that neurologic complications may be the only defining symptom of an immune-related reaction. Consultation calls from the cancer center are all too familiar for neurologists, and this pattern appears likely to persist in the era of immunotherapy. The horizon of new checkpoint targets continues to expand, and combination therapies are beginning to emerge. Neurologists and oncologists need to be aware of the important checkpoints ahead in patient care.
Roy E. Strowd III, MD, is with the section on hematology and oncology, department of neurology and internal medicine, Wake Forest University, Winston-Salem, N.C. He reported having no conflicts of interest. These comments are excerpted from his editorial (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1916).
Neurologic symptoms have been and continue to be one of the most common reasons for admission to a cancer center. Neurotoxic chemotherapy, direct invasion of cancer, and other neurologic complications of treatment contribute to the substantial cross talk between oncologists and neurologists. Over the past 5 years, oncology has witnessed an explosion of new immunotherapeutics that are revolutionizing drug development and patient care in oncology today. In contrast to traditional chemotherapy, which targets rapidly dividing cancer cells and can lead to adverse effects in other organs with rapid cell turnover, immunotherapies target and activate the immune system, potentially leading to a wide range of inflammatory and immune-mediated adverse events, including those in the nervous system.
Only 5 of the 10 patients described by Kao et al. experienced nonneurologic immune-related adverse events, suggesting that neurologic complications may be the only defining symptom of an immune-related reaction. Consultation calls from the cancer center are all too familiar for neurologists, and this pattern appears likely to persist in the era of immunotherapy. The horizon of new checkpoint targets continues to expand, and combination therapies are beginning to emerge. Neurologists and oncologists need to be aware of the important checkpoints ahead in patient care.
Roy E. Strowd III, MD, is with the section on hematology and oncology, department of neurology and internal medicine, Wake Forest University, Winston-Salem, N.C. He reported having no conflicts of interest. These comments are excerpted from his editorial (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1916).
Neurologic symptoms have been and continue to be one of the most common reasons for admission to a cancer center. Neurotoxic chemotherapy, direct invasion of cancer, and other neurologic complications of treatment contribute to the substantial cross talk between oncologists and neurologists. Over the past 5 years, oncology has witnessed an explosion of new immunotherapeutics that are revolutionizing drug development and patient care in oncology today. In contrast to traditional chemotherapy, which targets rapidly dividing cancer cells and can lead to adverse effects in other organs with rapid cell turnover, immunotherapies target and activate the immune system, potentially leading to a wide range of inflammatory and immune-mediated adverse events, including those in the nervous system.
Only 5 of the 10 patients described by Kao et al. experienced nonneurologic immune-related adverse events, suggesting that neurologic complications may be the only defining symptom of an immune-related reaction. Consultation calls from the cancer center are all too familiar for neurologists, and this pattern appears likely to persist in the era of immunotherapy. The horizon of new checkpoint targets continues to expand, and combination therapies are beginning to emerge. Neurologists and oncologists need to be aware of the important checkpoints ahead in patient care.
Roy E. Strowd III, MD, is with the section on hematology and oncology, department of neurology and internal medicine, Wake Forest University, Winston-Salem, N.C. He reported having no conflicts of interest. These comments are excerpted from his editorial (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1916).
Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.
These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.
Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).
Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.
If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.
The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.
Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.
These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.
Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).
Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.
If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.
The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.
FROM JAMA NEUROLOGY
Key clinical point: Watch for immune-related adverse effects of nivolumab and pembrolizumab.
Major finding: Ten of 347 patients (2.9%) developed subacute neurologic immune-related adverse events, typically neuromuscular syndromes.
Data source: A single-center, retrospective cohort study of 347 patients who received pembrolizumab or nivolumab for metastatic melanoma or solid tumors.
Disclosures: The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.
Big changes coming for thyroid cancer staging
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
Contralateral nodal thyroid metastases show slow progression
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: Thirty-seven percent of patients with unilateral N1b thyroid tumors also had metastases in their contralateral lateral-neck lymph nodes.
Data source: Review of 63 patients treated at a single French center during a 20-year period.
Disclosures: Dr. Hartl had no disclosures.
Revised thyroid Bethesda System resets malignant risks
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
VIDEO: Lenvatinib’s real-world thyroid cancer performance matches trial
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: The median time of progression-free survival was 10 months in the registry and 18 months in the pivotal trial.
Data source: A retrospective review of the first 75 French patients with advanced differentiated thyroid cancer who received lenvatinib following its marketing approval.
Disclosures: Dr. Schlumberger has received research funding from Eisai, the company that markets lenvatinib (Lenvima). He has also received research support and honoraria from AstraZeneca, Bayer, and Excelixis.
Cisplatin Ototoxicity: Evidence for Dosing Effect on the Risk of Hearing Shifts Among Head and Neck Cancer Patients Receiving Chemoradiation
Background: Between 2008 and 2014, 17,173 Veterans were treated with cisplatin-based chemotherapy. Many began treatment with pre-existing hearing loss and up to half likely sustained ototoxicity. Minor shifts in hearing, left untreated, can constrain effective provider-veteran
treatment partnerships, family and workplace communication, and limit quality of life. A better understanding of the risk factors and clinical presentation of ototoxicity is needed to inform ototoxicity monitoring programs and treatment decisions.
Methods: Data were examined in N = 21 head and neck cancer patients receiving concurrent chemoradiation therapy with cisplatin for whom audiometry data had been obtained prior to treatment and at 1 or more time points (35 days and 165 days) following the initial treatment.
Data were gathered as part of a larger prospective study on ototoxicity monitoring at the VA Portland HCS from 2014 to 2017. The primary outcome was a shift in the audiogram based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or greater, which was evaluated in relation to cisplatin dosing (> 75 mg/m2 every 3 weeks (bolus) vs weekly dosing < 40 mg/m2). Effects of dosing on the risk of CTCAE grade 1 or greater ototoxic event were estimated using Bayesian analysis. Descriptive statistics characterize additional
factors (age, pre-existing hearing loss and ototoxic hearing shifts, cisplatin cumulative dose, radiation dose).
Results: Ototoxicity meeting CTCAE grade 1 was found at a rate of 23.8%. The estimated risk of ototoxicity did not vary by hearing monitoring method. Veterans receiving bolus-dose cisplatin chemoradiation are estimated to be at double the risk of ototoxicity than those receiving lower weekly dosing.
Implications: Evidence supports the view that CTCAE grade 1 or higher ototoxicity was associated with cisplatin dosing in this sample. High-dose regimens are more likely to cause ototoxicity and this increased risk does not appear to vary based on method of delivery of ototoxicity monitoring. Effects of cisplatin cumulative dose and radiation dose, as well as implications for ototoxicity monitoring, will be discussed.
Background: Between 2008 and 2014, 17,173 Veterans were treated with cisplatin-based chemotherapy. Many began treatment with pre-existing hearing loss and up to half likely sustained ototoxicity. Minor shifts in hearing, left untreated, can constrain effective provider-veteran
treatment partnerships, family and workplace communication, and limit quality of life. A better understanding of the risk factors and clinical presentation of ototoxicity is needed to inform ototoxicity monitoring programs and treatment decisions.
Methods: Data were examined in N = 21 head and neck cancer patients receiving concurrent chemoradiation therapy with cisplatin for whom audiometry data had been obtained prior to treatment and at 1 or more time points (35 days and 165 days) following the initial treatment.
Data were gathered as part of a larger prospective study on ototoxicity monitoring at the VA Portland HCS from 2014 to 2017. The primary outcome was a shift in the audiogram based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or greater, which was evaluated in relation to cisplatin dosing (> 75 mg/m2 every 3 weeks (bolus) vs weekly dosing < 40 mg/m2). Effects of dosing on the risk of CTCAE grade 1 or greater ototoxic event were estimated using Bayesian analysis. Descriptive statistics characterize additional
factors (age, pre-existing hearing loss and ototoxic hearing shifts, cisplatin cumulative dose, radiation dose).
Results: Ototoxicity meeting CTCAE grade 1 was found at a rate of 23.8%. The estimated risk of ototoxicity did not vary by hearing monitoring method. Veterans receiving bolus-dose cisplatin chemoradiation are estimated to be at double the risk of ototoxicity than those receiving lower weekly dosing.
Implications: Evidence supports the view that CTCAE grade 1 or higher ototoxicity was associated with cisplatin dosing in this sample. High-dose regimens are more likely to cause ototoxicity and this increased risk does not appear to vary based on method of delivery of ototoxicity monitoring. Effects of cisplatin cumulative dose and radiation dose, as well as implications for ototoxicity monitoring, will be discussed.
Background: Between 2008 and 2014, 17,173 Veterans were treated with cisplatin-based chemotherapy. Many began treatment with pre-existing hearing loss and up to half likely sustained ototoxicity. Minor shifts in hearing, left untreated, can constrain effective provider-veteran
treatment partnerships, family and workplace communication, and limit quality of life. A better understanding of the risk factors and clinical presentation of ototoxicity is needed to inform ototoxicity monitoring programs and treatment decisions.
Methods: Data were examined in N = 21 head and neck cancer patients receiving concurrent chemoradiation therapy with cisplatin for whom audiometry data had been obtained prior to treatment and at 1 or more time points (35 days and 165 days) following the initial treatment.
Data were gathered as part of a larger prospective study on ototoxicity monitoring at the VA Portland HCS from 2014 to 2017. The primary outcome was a shift in the audiogram based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or greater, which was evaluated in relation to cisplatin dosing (> 75 mg/m2 every 3 weeks (bolus) vs weekly dosing < 40 mg/m2). Effects of dosing on the risk of CTCAE grade 1 or greater ototoxic event were estimated using Bayesian analysis. Descriptive statistics characterize additional
factors (age, pre-existing hearing loss and ototoxic hearing shifts, cisplatin cumulative dose, radiation dose).
Results: Ototoxicity meeting CTCAE grade 1 was found at a rate of 23.8%. The estimated risk of ototoxicity did not vary by hearing monitoring method. Veterans receiving bolus-dose cisplatin chemoradiation are estimated to be at double the risk of ototoxicity than those receiving lower weekly dosing.
Implications: Evidence supports the view that CTCAE grade 1 or higher ototoxicity was associated with cisplatin dosing in this sample. High-dose regimens are more likely to cause ototoxicity and this increased risk does not appear to vary based on method of delivery of ototoxicity monitoring. Effects of cisplatin cumulative dose and radiation dose, as well as implications for ototoxicity monitoring, will be discussed.
Combining Chemotherapy and Trastuzimab in Patients With HER2/ Neu-Positive Metastatic Salivary Gland Carcinoma
Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.
Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.
Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.
Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.
Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.
Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.
Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.
Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.
Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.
Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.
Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.
Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.
Overview of Oral Oncolytic Processes at Iowa City VAHCS Oncology Clinic
Background: The availability and use of oral oncolytic agents to treat malignancy is increasing. The use of oral agents to treat cancer introduces new complexities with regard to patient compliance, toxicity management, and cost containment. Veterans Affairs (VA) oncology clinics are uniquely equipped to manage oral chemotherapy processes because of direct access to health care records, pharmacy dispensing information, and oncology providers. A recent evaluation of a 14-day oral chemotherapy dispensing protocol at 1 VA facility demonstrated that patients had increased medication possession ratios and decreased cost associated with their care when compared to standard 30-day dispensing practices.
Methods: The Iowa City VA Health Care System Oncology Clinic (IC VAHCS) has developed a process to aid in tracking dispensed prescriptions, scheduling followup telephone calls, evaluating laboratory monitoring, and identification of future oncology appointments. A pharmacist has developed the ability to extract administrative from the VA Corporate Data Warehouse (CDW) for clinic operational use to support local processes. The management of oral oncolytic therapy is spearheaded by the local oncology clinical pharmacy specialist, in collaboration with oncologists and oncology nurse case managers.
The current practice at the IC VAHCS will be detailed to aid other VA oncology clinics in developing similar processes at their local site.
Background: The availability and use of oral oncolytic agents to treat malignancy is increasing. The use of oral agents to treat cancer introduces new complexities with regard to patient compliance, toxicity management, and cost containment. Veterans Affairs (VA) oncology clinics are uniquely equipped to manage oral chemotherapy processes because of direct access to health care records, pharmacy dispensing information, and oncology providers. A recent evaluation of a 14-day oral chemotherapy dispensing protocol at 1 VA facility demonstrated that patients had increased medication possession ratios and decreased cost associated with their care when compared to standard 30-day dispensing practices.
Methods: The Iowa City VA Health Care System Oncology Clinic (IC VAHCS) has developed a process to aid in tracking dispensed prescriptions, scheduling followup telephone calls, evaluating laboratory monitoring, and identification of future oncology appointments. A pharmacist has developed the ability to extract administrative from the VA Corporate Data Warehouse (CDW) for clinic operational use to support local processes. The management of oral oncolytic therapy is spearheaded by the local oncology clinical pharmacy specialist, in collaboration with oncologists and oncology nurse case managers.
The current practice at the IC VAHCS will be detailed to aid other VA oncology clinics in developing similar processes at their local site.
Background: The availability and use of oral oncolytic agents to treat malignancy is increasing. The use of oral agents to treat cancer introduces new complexities with regard to patient compliance, toxicity management, and cost containment. Veterans Affairs (VA) oncology clinics are uniquely equipped to manage oral chemotherapy processes because of direct access to health care records, pharmacy dispensing information, and oncology providers. A recent evaluation of a 14-day oral chemotherapy dispensing protocol at 1 VA facility demonstrated that patients had increased medication possession ratios and decreased cost associated with their care when compared to standard 30-day dispensing practices.
Methods: The Iowa City VA Health Care System Oncology Clinic (IC VAHCS) has developed a process to aid in tracking dispensed prescriptions, scheduling followup telephone calls, evaluating laboratory monitoring, and identification of future oncology appointments. A pharmacist has developed the ability to extract administrative from the VA Corporate Data Warehouse (CDW) for clinic operational use to support local processes. The management of oral oncolytic therapy is spearheaded by the local oncology clinical pharmacy specialist, in collaboration with oncologists and oncology nurse case managers.
The current practice at the IC VAHCS will be detailed to aid other VA oncology clinics in developing similar processes at their local site.