Head & Neck/Thyroid Cancers

Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.

Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).

“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).

Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.

Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.

An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.

Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.

Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.

Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).

“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).

Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.

Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.

An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.

Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.

Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.

Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).

“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).

Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.

Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.

An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.

Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.

BOSTON – An experimental agent that targets the byproducts of gene fusions has shown surprising clinical activity against notoriously treatment-refractory cancers in early results from a phase I trial.

“I think that’s what remarkable about this is that we have all these different histologies and many different fusions, but all seem to be having some kind of [response] to this molecule,” said lead investigator Dr. David S. Hong, deputy chair and associate professor in the department of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston.

The molecule, LOXO-101 is a selective inhibitor of abnormal TRKA, TRKAB, and TRKC kinases that arise from gene fusions. TRK fusions have been implicated in tumor development in preclinical studies, he reported at the AACR–NCI–EORTC International Conference on Molecular Targets and Cancer Therapeutics.

One patient, a 41-year-old woman with undifferentiated soft tissue sarcoma of the groin that had metastasized to her lungs had rapid and “substantial” tumor and lung-nodule regression that radiographically fell just shy of a complete response, Dr. Hong said.

The drug also induced robust partial responses in a 55-year-old man with a gastrointestinal stromal tumor (GIST) for whom five prior targeted agents had failed, and a 33-year-old man with mammary analogue secretory carcinoma of the salivary gland (MASC) that had progressed on chemotherapy with docetaxel, carboplatin, and 5-fluorauracil.

A fourth patient, a man (age unspecified) who had papillary thyroid cancer with palpable lymphadenopathy, had no palpable nodes at 1-month follow-up, and appears to be responding to the drug, Dr. Hong added.

“This is really a dramatic example, I think, of a targeted therapy that is not histology specific, and this is another area in oncology where it’s new, and we’re just feeling our way,” commented Dr. Lee C. Helman, a sarcoma specialist at the National Cancer Institute in Bethesda, Md., who moderated the briefing where Dr. Hong presented the data.

Tumor promoters

The TRK family of proteins consists of separate tyrosine kinases that, when functioning normally, are important for the development of peripheral central nervous system processes such as pain and thermoregulation, Dr. Hong explained.

“The NTRK 1, 2, and 3 genes which encode for the TRK proteins are subject to these gene rearrangements and fusions, and the resulting TRK gene fusions may become erroneously expressed, and the kinase domain constitutively activated,” he said.

Gene fusions resulting in constitutively active TRKA, B, and C kinases can occur in the range of about 2%-25% in a wide variety of tumors, including adenocarcinomas of the lung, gliomas, thyroid tumors, head and neck cancers, sarcomas, and other types. These fusions have also been detected in more than 75% of MASC tumors, secretory breast carcinomas, and infantile (congenital) fibrosarcoma.

LOXO-101 is an orally delivered small molecule that was rationally designed to target the TRK fusions while largely leaving other kinases alone. In preclinical studies, the compound showed potent tumor growth inhibition and regression in mice bearing NTRK fusions.

The phase I trial is a dose-finding study including a total of 24 patients with various treatment-refractory advanced or metastatic solid tumors. Patients were enrolled regardless of fusional status.

Well tolerated

At the selected dose of 100 mg twice daily, patients appeared to tolerate the drug very well, with few off-target adverse events, Dr. Hong said. The most common side effect was mild dizziness. Grade 3 or 4 adverse events occurring at all doses levels include fatigue (one patient), anemia (two), abdominal pain (one), increased alkaline phosphatase (one), increased aspartate aminotransferase, delirium, and syncope (two each).

A total of six of the 24 patients had TRK fusions in their tumors, and three of these patients were available for assessment as of Oct. 20, 2015.

Dr. Hong and colleagues previously reportedon the case of the 41-year old woman with sarcoma. She was found to have a fusion of LMNA (a gene that encodes for nuclear membrane proteins) with NTRK1. She was started on the 100-mg b.i.d. dose of LOX-101 and had rapid resolution of dyspnea and hypoxemia. She had a confirmed partial response, and a CT scan showed that her multiple pulmonary nodules had regressed, with just a single, small disease site remaining at most recent follow-up. This patient continues on treatment and has been followed for more than 8 months.

The man with GIST had experienced disease progression while on therapy with imatinib, sunitinib, sorafenib, nilotinib, and regorafenib. He was treated in the 150-mg b.i.d. dose cohort, had a confirmed partial response, and remains on study after 4-plus months.

The third patient, the 33-year-old man with MASC, was assigned to the 100-mg b.i.d. dose. He too had a partial response, with radiologic evidence of substantial tumor shrinkage, and a persistent, tumor-related cough that disappeared after about 10 days of treatment, and remains on study after more than 3 months of follow-up.

The investigators have begun accruing patients for a phase II “basket” trial in adult patients with advanced or metastatic solid tumors displaying TRK fusions, including non–small cell lung cancers, thyroid tumors, sarcomas, colorectal cancer, salivary gland cancers, primary central nervous system cancers, and all other solid tumors.

Dr. Hong said that the results indicate the importance of tumor profiling for the majority of patients, especially those whose disease is refractory to standard therapies.

The study was funded by Loxo Oncology. Dr. Hong disclosed receiving travel expenses from the company. Three coauthors are employees and shareholders of the company.

BOSTON – An experimental agent that targets the byproducts of gene fusions has shown surprising clinical activity against notoriously treatment-refractory cancers in early results from a phase I trial.

“I think that’s what remarkable about this is that we have all these different histologies and many different fusions, but all seem to be having some kind of [response] to this molecule,” said lead investigator Dr. David S. Hong, deputy chair and associate professor in the department of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston.

The molecule, LOXO-101 is a selective inhibitor of abnormal TRKA, TRKAB, and TRKC kinases that arise from gene fusions. TRK fusions have been implicated in tumor development in preclinical studies, he reported at the AACR–NCI–EORTC International Conference on Molecular Targets and Cancer Therapeutics.

One patient, a 41-year-old woman with undifferentiated soft tissue sarcoma of the groin that had metastasized to her lungs had rapid and “substantial” tumor and lung-nodule regression that radiographically fell just shy of a complete response, Dr. Hong said.

The drug also induced robust partial responses in a 55-year-old man with a gastrointestinal stromal tumor (GIST) for whom five prior targeted agents had failed, and a 33-year-old man with mammary analogue secretory carcinoma of the salivary gland (MASC) that had progressed on chemotherapy with docetaxel, carboplatin, and 5-fluorauracil.

A fourth patient, a man (age unspecified) who had papillary thyroid cancer with palpable lymphadenopathy, had no palpable nodes at 1-month follow-up, and appears to be responding to the drug, Dr. Hong added.

“This is really a dramatic example, I think, of a targeted therapy that is not histology specific, and this is another area in oncology where it’s new, and we’re just feeling our way,” commented Dr. Lee C. Helman, a sarcoma specialist at the National Cancer Institute in Bethesda, Md., who moderated the briefing where Dr. Hong presented the data.

Tumor promoters

The TRK family of proteins consists of separate tyrosine kinases that, when functioning normally, are important for the development of peripheral central nervous system processes such as pain and thermoregulation, Dr. Hong explained.

“The NTRK 1, 2, and 3 genes which encode for the TRK proteins are subject to these gene rearrangements and fusions, and the resulting TRK gene fusions may become erroneously expressed, and the kinase domain constitutively activated,” he said.

Gene fusions resulting in constitutively active TRKA, B, and C kinases can occur in the range of about 2%-25% in a wide variety of tumors, including adenocarcinomas of the lung, gliomas, thyroid tumors, head and neck cancers, sarcomas, and other types. These fusions have also been detected in more than 75% of MASC tumors, secretory breast carcinomas, and infantile (congenital) fibrosarcoma.

LOXO-101 is an orally delivered small molecule that was rationally designed to target the TRK fusions while largely leaving other kinases alone. In preclinical studies, the compound showed potent tumor growth inhibition and regression in mice bearing NTRK fusions.

The phase I trial is a dose-finding study including a total of 24 patients with various treatment-refractory advanced or metastatic solid tumors. Patients were enrolled regardless of fusional status.

Well tolerated

At the selected dose of 100 mg twice daily, patients appeared to tolerate the drug very well, with few off-target adverse events, Dr. Hong said. The most common side effect was mild dizziness. Grade 3 or 4 adverse events occurring at all doses levels include fatigue (one patient), anemia (two), abdominal pain (one), increased alkaline phosphatase (one), increased aspartate aminotransferase, delirium, and syncope (two each).

A total of six of the 24 patients had TRK fusions in their tumors, and three of these patients were available for assessment as of Oct. 20, 2015.

Dr. Hong and colleagues previously reportedon the case of the 41-year old woman with sarcoma. She was found to have a fusion of LMNA (a gene that encodes for nuclear membrane proteins) with NTRK1. She was started on the 100-mg b.i.d. dose of LOX-101 and had rapid resolution of dyspnea and hypoxemia. She had a confirmed partial response, and a CT scan showed that her multiple pulmonary nodules had regressed, with just a single, small disease site remaining at most recent follow-up. This patient continues on treatment and has been followed for more than 8 months.

The man with GIST had experienced disease progression while on therapy with imatinib, sunitinib, sorafenib, nilotinib, and regorafenib. He was treated in the 150-mg b.i.d. dose cohort, had a confirmed partial response, and remains on study after 4-plus months.

The third patient, the 33-year-old man with MASC, was assigned to the 100-mg b.i.d. dose. He too had a partial response, with radiologic evidence of substantial tumor shrinkage, and a persistent, tumor-related cough that disappeared after about 10 days of treatment, and remains on study after more than 3 months of follow-up.

The investigators have begun accruing patients for a phase II “basket” trial in adult patients with advanced or metastatic solid tumors displaying TRK fusions, including non–small cell lung cancers, thyroid tumors, sarcomas, colorectal cancer, salivary gland cancers, primary central nervous system cancers, and all other solid tumors.

Dr. Hong said that the results indicate the importance of tumor profiling for the majority of patients, especially those whose disease is refractory to standard therapies.

The study was funded by Loxo Oncology. Dr. Hong disclosed receiving travel expenses from the company. Three coauthors are employees and shareholders of the company.

BOSTON – An experimental agent that targets the byproducts of gene fusions has shown surprising clinical activity against notoriously treatment-refractory cancers in early results from a phase I trial.

“I think that’s what remarkable about this is that we have all these different histologies and many different fusions, but all seem to be having some kind of [response] to this molecule,” said lead investigator Dr. David S. Hong, deputy chair and associate professor in the department of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston.

The molecule, LOXO-101 is a selective inhibitor of abnormal TRKA, TRKAB, and TRKC kinases that arise from gene fusions. TRK fusions have been implicated in tumor development in preclinical studies, he reported at the AACR–NCI–EORTC International Conference on Molecular Targets and Cancer Therapeutics.

One patient, a 41-year-old woman with undifferentiated soft tissue sarcoma of the groin that had metastasized to her lungs had rapid and “substantial” tumor and lung-nodule regression that radiographically fell just shy of a complete response, Dr. Hong said.

The drug also induced robust partial responses in a 55-year-old man with a gastrointestinal stromal tumor (GIST) for whom five prior targeted agents had failed, and a 33-year-old man with mammary analogue secretory carcinoma of the salivary gland (MASC) that had progressed on chemotherapy with docetaxel, carboplatin, and 5-fluorauracil.

A fourth patient, a man (age unspecified) who had papillary thyroid cancer with palpable lymphadenopathy, had no palpable nodes at 1-month follow-up, and appears to be responding to the drug, Dr. Hong added.

“This is really a dramatic example, I think, of a targeted therapy that is not histology specific, and this is another area in oncology where it’s new, and we’re just feeling our way,” commented Dr. Lee C. Helman, a sarcoma specialist at the National Cancer Institute in Bethesda, Md., who moderated the briefing where Dr. Hong presented the data.

Tumor promoters

The TRK family of proteins consists of separate tyrosine kinases that, when functioning normally, are important for the development of peripheral central nervous system processes such as pain and thermoregulation, Dr. Hong explained.

“The NTRK 1, 2, and 3 genes which encode for the TRK proteins are subject to these gene rearrangements and fusions, and the resulting TRK gene fusions may become erroneously expressed, and the kinase domain constitutively activated,” he said.

Gene fusions resulting in constitutively active TRKA, B, and C kinases can occur in the range of about 2%-25% in a wide variety of tumors, including adenocarcinomas of the lung, gliomas, thyroid tumors, head and neck cancers, sarcomas, and other types. These fusions have also been detected in more than 75% of MASC tumors, secretory breast carcinomas, and infantile (congenital) fibrosarcoma.

LOXO-101 is an orally delivered small molecule that was rationally designed to target the TRK fusions while largely leaving other kinases alone. In preclinical studies, the compound showed potent tumor growth inhibition and regression in mice bearing NTRK fusions.

The phase I trial is a dose-finding study including a total of 24 patients with various treatment-refractory advanced or metastatic solid tumors. Patients were enrolled regardless of fusional status.

Well tolerated

At the selected dose of 100 mg twice daily, patients appeared to tolerate the drug very well, with few off-target adverse events, Dr. Hong said. The most common side effect was mild dizziness. Grade 3 or 4 adverse events occurring at all doses levels include fatigue (one patient), anemia (two), abdominal pain (one), increased alkaline phosphatase (one), increased aspartate aminotransferase, delirium, and syncope (two each).

A total of six of the 24 patients had TRK fusions in their tumors, and three of these patients were available for assessment as of Oct. 20, 2015.

Dr. Hong and colleagues previously reportedon the case of the 41-year old woman with sarcoma. She was found to have a fusion of LMNA (a gene that encodes for nuclear membrane proteins) with NTRK1. She was started on the 100-mg b.i.d. dose of LOX-101 and had rapid resolution of dyspnea and hypoxemia. She had a confirmed partial response, and a CT scan showed that her multiple pulmonary nodules had regressed, with just a single, small disease site remaining at most recent follow-up. This patient continues on treatment and has been followed for more than 8 months.

The man with GIST had experienced disease progression while on therapy with imatinib, sunitinib, sorafenib, nilotinib, and regorafenib. He was treated in the 150-mg b.i.d. dose cohort, had a confirmed partial response, and remains on study after 4-plus months.

The third patient, the 33-year-old man with MASC, was assigned to the 100-mg b.i.d. dose. He too had a partial response, with radiologic evidence of substantial tumor shrinkage, and a persistent, tumor-related cough that disappeared after about 10 days of treatment, and remains on study after more than 3 months of follow-up.

The investigators have begun accruing patients for a phase II “basket” trial in adult patients with advanced or metastatic solid tumors displaying TRK fusions, including non–small cell lung cancers, thyroid tumors, sarcomas, colorectal cancer, salivary gland cancers, primary central nervous system cancers, and all other solid tumors.

Dr. Hong said that the results indicate the importance of tumor profiling for the majority of patients, especially those whose disease is refractory to standard therapies.

The study was funded by Loxo Oncology. Dr. Hong disclosed receiving travel expenses from the company. Three coauthors are employees and shareholders of the company.

Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).

No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.

“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).

©KGH/Wikimedia Commons/Creative Commons ASA 3.0

The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.

DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.

Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.

Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.

Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).

No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.

“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).

©KGH/Wikimedia Commons/Creative Commons ASA 3.0

The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.

DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.

Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.

Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.

Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).

No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.

“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).

©KGH/Wikimedia Commons/Creative Commons ASA 3.0

The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.

DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.

Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.

Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

SAN ANTONIO – Patients who have low-risk, human papillomavirus (HPV)–associated oropharyngeal cancers may be effectively and safely treated with a reduced intensity chemoradiotherapy regimen, according to research presented at the annual meeting of the American Society for Radiation Oncology.

In the prospective, multi-institutional, phase II trial, complete pathologic responses (pCR) were seen in 86% of the 43 patients treated. The six cases that did not show a pCR were limited to microscopic areas of residual cancer.

ASTRO/Adam Donohue

The study provides strong preliminary evidence that reduced intensity chemoradiotherapy may be as effective as standard-dose chemoradiotherapy, Dr. Bhishamjit Chera of the University of North Carolina at Chapel Hill said at a press briefing. While it is too early to use outside of a clinical trial at present, he said, there is the potential for less intensive treatment to be given, and it could be the standard practice in years to come.

“At most institutions, the standard treatment for oropharynx cancer is definite chemoradiation,” Dr. Chera explained. This typically involves delivery of 70 Gy of radiation, given in 2-Gy fractions over 7 weeks for a total 35 days of treatment, and administration of three doses of cisplatin 100 mg/m² concurrently.

“This treatment provides the best chances of sparing the tonsil, the throat, and the tongue, basically preserving organ function,” he added. Surgery is not usually performed unless there are signs on imaging that the cancer has not completely resolved 12 weeks after treatment.

“We know that many patients are cured with oropharyngeal carcinoma, but many patients live with significant long-term side effects such as dry mouth and difficulty swallowing,” Dr. Chera observed. Thus the aim of the present trial was to see if reducing the intensity of the chemoradiotherapy might avoid some of the side effects seen.

The deintensified regimen used in the study consisted of a 10-Gy reduction in the total dose of radiation delivered to 60 Gy, which was given in 2-Gy fractions once daily over a period of 6 weeks. The dose of cisplatin also was reduced by approximately 40% to 30 mg/m² given in 6 weekly doses

Patients were eligible for inclusion if they had stage 0-3 squamous cell carcinoma of the oropharynx, with limited nodal (N0-N2c) and no metastatic involvement. Patients had to have a minimal smoking history and be HPV or p16 positive.

After the chemoradiation, all patients underwent a planned biopsy and limited neck dissection to remove any lymph nodes that had cancer in them prior to treatment. Thus the primary endpoint was the pCR rather a radiographically measured tumor response rate, Dr. Chera observed.

Considering just the primary site of the cancer (the base of tongue and tonsil), there were 41 patients who could be evaluated and all but one of these (98%) achieved a pCR. Looking at patients with neck involvement at baseline (n = 39), 84% achieved a pCR.

“All of these 43 patients are alive with no evidence of cancer recurrence with a follow-up of 21 months,” Dr. Chera reported.

Throughout the study, patient-reported outcomes were captured using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).

While patients did report an increase in adverse effects 6-8 weeks after the chemoradiation, the intensity of these side effects decreased to baseline levels over time. Not surprisingly, the two most common symptoms were dry mouth and problems with swallowing, with 75% and 55% of patients, respectively, experiencing severe or very severe xerostomia and dysphagia. Other grade 3-4 adverse events included mucositis in 45%, pain in 48%, nausea in 52%, and vomiting in 34%.

Results of the quality of life analyses show that patients’ quality of life is returning to baseline levels after 1 year.

“There is a lot of interest in reducing the intensity of treatment in these patients,” Dr. Chera said, adding that patients are likely being overtreated at present. In the current clinical environment, patients are very savvy, he said, so performing a large randomized phase III trial may not be possible if patients learn that deintensified therapy may be an option. So the results of larger and longer phase II trials may be the best evidence that will be obtained.

The NRG Oncology group is going to evaluate the same deintensified chemotherapy regimen in another, larger phase II trial, the NRG-HN002 trial, Dr. Chera said. This trial aims to accrue almost 300 patients and will compare the University of North Carolina regimen versus radiation alone, which will be given at a total dose of 50 Gy 5 days a week for 5 weeks.

And, as for his group’s further research plans, Dr. Chera noted in an interview that further follow-up would be required to determine if the regimen used was efficacious and safe. A second phase II trial with the same deintensified regimen in which surgery or biopsies were not mandated is about to close soon, and there is a third study that will look at using genetic information to determine if it is safe to deintensifty patients’ treatment.

Dr. Chera had no conflicts of interest to disclose.

[email protected]

SAN ANTONIO – Patients who have low-risk, human papillomavirus (HPV)–associated oropharyngeal cancers may be effectively and safely treated with a reduced intensity chemoradiotherapy regimen, according to research presented at the annual meeting of the American Society for Radiation Oncology.

In the prospective, multi-institutional, phase II trial, complete pathologic responses (pCR) were seen in 86% of the 43 patients treated. The six cases that did not show a pCR were limited to microscopic areas of residual cancer.

ASTRO/Adam Donohue

The study provides strong preliminary evidence that reduced intensity chemoradiotherapy may be as effective as standard-dose chemoradiotherapy, Dr. Bhishamjit Chera of the University of North Carolina at Chapel Hill said at a press briefing. While it is too early to use outside of a clinical trial at present, he said, there is the potential for less intensive treatment to be given, and it could be the standard practice in years to come.

“At most institutions, the standard treatment for oropharynx cancer is definite chemoradiation,” Dr. Chera explained. This typically involves delivery of 70 Gy of radiation, given in 2-Gy fractions over 7 weeks for a total 35 days of treatment, and administration of three doses of cisplatin 100 mg/m² concurrently.

“This treatment provides the best chances of sparing the tonsil, the throat, and the tongue, basically preserving organ function,” he added. Surgery is not usually performed unless there are signs on imaging that the cancer has not completely resolved 12 weeks after treatment.

“We know that many patients are cured with oropharyngeal carcinoma, but many patients live with significant long-term side effects such as dry mouth and difficulty swallowing,” Dr. Chera observed. Thus the aim of the present trial was to see if reducing the intensity of the chemoradiotherapy might avoid some of the side effects seen.

The deintensified regimen used in the study consisted of a 10-Gy reduction in the total dose of radiation delivered to 60 Gy, which was given in 2-Gy fractions once daily over a period of 6 weeks. The dose of cisplatin also was reduced by approximately 40% to 30 mg/m² given in 6 weekly doses

Patients were eligible for inclusion if they had stage 0-3 squamous cell carcinoma of the oropharynx, with limited nodal (N0-N2c) and no metastatic involvement. Patients had to have a minimal smoking history and be HPV or p16 positive.

After the chemoradiation, all patients underwent a planned biopsy and limited neck dissection to remove any lymph nodes that had cancer in them prior to treatment. Thus the primary endpoint was the pCR rather a radiographically measured tumor response rate, Dr. Chera observed.

Considering just the primary site of the cancer (the base of tongue and tonsil), there were 41 patients who could be evaluated and all but one of these (98%) achieved a pCR. Looking at patients with neck involvement at baseline (n = 39), 84% achieved a pCR.

“All of these 43 patients are alive with no evidence of cancer recurrence with a follow-up of 21 months,” Dr. Chera reported.

Throughout the study, patient-reported outcomes were captured using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).

While patients did report an increase in adverse effects 6-8 weeks after the chemoradiation, the intensity of these side effects decreased to baseline levels over time. Not surprisingly, the two most common symptoms were dry mouth and problems with swallowing, with 75% and 55% of patients, respectively, experiencing severe or very severe xerostomia and dysphagia. Other grade 3-4 adverse events included mucositis in 45%, pain in 48%, nausea in 52%, and vomiting in 34%.

Results of the quality of life analyses show that patients’ quality of life is returning to baseline levels after 1 year.

“There is a lot of interest in reducing the intensity of treatment in these patients,” Dr. Chera said, adding that patients are likely being overtreated at present. In the current clinical environment, patients are very savvy, he said, so performing a large randomized phase III trial may not be possible if patients learn that deintensified therapy may be an option. So the results of larger and longer phase II trials may be the best evidence that will be obtained.

The NRG Oncology group is going to evaluate the same deintensified chemotherapy regimen in another, larger phase II trial, the NRG-HN002 trial, Dr. Chera said. This trial aims to accrue almost 300 patients and will compare the University of North Carolina regimen versus radiation alone, which will be given at a total dose of 50 Gy 5 days a week for 5 weeks.

And, as for his group’s further research plans, Dr. Chera noted in an interview that further follow-up would be required to determine if the regimen used was efficacious and safe. A second phase II trial with the same deintensified regimen in which surgery or biopsies were not mandated is about to close soon, and there is a third study that will look at using genetic information to determine if it is safe to deintensifty patients’ treatment.

Dr. Chera had no conflicts of interest to disclose.

[email protected]

SAN ANTONIO – Patients who have low-risk, human papillomavirus (HPV)–associated oropharyngeal cancers may be effectively and safely treated with a reduced intensity chemoradiotherapy regimen, according to research presented at the annual meeting of the American Society for Radiation Oncology.

In the prospective, multi-institutional, phase II trial, complete pathologic responses (pCR) were seen in 86% of the 43 patients treated. The six cases that did not show a pCR were limited to microscopic areas of residual cancer.

ASTRO/Adam Donohue

The study provides strong preliminary evidence that reduced intensity chemoradiotherapy may be as effective as standard-dose chemoradiotherapy, Dr. Bhishamjit Chera of the University of North Carolina at Chapel Hill said at a press briefing. While it is too early to use outside of a clinical trial at present, he said, there is the potential for less intensive treatment to be given, and it could be the standard practice in years to come.

“At most institutions, the standard treatment for oropharynx cancer is definite chemoradiation,” Dr. Chera explained. This typically involves delivery of 70 Gy of radiation, given in 2-Gy fractions over 7 weeks for a total 35 days of treatment, and administration of three doses of cisplatin 100 mg/m² concurrently.

“This treatment provides the best chances of sparing the tonsil, the throat, and the tongue, basically preserving organ function,” he added. Surgery is not usually performed unless there are signs on imaging that the cancer has not completely resolved 12 weeks after treatment.

“We know that many patients are cured with oropharyngeal carcinoma, but many patients live with significant long-term side effects such as dry mouth and difficulty swallowing,” Dr. Chera observed. Thus the aim of the present trial was to see if reducing the intensity of the chemoradiotherapy might avoid some of the side effects seen.

The deintensified regimen used in the study consisted of a 10-Gy reduction in the total dose of radiation delivered to 60 Gy, which was given in 2-Gy fractions once daily over a period of 6 weeks. The dose of cisplatin also was reduced by approximately 40% to 30 mg/m² given in 6 weekly doses

Patients were eligible for inclusion if they had stage 0-3 squamous cell carcinoma of the oropharynx, with limited nodal (N0-N2c) and no metastatic involvement. Patients had to have a minimal smoking history and be HPV or p16 positive.

After the chemoradiation, all patients underwent a planned biopsy and limited neck dissection to remove any lymph nodes that had cancer in them prior to treatment. Thus the primary endpoint was the pCR rather a radiographically measured tumor response rate, Dr. Chera observed.

Considering just the primary site of the cancer (the base of tongue and tonsil), there were 41 patients who could be evaluated and all but one of these (98%) achieved a pCR. Looking at patients with neck involvement at baseline (n = 39), 84% achieved a pCR.

“All of these 43 patients are alive with no evidence of cancer recurrence with a follow-up of 21 months,” Dr. Chera reported.

Throughout the study, patient-reported outcomes were captured using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).

While patients did report an increase in adverse effects 6-8 weeks after the chemoradiation, the intensity of these side effects decreased to baseline levels over time. Not surprisingly, the two most common symptoms were dry mouth and problems with swallowing, with 75% and 55% of patients, respectively, experiencing severe or very severe xerostomia and dysphagia. Other grade 3-4 adverse events included mucositis in 45%, pain in 48%, nausea in 52%, and vomiting in 34%.

Results of the quality of life analyses show that patients’ quality of life is returning to baseline levels after 1 year.

“There is a lot of interest in reducing the intensity of treatment in these patients,” Dr. Chera said, adding that patients are likely being overtreated at present. In the current clinical environment, patients are very savvy, he said, so performing a large randomized phase III trial may not be possible if patients learn that deintensified therapy may be an option. So the results of larger and longer phase II trials may be the best evidence that will be obtained.

The NRG Oncology group is going to evaluate the same deintensified chemotherapy regimen in another, larger phase II trial, the NRG-HN002 trial, Dr. Chera said. This trial aims to accrue almost 300 patients and will compare the University of North Carolina regimen versus radiation alone, which will be given at a total dose of 50 Gy 5 days a week for 5 weeks.

And, as for his group’s further research plans, Dr. Chera noted in an interview that further follow-up would be required to determine if the regimen used was efficacious and safe. A second phase II trial with the same deintensified regimen in which surgery or biopsies were not mandated is about to close soon, and there is a third study that will look at using genetic information to determine if it is safe to deintensifty patients’ treatment.

Dr. Chera had no conflicts of interest to disclose.

[email protected]

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.

Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.

Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.

Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.

Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm³ (median 140 mm³).

All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.

Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.

Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.

Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.

Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.

Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm³ (median 140 mm³).

All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.

Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.

Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.

Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.

Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.

Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm³ (median 140 mm³).

All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.

Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.

The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.

Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.

For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.

An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.

Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.

In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).

“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.

[email protected]

LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.

The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.

Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.

For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.

An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.

Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.

In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).

“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.

[email protected]

LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.

The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.

Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.

For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.

An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.

Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.

In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).

“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.

[email protected]

Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.

An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.

“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”

Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).

Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).

The drug has not been successful in treating advanced anaplastic thyroid cancer, however.

Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.

The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.

Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.

Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).

“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.

Prior therapy also was not a response predictor, he added.

Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.

The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.

“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”

Dr. Bible had no financial declarations.

[email protected]

On Twitter @Alz_Gal

Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.

An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.

“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”

Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).

Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).

The drug has not been successful in treating advanced anaplastic thyroid cancer, however.

Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.

The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.

Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.

Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).

“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.

Prior therapy also was not a response predictor, he added.

Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.

The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.

“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”

Dr. Bible had no financial declarations.

[email protected]

On Twitter @Alz_Gal

Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.

An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.

“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”

Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).

Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).

The drug has not been successful in treating advanced anaplastic thyroid cancer, however.

Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.

The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.

Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.

Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).

“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.

Prior therapy also was not a response predictor, he added.

Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.

The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.

“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”

Dr. Bible had no financial declarations.

[email protected]

On Twitter @Alz_Gal