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Peptide vaccine shows early promise in ovarian, endometrial cancers
NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.
After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.
Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.
“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).
The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.
Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.
Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.
Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.
A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.
NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.
After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.
Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.
“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).
The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.
Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.
Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.
Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.
A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.
NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.
After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.
Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.
“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).
The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.
Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.
Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.
Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.
A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer.
Major finding: Most adverse events were of grade 1 or grade 2 severity and were local, not systemic. After a median follow-up of 12 months, cancer recurred in 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine, versus 55% controls (P = .01 compared with the control group).
Data source: A prospective controlled phase I/IIa trial of 51 patients with primary or recurrent ovarian or endometrial cancer.
Disclosures: Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.
Standardize opioid prescribing after endocrine neck surgery, researchers say
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Twenty oral morphine equivalents is the best option for pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery, according to researchers. The report was published online in Annals of Surgical Oncology.
Irene Lou, MD, of the department of surgery at the University of Wisconsin–Madison, and her coauthors conducted a prospective observational cohort study collecting data on pain scores and the oral morphine equivalents used by 313 adult patients undergoing thyroidectomy or parathyroidectomy at two large endocrine surgery centers.
While patients were prescribed a median of 30 oral morphine equivalents at discharge – with a range from 0 to 120 – the median number of equivalents taken was 3 (with a range of 0-60).
Overall, 68.4% of patients took at least one oral morphine equivalent. The majority of patients (83%) took 10 or fewer oral morphine equivalents, and only 7% of patients took more than 20 oral morphine equivalents (Ann Surg Oncol. 2017 Feb 3. doi: 10.1245/s10434-017-5781-y).
Among the patients who took more than 10 oral morphine equivalents, 85% said it was for incisional pain, 4% said it was for sore throat, and 11% said it was for some other pain.
While the overall mean pain score after surgery was 2, the study found that mean pain scores in the patients who took more than 10 oral morphine equivalents were significantly higher than in patients who took 10 or fewer. Among patients who used narcotic pain relief, 1% said they did so because they were instructed to despite having reported no pain.
Other factors predicting higher oral morphine equivalent use were age – patients tended to be younger than 45 years – total thyroidectomy, or a history of previous narcotic use.
“Based on our results, we have changed our practices to discharge all patients undergoing parathyroid or thyroid surgery and to request an oral narcotic prescription with no more than 20 equivalents, which translates to 20 tablets of hydrocodone/acetaminophen 5/325” the authors wrote.
Noting that the abuse and misuse of prescription opioids is the leading cause of overdose deaths in the United States, they argued that standardized prescribing practices are a way to not only reduce waste but also to improve patient safety.
“We also discovered that even between our two institutions, there was no standard prescribing pattern, with a wide range of prescriptions and number of equivalents dispensed.”
The authors also examined alternative and adjunctive methods of pain relief, pointing to previous studies suggesting benefits from preoperative gabapentin, postoperative music therapy, postoperative ice packs, and nonopioid analgesics.
They noted that because their study covered the breadth of endocrine neck operations, it did include patients who had minimally invasive surgery through to those who underwent total thyroidectomy with neck dissections. They also pointed out that the data pain scores and oral morphine equivalent use was based on patient recollection.
“Notwithstanding these limitations, our study is the first to examine outpatient narcotic pain medication use after thyroid and parathyroid surgery,” they said. “A standardized practice of prescribing stands to increase patient safety and minimize the risks of dependence and overdose.”
Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
FROM ANNALS OF SURGICAL ONCOLOGY
Key clinical point: Twenty oral morphine equivalents is the ideal amount of pain relief medication with which to discharge outpatients after thyroidectomy or parathyroidectomy surgery.
Major finding: Only 7% of patients who undergo thyroidectomy or parathyroidectomy use more than 20 oral morphine equivalents for postoperative pain relief.
Data source: Observational cohort study of 313 adult patients undergoing thyroidectomy or parathyroidectomy.
Disclosures: Two authors were supported by National Institutes of Health grants. No other conflicts of interest were declared.
Cabozantinib shows promise for carcinoid tumors, pNET
SAN FRANCISCO – Treatment with cabozantinib was associated with objective tumor responses and encouraging progression-free survival in patients with advanced carcinoid and pancreatic neuroendocrine tumors in a two-cohort phase II trial.
Of 41 patients in the carcinoid tumor cohort, 6 achieved RECIST-defined partial response (objective response rate, 15%), and 26 had stable disease. Median progression-free survival was 31.4 months.
Of 20 patients in the pancreatic neuroendocrine tumors (pNET) cohort, 3 achieved a partial response (objective response rate, 15%), and 15 had stable disease. Median progression-free survival was 21.8 months, Jennifer A. Chan, MD, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Although dose reduction was common – occurring in 81% of 53 patients who completed at least one treatment cycle – treatment was tolerable, said Dr. Chan of Dana-Farber Cancer Institute, Boston.
Study patients had progressive, well-differentiated grade 1-2 carcinoid tumors or pNET, and were treated with 60 mg of oral cabozantinib daily. There were no limits on prior therapy, and patients were restaged every 2 months for the first 6 months, then every 3 months thereafter.
The 41 patients with carcinoid tumors had a median age of 63 years and ECOG performance status of 0 or 1. Only 20 patients were enrolled in the pNET group, because accrual was halted, in part because of funding considerations. Patients in that group had a median age of 55 years, and also had ECOG performance status of 0 or 1, Dr. Chan said.
Carcinoid tumor patients completed a median of 8 28-day treatment cycles (range, 0-44), and pNET patients completed a median of 10 cycles (range, 0-25).
The most common reasons for discontinuation were progression or death in 51% of patients, withdrawal of consent or investigator decision in 28%, and adverse events in 21%, she noted.
The most common grade 3/4 toxicities included hypertension in 13% of patients, hypophosphatemia in 11%, and diarrhea in 10%.
Unexpected grade 3/4 events included heart failure and autoimmune hemolytic anemia, which each occurred in 1 patient.
This phase II study was initiated in light of promising preclinical work, Dr. Chan said.
“There has been much progress in recent years in the treatment of advanced neuroendocrine tumors,” she said. “The VEGF pathway inhibitors have been demonstrated to show activity, and the tyrosine kinase inhibitor sunitinib is approved for patients with progressive pancreatic neuroendocrine tumors.”
Recent studies also suggest that inhibition of MET may be an effective treatment strategy. MET activation has been shown to be associated with tumor growth, expression of MET has been observed in a significant proportion of neuroendocrine tumors, and increased expression of MET has been associated with decreased overall survival in pancreatic neuroendocrine tumors, she noted.
“Cabozantinib is a tyrosine kinase inhibitor that targets multiple receptors, including the VEGF receptors MET, ASL, and RET,” Dr. Chan explained. “It improves progression-free survival in advanced renal cell carcinoma in the first-line setting, compared with sunitinib, and also in the second-line setting, compared with everolimus in patients previously treated with anti-angiogenic therapy.” Cabozantinib is also approved for use in patients with progressive, metastatic medullary thyroid carcinoma, she added.
In preclinical models of neuroendocrine tumors, cabozantinib inhibited cell viability, and in a mouse model it decreased metastasis and invasion of pNET.
The current findings provide further evidence of cabozantinib’s safety and efficacy, Dr. Chan said. The progression-free survival in this phase II study is of particularly interest in the context of historical results, she added.
“Recognizing the limitations of interpreting progression-free survival data in an uncontrolled phase II trial, as well as comparing data to previous clinical trials, the progression-free survival results that we observed do appear encouraging,” she said. “It will be important to confirm the activity of cabozantinib in a randomized phase III setting.”
Dr. Chan reported having stock or other ownership interests in Merck; having a consulting or advisory role with Bayer, Ipsen, Novartis, Pfizer, and Pozen; and receiving research funding from Novartis and Sanofi.
SAN FRANCISCO – Treatment with cabozantinib was associated with objective tumor responses and encouraging progression-free survival in patients with advanced carcinoid and pancreatic neuroendocrine tumors in a two-cohort phase II trial.
Of 41 patients in the carcinoid tumor cohort, 6 achieved RECIST-defined partial response (objective response rate, 15%), and 26 had stable disease. Median progression-free survival was 31.4 months.
Of 20 patients in the pancreatic neuroendocrine tumors (pNET) cohort, 3 achieved a partial response (objective response rate, 15%), and 15 had stable disease. Median progression-free survival was 21.8 months, Jennifer A. Chan, MD, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Although dose reduction was common – occurring in 81% of 53 patients who completed at least one treatment cycle – treatment was tolerable, said Dr. Chan of Dana-Farber Cancer Institute, Boston.
Study patients had progressive, well-differentiated grade 1-2 carcinoid tumors or pNET, and were treated with 60 mg of oral cabozantinib daily. There were no limits on prior therapy, and patients were restaged every 2 months for the first 6 months, then every 3 months thereafter.
The 41 patients with carcinoid tumors had a median age of 63 years and ECOG performance status of 0 or 1. Only 20 patients were enrolled in the pNET group, because accrual was halted, in part because of funding considerations. Patients in that group had a median age of 55 years, and also had ECOG performance status of 0 or 1, Dr. Chan said.
Carcinoid tumor patients completed a median of 8 28-day treatment cycles (range, 0-44), and pNET patients completed a median of 10 cycles (range, 0-25).
The most common reasons for discontinuation were progression or death in 51% of patients, withdrawal of consent or investigator decision in 28%, and adverse events in 21%, she noted.
The most common grade 3/4 toxicities included hypertension in 13% of patients, hypophosphatemia in 11%, and diarrhea in 10%.
Unexpected grade 3/4 events included heart failure and autoimmune hemolytic anemia, which each occurred in 1 patient.
This phase II study was initiated in light of promising preclinical work, Dr. Chan said.
“There has been much progress in recent years in the treatment of advanced neuroendocrine tumors,” she said. “The VEGF pathway inhibitors have been demonstrated to show activity, and the tyrosine kinase inhibitor sunitinib is approved for patients with progressive pancreatic neuroendocrine tumors.”
Recent studies also suggest that inhibition of MET may be an effective treatment strategy. MET activation has been shown to be associated with tumor growth, expression of MET has been observed in a significant proportion of neuroendocrine tumors, and increased expression of MET has been associated with decreased overall survival in pancreatic neuroendocrine tumors, she noted.
“Cabozantinib is a tyrosine kinase inhibitor that targets multiple receptors, including the VEGF receptors MET, ASL, and RET,” Dr. Chan explained. “It improves progression-free survival in advanced renal cell carcinoma in the first-line setting, compared with sunitinib, and also in the second-line setting, compared with everolimus in patients previously treated with anti-angiogenic therapy.” Cabozantinib is also approved for use in patients with progressive, metastatic medullary thyroid carcinoma, she added.
In preclinical models of neuroendocrine tumors, cabozantinib inhibited cell viability, and in a mouse model it decreased metastasis and invasion of pNET.
The current findings provide further evidence of cabozantinib’s safety and efficacy, Dr. Chan said. The progression-free survival in this phase II study is of particularly interest in the context of historical results, she added.
“Recognizing the limitations of interpreting progression-free survival data in an uncontrolled phase II trial, as well as comparing data to previous clinical trials, the progression-free survival results that we observed do appear encouraging,” she said. “It will be important to confirm the activity of cabozantinib in a randomized phase III setting.”
Dr. Chan reported having stock or other ownership interests in Merck; having a consulting or advisory role with Bayer, Ipsen, Novartis, Pfizer, and Pozen; and receiving research funding from Novartis and Sanofi.
SAN FRANCISCO – Treatment with cabozantinib was associated with objective tumor responses and encouraging progression-free survival in patients with advanced carcinoid and pancreatic neuroendocrine tumors in a two-cohort phase II trial.
Of 41 patients in the carcinoid tumor cohort, 6 achieved RECIST-defined partial response (objective response rate, 15%), and 26 had stable disease. Median progression-free survival was 31.4 months.
Of 20 patients in the pancreatic neuroendocrine tumors (pNET) cohort, 3 achieved a partial response (objective response rate, 15%), and 15 had stable disease. Median progression-free survival was 21.8 months, Jennifer A. Chan, MD, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
Although dose reduction was common – occurring in 81% of 53 patients who completed at least one treatment cycle – treatment was tolerable, said Dr. Chan of Dana-Farber Cancer Institute, Boston.
Study patients had progressive, well-differentiated grade 1-2 carcinoid tumors or pNET, and were treated with 60 mg of oral cabozantinib daily. There were no limits on prior therapy, and patients were restaged every 2 months for the first 6 months, then every 3 months thereafter.
The 41 patients with carcinoid tumors had a median age of 63 years and ECOG performance status of 0 or 1. Only 20 patients were enrolled in the pNET group, because accrual was halted, in part because of funding considerations. Patients in that group had a median age of 55 years, and also had ECOG performance status of 0 or 1, Dr. Chan said.
Carcinoid tumor patients completed a median of 8 28-day treatment cycles (range, 0-44), and pNET patients completed a median of 10 cycles (range, 0-25).
The most common reasons for discontinuation were progression or death in 51% of patients, withdrawal of consent or investigator decision in 28%, and adverse events in 21%, she noted.
The most common grade 3/4 toxicities included hypertension in 13% of patients, hypophosphatemia in 11%, and diarrhea in 10%.
Unexpected grade 3/4 events included heart failure and autoimmune hemolytic anemia, which each occurred in 1 patient.
This phase II study was initiated in light of promising preclinical work, Dr. Chan said.
“There has been much progress in recent years in the treatment of advanced neuroendocrine tumors,” she said. “The VEGF pathway inhibitors have been demonstrated to show activity, and the tyrosine kinase inhibitor sunitinib is approved for patients with progressive pancreatic neuroendocrine tumors.”
Recent studies also suggest that inhibition of MET may be an effective treatment strategy. MET activation has been shown to be associated with tumor growth, expression of MET has been observed in a significant proportion of neuroendocrine tumors, and increased expression of MET has been associated with decreased overall survival in pancreatic neuroendocrine tumors, she noted.
“Cabozantinib is a tyrosine kinase inhibitor that targets multiple receptors, including the VEGF receptors MET, ASL, and RET,” Dr. Chan explained. “It improves progression-free survival in advanced renal cell carcinoma in the first-line setting, compared with sunitinib, and also in the second-line setting, compared with everolimus in patients previously treated with anti-angiogenic therapy.” Cabozantinib is also approved for use in patients with progressive, metastatic medullary thyroid carcinoma, she added.
In preclinical models of neuroendocrine tumors, cabozantinib inhibited cell viability, and in a mouse model it decreased metastasis and invasion of pNET.
The current findings provide further evidence of cabozantinib’s safety and efficacy, Dr. Chan said. The progression-free survival in this phase II study is of particularly interest in the context of historical results, she added.
“Recognizing the limitations of interpreting progression-free survival data in an uncontrolled phase II trial, as well as comparing data to previous clinical trials, the progression-free survival results that we observed do appear encouraging,” she said. “It will be important to confirm the activity of cabozantinib in a randomized phase III setting.”
Dr. Chan reported having stock or other ownership interests in Merck; having a consulting or advisory role with Bayer, Ipsen, Novartis, Pfizer, and Pozen; and receiving research funding from Novartis and Sanofi.
Key clinical point:
Major finding: The objective response rate was 15% in both groups; median progression-free survival was 31.4 and 21.8 months in the carcinoid and pNET groups, respectively.
Data source: A phase II trial involving 61 patients.
Disclosures: Dr. Chan reported having stock or other ownership interests in Merck; having a consulting or advisory role with Bayer, Ipsen, Novartis, Pfizer, and Pozen; and receiving research funding from Novartis and Sanofi.
Increase brings flu activity back to seasonal high
for the week ending Jan. 21, compared with three states the week before, according to the Centers for Disease Control and Prevention.
Alabama, Kansas, New Jersey, Oklahoma, and South Carolina were at level 10 on the CDC’s 1-10 scale of ILI activity, with Oklahoma reaching that level for the third consecutive week. Georgia (level 9) and Louisiana, Minnesota, Missouri, and Tennessee (level 8) were also in the “high” range, the CDC reported.
Three flu-related pediatric deaths were reported for the week, although two occurred during the week ending Jan. 14. The two earlier deaths were associated with an influenza A (H3) virus, and the more recent death was associated with an influenza B virus. For the 2016-2017 season so far, there have been a total of eight pediatric deaths, the CDC said.
for the week ending Jan. 21, compared with three states the week before, according to the Centers for Disease Control and Prevention.
Alabama, Kansas, New Jersey, Oklahoma, and South Carolina were at level 10 on the CDC’s 1-10 scale of ILI activity, with Oklahoma reaching that level for the third consecutive week. Georgia (level 9) and Louisiana, Minnesota, Missouri, and Tennessee (level 8) were also in the “high” range, the CDC reported.
Three flu-related pediatric deaths were reported for the week, although two occurred during the week ending Jan. 14. The two earlier deaths were associated with an influenza A (H3) virus, and the more recent death was associated with an influenza B virus. For the 2016-2017 season so far, there have been a total of eight pediatric deaths, the CDC said.
for the week ending Jan. 21, compared with three states the week before, according to the Centers for Disease Control and Prevention.
Alabama, Kansas, New Jersey, Oklahoma, and South Carolina were at level 10 on the CDC’s 1-10 scale of ILI activity, with Oklahoma reaching that level for the third consecutive week. Georgia (level 9) and Louisiana, Minnesota, Missouri, and Tennessee (level 8) were also in the “high” range, the CDC reported.
Three flu-related pediatric deaths were reported for the week, although two occurred during the week ending Jan. 14. The two earlier deaths were associated with an influenza A (H3) virus, and the more recent death was associated with an influenza B virus. For the 2016-2017 season so far, there have been a total of eight pediatric deaths, the CDC said.
VIDEO: Open, robotic, laparoscopic approaches equally effective in pancreatectomy
WASHINGTON – Minimally invasive surgery – whether robotic or laparoscopic – is just as effective as open surgery in pancreatectomy.
Both minimally invasive approaches had perioperative and oncologic outcomes that were similar to open approaches, as well as to each other, Katelin Mirkin, MD, reported at the annual clinical congress of the American College of Surgeons. And while minimally invasive surgery (MIS) techniques were associated with a slightly faster move to neoadjuvant chemotherapy, survival outcomes in all three surgical approaches were similar.
Dr. Mirkin, a surgery resident at Penn State Milton S. Hershey Medical Center, Hershey, Pa., plumbed the National Cancer Database for patients with stage I-III pancreatic cancer who were treated by surgical resection from 2010 to 2012. Her cohort comprised 9,047 patients; of these, 7,924 were treated with open surgery, 992 with laparoscopic surgery, and 131 with robotic surgery. She examined a number of factors including lymph node harvest and surgical margins, length of stay and time to adjuvant chemotherapy, and survival.
Patients who had MIS were older (67 vs. 66 years) and more often treated at an academic center, but otherwise there were no significant baseline differences.
Dr. Mirkin first compared the open surgeries with MIS. There were no significant associations with surgical approach and cancer stage. However, distal resections were significantly more likely to be dealt with by MIS, and Whipple procedures by open approaches. There were also more open than MIS total resections.
MIS was more likely to conclude with negative surgical margins (79% vs. 75%), and open surgery more likely to end with positive margins (22% vs. 19%).
Perioperative outcomes favored MIS approaches for all types of surgery, with a mean overall stay of 9.5 days vs. 11.3 days for open surgery. The mean length of stay for a distal resection was 7 days for MIS vs. 8 for open. For a Whipple procedure, the mean stay was 10.7 vs. 11.9 days. For a total resection, it was 10 vs. 11.8 days.
MIS was also associated with a significantly shorter time to the initiation of adjuvant chemotherapy overall (56 vs. 59 days). For a Whipple, time to chemotherapy was 58 vs. 60 days, respectively. For a distal resection, it was 52 vs. 56 days, and for a total resection, 52 vs. 58 days.
Neither approach offered a survival benefit over the other, Dr. Mirkin noted. For stage I cancers, less than 50% of MIS patients and less than 25% of open patients were alive by 50 months. For those with stage II tumors, less than 25% of each group was alive by 40 months. For stage III tumors, the 40-month survival rates were about 10% for MIS patients and 15% for open patients.
Dr. Mirkin then examined perioperative, oncologic, and survival outcomes among those who underwent laparoscopic and robotic surgeries. There were no demographic differences between these groups.
Oncologic outcomes were almost identical with regard to the number of positive regional nodes harvested (six), and surgical margins. Nodes were negative in 82% of robotic cases vs. 78% of laparoscopic cases and positive in 17.6% of robotic cases and 19.4% of laparoscopic cases.
Length of stay was significantly shorter for a laparoscopic approach overall (10 vs. 9.4 days) and particularly in distal resection (7 vs. 10 days). However, there were no differences in length of stay in any other surgery type. Nor was there any difference in the time to neoadjuvant chemotherapy.
Survival outcomes were similar as well. For stage I cancers, 40-month survival was about 40% in the laparoscopic group and 25% in the robotic group. For stage II cancers, 40-month survival was about 15% and 25%, respectively. For stage III tumors, 20-month survival in the robotic group was near 0 and 25% in the laparoscopic group. By 40 months almost all patients were deceased.
A multivariate survival analysis controlled for age, sex, race, comorbidities, facility type and location, surgery type, surgical margins, pathologic stage, and systemic therapy. It found only one significant association: Patients with 12 or more lymph nodes harvested were 19% more likely to die than those with fewer than 12 nodes harvested.
Time to chemotherapy (longer or shorter than 57 days) did not significantly impact survival, Dr. Mirkin said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @alz_gal
WASHINGTON – Minimally invasive surgery – whether robotic or laparoscopic – is just as effective as open surgery in pancreatectomy.
Both minimally invasive approaches had perioperative and oncologic outcomes that were similar to open approaches, as well as to each other, Katelin Mirkin, MD, reported at the annual clinical congress of the American College of Surgeons. And while minimally invasive surgery (MIS) techniques were associated with a slightly faster move to neoadjuvant chemotherapy, survival outcomes in all three surgical approaches were similar.
Dr. Mirkin, a surgery resident at Penn State Milton S. Hershey Medical Center, Hershey, Pa., plumbed the National Cancer Database for patients with stage I-III pancreatic cancer who were treated by surgical resection from 2010 to 2012. Her cohort comprised 9,047 patients; of these, 7,924 were treated with open surgery, 992 with laparoscopic surgery, and 131 with robotic surgery. She examined a number of factors including lymph node harvest and surgical margins, length of stay and time to adjuvant chemotherapy, and survival.
Patients who had MIS were older (67 vs. 66 years) and more often treated at an academic center, but otherwise there were no significant baseline differences.
Dr. Mirkin first compared the open surgeries with MIS. There were no significant associations with surgical approach and cancer stage. However, distal resections were significantly more likely to be dealt with by MIS, and Whipple procedures by open approaches. There were also more open than MIS total resections.
MIS was more likely to conclude with negative surgical margins (79% vs. 75%), and open surgery more likely to end with positive margins (22% vs. 19%).
Perioperative outcomes favored MIS approaches for all types of surgery, with a mean overall stay of 9.5 days vs. 11.3 days for open surgery. The mean length of stay for a distal resection was 7 days for MIS vs. 8 for open. For a Whipple procedure, the mean stay was 10.7 vs. 11.9 days. For a total resection, it was 10 vs. 11.8 days.
MIS was also associated with a significantly shorter time to the initiation of adjuvant chemotherapy overall (56 vs. 59 days). For a Whipple, time to chemotherapy was 58 vs. 60 days, respectively. For a distal resection, it was 52 vs. 56 days, and for a total resection, 52 vs. 58 days.
Neither approach offered a survival benefit over the other, Dr. Mirkin noted. For stage I cancers, less than 50% of MIS patients and less than 25% of open patients were alive by 50 months. For those with stage II tumors, less than 25% of each group was alive by 40 months. For stage III tumors, the 40-month survival rates were about 10% for MIS patients and 15% for open patients.
Dr. Mirkin then examined perioperative, oncologic, and survival outcomes among those who underwent laparoscopic and robotic surgeries. There were no demographic differences between these groups.
Oncologic outcomes were almost identical with regard to the number of positive regional nodes harvested (six), and surgical margins. Nodes were negative in 82% of robotic cases vs. 78% of laparoscopic cases and positive in 17.6% of robotic cases and 19.4% of laparoscopic cases.
Length of stay was significantly shorter for a laparoscopic approach overall (10 vs. 9.4 days) and particularly in distal resection (7 vs. 10 days). However, there were no differences in length of stay in any other surgery type. Nor was there any difference in the time to neoadjuvant chemotherapy.
Survival outcomes were similar as well. For stage I cancers, 40-month survival was about 40% in the laparoscopic group and 25% in the robotic group. For stage II cancers, 40-month survival was about 15% and 25%, respectively. For stage III tumors, 20-month survival in the robotic group was near 0 and 25% in the laparoscopic group. By 40 months almost all patients were deceased.
A multivariate survival analysis controlled for age, sex, race, comorbidities, facility type and location, surgery type, surgical margins, pathologic stage, and systemic therapy. It found only one significant association: Patients with 12 or more lymph nodes harvested were 19% more likely to die than those with fewer than 12 nodes harvested.
Time to chemotherapy (longer or shorter than 57 days) did not significantly impact survival, Dr. Mirkin said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @alz_gal
WASHINGTON – Minimally invasive surgery – whether robotic or laparoscopic – is just as effective as open surgery in pancreatectomy.
Both minimally invasive approaches had perioperative and oncologic outcomes that were similar to open approaches, as well as to each other, Katelin Mirkin, MD, reported at the annual clinical congress of the American College of Surgeons. And while minimally invasive surgery (MIS) techniques were associated with a slightly faster move to neoadjuvant chemotherapy, survival outcomes in all three surgical approaches were similar.
Dr. Mirkin, a surgery resident at Penn State Milton S. Hershey Medical Center, Hershey, Pa., plumbed the National Cancer Database for patients with stage I-III pancreatic cancer who were treated by surgical resection from 2010 to 2012. Her cohort comprised 9,047 patients; of these, 7,924 were treated with open surgery, 992 with laparoscopic surgery, and 131 with robotic surgery. She examined a number of factors including lymph node harvest and surgical margins, length of stay and time to adjuvant chemotherapy, and survival.
Patients who had MIS were older (67 vs. 66 years) and more often treated at an academic center, but otherwise there were no significant baseline differences.
Dr. Mirkin first compared the open surgeries with MIS. There were no significant associations with surgical approach and cancer stage. However, distal resections were significantly more likely to be dealt with by MIS, and Whipple procedures by open approaches. There were also more open than MIS total resections.
MIS was more likely to conclude with negative surgical margins (79% vs. 75%), and open surgery more likely to end with positive margins (22% vs. 19%).
Perioperative outcomes favored MIS approaches for all types of surgery, with a mean overall stay of 9.5 days vs. 11.3 days for open surgery. The mean length of stay for a distal resection was 7 days for MIS vs. 8 for open. For a Whipple procedure, the mean stay was 10.7 vs. 11.9 days. For a total resection, it was 10 vs. 11.8 days.
MIS was also associated with a significantly shorter time to the initiation of adjuvant chemotherapy overall (56 vs. 59 days). For a Whipple, time to chemotherapy was 58 vs. 60 days, respectively. For a distal resection, it was 52 vs. 56 days, and for a total resection, 52 vs. 58 days.
Neither approach offered a survival benefit over the other, Dr. Mirkin noted. For stage I cancers, less than 50% of MIS patients and less than 25% of open patients were alive by 50 months. For those with stage II tumors, less than 25% of each group was alive by 40 months. For stage III tumors, the 40-month survival rates were about 10% for MIS patients and 15% for open patients.
Dr. Mirkin then examined perioperative, oncologic, and survival outcomes among those who underwent laparoscopic and robotic surgeries. There were no demographic differences between these groups.
Oncologic outcomes were almost identical with regard to the number of positive regional nodes harvested (six), and surgical margins. Nodes were negative in 82% of robotic cases vs. 78% of laparoscopic cases and positive in 17.6% of robotic cases and 19.4% of laparoscopic cases.
Length of stay was significantly shorter for a laparoscopic approach overall (10 vs. 9.4 days) and particularly in distal resection (7 vs. 10 days). However, there were no differences in length of stay in any other surgery type. Nor was there any difference in the time to neoadjuvant chemotherapy.
Survival outcomes were similar as well. For stage I cancers, 40-month survival was about 40% in the laparoscopic group and 25% in the robotic group. For stage II cancers, 40-month survival was about 15% and 25%, respectively. For stage III tumors, 20-month survival in the robotic group was near 0 and 25% in the laparoscopic group. By 40 months almost all patients were deceased.
A multivariate survival analysis controlled for age, sex, race, comorbidities, facility type and location, surgery type, surgical margins, pathologic stage, and systemic therapy. It found only one significant association: Patients with 12 or more lymph nodes harvested were 19% more likely to die than those with fewer than 12 nodes harvested.
Time to chemotherapy (longer or shorter than 57 days) did not significantly impact survival, Dr. Mirkin said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @alz_gal
AT THE ACS CLINICAL CONGRESS
Key clinical point:
Major finding: For stage I cancers, less than 50% of minimally invasive surgery patients and less than 25% of open surgery patients were alive by 50 months. For those with stage II tumors, less than 25% of each group was alive by 40 months.
Data source: The database review comprised 9,047 cases.
Disclosures: Dr. Mirkin had no financial disclosures.
ATA’s risk assessment guidelines for thyroid nodules using sonography patterns validated
DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.
Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.
The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.
“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.
Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.
There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.
The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.
The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.
DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.
Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.
The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.
“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.
Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.
There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.
The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.
The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.
DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.
Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.
The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.
“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.
Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.
There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.
The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.
The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.
Key clinical point:
Major finding: Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound, according to the ATA.
Data source: Prospective validation of the ATA’s ultrasound risk assessment guidelines on 211 thyroid nodules excised from 199 patients.
Disclosures: The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.
Endoscopic, laparoscopic pseudocyst drainage comparable if necrotic debris minimal
SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.
Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.
Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.
Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.
Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.
Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.
Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.
Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.
Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.
Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.
Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.
There was no industry funding for the work, and Dr. Garg had no disclosures.
SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.
Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.
Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.
Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.
Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.
Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.
Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.
Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.
Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.
Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.
Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.
There was no industry funding for the work, and Dr. Garg had no disclosures.
SAN DIEGO – Endoscopic and laparoscopic drainage worked about equally well for pancreatic pseudocysts and walled off necrosis in a small randomized trial from India, the first to compare the two options.
Both are in common use, but until now it wasn’t clear if one was better than the other. The findings mean that “in general, one could do either; the choice of treatment depends [largely] on the expertise available. As an endoscopist, I prefer endoscopic drainage,” said gastroenterologist Pramod Garg, of the All India Institute of Medical Sciences, New Delhi.
Laparoscopic drainage was a technical success in 23 of the 30 patients (76.6%) randomized to it, six of whom (20%) had symptomatic pseudocysts larger than 6 cm for more than 6 weeks; the rest had walled off necrosis (WON) containing less than 30% necrotic debris. Five of the other patients were converted to open surgery, and two underwent percutaneous drainage. One of the 30 patients required endoscopic lavage and necrosectomy for secondary infection.
Endoscopic drainage, meanwhile, was technically successful in 22 of 30 patients (73.3%) with similar distributions of pseudocysts and WON. Most of the other patients needed subsequent endoscopic lavage and necrosectomy for secondary infection.
Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups; one endoscopic patient had a splenic artery pseudoaneurysm that required further surgery. The differences in technical and clinical success rates were not statistically significant. There were no recurrences and no deaths in either group after an average follow-up of 22 months.
Although it seems okay to opt for either approach, “it’s very important for us to assess the amount of necrotic debris. If the amount is sizable, say 50% or more of the volume, one should hesitate before doing purely endoscopic drainage.” As seen in the study, “the chances of developing an infection are pretty high, especially if,” like the investigators, “you place only a plastic stent,” Dr. Garg said at the annual Digestive Disease Week.
Laparoscopic drainage would probably be better when there’s a lot of necrotic tissue, and certainly so if patients need their gallbladder removed, because it can be taken out at the same time. If endoscopy is still the choice, “you should be prepared to do repeat procedures for endoscopic lavage and necrosectomy. The chance of infection may be less if you use a metal stent with a wide diameter,” Dr. Garg said. Before tackling WON with endoscopy, he suggested getting input from a radiologist and surgeon.
Laparoscopic cystogastrostomy was done in the usual manner, with an endostapler to create a wide cystogastrostomy, necrotic debris suction, and concomitant cholecystectomies as needed.
Endoscopic drainage was performed under endosonographic guidance in the 13 patients without bulging cysts, and directly in the 17 patients whose cysts bulged. A balloon was used to dilate the cystogastrostomy tract to 12-15 mm, and a 10 F double pigtail plastic stent placed to keep it open.
Patients in both groups received perioperative antibiotics. The demographic, clinical, and laboratory parameters and etiology of acute pancreatitis were comparable between the two groups. Patients tended to be in their mid-30s, and about 75% in both groups were women. Over a third in each group had gallstone disease. The median hospital stay in both groups was about a week. Fever was more common following endoscopic drainage, probably because of the higher incidence of secondary infection.
Patients with complicated pseudocysts, coagulopathies, or organ failure were excluded from the investigation, as well as those otherwise unfit for surgery.
There was no industry funding for the work, and Dr. Garg had no disclosures.
AT DDW 2016
Key clinical point: Choosing between endoscopic and laparoscopic drainage for pancreatic pseudocysts comes down to local expertise and the amount of necrotic tissue that needs to be removed.
Major finding: Clinical success – defined as resolution by week 4 – was 100% in the laparoscopic and 97% (29/30) in the endoscopic groups.
Data source: Randomized trial with 60 patients.
Disclosures: There was no industry funding for the work, and the presenter had no disclosures.
VIDEO: Asymptomatic pancreatic cysts rarely became malignant
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Kwong et al. present important data demonstrating a low risk of malignant transformation for pancreas cysts followed for more than 5 years, which is similar to the risk of surgical resection. Mortality from nonpancreatic causes was found to be eightfold higher than mortality from pancreatic cancer. The goal of pancreas cyst surveillance is to prevent death from pancreatic cancer, currently accomplished by identifying high-risk cysts for surgical resection. When evaluating the utility of surveillance, patient and cyst characteristics can be considered.
Elderly patients with multiple comorbidities are unlikely to benefit from long-term surveillance as they may be poor surgical candidates and are unlikely to die from the malignant progression of a pancreas cyst. Healthy patients with a family history of pancreatic cancer and/or identifiable genetic risk factors, however, may benefit from long-term surveillance. Although demonstrated to be infrequent, cysts that have been stable for 5-10 years rarely may progress to cancer. The presence of more than one high-risk cyst feature increased the risk of progression from approximately 1% to 15%. The study of larger groups of cysts with morphologic high-risk features is required. The addition of molecular and genetic cyst and patient features has the potential to assist in risk stratification.
Clarifying which cysts and patients are likely to benefit from surveillance and resection is of increasing importance as high-resolution, cross-sectional imaging identifies greater numbers of pancreas cysts.
Dr. Harry R. Aslanian, AGAF, is director, Advanced Endoscopy Fellowship, and associate professor, Yale University, New Haven, Conn. He is a consultant for Boston Scientific and Olympus.
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.
Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.
Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).
Source: American Gastroenterological Association
In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.
A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.
The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Asymptomatic neoplastic pancreatic cysts rarely become malignant, especially in the absence of multiple American Gastroenterological Association high-risk features.
Major finding: Only 1% of patients developed invasive pancreatic adenocarcinoma after more than 5 years of surveillance.
Data source: A multicenter retrospective study of 310 patients who underwent endoscopic ultrasound evaluations of pancreatic cysts.
Disclosures: The University of California San Diego Health Care System supported the study. The investigators had no disclosures.
Metabolic factors associated with pancreatic NETs
SAN DIEGO – Diabetes (not recent onset), obesity, and gallstone disease were associated with the occurrence of sporadic pancreatic neuroendocrine tumors (PNET) in the prospective, case-control European EpiNet study.
Cigarette smoking, first-degree family history of cancer, and alcohol consumption were not significantly associated with PNET in this study, which was reported at the annual Digestive Disease Week.
“This is the first prospective multicenter study investigating risk factors for the occurrence of PNET. We confirmed that diabetes, obesity and gallstone disease are significantly associated with PNET. The role of obesity is confirmed for the first time. However, the study failed to confirm an association with family history of cancer, smoking cigarettes, alcohol consumption, hormonal reproductive factors, or allergies. This is different from pancreatic cancer,” said lead author Dr. Roberto Valente, Sapienza University of Rome, Italy.
PNET is a rare tumor, comprising 1% of all pancreatic tumors and 10% of all pancreatic neoplasms.
“The incidence of PNET is rising over time and we don’t know why. Thus far, risk factors for PNET have been poorly investigated. Many factors associated with pancreatic cancer have not been previously studied in PNET, including allergies, use of aspirin, and reproductive/gynecologic factors in women,” he said.
Previous case-control studies in small samples identified diabetes, smoking, alcohol consumption, and a family history of cancer as potential risk factors. Dr. Valente and coinvestigators sought to evaluate risk and protective factors for PNET in a more rigorous study.
Participants were drawn from five European countries. The study included 201 cases of sporadic, histologically proven PNET diagnosed within 24 months of the initiation of the study, and 603 controls matched for age and sex. For both cases and controls, about 50% were male, mean age was 59 years, and 97% were Caucasian. Among cases, 76.6% had nonfunctioning PNET that were equally distributed anatomically.
Participants responded to standardized questionnaires about demographics, and environmental, and familial risk factors using a predefined standard questionnaire.
Obesity (defined as body mass index [BMI] greater than 30) was significantly more prevalent in cases than controls (26.5% versus 19.26%, respectively, P = .03). Diabetes was also significantly more prevalent in cases than controls (18.5% versus 12.5%, respectively P = .003).
No differences were found between cases and controls in family history of any cancer, alcohol consumption, coffee drinking, or cigarette smoking.
Looking at previous medical history, only gallstone disease was strongly associated with PNET, but this was of borderline statistical significance (19.2% versus 13.2%, respectively, P = .06).
The investigators looked at previously uninvestigated potentially protective factors such as allergies (asthma, eczema, hay fever), and use of aspirin. None of these was significantly more prevalent in cases compared with controls.
Reproductive/hormonal factors were analyzed in 98 cases and 294 controls. None of these factors was significantly different in cases or controls.
Univariate regression analysis adjusted for age found that diabetes (P = .02), diabetes for more than 1 year (P = .002), obesity (P = .02), and previous gallstone disease (P = .04) were significant risk factors for PNET.
Multivariate logistic regression analysis confirmed diabetes as a significant risk factor (P = .009), and obesity and gallstone disease were of borderline significance (P = .09 and P = .07, respectively).
“The reported risk factors partially overlap with those reported for pancreatic adenocarcinoma, thus suggesting a possible organ-specific carcinogenic effect,” Dr Valente noted.
SAN DIEGO – Diabetes (not recent onset), obesity, and gallstone disease were associated with the occurrence of sporadic pancreatic neuroendocrine tumors (PNET) in the prospective, case-control European EpiNet study.
Cigarette smoking, first-degree family history of cancer, and alcohol consumption were not significantly associated with PNET in this study, which was reported at the annual Digestive Disease Week.
“This is the first prospective multicenter study investigating risk factors for the occurrence of PNET. We confirmed that diabetes, obesity and gallstone disease are significantly associated with PNET. The role of obesity is confirmed for the first time. However, the study failed to confirm an association with family history of cancer, smoking cigarettes, alcohol consumption, hormonal reproductive factors, or allergies. This is different from pancreatic cancer,” said lead author Dr. Roberto Valente, Sapienza University of Rome, Italy.
PNET is a rare tumor, comprising 1% of all pancreatic tumors and 10% of all pancreatic neoplasms.
“The incidence of PNET is rising over time and we don’t know why. Thus far, risk factors for PNET have been poorly investigated. Many factors associated with pancreatic cancer have not been previously studied in PNET, including allergies, use of aspirin, and reproductive/gynecologic factors in women,” he said.
Previous case-control studies in small samples identified diabetes, smoking, alcohol consumption, and a family history of cancer as potential risk factors. Dr. Valente and coinvestigators sought to evaluate risk and protective factors for PNET in a more rigorous study.
Participants were drawn from five European countries. The study included 201 cases of sporadic, histologically proven PNET diagnosed within 24 months of the initiation of the study, and 603 controls matched for age and sex. For both cases and controls, about 50% were male, mean age was 59 years, and 97% were Caucasian. Among cases, 76.6% had nonfunctioning PNET that were equally distributed anatomically.
Participants responded to standardized questionnaires about demographics, and environmental, and familial risk factors using a predefined standard questionnaire.
Obesity (defined as body mass index [BMI] greater than 30) was significantly more prevalent in cases than controls (26.5% versus 19.26%, respectively, P = .03). Diabetes was also significantly more prevalent in cases than controls (18.5% versus 12.5%, respectively P = .003).
No differences were found between cases and controls in family history of any cancer, alcohol consumption, coffee drinking, or cigarette smoking.
Looking at previous medical history, only gallstone disease was strongly associated with PNET, but this was of borderline statistical significance (19.2% versus 13.2%, respectively, P = .06).
The investigators looked at previously uninvestigated potentially protective factors such as allergies (asthma, eczema, hay fever), and use of aspirin. None of these was significantly more prevalent in cases compared with controls.
Reproductive/hormonal factors were analyzed in 98 cases and 294 controls. None of these factors was significantly different in cases or controls.
Univariate regression analysis adjusted for age found that diabetes (P = .02), diabetes for more than 1 year (P = .002), obesity (P = .02), and previous gallstone disease (P = .04) were significant risk factors for PNET.
Multivariate logistic regression analysis confirmed diabetes as a significant risk factor (P = .009), and obesity and gallstone disease were of borderline significance (P = .09 and P = .07, respectively).
“The reported risk factors partially overlap with those reported for pancreatic adenocarcinoma, thus suggesting a possible organ-specific carcinogenic effect,” Dr Valente noted.
SAN DIEGO – Diabetes (not recent onset), obesity, and gallstone disease were associated with the occurrence of sporadic pancreatic neuroendocrine tumors (PNET) in the prospective, case-control European EpiNet study.
Cigarette smoking, first-degree family history of cancer, and alcohol consumption were not significantly associated with PNET in this study, which was reported at the annual Digestive Disease Week.
“This is the first prospective multicenter study investigating risk factors for the occurrence of PNET. We confirmed that diabetes, obesity and gallstone disease are significantly associated with PNET. The role of obesity is confirmed for the first time. However, the study failed to confirm an association with family history of cancer, smoking cigarettes, alcohol consumption, hormonal reproductive factors, or allergies. This is different from pancreatic cancer,” said lead author Dr. Roberto Valente, Sapienza University of Rome, Italy.
PNET is a rare tumor, comprising 1% of all pancreatic tumors and 10% of all pancreatic neoplasms.
“The incidence of PNET is rising over time and we don’t know why. Thus far, risk factors for PNET have been poorly investigated. Many factors associated with pancreatic cancer have not been previously studied in PNET, including allergies, use of aspirin, and reproductive/gynecologic factors in women,” he said.
Previous case-control studies in small samples identified diabetes, smoking, alcohol consumption, and a family history of cancer as potential risk factors. Dr. Valente and coinvestigators sought to evaluate risk and protective factors for PNET in a more rigorous study.
Participants were drawn from five European countries. The study included 201 cases of sporadic, histologically proven PNET diagnosed within 24 months of the initiation of the study, and 603 controls matched for age and sex. For both cases and controls, about 50% were male, mean age was 59 years, and 97% were Caucasian. Among cases, 76.6% had nonfunctioning PNET that were equally distributed anatomically.
Participants responded to standardized questionnaires about demographics, and environmental, and familial risk factors using a predefined standard questionnaire.
Obesity (defined as body mass index [BMI] greater than 30) was significantly more prevalent in cases than controls (26.5% versus 19.26%, respectively, P = .03). Diabetes was also significantly more prevalent in cases than controls (18.5% versus 12.5%, respectively P = .003).
No differences were found between cases and controls in family history of any cancer, alcohol consumption, coffee drinking, or cigarette smoking.
Looking at previous medical history, only gallstone disease was strongly associated with PNET, but this was of borderline statistical significance (19.2% versus 13.2%, respectively, P = .06).
The investigators looked at previously uninvestigated potentially protective factors such as allergies (asthma, eczema, hay fever), and use of aspirin. None of these was significantly more prevalent in cases compared with controls.
Reproductive/hormonal factors were analyzed in 98 cases and 294 controls. None of these factors was significantly different in cases or controls.
Univariate regression analysis adjusted for age found that diabetes (P = .02), diabetes for more than 1 year (P = .002), obesity (P = .02), and previous gallstone disease (P = .04) were significant risk factors for PNET.
Multivariate logistic regression analysis confirmed diabetes as a significant risk factor (P = .009), and obesity and gallstone disease were of borderline significance (P = .09 and P = .07, respectively).
“The reported risk factors partially overlap with those reported for pancreatic adenocarcinoma, thus suggesting a possible organ-specific carcinogenic effect,” Dr Valente noted.
AT DDW® 2016
Surgery has edge over surveillance for micropapillary thyroid cancer
BALTIMORE – Hemithyroidectomy for low-risk micropapillary thyroid cancer can have advantages over active surveillance, according to findings from a study that examined outcomes by cost and quality of life data.
Endocrinologists and surgeons need to have in-depth conversations with their patients to determine their level of anxiety about cancer, surgery, and about their quality of life, to determine the best course of treatment, researchers at the University of California, San Francisco (UCSF) reported at the annual meeting of the American Association of Endocrine Surgeons.
“Our study found that hemithyroidectomy is cost effective in the majority of scenarios,” presenter Shriya Venkatesh said. “However, patient perception of micropapillary thyroid cancer as well as [the patient’s] life expectancy can play a major role in deciding which therapeutic option to choose.”
The study involved a cost-effectiveness analysis of the surgery vs. active surveillance, “which is especially relevant in our current times,” Ms. Venkatesh said in an interview. “What we wanted to do is give physicians information for when they approach their patients, not only in assessing the tumor from the medical aspect but also when looking at it from quality-of-life and cost-benefit perspectives.”
Both courses of management were modeled over a 20-year period with Medicare data and literature review to calculate costs and health utilities. The UCSF researchers used Markov statistical models for both approaches in which the reference case was a 40-year-old, otherwise healthy patient with a recent diagnosis of micropapillary thyroid cancer without high-risk factors. Either hemithyroidectomy or surveillance would be reasonable treatment options.
“We found that hemithyroidectomy was about $8,000 more costly than active surveillance, but it also afforded an increase in about 1.09 quality-adjusted life years,” Ms. Venkatesh said. Hemithyroidectomy is most cost effective for patients with a life expectancy of 3 years or more and who perceive that living with low-grade thyroid cancer would have even a modest detriment on their quality of life, she said.
“Unfortunately there is no current published quality-of-life assessment of active surveillance for thyroid cancer,” Ms. Venkatesh said. “We believe that estimating active surveillance to the equivalent of surgery underestimates the anxiety some patients may feel upon receiving their diagnosis.”
The paucity of literature on active surveillance for thyroid cancer prompted the UCSF researchers to turn to the prostate cancer literature, which has more data on active surveillance, to try to determine the disutility of active surveillance for micropapillary thyroid cancer. “Our extrapolation from the literature yields a mean disutility of 0.11,” she said.
However, the utility estimates the researchers came up with were variable, Ms. Venkatesh said. “This really pushes physicians to have that conversation with their patients, not only about the physical aspects of how they’re doing but also the mental aspects,” she said.
But quality of life is difficult to quantify, senior author Dr. Insoo Suh said in an interview. “What we found is that no matter how one measures quality of life, the qualitative degree of quality of life decrease that people associate with ‘living with cancer’ need not be that significant in order for surgery to be a potentially cost-effective treatment for them,” said Dr. Suh, an endocrine surgeon at UCSF and an ACS Fellow.
During the discussion, Dr. Peter Angelos of the University of Chicago and an ACS Fellow, said, “I’m curious how this information should impact the individual decision-making and informed consent for a specific patient, because I’m not sure that an individual patient would care if active surveillance is more cost effective or not.”
“When speaking to your patients, obviously discussing the rates of progression of the disease is important and then [so is] talking to them about different therapeutic options,” Ms. Venkatesh said. “The physician should also make an assessment about the patient’s quality of life to see if there are likely to be any changes due to the diagnosis.”
The limitations of the study include the extrapolation of data from the prostate cancer literature to define a utility scale and also the reference case used in the Markov model. Other utility measures showed variability as well.
Ms. Venkatesh, Dr. Suh and their coauthors had no financial relationships to disclose.
BALTIMORE – Hemithyroidectomy for low-risk micropapillary thyroid cancer can have advantages over active surveillance, according to findings from a study that examined outcomes by cost and quality of life data.
Endocrinologists and surgeons need to have in-depth conversations with their patients to determine their level of anxiety about cancer, surgery, and about their quality of life, to determine the best course of treatment, researchers at the University of California, San Francisco (UCSF) reported at the annual meeting of the American Association of Endocrine Surgeons.
“Our study found that hemithyroidectomy is cost effective in the majority of scenarios,” presenter Shriya Venkatesh said. “However, patient perception of micropapillary thyroid cancer as well as [the patient’s] life expectancy can play a major role in deciding which therapeutic option to choose.”
The study involved a cost-effectiveness analysis of the surgery vs. active surveillance, “which is especially relevant in our current times,” Ms. Venkatesh said in an interview. “What we wanted to do is give physicians information for when they approach their patients, not only in assessing the tumor from the medical aspect but also when looking at it from quality-of-life and cost-benefit perspectives.”
Both courses of management were modeled over a 20-year period with Medicare data and literature review to calculate costs and health utilities. The UCSF researchers used Markov statistical models for both approaches in which the reference case was a 40-year-old, otherwise healthy patient with a recent diagnosis of micropapillary thyroid cancer without high-risk factors. Either hemithyroidectomy or surveillance would be reasonable treatment options.
“We found that hemithyroidectomy was about $8,000 more costly than active surveillance, but it also afforded an increase in about 1.09 quality-adjusted life years,” Ms. Venkatesh said. Hemithyroidectomy is most cost effective for patients with a life expectancy of 3 years or more and who perceive that living with low-grade thyroid cancer would have even a modest detriment on their quality of life, she said.
“Unfortunately there is no current published quality-of-life assessment of active surveillance for thyroid cancer,” Ms. Venkatesh said. “We believe that estimating active surveillance to the equivalent of surgery underestimates the anxiety some patients may feel upon receiving their diagnosis.”
The paucity of literature on active surveillance for thyroid cancer prompted the UCSF researchers to turn to the prostate cancer literature, which has more data on active surveillance, to try to determine the disutility of active surveillance for micropapillary thyroid cancer. “Our extrapolation from the literature yields a mean disutility of 0.11,” she said.
However, the utility estimates the researchers came up with were variable, Ms. Venkatesh said. “This really pushes physicians to have that conversation with their patients, not only about the physical aspects of how they’re doing but also the mental aspects,” she said.
But quality of life is difficult to quantify, senior author Dr. Insoo Suh said in an interview. “What we found is that no matter how one measures quality of life, the qualitative degree of quality of life decrease that people associate with ‘living with cancer’ need not be that significant in order for surgery to be a potentially cost-effective treatment for them,” said Dr. Suh, an endocrine surgeon at UCSF and an ACS Fellow.
During the discussion, Dr. Peter Angelos of the University of Chicago and an ACS Fellow, said, “I’m curious how this information should impact the individual decision-making and informed consent for a specific patient, because I’m not sure that an individual patient would care if active surveillance is more cost effective or not.”
“When speaking to your patients, obviously discussing the rates of progression of the disease is important and then [so is] talking to them about different therapeutic options,” Ms. Venkatesh said. “The physician should also make an assessment about the patient’s quality of life to see if there are likely to be any changes due to the diagnosis.”
The limitations of the study include the extrapolation of data from the prostate cancer literature to define a utility scale and also the reference case used in the Markov model. Other utility measures showed variability as well.
Ms. Venkatesh, Dr. Suh and their coauthors had no financial relationships to disclose.
BALTIMORE – Hemithyroidectomy for low-risk micropapillary thyroid cancer can have advantages over active surveillance, according to findings from a study that examined outcomes by cost and quality of life data.
Endocrinologists and surgeons need to have in-depth conversations with their patients to determine their level of anxiety about cancer, surgery, and about their quality of life, to determine the best course of treatment, researchers at the University of California, San Francisco (UCSF) reported at the annual meeting of the American Association of Endocrine Surgeons.
“Our study found that hemithyroidectomy is cost effective in the majority of scenarios,” presenter Shriya Venkatesh said. “However, patient perception of micropapillary thyroid cancer as well as [the patient’s] life expectancy can play a major role in deciding which therapeutic option to choose.”
The study involved a cost-effectiveness analysis of the surgery vs. active surveillance, “which is especially relevant in our current times,” Ms. Venkatesh said in an interview. “What we wanted to do is give physicians information for when they approach their patients, not only in assessing the tumor from the medical aspect but also when looking at it from quality-of-life and cost-benefit perspectives.”
Both courses of management were modeled over a 20-year period with Medicare data and literature review to calculate costs and health utilities. The UCSF researchers used Markov statistical models for both approaches in which the reference case was a 40-year-old, otherwise healthy patient with a recent diagnosis of micropapillary thyroid cancer without high-risk factors. Either hemithyroidectomy or surveillance would be reasonable treatment options.
“We found that hemithyroidectomy was about $8,000 more costly than active surveillance, but it also afforded an increase in about 1.09 quality-adjusted life years,” Ms. Venkatesh said. Hemithyroidectomy is most cost effective for patients with a life expectancy of 3 years or more and who perceive that living with low-grade thyroid cancer would have even a modest detriment on their quality of life, she said.
“Unfortunately there is no current published quality-of-life assessment of active surveillance for thyroid cancer,” Ms. Venkatesh said. “We believe that estimating active surveillance to the equivalent of surgery underestimates the anxiety some patients may feel upon receiving their diagnosis.”
The paucity of literature on active surveillance for thyroid cancer prompted the UCSF researchers to turn to the prostate cancer literature, which has more data on active surveillance, to try to determine the disutility of active surveillance for micropapillary thyroid cancer. “Our extrapolation from the literature yields a mean disutility of 0.11,” she said.
However, the utility estimates the researchers came up with were variable, Ms. Venkatesh said. “This really pushes physicians to have that conversation with their patients, not only about the physical aspects of how they’re doing but also the mental aspects,” she said.
But quality of life is difficult to quantify, senior author Dr. Insoo Suh said in an interview. “What we found is that no matter how one measures quality of life, the qualitative degree of quality of life decrease that people associate with ‘living with cancer’ need not be that significant in order for surgery to be a potentially cost-effective treatment for them,” said Dr. Suh, an endocrine surgeon at UCSF and an ACS Fellow.
During the discussion, Dr. Peter Angelos of the University of Chicago and an ACS Fellow, said, “I’m curious how this information should impact the individual decision-making and informed consent for a specific patient, because I’m not sure that an individual patient would care if active surveillance is more cost effective or not.”
“When speaking to your patients, obviously discussing the rates of progression of the disease is important and then [so is] talking to them about different therapeutic options,” Ms. Venkatesh said. “The physician should also make an assessment about the patient’s quality of life to see if there are likely to be any changes due to the diagnosis.”
The limitations of the study include the extrapolation of data from the prostate cancer literature to define a utility scale and also the reference case used in the Markov model. Other utility measures showed variability as well.
Ms. Venkatesh, Dr. Suh and their coauthors had no financial relationships to disclose.
AT AAES 2016
Key clinical point: Patient psychological factors are key determinants in choosing a course of management for low-risk micropapillary thyroid cancer.
Major finding: Hemithyroidectomy typically costs about $8,000 more than active surveillance but also accounts for improved quality of life in these patients.
Data source: Markov models for both courses of management over a 20-year period with Medicare data and literature review to calculate costs and health utilities.
Disclosures: Ms. Venkatesh and her coauthors reported having no financial disclosures.
