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Characteristics Associated With Health-Related Quality of Life of Patients With Neuroendocrine Tumor (NET)
AGA Abstracts
were abdominal pain (6), painless jaundice (5), incidental finding (5) and epigastric soreness (1). Radiological findings of computerized tomography were gallbladder cancer (7), cholangiocarcinoma (5) and ampulla of Vater tumor (6). Initially lymph nodes or other organ metastases were noticed in 9 and 6 patients, respectively. Thirteen patients received curative surgery and 1 experienced palliative cholecystectomy (including 2 who had received operations at outside hospital). Except 2 cases operated at outside hospital, 25% (3/12) had R2 resection margins and there were 5, 7 and 5 patients who had angiolymphatic, venous and perineural invasion within surgical specimen. Eight of 13 patients who had received curative surgery, experienced recurrence and the most common recurrent site was liver (6/8). Median disease free survival of 13 cases was 4.2 (0.4-53.6) months and median overall survival of all patients was 16.8 (1.9-102.1) months. By Cox regression analysis, age and WHO classification was statistically associated with overall survival (p=0.017 and 0.034, respectively) and there was no difference according to tumor location. Conclusion: WHO classification of neuroendocrine tumors in biliary tract was compatible with those in other organs. Further study is necessary for establishing a staging system with neuroendocrine tumors in bile duct or gallbladder.
Tu2027 Jejuno-Ileal Carcinoid Tumors Are Rarely Amenable to Endoscopic Resection Joshua E. Melson, Raja Koteswar Dhanekula, Peter Eichenseer, Abhitabh Patil, Kateri A. Evans, Maisa Abdalla, Shriram Jakate, Sohrab Mobarhan Background: Endoscopic resection of small bowel lesions is increasingly described. The clinical appropriateness of endoscopic mucosal resection (EMR) in jejunoileal carcinoids is not well evaluated. As imaging of the small bowel in obscure gastrointestinal bleeding is advocated increased rates of earlier and incidental jejunoileal carcinoids are likely. In this study we evaluated if endoscopic resection can be applied to jejunoileal carcinoids. Methods: Pathology reports of all patients diagnosed with jejunoileal carcinoids from 1993 to 2009 at Rush University Medical Center were reviewed. We evaluated tumor size, depth of tumor invasion, differentiation, multiplicity, lymph node invasion and distant metastases. Following surgery, patients were identified retrospectively as being amenable to EMR if there was absence of distant metastases, nodal disease and invasion of the tumor into the muscularis propria or multiplicity of carcinoid tumors. Exclusion criteria included liver or distant metastases at time of diagnosis, poor differentiation of carcinoid tumors and presence of adenomatous features in tumor. Results: A total of 32 jejunoileal carcinoid tumors were reviewed for amenability to EMR based on histopathology following surgical intervention. Following surgical pathology review, only 2/32 (6.2%) were considered to be potentially amenable to EMR. The two tumors amenable to EMR were both under 1 cm. None of the 28 tumors ≥1cm was amenable to EMR, as these tumors invariably invaded Muscularis Propria. The rate of lymph node invasion 24/28 (85.7%) was significantly high when tumor size exceeded 1 cm. Multiplicity of tumors occurred in 7/32 (22%) cases. Conclusions: We conclude from this study that size appears to be a key determining factor in deciding which jejunoileal carcinoids should not be considered appropriate for endoscopic resection. EMR of any jejunoileal carcinoid tumor in excess of 1cm would have left residual tumor in 28/ 28 cases and thus should not be attempted. Tumor multiplicity is not uncommon occurring in 7/32 (22%) cases in this series and should be investigated in jejunoileal carcinoids prior to resection. Jejunoileal carcinoids of 1 cm or greater in size in the absence of distant metastases, should be surgically resected with a lymph node resection done since they have a high rate of local regional disease. Small carcinoids of <1cm may or may not be amenable to an endoscopic resection and a prohibitive depth of invasion and multiplicity of tumors need to be considered in this smaller subset of patients. Table A
Tu2025 Characteristics Associated With Health-Related Quality of Life of Patients With Neuroendocrine Tumor (NET) James C. Yao, Jennifer Beaumont, David Cella, Seung Choi, Zhimei Liu, Alexandria T. Phan Introduction: The objective of this study was to evaluate demographic and clinical characteristics associated with health-related quality of life (HRQL) in patients with neuroendocrine tumor (NET). Methods: Patients with NET were invited via email to participate in an online anonymous survey. The survey consisted of two standardized HRQL measures: RAND-36 and PROMIS. In addition, a set of demographic and disease-related questions were included in the survey. General linear models were used to evaluate the associations between HRQL and age, gender, type of NET, years since diagnosis, whether NET has spread to lymph nodes or other part of body, whether NET is currently present in the body, treatment with a somatostatin analog in the past month, presence of carcinoid syndrome, average number of bowel movements per day, and total number of flushing episodes in the past two weeks. Variables with bivariate p < 0.05 were entered into a multivariable model, non-significant variables were removed one at a time, and interaction terms of clinical interest were explored. Results: A total of 663 eligible patients participated in the survey. Of these, 66% were female and 39% were 60 years or older. Mean (median) years since diagnosis with NET was 5 (4) years. One-third (34%) had an average of 4 or more bowel movements per day and 53% experienced at least one flushing episode in the past two weeks. Results from the univariate analysis showed HRQL, as measured by the General Health subscale of the RAND-36, was significantly associated with spread to lymph nodes or other part of body, current presence of tumor, somatostatin analog, carcinoid syndrome, frequency of bowel movements, and flushing episodes. Only spread to other part of body (aside from lymph nodes), current presence of tumor, carcinoid syndrome, and frequency of bowel movements remained significant in the multivariable model (all p<0.01). Conclusion: Patients with current NET, metastases, carcinoid syndrome, or an increased number of bowel movements experience worsened general health compared to NET patients without those characteristics. Optimal management of NET and carcinoid syndrome may significantly improve HRQL among patients with NETs.
Carcinoid lesions by tumor size, multiplicity, invasion of lymph nodes, liver and mesenteric metastases and MP invasion on surgical histopathology Tu2028 Prognostic Features in Patients With Metastatic Neuroendocrine Tumor Undergoing Y-90 Embolization Sarah Soltman, Sunil Amin, Richard R. Warner, Joshua L. Weintraub, Steven H. Itzkowitz, Michelle K. Kim
Tu2026 Stage I and II Follicular Lymphoma With Gastrointestinal Involvement: LongTerm Follow-up of No Initial Therapy Hiroyuki Okada, Katsuyoshi Takata, Yoshiro Kawahara, Masahumi Inoue, Seiji Kawano, Takao Tsuzuki, Masahide Kita, Keisuke Hori, Daisuke Kawai, Sayo Kobayashi, Junichiro Nasu, Tadashi Yoshino, Kazuhide Yamamoto
Background: Neuroendocrine tumors (NETs) are rare neoplasms originating from enterochromaffin cells. NET patients with liver metastases frequently undergo Yttrium-90 (Y90) embolization. Aim: To determine the prognostic features associated with poorer survival in NET patients undergoing Y90 embolization. In particular, we examined the survival benefit of post-procedure changes in the biomarkers chromogranin A (CgA) or serotonin (5-HT). Methods: We performed a retrospective review of 110 patients with metastatic NETs who received Y90 embolization between 2004-2010. Of these, 66 had CgA and or 5-HT values within 6 months before and after the procedure and were the population of interest in this study. Kaplan-Meier methods were used to test survival differences based on biomarker response and other features. Biomarkers were calculated as percent of upper limit of normal of reference values of the test, and the most recent value before the procedure was compared to the lowest value (best biomarker response) in the 6 month period after the procedure. Cox Proportional-Hazard Models were then constructed to control for additional variables. Results: 64% of the patients were male (median age 64 years). The median survival time after the procedure was 18.5 months. The most common primary sites of NET were small bowel (52%), pancreas (21%) and bronchopulmonary system (11%). At the time of Y90 procedure, 40 patients (62%) had extrahepatic metastases and all but one patient were on a somatostatin analog. On Kaplan-Meier analysis, statistically significant predictors of shorter survival time included age ≥65 years (17.3 months mean survival vs. 25.8 mos, p=0.036), and the occurrence of a single Y90 procedure (19.4 months with 1 procedure vs. 30.8 mos for repeat procedure, p=0.037). Neither CgA (p=0.099) nor serotonin (p=0.372) biomarker response was statistically significant, nor was the primary tumor site. After controlling for age, sex, race, and primary tumor site, we found that age at Y90 (hazard ratio 3.00, 95% CI 278.23, p=0.0036) and a higher Ki-67 index (HR 1.76, 95% CI 29.44, p=0.0061) predicted significantly worse survival after Y90 embolization. Conclusions: Patients with metastatic neuroendocrine tumors often undergo multiple procedures including Y90 embolization. Our results suggest that older age and the occurrence of a single Y90 procedure were statistically significant predictors of poorer survival. Neither CgA nor serotonin biomarker response served as prognostic indicators, perhaps due to small sample size. Greater age and higher Ki67 were significant independent predictors of worse survival. Future studies will correlate our biomarker findings with clinical and radiologic assessments.
Objectives: As follicular lymphoma (FLL) with gastrointestinal (GI) tract involvement is an indolent neoplasm, there is no established therapeutic strategy for early stage FLL. The aim of this study was to analyze the outcome of no initial therapy for stages I and II FLL with GI tract involvement in terms of the overall survival (OS), progression-free survival (PFS), time to treatment, incidence and cause of death. Methods: All cases diagnosed as having FLL with GI tract involvement at the time of initial diagnosis were retrieved from our pathological files during the past 14 years. The clinical and pathological data were collected retrospectively. The lesions were staged according to Lugano Staging System. The criteria for selection were patients with stages I and II FLL without initial therapy for at least 6 months after diagnosis and a minimum follow-up of 1 year. Results: Twenty-one patients (10 women and 11 men) were identified (16: stage I, 1: stage II1, 4: stage II2), with a median age of 60 (range: 37-84) years. The sites of GI tract involvement were as follows: the duodenum in 20 patients (17: duodenum alone, 1: duodenum and jejunum, 1: duodenum and terminal ileum, and 1: duodenum and mesenteric lymph nodes); and the stomach and regional lymph nodes in 1 patient. The reasons for no initial therapy were: physician's choice (n= 14), advanced age (n= 2), and patient's refusal (n= 5). During a median follow-up of 76 months, 14 patients (67%) had not been treated. Of these 14 patients with no treatment, complete remission (CR) was achieved in 1, no change (NC) in 12, and progressive disease (PD) in 1. The median time to treatment in the remaining 7 patients with progression of their FLL was 22 months (range: 8 months to 7 years). Among the 7 treated patients, 5 achieved CR after therapy (rituximab in 2; rituximab, cyclophosphamide, oncovin, adriamycin, and prednisolone (R-CHOP) in 3); 1 patient showed NC after R-CHOP; while 1 patient progressed distantly after R-CHOP, transformed to a diffuse large cell lymphoma 6 years after the initial diagnosis , and finally died of progressive lymphoma one year later. The OS rates at 5 and 10 years were 100% and 89%, and the PFS rates at 5 and 10 years were 78% and 54%, respectively. Conclusions: In selected stage I and II FLL patients, deferred therapy in an acceptable option, as more than half of our patients were untreated for at a median of 6 or more years, and long survival was anticipated. A prospective study comparing with immediate treatment of a larger number of cases over a longer period is required to assess the impact of no initial therapy.
AGA Abstracts
S-874
were abdominal pain (6), painless jaundice (5), incidental finding (5) and epigastric soreness (1). Radiological findings of computerized tomography were gallbladder cancer (7), cholangiocarcinoma (5) and ampulla of Vater tumor (6). Initially lymph nodes or other organ metastases were noticed in 9 and 6 patients, respectively. Thirteen patients received curative surgery and 1 experienced palliative cholecystectomy (including 2 who had received operations at outside hospital). Except 2 cases operated at outside hospital, 25% (3/12) had R2 resection margins and there were 5, 7 and 5 patients who had angiolymphatic, venous and perineural invasion within surgical specimen. Eight of 13 patients who had received curative surgery, experienced recurrence and the most common recurrent site was liver (6/8). Median disease free survival of 13 cases was 4.2 (0.4-53.6) months and median overall survival of all patients was 16.8 (1.9-102.1) months. By Cox regression analysis, age and WHO classification was statistically associated with overall survival (p=0.017 and 0.034, respectively) and there was no difference according to tumor location. Conclusion: WHO classification of neuroendocrine tumors in biliary tract was compatible with those in other organs. Further study is necessary for establishing a staging system with neuroendocrine tumors in bile duct or gallbladder.
Tu2027 Jejuno-Ileal Carcinoid Tumors Are Rarely Amenable to Endoscopic Resection Joshua E. Melson, Raja Koteswar Dhanekula, Peter Eichenseer, Abhitabh Patil, Kateri A. Evans, Maisa Abdalla, Shriram Jakate, Sohrab Mobarhan Background: Endoscopic resection of small bowel lesions is increasingly described. The clinical appropriateness of endoscopic mucosal resection (EMR) in jejunoileal carcinoids is not well evaluated. As imaging of the small bowel in obscure gastrointestinal bleeding is advocated increased rates of earlier and incidental jejunoileal carcinoids are likely. In this study we evaluated if endoscopic resection can be applied to jejunoileal carcinoids. Methods: Pathology reports of all patients diagnosed with jejunoileal carcinoids from 1993 to 2009 at Rush University Medical Center were reviewed. We evaluated tumor size, depth of tumor invasion, differentiation, multiplicity, lymph node invasion and distant metastases. Following surgery, patients were identified retrospectively as being amenable to EMR if there was absence of distant metastases, nodal disease and invasion of the tumor into the muscularis propria or multiplicity of carcinoid tumors. Exclusion criteria included liver or distant metastases at time of diagnosis, poor differentiation of carcinoid tumors and presence of adenomatous features in tumor. Results: A total of 32 jejunoileal carcinoid tumors were reviewed for amenability to EMR based on histopathology following surgical intervention. Following surgical pathology review, only 2/32 (6.2%) were considered to be potentially amenable to EMR. The two tumors amenable to EMR were both under 1 cm. None of the 28 tumors ≥1cm was amenable to EMR, as these tumors invariably invaded Muscularis Propria. The rate of lymph node invasion 24/28 (85.7%) was significantly high when tumor size exceeded 1 cm. Multiplicity of tumors occurred in 7/32 (22%) cases. Conclusions: We conclude from this study that size appears to be a key determining factor in deciding which jejunoileal carcinoids should not be considered appropriate for endoscopic resection. EMR of any jejunoileal carcinoid tumor in excess of 1cm would have left residual tumor in 28/ 28 cases and thus should not be attempted. Tumor multiplicity is not uncommon occurring in 7/32 (22%) cases in this series and should be investigated in jejunoileal carcinoids prior to resection. Jejunoileal carcinoids of 1 cm or greater in size in the absence of distant metastases, should be surgically resected with a lymph node resection done since they have a high rate of local regional disease. Small carcinoids of <1cm may or may not be amenable to an endoscopic resection and a prohibitive depth of invasion and multiplicity of tumors need to be considered in this smaller subset of patients. Table A
Tu2025 Characteristics Associated With Health-Related Quality of Life of Patients With Neuroendocrine Tumor (NET) James C. Yao, Jennifer Beaumont, David Cella, Seung Choi, Zhimei Liu, Alexandria T. Phan Introduction: The objective of this study was to evaluate demographic and clinical characteristics associated with health-related quality of life (HRQL) in patients with neuroendocrine tumor (NET). Methods: Patients with NET were invited via email to participate in an online anonymous survey. The survey consisted of two standardized HRQL measures: RAND-36 and PROMIS. In addition, a set of demographic and disease-related questions were included in the survey. General linear models were used to evaluate the associations between HRQL and age, gender, type of NET, years since diagnosis, whether NET has spread to lymph nodes or other part of body, whether NET is currently present in the body, treatment with a somatostatin analog in the past month, presence of carcinoid syndrome, average number of bowel movements per day, and total number of flushing episodes in the past two weeks. Variables with bivariate p < 0.05 were entered into a multivariable model, non-significant variables were removed one at a time, and interaction terms of clinical interest were explored. Results: A total of 663 eligible patients participated in the survey. Of these, 66% were female and 39% were 60 years or older. Mean (median) years since diagnosis with NET was 5 (4) years. One-third (34%) had an average of 4 or more bowel movements per day and 53% experienced at least one flushing episode in the past two weeks. Results from the univariate analysis showed HRQL, as measured by the General Health subscale of the RAND-36, was significantly associated with spread to lymph nodes or other part of body, current presence of tumor, somatostatin analog, carcinoid syndrome, frequency of bowel movements, and flushing episodes. Only spread to other part of body (aside from lymph nodes), current presence of tumor, carcinoid syndrome, and frequency of bowel movements remained significant in the multivariable model (all p<0.01). Conclusion: Patients with current NET, metastases, carcinoid syndrome, or an increased number of bowel movements experience worsened general health compared to NET patients without those characteristics. Optimal management of NET and carcinoid syndrome may significantly improve HRQL among patients with NETs.
Carcinoid lesions by tumor size, multiplicity, invasion of lymph nodes, liver and mesenteric metastases and MP invasion on surgical histopathology Tu2028 Prognostic Features in Patients With Metastatic Neuroendocrine Tumor Undergoing Y-90 Embolization Sarah Soltman, Sunil Amin, Richard R. Warner, Joshua L. Weintraub, Steven H. Itzkowitz, Michelle K. Kim
Tu2026 Stage I and II Follicular Lymphoma With Gastrointestinal Involvement: LongTerm Follow-up of No Initial Therapy Hiroyuki Okada, Katsuyoshi Takata, Yoshiro Kawahara, Masahumi Inoue, Seiji Kawano, Takao Tsuzuki, Masahide Kita, Keisuke Hori, Daisuke Kawai, Sayo Kobayashi, Junichiro Nasu, Tadashi Yoshino, Kazuhide Yamamoto
Background: Neuroendocrine tumors (NETs) are rare neoplasms originating from enterochromaffin cells. NET patients with liver metastases frequently undergo Yttrium-90 (Y90) embolization. Aim: To determine the prognostic features associated with poorer survival in NET patients undergoing Y90 embolization. In particular, we examined the survival benefit of post-procedure changes in the biomarkers chromogranin A (CgA) or serotonin (5-HT). Methods: We performed a retrospective review of 110 patients with metastatic NETs who received Y90 embolization between 2004-2010. Of these, 66 had CgA and or 5-HT values within 6 months before and after the procedure and were the population of interest in this study. Kaplan-Meier methods were used to test survival differences based on biomarker response and other features. Biomarkers were calculated as percent of upper limit of normal of reference values of the test, and the most recent value before the procedure was compared to the lowest value (best biomarker response) in the 6 month period after the procedure. Cox Proportional-Hazard Models were then constructed to control for additional variables. Results: 64% of the patients were male (median age 64 years). The median survival time after the procedure was 18.5 months. The most common primary sites of NET were small bowel (52%), pancreas (21%) and bronchopulmonary system (11%). At the time of Y90 procedure, 40 patients (62%) had extrahepatic metastases and all but one patient were on a somatostatin analog. On Kaplan-Meier analysis, statistically significant predictors of shorter survival time included age ≥65 years (17.3 months mean survival vs. 25.8 mos, p=0.036), and the occurrence of a single Y90 procedure (19.4 months with 1 procedure vs. 30.8 mos for repeat procedure, p=0.037). Neither CgA (p=0.099) nor serotonin (p=0.372) biomarker response was statistically significant, nor was the primary tumor site. After controlling for age, sex, race, and primary tumor site, we found that age at Y90 (hazard ratio 3.00, 95% CI 278.23, p=0.0036) and a higher Ki-67 index (HR 1.76, 95% CI 29.44, p=0.0061) predicted significantly worse survival after Y90 embolization. Conclusions: Patients with metastatic neuroendocrine tumors often undergo multiple procedures including Y90 embolization. Our results suggest that older age and the occurrence of a single Y90 procedure were statistically significant predictors of poorer survival. Neither CgA nor serotonin biomarker response served as prognostic indicators, perhaps due to small sample size. Greater age and higher Ki67 were significant independent predictors of worse survival. Future studies will correlate our biomarker findings with clinical and radiologic assessments.
Objectives: As follicular lymphoma (FLL) with gastrointestinal (GI) tract involvement is an indolent neoplasm, there is no established therapeutic strategy for early stage FLL. The aim of this study was to analyze the outcome of no initial therapy for stages I and II FLL with GI tract involvement in terms of the overall survival (OS), progression-free survival (PFS), time to treatment, incidence and cause of death. Methods: All cases diagnosed as having FLL with GI tract involvement at the time of initial diagnosis were retrieved from our pathological files during the past 14 years. The clinical and pathological data were collected retrospectively. The lesions were staged according to Lugano Staging System. The criteria for selection were patients with stages I and II FLL without initial therapy for at least 6 months after diagnosis and a minimum follow-up of 1 year. Results: Twenty-one patients (10 women and 11 men) were identified (16: stage I, 1: stage II1, 4: stage II2), with a median age of 60 (range: 37-84) years. The sites of GI tract involvement were as follows: the duodenum in 20 patients (17: duodenum alone, 1: duodenum and jejunum, 1: duodenum and terminal ileum, and 1: duodenum and mesenteric lymph nodes); and the stomach and regional lymph nodes in 1 patient. The reasons for no initial therapy were: physician's choice (n= 14), advanced age (n= 2), and patient's refusal (n= 5). During a median follow-up of 76 months, 14 patients (67%) had not been treated. Of these 14 patients with no treatment, complete remission (CR) was achieved in 1, no change (NC) in 12, and progressive disease (PD) in 1. The median time to treatment in the remaining 7 patients with progression of their FLL was 22 months (range: 8 months to 7 years). Among the 7 treated patients, 5 achieved CR after therapy (rituximab in 2; rituximab, cyclophosphamide, oncovin, adriamycin, and prednisolone (R-CHOP) in 3); 1 patient showed NC after R-CHOP; while 1 patient progressed distantly after R-CHOP, transformed to a diffuse large cell lymphoma 6 years after the initial diagnosis , and finally died of progressive lymphoma one year later. The OS rates at 5 and 10 years were 100% and 89%, and the PFS rates at 5 and 10 years were 78% and 54%, respectively. Conclusions: In selected stage I and II FLL patients, deferred therapy in an acceptable option, as more than half of our patients were untreated for at a median of 6 or more years, and long survival was anticipated. A prospective study comparing with immediate treatment of a larger number of cases over a longer period is required to assess the impact of no initial therapy.
AGA Abstracts
S-874