1. Neuroendocrine tumors (NETs) have been increasing in incidence in the United States and Europe over the past few decades according to several studies.
2. NETs are a heterogeneous group of tumors that are characterized through a variety of factors including hormone production, grade, stage, and tumor morphology. Proper characterization is important for determining prognosis and treatment.
3. Treatment options depend on the grade and stage of the NET. Localized, well-differentiated NETs may be treated with surgery alone. For advanced or poorly differentiated NETs, options include chemotherapy, targeted drugs, and control of hormone-related symptoms.
This document summarizes recent advances in the treatment of neuroendocrine tumors. Several new agents have shown promising results in phase II trials, including pasireotide for tumors resistant to octreotide, everolimus combined with octreotide, sorafenib, sunitinib, and temsirolimus. These agents have multiple mechanisms of action and have led to partial responses and prolonged progression-free survival in early studies. While significant progress has been made, treatment of neuroendocrine tumors remains a work in progress as several phase III trials are currently evaluating mTOR and tyrosine kinase inhibitors.
This document provides the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Neuroendocrine and Adrenal Tumors. It was last updated in January 2019 and is authored by an expert panel assembled by NCCN. The guidelines provide evidence-based recommendations for diagnosis, staging, treatment and surveillance of neuroendocrine tumors and adrenal tumors. The key updates from the previous version include expanding the name to include adrenal tumors, preferring gallium-68 dotatate PET/CT for somatostatin receptor imaging, and adding peptide receptor radionuclide therapy with lutetium-177 as a treatment option.
2018 Update on Neuroendocrine neoplasms Nilay Nishith
This document discusses a proposed uniform classification framework for neuroendocrine neoplasms (NENs) presented at a consensus meeting in 2017.
The key points are:
1) A common classification framework was developed to standardize NEN classification across different anatomical sites.
2) NENs are classified into two families: well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC).
3) Parameters like mitosis, Ki-67 index and necrosis are recommended for grading NETs, while NECs are always considered high grade.
4) Site-specific experts provided input on adapting the common framework for different organ systems.
The framework aims
Gastrointestinal-Pancreatic NET managementChandan K Das
1. The document discusses the management of neuroendocrine tumors (NETs), including their definition, classification, diagnostic evaluation, and treatment approaches.
2. NETs are defined and classified based on their histology, grade, and biomarkers like Ki-67 index. Higher grades (G2/G3) have worse survival outcomes than lower grades (G1).
3. Diagnostic evaluation involves biomarkers, imaging modalities, and pathology. Treatment focuses on controlling symptoms, tumor growth, and improving survival through surgery, liver-directed therapies, and somatostatin analogs like octreotide which has been shown to prolong time to progression in midgut NETs.
Takes Guts to be a Neuroendocrine PatientBill Claxton
perspectives on the importance of raising awareness about NETs as well as the challenges a patient faces, and how the World NET Awareness Day campaign may benefit patients
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
Neuroendocrinal tumor of stomach and duodenumanirudha doshi
Multiple Endocrinal Neoplasm (MEN) syndromes are hereditary conditions characterized by tumors in multiple endocrine glands. There are two main types: MEN1, caused by a mutation in the MEN1 gene, and MEN2, caused by a mutation in the RET proto-oncogene. MEN1 is associated with tumors of the parathyroid glands, pancreas, and pituitary gland. MEN2 causes medullary thyroid cancer and other tumors. Gastrointestinal neuroendocrine tumors (NETs) are classified based on location, hormones produced, and grade. Treatment involves surgical removal when possible as well as other approaches depending on tumor characteristics and stage.
This document summarizes recent advances in the treatment of neuroendocrine tumors. Several new agents have shown promising results in phase II trials, including pasireotide for tumors resistant to octreotide, everolimus combined with octreotide, sorafenib, sunitinib, and temsirolimus. These agents have multiple mechanisms of action and have led to partial responses and prolonged progression-free survival in early studies. While significant progress has been made, treatment of neuroendocrine tumors remains a work in progress as several phase III trials are currently evaluating mTOR and tyrosine kinase inhibitors.
This document provides the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Neuroendocrine and Adrenal Tumors. It was last updated in January 2019 and is authored by an expert panel assembled by NCCN. The guidelines provide evidence-based recommendations for diagnosis, staging, treatment and surveillance of neuroendocrine tumors and adrenal tumors. The key updates from the previous version include expanding the name to include adrenal tumors, preferring gallium-68 dotatate PET/CT for somatostatin receptor imaging, and adding peptide receptor radionuclide therapy with lutetium-177 as a treatment option.
2018 Update on Neuroendocrine neoplasms Nilay Nishith
This document discusses a proposed uniform classification framework for neuroendocrine neoplasms (NENs) presented at a consensus meeting in 2017.
The key points are:
1) A common classification framework was developed to standardize NEN classification across different anatomical sites.
2) NENs are classified into two families: well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC).
3) Parameters like mitosis, Ki-67 index and necrosis are recommended for grading NETs, while NECs are always considered high grade.
4) Site-specific experts provided input on adapting the common framework for different organ systems.
The framework aims
Gastrointestinal-Pancreatic NET managementChandan K Das
1. The document discusses the management of neuroendocrine tumors (NETs), including their definition, classification, diagnostic evaluation, and treatment approaches.
2. NETs are defined and classified based on their histology, grade, and biomarkers like Ki-67 index. Higher grades (G2/G3) have worse survival outcomes than lower grades (G1).
3. Diagnostic evaluation involves biomarkers, imaging modalities, and pathology. Treatment focuses on controlling symptoms, tumor growth, and improving survival through surgery, liver-directed therapies, and somatostatin analogs like octreotide which has been shown to prolong time to progression in midgut NETs.
Takes Guts to be a Neuroendocrine PatientBill Claxton
perspectives on the importance of raising awareness about NETs as well as the challenges a patient faces, and how the World NET Awareness Day campaign may benefit patients
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
Neuroendocrinal tumor of stomach and duodenumanirudha doshi
Multiple Endocrinal Neoplasm (MEN) syndromes are hereditary conditions characterized by tumors in multiple endocrine glands. There are two main types: MEN1, caused by a mutation in the MEN1 gene, and MEN2, caused by a mutation in the RET proto-oncogene. MEN1 is associated with tumors of the parathyroid glands, pancreas, and pituitary gland. MEN2 causes medullary thyroid cancer and other tumors. Gastrointestinal neuroendocrine tumors (NETs) are classified based on location, hormones produced, and grade. Treatment involves surgical removal when possible as well as other approaches depending on tumor characteristics and stage.
This document discusses radiopharmaceutical imaging of neuroendocrine tumors. It begins by defining neuroendocrine tumors and their most common sites of origin. It then discusses the radiopharmaceuticals used in imaging NETs, including somatostatin analogues that target somatostatin receptors, catecholamine analogues that target sympathetic nervous system tumors, and FDG that targets glucose metabolism. The document provides examples of different radiopharmaceutical scans and their findings in common NETs like carcinoid tumors, pheochromocytomas, and paragangliomas. It also discusses the added value of SPECT/CT in image interpretation.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
Abstract
OBJECTIVE: Complete surgical resection is the only potentially curative treatment of localized pancreatic neuroendocrine tumors. Unfortunately, a significant proportion of these patients present with unresectable locally advanced tumors or massive metastatic disease. Recently, a new therapeutic approach for this subset of patients has emerged consisting of neoadjuvant therapy followed by surgical exploration in responders.
DESIGN: We searched MEDLINE for the purpose of identifying reports regarding neoadjuvant treatment modalities for advanced pancreatic neuroendocrine tumors.
RESULTS: We identified 12 studies, the vast majority of which were either case reports or small case series. Treatment options included chemotherapy, radiotherapy, peptide receptor radionuclide therapy, biological agents or various combina- tions of them.
CONCLUSIONS: Increasing evidence supports the application of neoadjuvant protocols in advanced pancreatic neuroendocrine tumors aiming at tumor downsizing, thus rendering curative resection feasible. Given that prospective and controlled randomized clini- cal trials from high-volume institutions are not feasible, expert panel consensus is needed to define the optimal treatment algorithm.
This document discusses adjuvant chemotherapy for stage III colon cancer. It summarizes several key studies showing improved disease-free and overall survival when oxaliplatin is added to 5-fluorouracil (5FU) chemotherapy. While all prognostic subgroups appear to benefit, the benefit may be less for older patients. Currently, there are no definitive clinical markers that can identify which stage III colon cancer patients do not benefit from oxaliplatin-based adjuvant therapy. The decision to use oxaliplatin should be individualized based on risk factors and patient preferences.
NIH Presentation Nov 2016 Neuroendocrine Tumor Clinical TrialsCACSNETS
NIH/NCI presentation provides an overview of and NIH clinical trials. Briefing covers: 1) Overview of GI and pancreatic Neuroendocrine Tumors (NETs) /Carcinoid Cancer;
2) Treatment options for patients with advanced GI and pancreatic NETs; 3) Clinical trials for/in patients with NETs
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
This document summarizes a presentation on rare central nervous system (CNS) cancers. It discusses molecular markers in gliomas, treatment with antiangiogenic drugs like bevacizumab, and management of low-grade tumors. It also reviews studies on chemotherapy for recurrent and newly diagnosed low-grade gliomas, ongoing clinical trials, and risks of distant spread with bevacizumab treatment.
1) Adjuvant chemotherapy is recommended for stage III colon cancer and high-risk stage II cancer to reduce the risk of recurrence. 2) For stage III, 5-FU plus folinic acid or capecitabine are standard options, while adding oxaliplatin to these regimens may provide additional benefit. 3) The value of adjuvant therapies like bevacizumab, cetuximab, and irinotecan is still unclear, with studies showing mixed results.
This oral presentation made during ESMO 2016 highlight novel targets and drugs developed for patients with advanced neuroendocrine tumors. This includes targeted agents aiming probing cell signaling in tumor microenvironment and immune responses. Genetic alterations on major anti-oncogenes are reported in the perspective of pathway activations. Combinations using VEGFR, mTOR, Somatostatin receptors inhibitors with novel strategies and immunotherapy are also suggested. This presentation focuses mainly on gastrointestinal neuroendocrine tumors but may also be of interest for those involved in the care of patients with thoracic neuroendocrine tumors.
PSEDM 2019: Thyroid cancer among FilipinosCeciliaJimeno
This document discusses thyroid diseases and malignancies in the Philippines. It provides epidemiological data on thyroid diseases and cancer incidence and mortality rates. It finds that 9% of Filipinos have goiter and 9% have thyroid dysfunction. Thyroid cancer is the 7th most common cancer in the Philippines. Factors that predict malignancy in Filipino thyroid nodules include hard or firm texture, microcalcifications, and irregular margins on ultrasound. Recurrence rates after surgery for differentiated thyroid cancer in the Philippines are high at 33% for papillary and 29% for follicular thyroid cancer.
The document summarizes a study that aimed to predict clinical failure in patients with metastatic prostate cancer by identifying genes related to prostate cancer. Researchers analyzed gene expression levels of androgen receptor, estrogen receptor, and stem cell markers in cancer and stromal cells collected via laser capture microdissection from biopsy samples of 76 patients. Logistic regression analysis showed that expression of Sox2, Her2, and CRP in cancer cells and AR and ER in stromal cells highly predicted prostate-specific antigen recurrence. Ten factors were identified as prognostic for cancer-specific survival, including expression of Oct1, TRIM36, Sox2, c-Myc, AR, Klf4, ER, and clinical parameters. Patients were divided into risk
Presented at the American Society for Clinical Oncology Gastroenterology in January 2017 in San Francisco by Eric Raymond
Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings.
Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing.
Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%).
Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib.
This document discusses prostate cancer and its treatment. It notes that prostate cancer is the second most common cancer in men worldwide and a leading cause of cancer death in developed countries. Key risk factors include increasing age, race (higher rates in black men), and family history. Many patients in the US and Europe present with metastatic disease at diagnosis. Treatment depends on disease stage and symptoms, and may involve hormone therapy, chemotherapy, radiation, or multidisciplinary care. Newer agents like cabazitaxel show promise for treating metastatic castration-resistant prostate cancer after disease progression on docetaxel.
Colorectal cancer - adjuvant Rx - Nicola Tannerwelshbarbers
This document discusses treatment principles for colorectal cancer including histological staging, chemotherapy, surgery, and trials. It covers adjuvant therapies for colon and rectal cancers including chemotherapy with or without radiotherapy. It also discusses neoadjuvant treatments and timelines for administering adjuvant therapies. Key points covered include Dukes staging, 5-year survival rates by stage, aims of adjuvant therapy, and common surgeries for colon and rectal cancers.
1. Lung neuroendocrine tumors (NETs) have been increasing in incidence and include typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC).
2. Diagnosis of lung NETs can be difficult due to non-specific symptoms and frequently involves histopathological examination. Treatment depends on tumor grade and stage.
3. For localized disease, surgery is the primary treatment. For advanced or metastatic NETs, options include somatostatin analogues, targeted therapies like everolimus, chemotherapy, and peptide receptor radionuclide therapy.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
This document discusses treatment options for operable gastric cancer. It notes that surgical resection is currently the only potentially curative treatment, and recommends resection for all non-metastatic cancers. While the optimal extent of lymphadenectomy is still debated, removing a minimum of 15 lymph nodes is recommended. Adjuvant chemotherapy, chemoradiation, and perioperative chemotherapy are strategies that can increase cure rates. Preoperative chemotherapy followed by postoperative chemoradiation may also improve outcomes compared to postoperative treatment alone.
The document summarizes current diagnosis and treatment strategies for neuroendocrine tumors. It discusses the classification and grading of neuroendocrine tumors based on primary tumor site and biomarkers like Ki67. Imaging techniques like octreoscan, MIBG scintigraphy, and PET using tracers like 18F-DOPA and 68Ga-DOTA-octreotide are described. Treatment options discussed include surgery, medical therapies like somatostatin analogs, chemotherapy, targeted radionuclide therapy using 177Lu-DOTA-octreotate and peptide receptor radionuclide therapy.
Presentation by Dr Lim Hwee Yong, Medical Oncologist, National Cancer Centre Singapore, at a NET cancer awareness seminar in Singapore on 20 November 2010.
This document discusses neuroendocrine tumors (NETs) which originate from diffuse endocrine system cells. NETs can occur in the pancreas (e.g. insulinomas, gastrinomas) and gastrointestinal tract (e.g. carcinoid tumors). Diagnosis involves biopsy, imaging and laboratory tests. Treatment options include surgery, somatostatin analogs, interferon alpha and chemotherapy - though surgery offers the best chance of cure if the disease is localized.
This document discusses radiopharmaceutical imaging of neuroendocrine tumors. It begins by defining neuroendocrine tumors and their most common sites of origin. It then discusses the radiopharmaceuticals used in imaging NETs, including somatostatin analogues that target somatostatin receptors, catecholamine analogues that target sympathetic nervous system tumors, and FDG that targets glucose metabolism. The document provides examples of different radiopharmaceutical scans and their findings in common NETs like carcinoid tumors, pheochromocytomas, and paragangliomas. It also discusses the added value of SPECT/CT in image interpretation.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
Abstract
OBJECTIVE: Complete surgical resection is the only potentially curative treatment of localized pancreatic neuroendocrine tumors. Unfortunately, a significant proportion of these patients present with unresectable locally advanced tumors or massive metastatic disease. Recently, a new therapeutic approach for this subset of patients has emerged consisting of neoadjuvant therapy followed by surgical exploration in responders.
DESIGN: We searched MEDLINE for the purpose of identifying reports regarding neoadjuvant treatment modalities for advanced pancreatic neuroendocrine tumors.
RESULTS: We identified 12 studies, the vast majority of which were either case reports or small case series. Treatment options included chemotherapy, radiotherapy, peptide receptor radionuclide therapy, biological agents or various combina- tions of them.
CONCLUSIONS: Increasing evidence supports the application of neoadjuvant protocols in advanced pancreatic neuroendocrine tumors aiming at tumor downsizing, thus rendering curative resection feasible. Given that prospective and controlled randomized clini- cal trials from high-volume institutions are not feasible, expert panel consensus is needed to define the optimal treatment algorithm.
This document discusses adjuvant chemotherapy for stage III colon cancer. It summarizes several key studies showing improved disease-free and overall survival when oxaliplatin is added to 5-fluorouracil (5FU) chemotherapy. While all prognostic subgroups appear to benefit, the benefit may be less for older patients. Currently, there are no definitive clinical markers that can identify which stage III colon cancer patients do not benefit from oxaliplatin-based adjuvant therapy. The decision to use oxaliplatin should be individualized based on risk factors and patient preferences.
NIH Presentation Nov 2016 Neuroendocrine Tumor Clinical TrialsCACSNETS
NIH/NCI presentation provides an overview of and NIH clinical trials. Briefing covers: 1) Overview of GI and pancreatic Neuroendocrine Tumors (NETs) /Carcinoid Cancer;
2) Treatment options for patients with advanced GI and pancreatic NETs; 3) Clinical trials for/in patients with NETs
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
This document summarizes a presentation on rare central nervous system (CNS) cancers. It discusses molecular markers in gliomas, treatment with antiangiogenic drugs like bevacizumab, and management of low-grade tumors. It also reviews studies on chemotherapy for recurrent and newly diagnosed low-grade gliomas, ongoing clinical trials, and risks of distant spread with bevacizumab treatment.
1) Adjuvant chemotherapy is recommended for stage III colon cancer and high-risk stage II cancer to reduce the risk of recurrence. 2) For stage III, 5-FU plus folinic acid or capecitabine are standard options, while adding oxaliplatin to these regimens may provide additional benefit. 3) The value of adjuvant therapies like bevacizumab, cetuximab, and irinotecan is still unclear, with studies showing mixed results.
This oral presentation made during ESMO 2016 highlight novel targets and drugs developed for patients with advanced neuroendocrine tumors. This includes targeted agents aiming probing cell signaling in tumor microenvironment and immune responses. Genetic alterations on major anti-oncogenes are reported in the perspective of pathway activations. Combinations using VEGFR, mTOR, Somatostatin receptors inhibitors with novel strategies and immunotherapy are also suggested. This presentation focuses mainly on gastrointestinal neuroendocrine tumors but may also be of interest for those involved in the care of patients with thoracic neuroendocrine tumors.
PSEDM 2019: Thyroid cancer among FilipinosCeciliaJimeno
This document discusses thyroid diseases and malignancies in the Philippines. It provides epidemiological data on thyroid diseases and cancer incidence and mortality rates. It finds that 9% of Filipinos have goiter and 9% have thyroid dysfunction. Thyroid cancer is the 7th most common cancer in the Philippines. Factors that predict malignancy in Filipino thyroid nodules include hard or firm texture, microcalcifications, and irregular margins on ultrasound. Recurrence rates after surgery for differentiated thyroid cancer in the Philippines are high at 33% for papillary and 29% for follicular thyroid cancer.
The document summarizes a study that aimed to predict clinical failure in patients with metastatic prostate cancer by identifying genes related to prostate cancer. Researchers analyzed gene expression levels of androgen receptor, estrogen receptor, and stem cell markers in cancer and stromal cells collected via laser capture microdissection from biopsy samples of 76 patients. Logistic regression analysis showed that expression of Sox2, Her2, and CRP in cancer cells and AR and ER in stromal cells highly predicted prostate-specific antigen recurrence. Ten factors were identified as prognostic for cancer-specific survival, including expression of Oct1, TRIM36, Sox2, c-Myc, AR, Klf4, ER, and clinical parameters. Patients were divided into risk
Presented at the American Society for Clinical Oncology Gastroenterology in January 2017 in San Francisco by Eric Raymond
Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings.
Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing.
Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%).
Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib.
This document discusses prostate cancer and its treatment. It notes that prostate cancer is the second most common cancer in men worldwide and a leading cause of cancer death in developed countries. Key risk factors include increasing age, race (higher rates in black men), and family history. Many patients in the US and Europe present with metastatic disease at diagnosis. Treatment depends on disease stage and symptoms, and may involve hormone therapy, chemotherapy, radiation, or multidisciplinary care. Newer agents like cabazitaxel show promise for treating metastatic castration-resistant prostate cancer after disease progression on docetaxel.
Colorectal cancer - adjuvant Rx - Nicola Tannerwelshbarbers
This document discusses treatment principles for colorectal cancer including histological staging, chemotherapy, surgery, and trials. It covers adjuvant therapies for colon and rectal cancers including chemotherapy with or without radiotherapy. It also discusses neoadjuvant treatments and timelines for administering adjuvant therapies. Key points covered include Dukes staging, 5-year survival rates by stage, aims of adjuvant therapy, and common surgeries for colon and rectal cancers.
1. Lung neuroendocrine tumors (NETs) have been increasing in incidence and include typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC).
2. Diagnosis of lung NETs can be difficult due to non-specific symptoms and frequently involves histopathological examination. Treatment depends on tumor grade and stage.
3. For localized disease, surgery is the primary treatment. For advanced or metastatic NETs, options include somatostatin analogues, targeted therapies like everolimus, chemotherapy, and peptide receptor radionuclide therapy.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
This document discusses treatment options for operable gastric cancer. It notes that surgical resection is currently the only potentially curative treatment, and recommends resection for all non-metastatic cancers. While the optimal extent of lymphadenectomy is still debated, removing a minimum of 15 lymph nodes is recommended. Adjuvant chemotherapy, chemoradiation, and perioperative chemotherapy are strategies that can increase cure rates. Preoperative chemotherapy followed by postoperative chemoradiation may also improve outcomes compared to postoperative treatment alone.
The document summarizes current diagnosis and treatment strategies for neuroendocrine tumors. It discusses the classification and grading of neuroendocrine tumors based on primary tumor site and biomarkers like Ki67. Imaging techniques like octreoscan, MIBG scintigraphy, and PET using tracers like 18F-DOPA and 68Ga-DOTA-octreotide are described. Treatment options discussed include surgery, medical therapies like somatostatin analogs, chemotherapy, targeted radionuclide therapy using 177Lu-DOTA-octreotate and peptide receptor radionuclide therapy.
Presentation by Dr Lim Hwee Yong, Medical Oncologist, National Cancer Centre Singapore, at a NET cancer awareness seminar in Singapore on 20 November 2010.
This document discusses neuroendocrine tumors (NETs) which originate from diffuse endocrine system cells. NETs can occur in the pancreas (e.g. insulinomas, gastrinomas) and gastrointestinal tract (e.g. carcinoid tumors). Diagnosis involves biopsy, imaging and laboratory tests. Treatment options include surgery, somatostatin analogs, interferon alpha and chemotherapy - though surgery offers the best chance of cure if the disease is localized.
1) The document discusses the role of targeted therapy in neuroendocrine tumors. It covers topics such as the evolution of terminology and classification of NETs, the use of biomarkers and imaging in diagnosis and monitoring, and current therapeutic approaches including somatostatin analogs.
2) Somatostatin analogs like octreotide and lanreotide are effective in controlling hormonal symptoms in NET patients by binding to somatostatin receptors that are prevalent on many NETs. They have also shown inhibitory effects on tumor proliferation.
3) A phase III study showed octreotide LAR extended time to tumor progression compared to placebo in treatment-naïve patients with well-differentiated midgut NETs
This document discusses pulmonary neuroendocrine tumors (NETs). It begins by explaining that lung cancer is the leading cause of cancer death worldwide and smoking is the primary risk factor. It then discusses the four main types of lung NETs: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), typical carcinoid (TC), and atypical carcinoid (AC). SCLC grows and spreads the fastest while TC spreads the slowest. The document examines different classification systems for NETs and highlights issues with inconsistencies. Pathologists examine cells under microscopy to classify the specific tumor and determine a diagnosis and prognosis.
Lung - Large Cell Neuroendocrine CarcinomaHazem Ali
Large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive type of lung cancer that comprises less than 3% of primary lung tumors. It resembles non-small cell lung carcinoma cytologically but displays neuroendocrine architecture. LCNEC is associated with smoking and tends to widely spread in the lungs. Patients typically have a poor prognosis with 5-year survival rates of only 20% and treatment involves chemotherapy rather than surgery. Pathologically, LCNEC demonstrates organoid and trabecular growth patterns with large cells, prominent nucleoli, high mitotic rates, and necrosis. Immunohistochemistry staining helps establish the neuroendocrine nature of the tumor by labeling for markers like chromogranin, synaptophys
Tumors of lung with its 2015 WHO classification along with cytological evidences to rule out various differential diagnosis. The difference between small biopsy and resected specimen terminology has been briefed in a precise manner.
Recent advances in lung tumors and tumor like lesionsEkta Jajodia
This document summarizes recent advances in lung tumors and tumor-like lesions. It discusses the WHO classification of common lung cancers including squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and carcinoid tumors. It also reviews tumor-like lung lesions and the IASLC/ATS/ERS classification of lung adenocarcinoma. Molecular subtypes of lung cancer characterized by mutations in genes such as EGFR, KRAS, ALK are described. Guidelines for molecular testing to select patients for targeted therapy are provided.
This document discusses imaging of gastroenteropancreatic neuroendocrine tumors. It covers pathology, diagnosis and staging of tumors in the pancreas and small bowel using various imaging modalities like CT, MRI, EUS. Tumors are classified based on grade and stage. Characteristic features on CT and MRI include arterial phase enhancement and appearance on T2-weighted MRI sequences. Imaging helps in local staging, detecting metastases, and monitoring response to treatment. A multidisciplinary approach is important for management.
This document provides a summary of neuroendocrine tumors (NETs):
- NETs arise from neuroendocrine cells throughout the body and can be functional or nonfunctional. Gastroenteropancreatic NETs are the most prevalent.
- NET incidence has increased 5-fold over the past 30 years. They are often advanced at diagnosis due to nonspecific symptoms and long diagnostic delays.
- Treatment options include surgery, chemotherapy, targeted therapies like somatostatin analogues, interferon, and newer agents inhibiting angiogenesis and mTOR pathways. Clinical trials are evaluating these targeted agents.
- The PI3K/Akt/mTOR pathway is frequently deregulated in cancers including NETs and represents a
The document discusses neuroendocrine tumours (NETs), including their epidemiology, histology, classification, molecular pathogenesis, syndromes associated with NETs, and details specific neuroendocrine tumours like insulinomas, gastrinomas, their diagnosis and treatment. NETs originate from neuroendocrine cells in the gastrointestinal tract and other organs and can secrete hormones. Diagnosis and treatment of functional NETs depends on identifying the syndrome caused by hormone secretion and controlling the clinical effects.
This document discusses neuroendocrine tumors (NETs), which arise from neuroendocrine cells derived from neural crest cells. NETs were previously called APUDomas and carcinoids but are now classified as neuroendocrine gastroenteropancreatic tumors. Specific NETs discussed include insulinomas, glucagonomas, gastrinomas, vipomas, and somatostatinomas. Diagnosis and treatment options are described for each tumor type. The document also covers carcinoid syndrome, typical and atypical carcinoid tumors, and treatment approaches for NETs such as surgery, medical therapy, peptide receptor radionuclide therapy, and hepatic artery embolization.
Carcinoid tumors arise from neuroendocrine cells in the gastrointestinal tract. They most commonly occur in the appendix, ileum, and rectum. While often asymptomatic, they may secrete serotonin and cause carcinoid syndrome in rare cases. Diagnosis involves urinary tests for serotonin metabolites and imaging exams. Treatment of localized tumors is surgical resection, while metastatic tumors may also require chemotherapy. Prognosis is generally good if the tumor is localized but worsens with increased size and spread.
The document discusses pancreatic neuroendocrine tumors. It covers types like insulinomas, gastrinomas, vipomas, glucagonomas, and somatostatinomas. For each type it discusses incidence, location, clinical features, diagnostic tests, management options like surgery or medication, and prognosis. It also covers non-functional pancreatic neuroendocrine tumors and tumors associated with MEN1 syndrome. Surgical resection is the primary treatment when possible but some types are often metastatic at diagnosis.
This document discusses neuroendocrine tumors (NETs). It begins with disclosing the speaker's relationships with various pharmaceutical companies. It then outlines some of the challenges in diagnosing and treating NETs, which are rare tumors that can occur in many locations. The document discusses the increasing incidence of NETs and covers their pathology, classification, biomarkers, and imaging. It notes that metastatic disease is common at initial presentation for many patients. Finally, it briefly discusses the goals and options for therapy in advanced NETs, including symptom control and cytotoxic therapy.
This document provides information on pancreatic neuroendocrine tumors (NETs). It discusses that NETs arise from cells that produce and secrete hormones. The pancreas is a common site of origin for NETs. NETs are typically slow growing but can metastasize. Classification systems take into account factors like origin, characteristics, behavior, grade, and stage. The WHO classification defines NETs based on differentiation, metastases, Ki-67 index, invasion and other criteria. Pancreatic NETs (pNETs) are rare but increasing in incidence. pNETs may or may not cause symptoms through hormone secretion. Common pNET types include insulinomas, gastrinomas, and non-functional tumors. Nonspecific
1) A phase 3 trial compared nivolumab to everolimus in advanced renal cell carcinoma patients who had received 1-2 prior anti-angiogenic therapies. Nivolumab demonstrated significantly longer overall survival compared to everolimus, with median overall survival of 25 months versus 19.6 months.
2) Nivolumab had a higher objective response rate compared to everolimus (25% vs 5%) and longer median duration of response.
3) The overall survival benefit of nivolumab was consistent across patient subgroups and was independent of PD-L1 expression levels.
This document summarizes the state of the art in head and neck cancer treatment. It discusses epidemiology, risk factors, staging, treatment modalities including surgery, radiotherapy, chemotherapy, targeted therapy. It highlights recent findings like the role of HPV and molecular targeted agents. It also discusses the benefits of concurrent chemoradiation compared to radiotherapy alone as well as induction chemotherapy followed by chemoradiation for locally advanced disease.
Chair, David M. O'Malley, MD, Ana Oaknin, MD, PhD, and Matthew A. Powell, MD, prepared useful Practice Aids pertaining to endometrial cancer for this CME/MOC/AAPA activity titled “Endometrial Cancer Care in the Age of Immunotherapy: Translating Clinical Evidence Into Meaningful Improvements in Patient Outcomes Across the Disease Continuum.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40bmalK. CME/MOC/AAPA credit will be available until July 3, 2024.
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
The document summarizes current standards and next steps in treating gastric cancer. It discusses how adjuvant chemotherapy and neoadjuvant/perioperative chemotherapy have been shown to improve survival rates compared to surgery alone, increasing 5-year survival by 5-10% and 18% risk reduction respectively. However, tolerance of adjuvant treatments is often poor with high rates of delays, reductions and early termination. Neoadjuvant chemotherapy is better tolerated and may improve R0 resection rates and survival, as supported by several randomized clinical trials.
The document summarizes current standards and next steps in treating gastric cancer. It discusses trends showing falling incidence of distal gastric cancer but rising incidence of proximal gastric cancer. It reviews primary staging procedures and treatments for gastric cancer including surgery, adjuvant treatments, and treatments for advanced cases. It provides evidence that adjuvant chemotherapy and perioperative chemotherapy can increase overall survival rates compared to surgery alone.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
Roy H. Decker, MD, PhD, and Sarah B. Goldberg, MD, MPH, prepared useful practice aids pertaining to lung cancer for this CME activity titled "The Era of Immunotherapy in Stage III NSCLC: Exploring the Evidence and Practicalities of Integrating Checkpoint Inhibition Into the Multimodal Treatment Arsenal." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2PU3iaZ. CME credit will be available until December 6, 2019.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
The document discusses treatment options for a 66-year-old man from Nigeria diagnosed with locally advanced head and neck squamous cell carcinoma. The man was treated initially with induction chemotherapy consisting of a PF regimen, followed by concurrent chemoradiation with gemcitabine and radiotherapy, achieving a partial response. The document then outlines general treatment modalities and strategies for locoregionally advanced head and neck cancer.
The document discusses treatment options for a 66-year-old man from Nigeria diagnosed with locally advanced head and neck squamous cell carcinoma. The man was treated initially with induction chemotherapy consisting of a PF regimen, followed by concurrent chemoradiation with gemcitabine and radiotherapy, achieving a partial response. The document then outlines general treatment modalities and strategies for locoregionally advanced head and neck cancer.
The document describes a case study of a 72-year-old male patient with metastatic gastric cancer who showed a partial response after 20 months of treatment with pembrolizumab immunotherapy, with reduction in tumor size of multiple lesions of over 70%. It then reviews the KEYNOTE-012 trial which found that pembrolizumab achieved an objective response rate of 33% in patients with advanced gastric cancer. Ongoing trials are investigating nivolumab as a potential treatment for gastric cancer patients who have progressed on two or more prior chemotherapy regimens.
C:\Documents And Settings\User\Desktop\Head And NeckGamal Abdul Hamid
This document summarizes recent advances in the treatment of head and neck cancer. It discusses the incidence, risk factors, staging, and historical treatment approaches including chemotherapy and chemoradiation. Recent randomized trials show improved outcomes with induction taxane-based chemotherapy followed by chemoradiation compared to chemotherapy and radiation alone. Ongoing trials are further exploring the benefits of induction chemotherapy prior to definitive treatment.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
This document discusses adrenal cortical carcinoma (ACC), a rare but aggressive form of cancer. It provides information on the epidemiology, clinical presentation, prognostic factors, treatment approaches including mitotane and chemotherapy, and clinical trials for ACC. Recent studies have found that achieving mitotane plasma levels above 14 mg/L within 3 months of treatment and maintaining these levels is associated with better outcomes for patients with ACC. Larger international collaborations are working to advance the treatment of this disease.
The document summarizes a clinical trial comparing FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) to gemcitabine as first-line treatment for metastatic pancreatic cancer. The trial showed FOLFIRINOX resulted in significantly higher response rates, longer progression-free survival and overall survival, though it also had more grade 3/4 adverse events. Based on these results, the document concludes FOLFIRINOX is a new standard first-line treatment for patients with good performance status.
The document summarizes a clinical trial comparing FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) chemotherapy to gemcitabine for treatment of metastatic pancreatic cancer. The trial showed that FOLFIRINOX resulted in significantly higher response rates and longer progression-free and overall survival compared to gemcitabine. FOLFIRINOX is now considered a new standard first-line treatment for metastatic pancreatic cancer, despite its greater toxicity requiring careful patient selection and management.
This document discusses adjuvant and neoadjuvant therapy for colon cancer. It presents two case studies of patients with colon cancer and discusses their prognosis and treatment options based on their postoperative biopsy results and stage. It then compares prognosis and treatment for stage II versus stage III colon cancer. The document also discusses international clinical trials evaluating different adjuvant chemotherapy regimens and their benefits and toxicities. It addresses recommendations for adjuvant chemotherapy in elderly patients with stage III colon cancer.
The document summarizes clinical updates and advances in the treatment of non-small cell lung cancer (NSCLC). It discusses the incidence, subtypes and staging of NSCLC and recommendations for adjuvant therapy, targeted therapy and treatment of metastatic disease. It also reviews results from randomized trials of adjuvant chemotherapy showing improved survival compared to observation alone.
Similar to Rare Solid Cancers: An Introduction - Slide 14 - E. Baudin - Neuroendocrine tumors (20)
1) The study examines how and why certain breast cancer cells metastasize to bone through a "seed pre-selection" process.
2) It finds that high Src activity (denoted by a "Src activity signature" or SRS) in primary tumors associates with bone metastasis.
3) In ER-/ERBB2- breast cancers, cytokines CXCL12 and IGF1 in the tumor microenvironment activate Src which promotes cell survival and bone metastasis. Long term exposure to these cytokines in vitro selects for breast cancer cells with higher Src activity and bone metastatic ability.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
This document summarizes the management of urinary bladder cancer. It discusses staging, histopathologic types, and treatment options for non-muscle invasive and muscle invasive bladder cancer as well as metastatic disease. Standard first-line chemotherapy for metastatic bladder cancer includes gemcitabine and cisplatin or MVAC. Newer chemotherapy regimens and agents are also discussed.
The document discusses new drugs for the treatment of lymphomas. It outlines several monoclonal antibodies that target antigens on B-cells, including CD20, CD19, CD22 and CD37. Ofatumumab and GA-101 are new anti-CD20 monoclonal antibodies that exhibit enhanced binding and cell-killing properties compared to Rituximab. Inotuzumab Ozogamicin is an antibody-drug conjugate targeting CD22 that is internalized and releases a cytotoxic drug, showing promising activity in early clinical trials.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy improves outcomes for DLBCL compared to chemotherapy alone. Strategies discussed to improve outcomes include increasing chemotherapy dose intensity and the potential role of the drug bortezomib for the activated B-cell subtype.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy like CHOP has improved outcomes for DLBCL compared to chemotherapy alone in the post-rituximab era. Strategies to further improve outcomes include targeting specific genetic subgroups like the activated B-cell subtype using drugs like bortezomib that inhibit pathways like NF-kB.
The document discusses the current state of cancer vaccines, focusing on HPV vaccines. It outlines the types of vaccines as prophylactic, preventive, or therapeutic. HPV vaccines have proven highly effective as prophylactic vaccines in preventing cervical cancer. Clinical trials demonstrated up to 100% efficacy of the HPV vaccines Gardasil and Cervarix in preventing precancerous lesions. However, challenges remain regarding cross-protection against other HPV types, long-term duration of protection, and reducing production costs to increase global access.
- Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in women. Risk factors include age over 60, obesity, talcum powder use, fertility drugs, genetic predispositions like BRCA mutations.
- Surgical staging is essential for determining prognosis and appropriate treatment. For early stage disease adjuvant chemotherapy is recommended. Advanced stage disease is treated with cytoreductive surgery followed by platinum/taxane chemotherapy.
- Prognosis depends on stage and completeness of cytoreduction. Median survival is 39 months for optimal vs 17 months for suboptimal cytoreduction. Secondary surgery and chemotherapy may provide benefit for recurrence in some patients.
This document summarizes key information about ovarian cancer, including epidemiology, staging, treatment milestones, prognostic factors, and recent clinical trials. It notes that the median age of diagnosis is 63 years and discusses improvements in 5-year survival over time. New developments discussed include the role of surgery, chemotherapy regimens, targeted therapies like bevacizumab, and trials in recurrent settings.
Nearly 500,000 new cases of cervical cancer occur worldwide each year, with the majority in developing countries. Infection with HPV is responsible for virtually all cervical cancer cases. Screening includes Pap smears and HPV testing, while vaccination may prevent up to 70% of cases but is not widely available due to cost. Diagnosis is through biopsy and histopathological examination, while staging uses the FIGO system based on tumor size and spread. Treatment depends on stage but commonly includes surgery such as hysterectomy with or without radiation or chemotherapy.
- Cervical cancer is a major cause of cancer deaths worldwide, with over 500,000 new cases and 260,000 deaths estimated annually. Most deaths occur in developing countries where screening and prevention programs are lacking.
- Early detection through screening programs can make cervical cancer highly curable, but the majority of cases in developing nations are diagnosed at late stages when survival rates are low. Vaccination and screening can help prevent a large percentage of cervical cancer cases.
- Risk factors for cervical cancer include human papillomavirus infection and lack of access to healthcare. While HPV infection is necessary, most infections clear without causing cancer. Other factors like multiple pregnancies, smoking, and HIV infection can increase the risk.
The document summarizes the current state of metastatic breast cancer treatment. It discusses how survival rates have improved over time and metastatic breast cancer is now considered a chronic, treatable disease rather than an immediately terminal condition. Treatment involves systemic therapies like chemotherapy, endocrine therapy, targeted therapies, as well as radiation, surgery, and supportive care. Selection of optimal first-line systemic treatment depends on disease characteristics and patient factors. Ongoing research focuses on tailoring and sequencing treatments to overcome resistance and further extend patient survival and quality of life.
1) Breast cancer is heterogeneous with different subtypes defined by receptor status and gene expression profiles. The subtypes have different biological behaviors and clinical outcomes.
2) Accurate diagnosis requires biopsy (FNA or core) followed by receptor testing before treatment decisions. Surgery options include breast conserving therapy or mastectomy with/without reconstruction.
3) For early breast cancer, sentinel lymph node biopsy guides the need for further axillary lymph node dissection. Omission of further dissection may be adequate for sentinel node positive patients.
- The document discusses liver and hepatobiliary cancers, focusing on hepatocellular carcinoma (HCC). It covers the epidemiology, risk factors, screening and diagnosis of HCC as well as staging systems and treatment options.
- Risk factors for HCC include hepatitis B and C infection, alcohol consumption, and aflatoxin intake. Screening ultrasound and AFP tests are used for early diagnosis in high-risk patients. The BCLC staging system guides treatment which includes resection, transplantation, ablation, and embolization.
- For intermediate stage HCC, transarterial chemoembolization provides the best outcomes, with 70-80% of patients surviving 1 year and 50% surviving 3 years. However
The document discusses guidelines for screening, diagnosis, staging, adjuvant therapy, advanced disease treatment, and follow-up for colorectal cancer from both the ESMO and NCCN perspectives. It provides recommendations for screening the general and high-risk populations. It also outlines the diagnostic and staging workup, including endoscopy, biopsy, imaging, and surgical staging. Guidelines are presented for adjuvant therapy based on cancer stage. Recommendations are provided for managing both synchronous and metachronous metastatic disease, as well as rectal cancer treatment.
1) A trial found that adding bevacizumab to chemotherapy for stage III colon cancer extended disease-free survival compared to chemotherapy alone, delaying cancer relapse but not preventing it completely.
2) There was no overall survival benefit observed from adding bevacizumab, suggesting it delays but does not alter the underlying biology of the disease.
3) The interpretation is that relapses were delayed by bevacizumab treatment but then occurred at a steady rate later on, similar to the chemotherapy alone group.
This document provides an overview of squamous cell carcinoma of the head and neck (SCCHN), including its anatomical sites, incidence and mortality rates, risk factors, staging guidelines, and treatment approaches. It discusses the roles of surgery, radiation therapy, chemotherapy, concurrent chemoradiation, and targeted therapies like cetuximab in managing localized and advanced SCCHN. Concurrent chemoradiation is now standard for improving local control and organ preservation compared to radiation alone. The addition of cetuximab to radiation was shown to improve locoregional control and overall survival.
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
Rare Solid Cancers: An Introduction - Slide 14 - E. Baudin - Neuroendocrine tumors
1. Neuroendocrine tumors : introduction E.Baudin Endocrine oncology - Reference center Institut Gustave Roussy Villejuif France
2. US and European Incidence of NETs 2000–2004 1983–1998 1989–1996 1993–2004 1974–1997 1985–1991 Study Period: 1. Yao JC, Hassan M, Phan A, et al. J Clin Oncol . 2008;26:3063-3072. 2. Taal BG, Visser O. Neuroendocrinology . 2004;80(suppl 1):3-7. 3. Hauso O, Gustafsson BI, Kidd M, et al. Cancer. 2008;113:2655-2664. Incidence Rates Per 100,000 0.0 2.0 4.0 6.0 8.0 US 1 (SEER) Netherlands 2 Sweden 2 Men Women Italy 2 (Tuscany) Switzerland 2 (Vaud) Norway 3 Country: SEER = Surveillance, Epidemiology, and End Results (for malignant NETs)
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4. NET : various terminologies but a simple definition Endocrine Tumors Others : gastrinomas, insulinomas ….. Endocrine morphology Positive Chromogranine A / Synaptophysine / CD 56 … staining
5. Yao J et al. JCOC 2008, Hauso O et al. Cancer 2008 : SEER (US, 17312 pts) and NRC (Norway, 2030 pts) from 1993 to 2004 NET : a network of tumors
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8. Functioning NET are characterized by hormone-related symptoms at diagnosis : dedicated management required O’Toole et al. Neuroendocrinology 2009 : measure Chromogranine A in all cases, and additional markers or tests depending on patients’ history (insulinomas, gastrinomas, Cushing Syndrome) 5-HIAA Glucagon ACTH, UFC
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10. WHO 2000/10 of NET WHO Lung 2000 Digestive 2010 Well differentiated 1.Typical carcinoid 2.Atypical carcinoid 1. Neoplasm, Grade1 2. Neoplasm, Grade2 Poorly Differentiated 3.Large cell 4.Small cell 3.Carcinoma, large or small cell, Grade 3
11. Travis et al. Am J Surg Pathol 1998 : analysis of 200 bronchial ET WHO classification of lung NET is prognostic Typical carcinoid < 2 mitoses/10 GC no necrosis Atypical Carcinoid >= 2-10 mitoses/ 10 GC no,punctiform necrosis 87% 35% Poorly different. EC cell size : large/small >10 mitoses/ 10 GC large necrosis 9% Well differentiated Poorly differentiated
12. Digestive NET : tumour Grade and Survival 1. Rindi G, Klöppel G, Alhman H, et al. Virchows Arch . 2006;449:395-401. 2. Rindi G, Klöppel G, Couvelard A, et al. Virchows Arch. 2007;451:757-762. 3. Pape UF, Jann H, Müller-Nordhorn J, et al. Cancer. 2008;113:256-265. 0 50 100 150 200 250 Survival Time (mo) 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative Survival G1 G2 G3 G1 vs G2 G1 vs G3 G2 vs G3 P =0.040 P <0.001 P <0.001 *ENETS and AJCC grading system N=193 Grade* Mitotic count (10 HPF) Ki67 index (%) G1 <2 ≤ 2 G2 2-20 3-20 G3 >20 >20
13. pTNM staging for lung cancer T based on : Size Nodules same lobe (T3) or side (T4) Invasion (T3) / Extension (T4) N1 : peribronchial/hilar N2 : mediastinum N3 : supraclavicular/controlateral M1 includes controlateral nodules Travis WD et al. JTO 2008 Stage T N M IA IB T1 T2a N0 N0 M0 M0 IIA IIB T1-2a T2b-3 N1 N0 M0 M0 IIIA IIIB T1-2 T3- 4 N2 N3 M0 M0 IV _ _ M1
14. NET : pTNM – ENET classification T: size, local spread N : N1/N analyzed (>12) Stade T N-regional M I T1 N0 M0 II T2-3 N0 M0 III T4 - N0 N1 M0 M0 IV - - M1(N1 distal)
15. NET : pTNM – ENET classification T: size, local spread N : N1/N analyzed (>12) NEW UICC TNM CLASSIFICATION 2010 = ENET 2010 but pancreas, appendix Stade T N-regional M I T1 N0 M0 II T2-3 N0 M0 III T4 - N0 N1 M0 M0 IV - - M1(N1 distal)
20. NET therapy Poorly differentiated NEC WHO classification Hormone-related symptoms Well differentiated NEC
21. Control of Hormone-related symptoms Treat before and or during surgery : Akerström G et al Neuroendocrinology 2009 >7O% of NET express somatostatin receptors, most patients are responders Hormone-related syndromes First line Additional therapies for Gastrinoma Proton Pump Inhibitors - Insulinoma Diazoxid Glucose Glucagonoma SMS analogs Nutritional status, diabetes, thrombosis VIPoma SMS analogs Hydratation ,HypoK Cushing Various Diabetes, HTA, HypoK,decreased BMD Carcinoid SMS analogs Right-sided heart dysfct, Diarrhea, nutritional status Acromegalic SMS analogs Diabetes
22. NET therapy Poorly differentiated NEC WHO classification Hormone-related symptoms Well differentiated NET
23. NET therapy Poorly differentiated NEC WHO classification Hormone-related symptoms Well differentiated NET Localized Stage I-III
24. NET staging by imaging combined CT/MRI and scintigraphy Dromain C et al JCO 2005 PET/SPECT somatostatin receptor scintigraphy or PET FDG
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26. NET therapy Poorly differentiated NEC WHO classification Hormone-related symptoms Well differentiated NET Localized Stage I-III Diffuse Stage III-IV Surgery / Survey No adjuvant therapy
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30. Octreotide LAR improves time to progression (PROMID study) in good prognostic metastatic well differentiated digestive NET TTP SDSLAR Placebo OR 1 1 S 28 16 P 10 23 SSP 6m 66% 37% Ongoing-phase III : Lanreotide versus Placebo Rinke A et al. JCO 2009 : 40% functioning, 95% Ki67<2%, 75% liver involvement < 10% / centralized imaging and WHO criteria Octreotide LAR vs placebo HR=0.34 P =0.000072 [95% CI: 0.20–0.59] Octreotide LAR (42) : Median 14.3 months Placebo (43) : Median 6.0 months Time (months) Proportion without progression 0 0.25 0.5 0.75 1 0 6 12 18 24 30 36 42 48 54 60 66 72 78
31. Comparable antitumor effect of somatostatin analogs and or interferon Randomized studies in patients with progressive tumors J Clin Oncol 2003 (1) ; Clin Gastroenterol Hepato 2005 (2) n Duration PR and SD FAISS S Progressive over 3 months LAN 1 mg x 3/d SC 25 1 yr 32% NS IFN 5 mUx3/sem SC 27 30% LAN+IFN 28 25% ARNOLD R Progressive WHO OCT 200µg x 3/j SC 51 1 yr , till progression 17% OCT+IFN 4.5 millionU x 3/sem sc 54 24% NS
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33. Chemotherapy in unresectable Islet Cell Carcinoma : DXR-STZ a standard that remains to be validated TTP OS Moertel et al NEJM 1992 : old WHO criteria, unknown progressive status 17% OR as second line DXR-STZ 5Fu-STZ CZT OR 69% 45% 39% PFS m 18 14 17 OS yr 2.2 1.5 1.4
34. Chemotherapy in unresectable Islet Cell Carcinoma : DXR-STZ a standard that remains to be validated TTP OS Moertel et al NEJM 1992 : old WHO criteria, unknown progressive status 17% OR as second line STZ-DXR regimen for pancreatic WD NEC : objective response rate between 6-36% with a duration of 9-19 months in the litterature DXR-STZ 5Fu-STZ CZT OR 69% 45% 39% PFS m 18 14 17 OS yr 2.2 1.5 1.4
35. Before treatment After treatment ENET recommendations : DXR or 5Fu- STZ for metastatic Well diff pancreatic NET Dacarbazine as second line Chemotherapy not recommend for other primaries Eriksson b et al Neuroendocrinology 2009 Pancreatic NET is relatively chemosensitive
36. Pancreas well differentiated metastatic neoplasms : other or new polychemotherapy WHO or RECIST except * STUDY N OR DURATION MEDIANE Eriksson 1990* 5Fu-STZ / 3 wks Retrospective study 19/ 1st line 31% - Bukowski 1992 * 5Fu-CTZ / 6 wks P II 44 32% 11 Beretta 2006 XELOX , P II progressive 11 27 % - Isacoff ASCO 2006 CAPE-TMZ Retrospective study 33 ? 67% 18 ? Strosberg ASCO 2009 CAPE-TMZ Retrospective study Prog ? 17/ 1st line 71% 12 + Cassier 2009 GEMOX/ Retrospective study/ progressive >2 nd line 5 40% -
37. Peptide receptor radionucleide therapy (PRRT) : limited availability, used in positive SRS tumors Kaltsas GA et al. Endoc Relat Cancer 2005 SRS : somatostatin receptor scintigraphy SRS posterior view sst 2 sst 1 sst 3 sst 4 sst 5
38. Peptide receptor radionucleide therapy : academic research studies in positive SRS patients Kwekkeboom D et al. ENET consensus 2009 Study PRRT agent n OR-CR PFS Months Waldher 2001 [90Y-DOTA, Tyr3] –Octreotide 41 24% >26 Kwekkeboom 2008 [ 177 Lu-DOTA,Tyr 3 ] –Octreotate 310 30% 40
39. PRRT with Octreotate – 177 Lu is able to provide partial response Avant +2 OCLU + 4 OCLU SRS IRM-T2 préparé par C.-T. Pham
40. mTOR Pathway in Sporadic pNETs Missiaglia E, Dalai I, Barbi S, et al. J Clin Oncol. 2010;28:245-255. TSC2 Expression PTEN Expression 0 5 10 15 20 High-level TSC2 Low-level TSC2 Overall Survival Time (yr) 1.0 0.5 0 5 10 15 20 High-level TSC2 Low-level TSC2 Progression-free Survival Time (yr) 1.0 0.5 Time (yr) 0 High-level PTEN Low-level PTEN Progression-free Survival 1.0 0.5 5 10 15 20
41. mTOR inhibitors in NET : phases II rational increased IGF1-VEGF, downregulation of PTEN-TSC2 in NET Traitement Population RECIST PFS Duran B 2006 N=32 Temsirolimus 25 mg IV/sem Multiple primaries Progressive disease First line or not OR 5% S 58% 6 months Yao J 2008 N=60 Everolimus 5-10 mg po/j Octreotide Multiple primaries Progressive or not First line or not OR 22% S 70% 15 months Yao j 2009 N=146 Everolimus 10 mg po/j +/- SDS LAR* (stratification) Pancreas Progressive Post first line OR 4-9*% S 67-80*% 9-16* months
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45. Takahashi Y et al. Clin Cancer Res 2007;13:187-196 Angiogenesis inhibitors in GEP NET: rationale High micro vascular density is associated with a favourable outcome High proliferative index in Endothelial cell is associated with a poor outcome
46. Antiangiogenic therapy in non-pancreatic NET SDS LAR + BEVA 0R + IFN : a randomized phase II study Yao J et al JCO 2008 : non pancreatic metastatic well differentiated NEC Phase III ongong Treatment (n) SDS +BEVA (22) SDS+IFN * (22) OR at 18 sem 4(18%) 0 PFS at 18 sem 95% 68%
48. Sunitinib vs Placebo: Phase III, a randomized study in progressive well differentiated pancreatic NEC RANDOM I ZAT I ON 340 patients First line or not Fonctioning or not Sunitinib 37.5 mg/jour Arm A Placebo Arm B Objectif principal : Survie sans progression 1:1 E Raymond et al : 169 patients : positive interim analysis, median survival 5 (IC 95, 3.5-7.4) vs 11 (IC 95, 7.4-NR) months HR 0.397 ( p < 0.001)
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50. Progression-free Survival* Kaplan-Meier median PFS Sunitinib : 11.4 mo Placebo: 5.5 mo HR = 0.42 (95% CI, 0.26–0.66) P <0.001 Raymond E, Dahan L, Raoul J-L, et al. N Engl J Med. 2011;364:501-513. * Local review 0.8 0.6 0.4 0.2 0 1.0 Proportion of Patients 5 10 15 20 25 0 Sunitinib 39 19 4 0 0 86 Sunitinib 28 7 2 1 0 85 Placebo Number at risk Time (mo) Placebo
51.
52. Metastatic NET : locoregional therapy Steinmüller T et aL ENET guideline Neuroendocrinology 2008 : in case of extra-hepatic spread = non surgical treatment in most cases unless palliation needed (RF, TACE…) HEPATIC MET UNILOBAR / LIMITED BILOBAR LIVER SURGERY Surg contra-indicated ABLATION TACE SURGERY TACE ou TAE DIFFUSE MEDICAL THERAPY Transplantation Selected cases
56. NET specialist Pathologist Biomarkers Imaging Molecular Imaging Genetics Surgeon Embolisation, RFA Organ-specialist Supportive care Endoscopic investigation Chemotherapy Radiotherapy WORK WITHIN MULTIDISCPLINARY TEAMS and NETWORKS, THANK YOU
Editor's Notes
Epidemiologic studies from 1974 to1998 from 5 European countries and the United States showed the levels of incidence as lowest in the Tuscany region of Italy with the highest incidence in the United States (5.35 per 100,000 in US men and 4.76 per 100,000 in US women). The data collection in Europe is mainly from population-based studies, whereas the US SEER data comprise a random sampling representative of the entire country. Yao JC, Hassan M, Phan A, et al. J Clin Oncol . 2008;26:3063-3072. Taal BG, Visser O. Neuroendocrinology . 2004;80(suppl 1):3-7. Hauso O, Gustafsson BI, Kidd M, et al. Cancer. 2008;113:2655-2664. US Department of Health and Human Services, National Institutes of Health, SEER Brochure.
Retrospective data from 158 patients with histopathologic confirmed diagnosis of gastric, duodenal, or pNET underwent survival analysis according to the ENET/AJCC grading system. The analysis indicated that survival was significantly poorer for patients who had grade 3 tumours compared with patients who had grade 1 and grade 2 tumours and for patients who had grade 2 tumours compared with patients who had grade 1 tumours. A key concept that needs to be emphasized is that poorly differentiated tumours are always grade 3. However, grade 3 tumours are not always poorly differentiated. Rindi G, Klöppel G, Alman H, et al. Virchows Arch. 2006;449:395-401. Rindi G, Klöppel G, Couvelard A, et al. Virchows Arch. 2007;451:757-762. 3. Pape UF, Jann H, Müller-Nordhorn J, et al. Cancer. 2008;113:256-265.
PROMID was a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated advanced (metastatic and locally inoperable) small intestine (midgut) NETs. The hypothesis was that octreotide LAR prolongs time to tumour progression. After randomization, patients received octreotide LAR 30 mg or placebo every 28 days until tumour progression, documented by CT or MRI, or death. Octreotide LAR 30 mg or placebo were administered by a study nurse or physician not involved in further patient care. Patients were blinded and all clinical assessments were performed without knowledge of the assigned treatment. During the study, additional antiproliferative therapy was not allowed. Poststudy treatment in patients with tumour progression was at the discretion of the investigator. All patients will be followed-up until death. Tumour progression was evaluated using the WHO criteria. Importantly, CT and/or MRI scans were evaluated by a blinded central reader. In the event of progression, patients were unblinded to the investigator, who could then decide further treatment options for the patient. Once the study was finished, the investigator was unblinded with regard to the treatment. In patients who progressed while receiving placebo, octreotide LAR or a different treatment could be administered. Patients enrolled in the PROMID study were treatment-naïve with locally inoperable or metastatic well-differentiated NET with a small intestinal primary tumour without curative therapeutic options. Patients could have either a functioning or nonfunctioning tumour. Patients with a tumour of unknown origin were believed to have a small intestinal tumour if a primary within the pancreas, chest, and elsewhere was excluded by multiphasic CT and/or MRI. Progressive metastatic disease was not required for enrollment; however, all patients were required to demonstrate metastatic or inoperable disease measurable by CT or MRI. Patients with symptoms of carcinoid syndrome and increased urinary 5-hydroxyindole acetic acid (5-HIAA) were classified as having a functioning tumour. Only those patients with carcinoid syndrome who tolerated flushing without intervention or responded to treatment with loperamide and/or cholestyramine in case of diarrhea were included. Rinke A, Müller HH, Schade-Brittinger C, et al. J Clin Oncol . 2009;27:4656-4663.
A better control in terms of stable didease
Downregulation of TSC2 and PTEN expression in primary tumours were significantly associated with shorter disease-free survival and OS. 1. Missiaglia E, Dalai I, Barbi S, et al. J Clin Oncol. 2010;28:245-255.
RADIANT-3, was the largest phase III trial ever conducted in advanced pancreatic NET (pNET). This prospective, double-blind, randomized, placebo-controlled, phase III trial, assessed the efficacy and safety of everolimus + best supportive care vs placebo + best supportive care in patients with advanced pNET. It accrued more rapidly than anticipated, meeting full enrollment in <2 years—410 patients. The study was designed to detect an HR of 0.67 with 282 events needed to achieve 92% power. The primary endpoint of this trial was PFS per investigator assessment. Secondary endpoints include safety and OS. Patients with advanced pNET and radiologic progression within the preceding 12 months were randomized 1:1 to everolimus + best supportive care vs placebo + best supportive care. Best supportive care may include the use of somatostatin analogues. There are 2 stratification factors: Prior cytotoxic chemotherapy WHO PS at baseline (0 vs 1-2) Multiphasic CTs and/or MRIs were performed every 12 weeks for response evaluation. Treatment continued until progression, unacceptable toxicity, or withdrawal. The patient may have discontinued participation in the study for any of the following: Disease progression Subject withdrew consent AEs Lost to follow-up Abnormal laboratory value(s) Administrative problems Abnormal test procedure result(s) New cancer therapy Protocol deviation Death At progression, patients were unblinded and if on placebo allowed to crossover to open label everolimus. 91% of eligible patients who had progressed (148 of 163) on the placebo arm received open-label everolimus at the time of progression. 1. Yao JC, Shah MH, Ito T, et al. N Engl J Med. 2011;364:514-523.
Results of the PFS analysis as per central review were consistent with and support those generated from the local investigator assessment. Central review results: HR=0.34 (95% CI:0.26–0.44); P <0.001, reflecting a 66% PFS risk reduction. Median PFS values were also consistent with those reported for the local investigator assessment. The median PFS was 11.4 months with everolimus and 5.4 months with placebo. The prolongation in median PFS was 6.0 months 1. Yao JC, Shah MH, Ito T, et al. N Engl J Med. 2011;364:514-523.
RADIANT-2 is a randomized, double-blind, placebo-controlled, phase III study with the primary endpoint of PFS comparing everolimus 10 mg/day + octreotide LAR 30 mg/28 days to octreotide LAR 30 mg/28 days + placebo. RADIANT-2 was the largest phase III trial ever conducted in patients with advanced NET Patients with advanced NETs who have had a history of symptoms attributed to carcinoid syndrome (eg, flushing or diarrhea) were included in the study. Patients need not have flushing or diarrhea at the time of entry. Secondary endpoints included comparing OS between the treatment arms and determining the safety and tolerability of everolimus + octreotide LAR. Patients were allowed to cross over from the control arm to receive everolimus + octreotide LAR at the time disease progression was documented by the investigator. The study was blinded until there was documented disease progression, at which point the patient could be unblinded and, if on the control arm, allowed to cross over to receive open-label everolimus 10 mg/day + octreotide LAR 30 mg/28 days The study was designed for well- or moderately differentiated NETs (low- or intermediate-grade); poorly differentiated tumours were excluded. 1. Pavel M, Hainsworth J, Baudin E, et al. Presented at: 35th ESMO Congress; October 8-12, 2010; Milan, Italy. Abstr LBA8.
A, C, and D, relationship between vascular index and WHO classification. B, E, and F, Kaplan-Meier survival curves of 37 patients with PETs. A, S-MVD significantly decreased according to progression of PETs in terms of the WHO classification (Kruskal-Wallis test, P = 0.003). B, patients were divided into two groups by median S-MVD. The high S-MVD group showed significantly longer survival than the low S-MVD group (log-rank test, P = 0.002). C, EPC significantly increased according to progression of PETs in terms of the WHO classification (Kruskal-Wallis test, P = 0.019). D, EPI significantly increased according to progression of PETs in terms of the WHO classification (Kruskal-Wallis test, P = 0.001). E, patients were divided into two groups by median EPI. The high EPI group showed significantly shorter survival than the low EPI group (log-rank test, P = 0.005). F, patients were divided into two groups by the quartile value of CXCL-12 expressed in the tumor cells. Patients with PETs showing high expression of CXCL-12 in the tumor cells had significantly shorter than those whose tumors showed low expression (log-rank test, P = 0.018).
This multinational (42 centers in 11 countries) , randomized, double-blind, placebo-controlled, phase III trial was conducted to assess the efficacy and safety of continuous daily administration of sunitinib 37.5 mg in patients with advanced pNETs. Eligible patients had pathologically confirmed, well-differentiated pNETs (advanced, metastatic, or both) and were not eligible for surgery, ECOG PS 0 or 1, documented disease progression within the previous 12 months (defined by RECIST criteria), and adequate hematologic, hepatic, and renal function. Patients with poorly differentiated pNETs; previous tyrosine kinase or VEGF inhibitor treatment, cardiac events, or pulmonary embolism in the previous 12 months; ongoing cardiac dysrhythmias or a prolonged QT interval corrected for heart rate (QTc); symptomatic brain metastases; or a left ventricular ejection fraction of ≤50% were excluded. Treatment: once-daily oral sunitinib 37.5 mg or matching placebo was given until RECIST-defined disease progression was documented, unacceptable AEs occurred, or the patient died. Dose reduction to 25 mg daily and treatment interruption were permitted to manage AEs, with a subsequent increase in dose if grade ≥2 toxicity did not recur. Dose escalation to 50 mg daily was permitted for patients without an objective tumour response who had grade ≤1 nonhematologic or grade ≤2 hematologic treatment-related AEs during first 8 weeks. Endpoints: The primary endpoint was PFS, defined as the time from randomization to the first evidence of progression or death from any cause. For patients with inadequate baseline assessments, data on PFS time were censored on the date of randomization, with a 1-day duration. Secondary efficacy endpoints were OS, objective response rate (ORR), time to tumour response (TTR), duration of response, safety, and patient-reported outcomes. Tumour response was assessed by investigators (RECIST version 1.1). Confirmed responses were those that persisted on repeat imaging ≥4 weeks after initial documentation. Safety assessments included documentation of AEs (NCI CTC version 3.0), hematologic and biochemical laboratory tests, physical examination, and vital-sign measurements. The self-administered European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ-C30, version 3.0) was used to measure patient-reported outcomes. 1. Raymond E, Dahan L, Raoul J-L, et al. N Engl J Med. 2011;364:501-513 .
Disease progression or death was reported for 81 patients (local review). Median PFS was 11.4 months in the sunitinib group and 5.5 months in the placebo group; HR=0.42 (95% CI: 0.26–0.66; P <0.001). The probability of PFS at 6 months was 71.3% in the sunitinib group and 43.2% in the placebo group. 1. Raymond E, Dahan L, Raoul J-L, et al. N Engl J Med. 2011;364:501-513.