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1
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Gao LL, Gao DN, Yuan HT, Chen WQ, Yang J, Peng JQ. Combining anti-PD-1 antibodies with surufatinib for gastrointestinal neuroendocrine carcinoma: Two cases report and review of literature. World J Clin Oncol 2025; 16:102297. [DOI: 10.5306/wjco.v16.i4.102297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/20/2024] [Accepted: 02/27/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Gastrointestinal neuroendocrine carcinoma (GI NEC) has a low incidence rate and poor prognosis. Most patients already have metastatic disease when they are diagnosed. Platinum chemotherapy is the main means of treating metastatic GI NECs. There is a lack of effective treatment methods after chemotherapy failure. Therefore, Therefore, selecting appropriate posterior-line treatment programs to improve the prognosis of patients is urgently needed.
CASE SUMMARY A 64-year-old female was diagnosed with stage IV NEC of the rectum due to abdominal pain and rectal bleeding. After multiline chemotherapy, the condition progressed, and the patient was treated with a combination of camrelizumab and surufatinib. The efficacy evaluation revealed partial remission (PR) and stable conditions, with the expression of the tumor marker neuron-specific enolase (NSE) returning to normal. The adverse reactions were controllable, and the overall condition was good, with weight gain achieved in the past four years. Another 51-year-old female experienced recurrence and metastasis of a duodenal NEC after surgery. After multiline chemotherapy, she received sintilimab combined with surufatinib. The curative effect fluctuated between PR and stability. During treatment, she recovered from immune-related diabetes and later died due to deterioration of her condition. During the treatment, the patient’s NSE level returned to normal.
CONCLUSION The combination of antiangiogenic targeted drugs and immunotherapy provides a new therapeutic approach for the treatment of metastatic GI-NECs.
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Affiliation(s)
- Lou-Lu Gao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Dong-Ni Gao
- Department of Oncology, Shandong Public Health Clinical Center, Jinan 250100, Shandong Province, China
| | - Hong-Tu Yuan
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
| | - Wen-Qiang Chen
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Jing Yang
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
| | - Jie-Qiong Peng
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
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2
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Saito Y, Suzuki S, Sanomachi T, Kato K, Otake H, Nishise Y, Yamada Y, Saito K, Takahashi K, Kumanishi R, Fukui T, Yoshioka T. Pancreatic Mixed Acinar-neuroendocrine Carcinoma in a Patient With a Germline PTEN Variant: A Case Report and Genomic Literature Review. In Vivo 2025; 39:1173-1181. [PMID: 40010976 PMCID: PMC11884457 DOI: 10.21873/invivo.13921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND/AIM Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline PTEN variants. While patients with CS/PHTS have increased risk of various cancers, pancreatic cancer is not typically associated with this syndrome. We report a rare case of pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline PTEN variant, aiming to understand its molecular characteristics and clinical implications. CASE REPORT A male in his late 40s presented with pancreatic cancer and hepatic metastases. His medical history included thyroid cancer and familial gastrointestinal malignancies. Liver biopsy revealed mixed acinar-endocrine carcinoma. Cancer genome profiling identified pathogenic variants in GNAS and TP53, along with a germline PTEN variant (V201fs*1), leading to a diagnosis of CS. Notably, KRAS mutations, commonly found in pancreatic cancer, were absent. The patient showed extreme resistance to multiple chemotherapy regimens, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, and cisplatin plus etoposide, resulting in rapid clinical decline. CONCLUSION This case highlights a rare presentation of pancreatic cancer in CS/PHTS with distinct molecular and histological features. The absence of KRAS mutation and presence of germline PTEN variant may have contributed to the aggressive clinical course and treatment resistance. These findings underscore the need for further research into the molecular mechanisms of PTEN-associated pancreatic cancers and the development of targeted therapeutic strategies.
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Affiliation(s)
- Yosuke Saito
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
| | - Shuhei Suzuki
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan;
- Yamagata Hereditary Tumor Research Center, Yamagata University, Yamagata, Japan
| | - Tomomi Sanomachi
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kaho Kato
- Master of Public Health, Human Genetics, University of Pittsburgh, Pittsburgh, PA, U.S.A
- Nihonkai General Hospital, Yamagata, Japan
| | - Hiroya Otake
- Department of Pathology, Yamagata City Hospital Saiseikan, Yamagata, Japan
| | - Yuko Nishise
- Department of Gastroenterology, Yamagata City Hospital Saiseikan, Yamagata, Japan
| | - Yuta Yamada
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
| | | | - Koshi Takahashi
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
| | - Ryosuke Kumanishi
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
| | - Tadahisa Fukui
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
| | - Takashi Yoshioka
- Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan
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Urman A, Schonman I, De Jesus-Acosta A. Evolving Immunotherapy Strategies in Gastrointestinal Neuroendocrine Neoplasms. Curr Treat Options Oncol 2025; 26:92-102. [PMID: 39843688 DOI: 10.1007/s11864-024-01283-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/02/2024] [Indexed: 01/24/2025]
Abstract
OPINION STATEMENT Treatment for neuroendocrine neoplasms (NENs) is tailored to the tumor's site of origin, grade, and differentiation. NENs are categorized into two main types: well-differentiated neuroendocrine tumors (NETs), which tend to grow more slowly and are less aggressive, and poorly differentiated neuroendocrine carcinomas (NECs), which are highly aggressive and harder to treat. Treatment options for NETs range from somatostatin analogues and mTOR inhibitors to peptide receptor radionuclide therapy (PRRT) with Lutetium-177 dotatate. In cases where the disease progresses more rapidly, cytotoxic chemotherapy may also be considered. In contrast, chemotherapy plays a central role in treating NECs, often following protocols similar to those used for small cell lung cancer. Exciting progress is being made in the development of new therapies for NENs. Inspired by the success of immunotherapy in other cancers, clinical trials have begun to explore its potential in NENs. Early findings suggest that immune checkpoint inhibitors (ICIs) may offer benefits, especially in patients with higher-grade NETs and NECs. However, because NENs have an immunologically "cold" tumor microenvironment-meaning they are less likely to trigger an immune response-new strategies are needed to boost ICI efficacy. To overcome this challenge, researchers are exploring innovative approaches, such as combining dual ICIs or pairing ICIs with other therapeutic agents to make the tumors more responsive to immune attack. Moreover, there is growing enthusiasm for cutting-edge therapies designed to enhance the immune system's ability to recognize and destroy cancer cells. These include bispecific T cell engagers, chimeric antigen receptor T cells, tumor-infiltrating lymphocytes, oncolytic viruses, and cancer vaccines. While their effectiveness in NENs is still being studied, these approaches hold considerable promise, offering new hope for patients with this challenging and complex cancer type.
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Affiliation(s)
- Arielle Urman
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Ian Schonman
- Johns Hopkins Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Ana De Jesus-Acosta
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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Petrillo A, Ottaviano M, Pompella L, Giunta EF, Pisapia P, Marte G, Tufo A, Di Lorenzo S, Orefice J, Miceli C, Malapelle U, Daniele B, De Vita F. Rare epithelial gastric cancers: a review of the current treatment knowledge. Ther Adv Med Oncol 2025; 17:17588359241255628. [PMID: 39867743 PMCID: PMC11760139 DOI: 10.1177/17588359241255628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 04/30/2024] [Indexed: 01/28/2025] Open
Abstract
Gastric cancer (GC), one of the tumours with the highest mortality worldwide, is not a homogeneous disease, showing different features according to location, macroscopic aspect, histotype and molecular alterations. Adenocarcinoma is the most frequent epithelial GC (95%), the remaining 5% comprising rare epithelial tumours with their peculiarities, behaviour and incidence <6 cases/100,000/year. Due to the low number of cases, many aspects must be elucidated in this context. In this narrative review, we highlight the importance of a better understanding of rare GCs to personalize the cures in the light of the precision medicine concept. Our main aim is to translate the scarce evidence from the literature into daily clinical practice, never forgetting that all the clinicians dedicated to rare GCs should encourage such patients' enrolment in clinical trials and promote international collaborations. Hence, we focused on the treatment of the following rare GCs: rare gastric adenocarcinomas (hepatoid adenocarcinoma, medullary carcinoma with lymphoid stroma, Paneth cell carcinoma and Salivary Gland carcinoma); squamous cell carcinoma; adenosquamous carcinoma; neuroendocrine gastric neoplasms; gastroblastoma.
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Affiliation(s)
- Angelica Petrillo
- Medical Oncology Unit, Ospedale del Mare, Via E. Russo, Naples 80147, Italy
| | - Margaret Ottaviano
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
| | - Luca Pompella
- Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy
| | - Emilio Francesco Giunta
- Department of Experimental Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Pasquale Pisapia
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | | | - Andrea Tufo
- Surgical Unit, Ospedale del Mare, Naples, Italy
| | - Sara Di Lorenzo
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Jessica Orefice
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Chiara Miceli
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Umberto Malapelle
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Bruno Daniele
- Medical Oncology Unit, Ospedale del Mare, Naples, Italy
| | - Ferdinando De Vita
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
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Tissera NS, Balconi F, García-Álvarez A, Cubero JH, O'Connor JM, Chacón M, Capdevila J. Maintenance therapy after first-line platinum-based chemotherapy in gastroenteropancreatic neuroendocrine carcinomas: A literature review. Cancer Treat Rev 2025; 132:102863. [PMID: 39721305 DOI: 10.1016/j.ctrv.2024.102863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 12/28/2024]
Abstract
Neuroendocrine carcinomas are rare and aggressive malignancies, often diagnosed at advanced stages, leading to poor prognosis. Platinum-based chemotherapy is the standard first-line treatment for advanced neuroendocrine carcinomas; however after achieving response no consensus exists on maintenance therapies and the results are inconsistent. This review examines the role of maintenance therapy following response to first-line chemotherapy in gastroenteropancreatic neuroendocrine carcinomas. We identified limited supporting evidence, primarily from phase II trials and case reports, that suggested maintenance therapy could be considered for prolonging progression-free survival, balancing toxicity, and maintaining quality of life. Nevertheless, prospective studies are needed to validate its clinical efficacy.
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Affiliation(s)
- Natalia Soledad Tissera
- Upper Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
| | - Francesca Balconi
- Medical Oncologist, Oncological Hospital Armando Businco Cagliari, Cagliari, Italy
| | - Alejandro García-Álvarez
- Upper Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Jorge Hernando Cubero
- Upper Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | | | - Matías Chacón
- Head of the Oncology Department, Alexander Fleming Institute, Buenos Aires, Argentina
| | - Jaume Capdevila
- Upper Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
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6
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Chen Q, Guo Y, Wang Z, Chen X, Tian C, Zheng J, Tan H. Development and validation of a nomogram to predict overall survival of gastroenteropancreatic neuroendocrine carcinoma: a SEER database analysis. Transl Cancer Res 2024; 13:4678-4693. [PMID: 39430841 PMCID: PMC11483443 DOI: 10.21037/tcr-23-2215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 08/01/2024] [Indexed: 10/22/2024]
Abstract
Background Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a rare group of diseases with poor prognosis and the assessment of its prognosis is a significant challenge. This study aimed to develop and validate a prognostic nomogram to assess overall survival (OS) in patients with GEP-NEC. Methods Patients diagnosed with poorly differentiated GEP-NEC were collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2015 and were randomly assigned to the training or validation cohort in a 7:3 ratio. The data included details of clinicopathological characteristics, therapeutic interventions and survival outcomes. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Nomogram was used to predict OS at 1 and 2 years. The nomogram was internally validated with validation cohort, and its predictive ability was evaluated using concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and integrated discrimination improvement (IDI) index. Results A total of 887 patients were divided into the training group (n=623) and the validation group (n=264). A total of 476 patients (53.66%) were in stage IV. Based on multivariate analysis, a nomogram was constructed with age, gender, N stage, tumor size, primary tumor resection, radiotherapy and chemotherapy (P<0.05). The C-index was 0.701 [95% confidential interval (CI): 0.677-0.725] and 0.731 (95% CI: 0.698-0.764) for the training and validation groups, respectively. The C-index, ROC, IDI and DCA results indicated that this nomogram model has a good predictive value. Conclusions In this study, a nomogram model based on seven independent prognostic factors provided visualization of the risk and could help clinicians predict the 1-year and 2-year OS for GEP-NEC. This tool can provide personalized survival predictions and improve clinical decision making for the management of GEP-NEC.
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Affiliation(s)
- Qishuang Chen
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Yiying Guo
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zihan Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Traditional Chinese Medicine Department of Rheumatism, China-Japan Friendship Hospital, Beijing, China
| | - Xiaoying Chen
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Chao Tian
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Jiabin Zheng
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
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7
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Takenaka S, Tsuji T, Doden K, Hayashi S, Shimada M, Saito H, Yamamoto D, Okamoto K, Ikeda H, Moriyama H, Kinoshita J, Sato Y, Ninomiya I, Inaki N. Advanced esophagogastric junction mixed neuroendocrine-non-neuroendocrine neoplasm with long-term recurrence-free survival. Surg Case Rep 2024; 10:217. [PMID: 39259237 PMCID: PMC11390994 DOI: 10.1186/s40792-024-02011-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/27/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years. CASE PRESENTATION A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN. CONCLUSION MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy.
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Affiliation(s)
- Shunsuke Takenaka
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Toshikatsu Tsuji
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan.
| | - Kenta Doden
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Saki Hayashi
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Mari Shimada
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hiroto Saito
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Daisuke Yamamoto
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Koichi Okamoto
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Hiroko Ikeda
- Department of Pathology, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Jun Kinoshita
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Itasu Ninomiya
- Department of Surgery, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui, Fukui, 910-8526, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Kanazawa University Hospital, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
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Hanzawa S, Asami S, Kanazawa T, Oono S, Takakura N. Multimodal Treatment With Nivolumab Contributes to Long-Term Survival in a Case of Unresectable Esophagogastric Junction Neuroendocrine Carcinoma. Cureus 2024; 16:e65981. [PMID: 39221328 PMCID: PMC11366065 DOI: 10.7759/cureus.65981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 09/04/2024] Open
Abstract
Advanced neuroendocrine carcinoma (NEC) has an extremely poor prognosis, partly explained by the rarity and diagnostic difficulty, for which the most appropriate treatment strategy has not been established. In this report, we discuss a case of unresectable advanced esophagogastric junction NEC, which was difficult to diagnose, that has achieved relatively long-term survival with multidisciplinary treatment centered on nivolumab. A man in his 60s was initially diagnosed with an advanced esophagogastric junction squamous cell carcinoma (SCC). The lymph node metastasis was detected in the regional lymph nodes and para-aortic region. We diagnosed the patient with T3, N3, M1 (Lym), stage IVB, and administered systemic chemotherapy. Due to the failure of first-line, fluorouracil, and cisplatin therapy, we administered nivolumab as the second-line therapy. This therapy demonstrated partial response, so we performed conversion surgery, however the postoperative diagnosis was NEC. Three years after treatment initiation, a single lymph node metastasis has recurred, which is under control with nivolumab and radiation therapy. However, 4.5 years after the start of treatment, with the advent of immune-related adverse events (irAE), nivolumab was discontinued and the patient was placed on surveillance. Six months after that, metastasis to the hilar lymph node and adrenal gland was observed. Both times that recurrence/metastasis appeared, they occurred while nivolumab was being discontinued, suggesting its significant systemic anti-cancer effect. Therefore, nivolumab in particular may be an effective treatment for advanced esophageal NEC, and this case suggests that it may contribute to prolonged progression-free survival.
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Affiliation(s)
- Shunya Hanzawa
- Department of Surgery, Fukuyama City Hospital, Fukuyama, JPN
- Department of Gastrointestinal Surgery, Okayama University Hospital, Okayama, JPN
| | - Shinya Asami
- Department of Surgery, Fukuyama City Hospital, Fukuyama, JPN
| | | | - Satoshi Oono
- Department of Surgery, Fukuyama City Hospital, Fukuyama, JPN
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Owaki S, Mori Y, Nakai S, Maeda H, Imazu M, Tomita Y, Kanaiwa H, Yamaguchi A, Kitagawa M, Hirano A, Kimura Y, Tsuchida K, Kataoka H. BRAF V600E-mutated Colorectal Neuroendocrine Carcinoma Effectively Treated with a Chemotherapy Protocol for BRAF-mutated Metastatic Colorectal Cancer. Intern Med 2024; 63:1995-1999. [PMID: 37981300 PMCID: PMC11309870 DOI: 10.2169/internalmedicine.2870-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 10/05/2023] [Indexed: 11/21/2023] Open
Abstract
Metastatic colorectal neuroendocrine carcinoma (NEC) is often treated using a chemotherapy protocol for small-cell lung cancer; however, the prognosis is extremely poor. A 55-year-old woman with BRAF V600E-mutated transverse colon NEC and liver metastases underwent colectomy followed by FOLFOXIRI plus bevacizumab. Consequently, the liver metastases markedly shrank. Owing to later worsening of the liver metastases, she received encorafenib and binimetinib plus cetuximab. Despite discontinuing binimetinib due to myalgia, she had a long-term response with a progression-free survival of 14 months and an overall survival of more than 27 months. A chemotherapy protocol for BRAF-mutated metastatic colorectal cancer may be a treatment option for BRAF V600E-mutated colorectal NEC.
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Affiliation(s)
- Seira Owaki
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
- Department of Medical Oncology, National Hospital Organization Nagoya Medical Center, Japan
| | - Yoshinori Mori
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Shunsuke Nakai
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hideki Maeda
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Mitsuki Imazu
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Yusaku Tomita
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hiroki Kanaiwa
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Ayana Yamaguchi
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Mika Kitagawa
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Atsuyuki Hirano
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Yoshihide Kimura
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Kenji Tsuchida
- Department of Gastroenterology, Nagoya City University West Medical Center, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
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10
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Yıldırım ÜM, Koca D, Kebudi R. Gastroenteropancreatic neuroendocrine tumors in children and adolescents. Turk J Pediatr 2024; 66:332-339. [PMID: 39024601 DOI: 10.24953/turkjpediatr.2024.4526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 05/30/2024] [Indexed: 07/20/2024]
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS The medical records of patients with GEP-NETs were reviewed. RESULTS Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.
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Affiliation(s)
- Ülkü Miray Yıldırım
- Division of Pediatric Hematology Oncology, Institute of Oncology, İstanbul University, İstanbul, Türkiye
| | - Dilşad Koca
- Division of Pediatric Hematology Oncology, Institute of Oncology, İstanbul University, İstanbul, Türkiye
| | - Rejin Kebudi
- Division of Pediatric Hematology Oncology, Institute of Oncology, İstanbul University, İstanbul, Türkiye
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11
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Nakasone ES, Bustillos HC, Gui X, Konnick EQ, Sham JG, Cohen SA. Multidisciplinary Approach for the Management of Metastatic Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas: A Case Report of an Exceptional Responder. Pancreas 2024; 53:e487-e491. [PMID: 38460151 DOI: 10.1097/mpa.0000000000002322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/11/2024]
Abstract
ABSTRACT Poorly differentiated pancreatic neuroendocrine carcinomas (pNECs) are rare, highly aggressive neoplasms. Frequently metastatic at diagnosis, prognosis is poor with median overall survival estimated to be less than 1 year. Although multidisciplinary management, including systemic medications and locoregional therapies aimed at reducing and preventing symptoms caused by mass effect, is the mainstay of treatment for patients with metastatic well-differentiated pancreatic neuroendocrine tumors, rapid progression, organ dysfunction, and poor performance status often preclude initiation of even single-modality palliative chemotherapy for patients with metastatic pNEC, limiting the use of and recommendation for multidisciplinary management.We describe the case of a 51-year-old male patient diagnosed with pNEC metastatic to liver and lymph nodes presenting with impending cholestatic liver failure for whom we were able to successfully initiate and dose-escalate cytotoxic chemotherapy with excellent radiographic response. After multidisciplinary review of his case, the patient underwent pancreaticoduodenectomy and hepatic wedge biopsies, with pathology demonstrating a pathologic complete response to chemotherapy in both the pancreas and liver. Surveillance scans at 2 years from initial diagnosis and 1 year from surgery remain without evidence of locoregional or distant recurrence, highlighting the importance and utility of multidisciplinary management in select cases.
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Affiliation(s)
| | - Hannah C Bustillos
- Clinical Pharmacy, University of Washington/Fred Hutchinson Cancer Center
| | - Xianyong Gui
- Departments of Laboratory Medicine and Pathology
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12
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Shen H, Gu Y, Fang Y, Xu T, Xu Y, Wu X, Shu Y, Ma P. Efficacy of first-line chemotherapy based on primary site of tumor versus etoposide-platinum in advanced gastroenteropancreatic neuroendocrine carcinoma. J Gastrointest Oncol 2024; 15:921-930. [PMID: 38989422 PMCID: PMC11231865 DOI: 10.21037/jgo-24-64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 05/11/2024] [Indexed: 07/12/2024] Open
Abstract
Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) constitute a rare and aggressive group of malignancies usually with widespread disease. There are limited studies on GEP-NECs, and therefore, we aim to acquire more information on the clinical features, treatment regimens, and prognosis. Methods Data from advanced GEP-NECs patients who had not previously received systemic treatment for advanced disease at The First Affiliated Hospital of Nanjing Medical University from 2010 to 2022 were retrospectively collected. Relationships between clinical-pathological features, treatment regimens, and prognosis were investigated using Kaplan-Meier curves and cox regression models. Results A total of fifty-four patients were enrolled in the study. The median age was 65.5 years and 79.6% were male. At diagnosis, 51.9% and 3.7% of patients developed liver and brain metastasis respectively. Sixteen (29.6%) patients received chemotherapy according to primary site of tumor (PST), while thirty-eight (70.4%) were treated with etoposide-platinum (EP) regimen, which based on the first-line treatment of advanced small cell lung cancer (SCLC). No significant differences on progression-free survival (PFS) and response rate were observed between these two groups. Univariate survival analysis showed that liver metastasis, elevated baseline serum carcinoembryonic antigen, elevated baseline serum neuron-specific enolase, elevated baseline serum lactate dehydrogenase, and elevated baseline serum neutrophil-to-lymphocyte ratio (NLR) were associated with shorter PFS. After multivariate analysis, elevated NLR was the only factor that remained significantly associated with shorter PFS (P=0.01). Conclusions GEP-NECs are aggressive neoplasms, of which elevated NLR is proven to be an independent negative predictor. Treatment regimens based on PST are not inferior to regiments based on SCLC (EP) for GEP-NECs patients. Large-scale, prospective randomized controlled trials are required to establish the standard of care.
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Affiliation(s)
- Haoyang Shen
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yunru Gu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuan Fang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tingting Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yangyue Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xi Wu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yongqian Shu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Pei Ma
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
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13
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Suraju MO, Freischlag K, McKeen A, Nayyar A, Thompson D, Gordon DM, Mishra A, Sherman SK, Goffredo P, Hassan I. Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma. J Surg Oncol 2024; 129:1449-1455. [PMID: 38685721 DOI: 10.1002/jso.27645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 03/18/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.
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Affiliation(s)
- Mohammed O Suraju
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Kyle Freischlag
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Andrew McKeen
- Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Apoorve Nayyar
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Dakota Thompson
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Darren M Gordon
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Aditi Mishra
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Scott K Sherman
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Paolo Goffredo
- Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Imran Hassan
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Department of Surgery, Mercy Hospital, Cedar Rapids, Iowa, USA
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14
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Díaz-López S, Jiménez-Castro J, Robles-Barraza CE, Ayala-de Miguel C, Chaves-Conde M. Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract. World J Gastrointest Oncol 2024; 16:1166-1179. [PMID: 38660639 PMCID: PMC11037054 DOI: 10.4251/wjgo.v16.i4.1166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/17/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.
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Affiliation(s)
- Sebastián Díaz-López
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | | | | | - Carlos Ayala-de Miguel
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | - Manuel Chaves-Conde
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
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15
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Suraju MO, Freischlag K, Jacob D, Thompson D, Mckeen A, Tran C, Sherman SK, Goffredo P, Weigel RJ, Hassan I. Epidemiology and survival outcomes of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinoma. Surgery 2024; 175:735-742. [PMID: 37867105 DOI: 10.1016/j.surg.2023.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/01/2023] [Accepted: 09/05/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Mixed neuroendocrine-non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. METHODS We identified patients diagnosed with stage I-III colorectal (excluding appendix) mixed neuroendocrine-non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. RESULTS We identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine-non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. CONCLUSION Adjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.
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Affiliation(s)
- Mohammed O Suraju
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. https://twitter.com/Femisuraju
| | - Kyle Freischlag
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Denise Jacob
- Department of Pathology, Albert Einstein College of Medicine, Bronx, NY
| | - Dakota Thompson
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Andrew Mckeen
- Carver College of Medicine, University of Iowa, Iowa City, IA
| | - Catherine Tran
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Scott K Sherman
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Paolo Goffredo
- Department of Surgery, University of Minnesota, Minneapolis, MN. https://twitter.com/GoffredoPaolo
| | - Ronald J Weigel
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Imran Hassan
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA; Department of Surgery, Mercy Hospital, Cedar Rapids, IA.
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16
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Yoshinami Y, Nishimura E, Hosokai T, Yamamoto S, Matsuda S, Nomura M, Kawakubo H, Kato K, Kitagawa Y. Rare malignant neoplasm of the esophagus: current status and future perspectives. Jpn J Clin Oncol 2024; 54:111-120. [PMID: 37861097 PMCID: PMC10849183 DOI: 10.1093/jjco/hyad144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/29/2023] [Indexed: 10/21/2023] Open
Abstract
Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus.
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Affiliation(s)
- Yuri Yoshinami
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Erica Nishimura
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Taisuke Hosokai
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Shun Yamamoto
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Motoo Nomura
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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17
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Morken S, Langer SW, Sundlöv A, Vestermark LW, Ladekarl M, Hjortland GO, Svensson JB, Tabaksblat EM, Haslerud TM, Assmus J, Detlefsen S, Couvelard A, Perren A, Sorbye H. Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms. Br J Cancer 2023; 129:1930-1939. [PMID: 37872405 PMCID: PMC10703888 DOI: 10.1038/s41416-023-02462-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/22/2023] [Accepted: 10/04/2023] [Indexed: 10/25/2023] Open
Abstract
BACKGROUND The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. METHODS Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. RESULTS For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment. CONCLUSION Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NTC02248012).
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Affiliation(s)
- Siren Morken
- Department of Oncology, Haukeland University Hospital, Bergen, Norway.
| | - Seppo W Langer
- Department of Oncology, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Anna Sundlöv
- Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | | | - Morten Ladekarl
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | - Johanna B Svensson
- Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | | | - Torjan Magne Haslerud
- Department of Radiology and Nuclear Medicine, Haukeland University Hospital, Bergen, Norway
| | - Jörg Assmus
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | | | - Aurel Perren
- Institute of Tissue medicine and Pathology, University of Bern, Bern, Switzerland
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
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18
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Zemerly S, Thurairajasingam K, Deeb B, Tilby M. Small Cell Oesophageal Carcinoma: A Retrospective Case Series From a UK Tertiary Centre and a Review of the Literature. Cureus 2023; 15:e49435. [PMID: 38149143 PMCID: PMC10750842 DOI: 10.7759/cureus.49435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2023] [Indexed: 12/28/2023] Open
Abstract
Background Small cell oesophageal carcinoma (SCEC), a rare neuroendocrine malignancy, presents various challenges in diagnosis and treatment. The condition is characterised by rapid dissemination, a marked responsiveness to chemotherapy, and a guarded prognosis. While the European Neuroendocrine Tumour Society has recommended platinum-based chemotherapy, ongoing debates on optimal strategies and the lack of clear guidelines underscore the need for further comprehensive research efforts. Methods This study retrospectively analysed 12 cases of localised pure SCEC treated at a UK tertiary care centre between 2006 and 2020. We systematically analysed and categorised the cases based on stage, performance status, and patient age. This comprehensive approach enabled a nuanced examination of overall survival (OS), thereby providing valuable insights into the differences between outcomes. Results The study revealed a median OS of 12.01 months for treated non-metastatic cases, highlighting the challenges of SCEC management. Conversely, treated metastatic cases exhibited a mean survival of 9.15 months, which contrasts starkly with the 2.55 months demonstrated by those receiving best supportive care (BSC). These figures underscore the urgency for refined strategies in handling advanced localised disease and the need to continue research endeavours to devise methods to enhance the precision and optimise outcomes beyond the presented data. Conclusion Based on our findings, the combination of chemoradiotherapy and surgery to manage SCEC holds promise; however, further research is needed to optimise the management approach. The lack of clear guidelines underscores the imperative for personalised treatment approaches.
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Affiliation(s)
- Sari Zemerly
- Oncology, University Hospitals Coventry and Warwickshire, Coventry, GBR
| | | | - Bassam Deeb
- Faculty of Medical Sciences, Lebanese University, Beirut, LBN
| | - Michael Tilby
- Oncology, University Hospitals Coventry and Warwickshire, Coventry, GBR
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19
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Litmeyer A, Konukiewitz B, Kasajima A, Foersch S, Schicktanz F, Schmitt M, Kellers F, Grass A, Jank P, Lehman B, Gress TM, Rinke A, Bartsch DK, Denkert C, Weichert W, Klöppel G, Jesinghaus M. High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin. J Pathol Clin Res 2023; 9:498-509. [PMID: 37608427 PMCID: PMC10556265 DOI: 10.1002/cjp2.339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/06/2023] [Accepted: 07/27/2023] [Indexed: 08/24/2023]
Abstract
Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC. We investigated INSM1 according to the immunoreactive score in our main cohort of 1,033 conventional CRCs and 21 MANECs/NECs in comparison to the expression of synaptophysin and chromogranin A and correlated the results with clinicopathological parameters and patient survival. All MANECs/NECs expressed INSM1, usually showing high or moderate expression (57% high, 34% moderate, and 9% low), which distinguished them from conventional CRCs, which were usually INSM1 negative or low, even if they diffusely expressed synaptophysin. High expression of INSM1 was not observed in conventional CRCs. Chromogranin A was negative/low in most conventional CRCs (99%), but also in most MANECs/NECs (66%). Comparable results were observed in our independent validation cohorts of conventional CRC (n = 274) and MANEC/NEC (n = 19). Similar to synaptophysin, INSM1 expression had no prognostic relevance in conventional CRCs, while true MANEC/NEC showed a highly impaired survival in univariate and multivariate analyses (e.g. disease-specific survival: p < 0.001). MANECs/NECs are a highly aggressive variant of colorectal cancer, which must be reliably identified. High expression of INSM1 distinguishes MANEC/NEC from conventional CRCs with diffuse expression of the standard neuroendocrine marker synaptophysin, which do not share the same dismal prognosis. Therefore, high INSM1 expression is a highly specific/sensitive marker that is supportive for the diagnosis of true colorectal MANEC/NEC.
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Affiliation(s)
- Anne‐Sophie Litmeyer
- Institute of PathologyPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Björn Konukiewitz
- Department of PathologyUniversity Hospital Schleswig‐Holstein, Campus Kiel, Christian‐Albrechts‐Universität zu KielKielGermany
- Institute of PathologyTechnical University of MunichMunichGermany
| | - Atsuko Kasajima
- Institute of PathologyTechnical University of MunichMunichGermany
| | | | - Felix Schicktanz
- Institute of PathologyTechnical University of MunichMunichGermany
| | - Maxime Schmitt
- Institute of PathologyTechnical University of MunichMunichGermany
| | - Franziska Kellers
- Department of PathologyUniversity Hospital Schleswig‐Holstein, Campus Kiel, Christian‐Albrechts‐Universität zu KielKielGermany
| | - Albert Grass
- Institute of PathologyPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Paul Jank
- Institute of PathologyPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Bettina Lehman
- Department of SurgeryPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Thomas M Gress
- Department of Gastroenterology, Endocrinology and Infectious DiseasesPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Anja Rinke
- Department of Gastroenterology, Endocrinology and Infectious DiseasesPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Detlef K Bartsch
- Department of SurgeryPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Carsten Denkert
- Institute of PathologyPhillips University Marburg and University Hospital MarburgMarburgGermany
| | - Wilko Weichert
- Institute of PathologyTechnical University of MunichMunichGermany
| | - Günter Klöppel
- Institute of PathologyTechnical University of MunichMunichGermany
| | - Moritz Jesinghaus
- Institute of PathologyPhillips University Marburg and University Hospital MarburgMarburgGermany
- Institute of PathologyTechnical University of MunichMunichGermany
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20
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Weaver JMJ, Hubner RA, Valle JW, McNamara MG. Selection of Chemotherapy in Advanced Poorly Differentiated Extra-Pulmonary Neuroendocrine Carcinoma. Cancers (Basel) 2023; 15:4951. [PMID: 37894318 PMCID: PMC10604995 DOI: 10.3390/cancers15204951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 10/02/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023] Open
Abstract
Extra-pulmonary poorly differentiated neuroendocrine carcinoma is rare, and evidence for treatment has been limited. In this article, the evidence behind the cytotoxic chemotherapy choices used for metastatic or unresectable EP-PD-NEC is reviewed. In the first-line setting, etoposide and platinum chemotherapy or irinotecan and platinum have been demonstrated to be equivalent in a large phase III trial. Questions remain regarding the optimal number of cycles, mode of delivery, and the precise definition of platinum resistance in this setting. In the second-line setting, FOLFIRI has emerged as an option, with randomized phase 2 trials demonstrating modest, but significant, response rates. Beyond this, data are extremely limited, and several regimens have been used. Heterogeneity in biological behaviour is a major barrier to optimal EP-PD-NEC management. Available data support the potential role of the Ki-67 index as a predictive biomarker for chemotherapy response. A more personalised approach to management in future studies will be essential, and comprehensive multi-omic approaches are required to understand tumour somatic genetic changes in relation to their effects on the surrounding microenvironment.
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Affiliation(s)
- Jamie M. J. Weaver
- The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK; (J.M.J.W.); (R.A.H.); (J.W.V.)
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Richard A. Hubner
- The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK; (J.M.J.W.); (R.A.H.); (J.W.V.)
| | - Juan W. Valle
- The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK; (J.M.J.W.); (R.A.H.); (J.W.V.)
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Mairead G. McNamara
- The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK; (J.M.J.W.); (R.A.H.); (J.W.V.)
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester M20 4BX, UK
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21
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Kanda S, Hiyama K, Kirino I, Fukui Y, Terashima H. Effective treatment of gallbladder neuroendocrine carcinoma with nivolumab. Clin Case Rep 2023; 11:e8040. [PMID: 37841882 PMCID: PMC10568049 DOI: 10.1002/ccr3.8040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/05/2023] [Accepted: 09/27/2023] [Indexed: 10/17/2023] Open
Abstract
An 89-year-old patient with gallbladder neuroendocrine neoplasms (GB-NENs) and lung cancer metastasis underwent nivolumab monotherapy, resulting in tumor shrinkage. Surgery and adjuvant nivolumab showed efficiency despite low expression of PD-L1.
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Affiliation(s)
| | | | | | - Yasuo Fukui
- Department of SurgeryAtagi HospitalKochiJapan
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22
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Seyama Y, Yamada T, Suzuki H, Fukuda S, Tsuji M, Niisato Y, Hirose S, Yamamoto Y, Moriwaki T, Hyodo I. Gastric neuroendocrine carcinoma presenting complete durable response by nivolumab treatment for multiple metastases and radiotherapy to oligoprogressive metastasis. Int Cancer Conf J 2023; 12:268-273. [PMID: 37577341 PMCID: PMC10421835 DOI: 10.1007/s13691-023-00611-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/24/2023] [Indexed: 08/15/2023] Open
Abstract
Gastric neuroendocrine carcinomas (NEC) are highly aggressive cancer with dismal prognosis. Platinum-based chemotherapy is used as the first-line treatment for this entity. However, there are no established therapeutic guidelines for platinum-resistant gastric NEC. We herein report a patient with metastatic gastric NEC who achieved durable and complete response to nivolumab with radiotherapy for oligoprogressive metastasis. A 70-year-old male patient had recurrences of resected gastric NEC, involving the liver and lymph nodes. His disease became refractory to cisplatin and etoposide combination therapy, after which he was treated with nivolumab. All the tumors showed marked shrinkage. However, 1 year after starting nivolumab, one metastatic lesion of the liver began to enlarge, and radiotherapy was performed to the lesion. Thereafter, a complete response was obtained, which has been maintained without any treatment for the past 2 years.
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Affiliation(s)
- Yusuke Seyama
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Takeshi Yamada
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Hirosumi Suzuki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Satoshi Fukuda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Miki Tsuji
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Yusuke Niisato
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Suguru Hirose
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Yoshiyuki Yamamoto
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Toshikazu Moriwaki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Ichinosuke Hyodo
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime Japan
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23
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Andreatos N, McGarrah PW, Sonbol MB, Starr JS, Capdevila J, Sorbye H, Halfdanarson TR. Managing Metastatic Extrapulmonary Neuroendocrine Carcinoma After First-Line Treatment. Curr Oncol Rep 2023; 25:1127-1139. [PMID: 37606874 DOI: 10.1007/s11912-023-01438-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2023] [Indexed: 08/23/2023]
Abstract
PURPOSE OF REVIEW Extrapulmonary neuroendocrine carcinoma (EP-NEC) is a rare, aggressive malignancy that can arise from any organ and frequently presents with distant metastases. Advanced disease has a poor prognosis with median overall survival (OS) rarely exceeding 1 year even with systemic therapy. The management paradigm of advanced/metastatic EP-NEC has been extrapolated from small cell lung cancer (SCLC) and commonly consists of 1st line therapy with etoposide and platinum (cisplatin or carboplatin), followed by alternative cytotoxic regimens at the time of progression. Only a minority of patients are able to receive 2nd line therapy, and cytotoxics derived from the SCLC paradigm such as topotecan or lurbinectedin have very limited activity. We aimed to evaluate emerging therapeutic options in the 2nd and later lines and survey potential future developments in this space. RECENT FINDINGS After a long period of stagnation in treatment options and outcomes, more promising regimens are gradually being utilized in the 2nd line setting including systemic therapy combinations such as FOLFIRI, FOLFOX, modified FOLFIRINOX, CAPTEM, and, more recently, novel checkpoint inhibitors such as nivolumab and ipilimumab. Simultaneously, advances in the understanding of disease biology are helping to refine patient selection and identify commonalities between NEC and their sites of origin which may eventually lead to additional targeted therapy options. While many questions remain, contemporary developments give grounds for optimism that improved outcomes for EP-NEC will soon be within reach.
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Affiliation(s)
- Nikolaos Andreatos
- Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Patrick W McGarrah
- Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | | | - Jason S Starr
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL, USA
| | - Jaume Capdevila
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
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24
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Ooki A, Osumi H, Fukuda K, Yamaguchi K. Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma. Cancer Metastasis Rev 2023; 42:1021-1054. [PMID: 37422534 PMCID: PMC10584733 DOI: 10.1007/s10555-023-10121-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 06/16/2023] [Indexed: 07/10/2023]
Abstract
Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeutic option for recurrent or metastatic GEP-NEC patients, the clinical benefits are limited and associated with a poor prognosis, indicating the clinically urgent need for effective therapeutic agents. The clinical development of molecular-targeted therapies has been hampered due to the rarity of GEP-NECs and the paucity of knowledge on their biology. In this review, we summarize the biology, current treatments, and molecular profiles of GEP-NECs based on the findings of pivotal comprehensive molecular analyses; we also highlight potent therapeutic targets for future precision medicine based on the most recent results of clinical trials.
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Affiliation(s)
- Akira Ooki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Hiroki Osumi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koshiro Fukuda
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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25
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5323-5331. [DOI: 10.12998/wjcc.v11.i22.5323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer.
CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively.
CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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26
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5329-5337. [PMID: 37621602 PMCID: PMC10445072 DOI: 10.12998/wjcc.v11.i22.5329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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27
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Eads JR, Halfdanarson TR, Asmis T, Bellizzi AM, Bergsland EK, Dasari A, El-Haddad G, Frumovitz M, Meyer J, Mittra E, Myrehaug S, Nakakura E, Raj N, Soares HP, Untch B, Vijayvergia N, Chan JA. Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms. Endocr Relat Cancer 2023; 30:e220206. [PMID: 37184955 PMCID: PMC10388681 DOI: 10.1530/erc-22-0206] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 05/15/2023] [Indexed: 05/16/2023]
Abstract
High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.
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Affiliation(s)
- Jennifer R Eads
- Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Pennsylvania, USA
| | | | - Tim Asmis
- Division of Medical Oncology, University of Ottawa, Ottawa, Ontario, Canada
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Emily K Bergsland
- Department of Medicine, University of California, San Francisco, California, USA
| | - Arvind Dasari
- Division of Gastrointestinal Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Michael Frumovitz
- Division of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Joshua Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Erik Mittra
- Division of Molecular Imaging and Therapy, Oregon Health & Science University, Portland, Oregon, USA
| | - Sten Myrehaug
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Eric Nakakura
- Department of Surgery, University of California, San Francisco, California, USA
| | - Nitya Raj
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Heloisa P Soares
- Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Salt Lake City, Utah, USA
| | - Brian Untch
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Namrata Vijayvergia
- Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
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28
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Zhang X, Barnett E, Smith J, Wilkinson E, Subramaniam RM, Zarrabi A, Rodger EJ, Chatterjee A. Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2023; 383:41-66. [PMID: 38359970 DOI: 10.1016/bs.ircmb.2023.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.
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Affiliation(s)
- Xintong Zhang
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Edward Barnett
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Jim Smith
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Te Whatu Ora/Health New Zealand, Wellington, New Zealand
| | - Emma Wilkinson
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Rathan M Subramaniam
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Faculty of Medicine, Nursing, Midwifery and Health Sciences, The University of Notre Dame Australia, Fremantle, WA, Australia; Department of Radiology, Duke University, Durham, NC, United States
| | - Amir Zarrabi
- Te Whatu Ora/Health New Zealand, Wellington, New Zealand; Precision Urology, Dunedin, New Zealand
| | - Euan J Rodger
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Aniruddha Chatterjee
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Honorary Professor, School of Health Sciences and Technology, UPES University, Dehradun, India.
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29
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Zhang Y, Liu X, Liang H, Liu W, Wang H, Li T. Late-stage esophageal neuroendocrine carcinoma in a patient treated with tislelizumab combined with anlotinib: a case report. J Int Med Res 2023; 51:3000605231187942. [PMID: 37498227 PMCID: PMC10387792 DOI: 10.1177/03000605231187942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2023] Open
Abstract
Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare tumor with highly malignant potential, rapid growth, and a poor prognosis. Advanced extrapulmonary neuroendocrine carcinoma should be treated with chemotherapeutic regimens suitable for small cell lung cancer. However, ENEC has no clear second-line treatment options. The clinical application of immunotherapy and targeted therapy in small cell lung cancer has produced good therapeutic effects. We describe the case of an elderly woman with multiple metastatic advanced ENEC treated with tislelizumab combined with anlotinib as second-line therapy, achieving complete remission in a short period and long-term survival. In total, 21 cycles of tislelizumab combined with anlotinib were given to this patient. After two cycles, the patient's neuron-specific enolase level decreased from 181.8 to 22.9 µg/L and remained at normal levels throughout treatment. Progression-free survival and overall survival were 16 and 21 months, respectively, in this patient. No obvious side effects were observed. Thus, tislelizumab and anlotinib could represent a novel therapeutic option for advanced ENEC.
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Affiliation(s)
- Yanqi Zhang
- Department of Oncology, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
| | - Xiaoyu Liu
- Department of Oncology, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
| | - Honglu Liang
- Department of Radiotherapy, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
| | - Weihua Liu
- Department of Gastroenterology, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
| | - Haiyan Wang
- Department of Infectious Diseases, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
| | - Tao Li
- Department of Oncology, Dezhou People's Hospital (Qilu Hospital of Shandong University Dezhou Hospital), 1166 Dongfanghong West Road, Dezhou, P.R. China
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30
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Cattaneo L, Centonze G, Sabella G, Lagano V, Angerilli V, Pardo C, Bertani E, Spada F, Prinzi N, Pusceddu S, Fassan M, Fazio N, Milione M. Digestive MiNENs: Could histological classification and molecular characterization drive clinical outcome and therapeutic approach? Crit Rev Oncol Hematol 2023:104044. [PMID: 37268174 DOI: 10.1016/j.critrevonc.2023.104044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/19/2023] [Accepted: 05/30/2023] [Indexed: 06/04/2023] Open
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are epithelial neoplasms in which neuroendocrine and non-neuroendocrine discrete components are combined, each of which constitutes ≥ 30% of the neoplasm. The finding of an additional neuroendocrine component seems to characterize the tumor's biological behavior. Few studies have proved MiNENs histogenetic and molecular characterization, and the development of molecular markers for more accurate classification of MiNENs represents a clinical need. However, a common origin of the neuroendocrine and non-neuroendocrine components from a pluripotent cancer stem cell could be suggested. The optimal clinical management of MiNENS is largely unknown. Whenever feasible, curative-intent resection should be performed for localized disease; in advanced disease, the treatment should be targeted to the component responsible for the metastatic spreading. This paper provides a revision of the current knowledge on MiNENs, focusing on available evidence about their molecular characterization to suggest a prognostic stratification of these rare forms.
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Affiliation(s)
- Laura Cattaneo
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Centonze
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy; Department of Research, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Sabella
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Vincenzo Lagano
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Angerilli
- Department of Medicine - DIMED, University of Padua, Padua, Italy; Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Carlotta Pardo
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Emilio Bertani
- Division of Gastrointestinal Surgery, European Institute of Oncology, Milan, Italy
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan
| | - Natalie Prinzi
- Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sara Pusceddu
- Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Matteo Fassan
- Department of Medicine - DIMED, University of Padua, Padua, Italy; Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan
| | - Massimo Milione
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
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Riechelmann RP, Taboada RG, de Jesus VHF, Iglesia M, Trikalinos NA. Therapy Sequencing in Patients With Advanced Neuroendocrine Neoplasms. Am Soc Clin Oncol Educ Book 2023; 43:e389278. [PMID: 37257140 DOI: 10.1200/edbk_389278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Neuroendocrine neoplasms (NENs) comprise a beautifully complicated, exciting landscape of histologies and clinical behaviors. However, the nuanced complexity of low- and high-grade variants can easily overwhelm both patients and providers. In this chapter, we review the ever-expanding literature on both functioning and nonfunctioning small bowel and pancreatic NENs, touching on somatostatin analogs, hepatic-directed therapies, small molecules, radiopharmaceuticals, immunotherapy, cytotoxic chemotherapy, and new promising agents. Furthermore, we suggest some strategies to address the most challenging scenarios seen in clinical practice, including sequencing of agents, treatment of carcinoid syndrome, and options for well-differentiated high-grade disease.
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Affiliation(s)
| | - Rodrigo G Taboada
- Department of Clinical Oncology, A.C.Camargo Cancer Center, Sao Paulo, Brazil
| | | | - Michael Iglesia
- Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
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Shaheen J, Al Laham O, Ibrahim Basha Z, Atia F, Sharaf Aldeen R, Isaac M, Alhanwt A. Bouveret Syndrome simultaneous with an incidental solitary Gastric Neuroendocrine Tumor in a 44-year-old female - A Case Report. Ann Med Surg (Lond) 2023; 85:1206-1212. [PMID: 37113963 PMCID: PMC10129185 DOI: 10.1097/ms9.0000000000000459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/16/2023] [Indexed: 04/29/2023] Open
Abstract
Bouveret Syndrome (BS) is a rare type of gallstone ileus, where a gallstone passes via a cholecystoduodenal fistula and causes gastric outlet obstruction. It comprises 0.3-0.5% of cholelithiasis complications. It primarily affects females with an average incidence age of 74 years. Gastric Neuroendocrine Tumors (G-NETs) make up merely 2% of all forms of gastric neoplasia and are known to be an extremely rare occurrence. Their annual incidence is estimated to be one to two per 1 million individuals, and they comprise 8.7% of all known neuroendocrine neoplasia of the gastrointestinal system. Case presentation We present the case of a 44-year-old Middle Eastern female who presented to the clinic due to multiple episodes of food containing biliary nonprojectile emesis accompanied by epigastric pain. Preoperative radiological workup revealed a Bezoar blocking the gastric outlet and a G-NET in the mucosal layer of the stomach. Clinical discussion Surgical intervention consisted of excising the impacted calculus to relieve the existing gastric outlet obstruction simultaneous to performing an uncut Roux-en-Y to treat the G-NET condition. The patient underwent complete recovery. Conclusion BS is an extremely rare form of gallstone ileus and gastric outlet obstruction. Its clinical presentation is nonspecific and results in misdiagnosis. Additionally, it is rare to occur in our patient's age group. NETs are also profoundly rare forms of neoplasia. To the best of our knowledge, no previous cases of simultaneous BS and G-NET have been documented. Therefore, clinical awareness should be raised to timely implement the necessary therapeutic interventions.
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Affiliation(s)
- Jack Shaheen
- Department of Surgery, Al Assad University Hospital
- Department of Surgery, Faculty of Medicine
| | - Omar Al Laham
- Department of Surgery, Faculty of Medicine
- Corresponding author. Address: Department of Surgery, Faculty of Medicine, Damascus University, Damascus, (The) Syrian Arab Republic. E-mail address: (O. Al Laham)
| | - Zein Ibrahim Basha
- Department of Pathology, Al Assad University Hospital
- Department of Pathology, Faculty of Medicine, Damascus University, Damascus, (The) Syrian Arab Republic
| | - Fareed Atia
- Department of Surgery, Al Assad University Hospital
- Department of Surgery, Faculty of Medicine
| | - Rahaf Sharaf Aldeen
- Department of Surgery, Al Assad University Hospital
- Department of Surgery, Al-Mouwasat University Hospital
- Department of Surgery, Faculty of Medicine
| | | | - Alaa Alhanwt
- Department of Surgery, Al Assad University Hospital
- Department of Surgery, Faculty of Medicine
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Sorbye H, Grande E, Pavel M, Tesselaar M, Fazio N, Reed NS, Knigge U, Christ E, Ambrosini V, Couvelard A, Tiensuu Janson E. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for digestive neuroendocrine carcinoma. J Neuroendocrinol 2023; 35:e13249. [PMID: 36924180 DOI: 10.1111/jne.13249] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/20/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023]
Abstract
This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11-12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first-line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second-line treatment. Immunotherapy plays a minor role in biomarker-unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease.
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Affiliation(s)
- Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Enrique Grande
- Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Margot Tesselaar
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | | | - Ulrich Knigge
- Departments of Surgery and Clinical Endocrinology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Emanuel Christ
- Department of Endocrinology, Diabetes and Metabolism, ENETS Center of Excellence, University Hospital of Basel, Basel, Switzerland
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Anne Couvelard
- Department of Pathology, AP-HP Bichat Hospital, Université Paris Cité, Paris, France
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden
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Knappskog S, Grob T, Venizelos A, Amstutz U, Hjortland GO, Lothe IM, Kersten C, Hofsli E, Sundlöv A, Elvebakken H, Garresori H, Couvelard A, Svensson J, Sorbye H, Perren A. Mutation Spectrum in Liquid Versus Solid Biopsies From Patients With Advanced Gastroenteropancreatic Neuroendocrine Carcinoma. JCO Precis Oncol 2023; 7:e2200336. [PMID: 36753687 PMCID: PMC9928986 DOI: 10.1200/po.22.00336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
Abstract
PURPOSE Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and have a poor prognosis. Most GEP-NEC are diagnosed with metastatic disease, with only minor biopsies available for molecular diagnostics. We assessed the applicability of liquid biopsies for molecular profiling of GEP-NEC. MATERIALS AND METHODS We performed massive parallel sequencing of 76 cancer-related genes in circulating tumor DNA from 50 patients with advanced GEP-NEC and compared findings to previous analyses of solid tumor biopsies from the same patients. Plasma samples were collected before therapy, and the median time span between blood and tissue sampling was 25 days. RESULTS We detected 178 somatic mutations in the liquid biopsies, 127 (71%) were also detected in the solid biopsies, whereas 51 (29%) were unique to the liquid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (single nucleotide variants) in solid biopsies, of which 127 (64%) were also now detected in liquid biopsies. In exploratory subgroup assessments, concordance was higher in patients with liver metastases (P = 1.5 × 10-5) and increasing with level of liver involvement (P = 1.2 × 10-4). The concordance was similar between GEP-NEC with different primary sites, except being lower in esophageal cases (P = .001). Concordance was not associated with tumor mutation burden. Tumor tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumors (70%; P = 7.8 × 10-4). We identified potentially targetable mutations in plasma of 26 (52%) of patients with GEP-NEC; nine patients (18%) had potentially targetable mutation detected only in liquid biopsies. CONCLUSION Liquid biopsy analyses may be an applicable alternative to solid biopsies in GEP-NEC. Liquid biopsies may add additional mutations compared with tumor biopsies alone and could be useful for biomarker assessment in clinical trials for these patients.
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Affiliation(s)
- Stian Knappskog
- K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway,Department of Oncology, Haukeland University Hospital, Bergen, Norway,Stian Knappskog, PhD, K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway; Twitter: @KnappskogStian; e-mail:
| | - Tobias Grob
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Andreas Venizelos
- K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway,Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Ursula Amstutz
- Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
| | | | - Inger M. Lothe
- Department of Pathology, Oslo University Hospital, Oslo, Norway
| | - Christian Kersten
- Department of Research, Hospital of Southern Norway, Kristiansand, Norway
| | - Eva Hofsli
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway,Department of Oncology, St Olavs Hospital, Trondheim, Norway
| | - Anna Sundlöv
- Department of Oncology, Skåne University Hospital, Lund, Sweden,Department of Medical Radiation Physics, Lund University, Lund, Sweden
| | - Hege Elvebakken
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway,Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
| | - Herish Garresori
- Department of Oncology, Stavanger University Hospital, Stavanger, Norway
| | - Anne Couvelard
- Department of Pathology, Université Paris Cité and AP-HP, Bichat Hospital, Paris, France
| | - Johanna Svensson
- Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway,Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Aurel Perren
- Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
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Yamamoto S, Sakakibara N, Hirano H, Morizane C, Honma Y, Hijioka S, Okusaka T, Higashi T, Kawai A. The real-world selection of first-line systemic therapy regimen for metastatic gastroenteropancreatic neuroendocrine neoplasm in Japan. Sci Rep 2022; 12:17601. [PMID: 36266484 PMCID: PMC9585066 DOI: 10.1038/s41598-022-22718-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 10/18/2022] [Indexed: 01/13/2023] Open
Abstract
In November 2013, the first edition of evidence-based guidelines for treatment of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) was published in Japan. However, whether medical practitioners have adopted the first-line regimens recommended for metastatic GEP-NEN in clinical practice is not yet known. The purpose of this study was to identify which first-line systemic therapy regimens have been selected and the proportion of cases that are adherent to the guidelines (i.e., number of patients receiving recommended therapy/total number of patients). We combined hospital-based cancer registry data and insurance claims-equivalent data for patients with GEP-NEN treated between January 2013 and December 2014 and extracted those with metastatic GEP-NEN who received systemic therapy. The proportions that were adherent with the guideline were calculated according to tumor classification (neuroendocrine tumor [NET] or neuroendocrine carcinoma [NEC]), primary site (gastrointestinal or pancreatic), and hospital volume (high, medium, or low). The study included 109 patients with GEP-NET and 424 with GEP-NEC. Overall, guideline-adherent treatment was provided in only 54.8% of cases (58.1% for gastrointestinal NET, 63.6% for pancreatic NET, 56.6% for gastrointestinal NEC, and 44.9% for pancreatic NEC). The recommended therapy for GEP-NET was used in 16.5% of patients with GEP-NEC, and 21.5% received fluoropyrimidine-containing chemotherapy. This report is the first to describe real-world selection of first-line regimens for metastatic GEP-NEN. About half of all these patients received systemic therapy that was not recommended in the guidelines.
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Affiliation(s)
- Shun Yamamoto
- grid.272242.30000 0001 2168 5385Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan ,grid.272242.30000 0001 2168 5385Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Naoki Sakakibara
- grid.272242.30000 0001 2168 5385Division of Health Services Research, Institute for Cancer Control, National Cancer Center, Tokyo, Japan
| | - Hidekazu Hirano
- grid.272242.30000 0001 2168 5385Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Chigusa Morizane
- grid.272242.30000 0001 2168 5385Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 1040045 Japan
| | - Yoshitaka Honma
- grid.272242.30000 0001 2168 5385Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan ,grid.272242.30000 0001 2168 5385Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Susumu Hijioka
- grid.272242.30000 0001 2168 5385Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 1040045 Japan
| | - Takuji Okusaka
- grid.272242.30000 0001 2168 5385Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 1040045 Japan
| | - Takahiro Higashi
- grid.272242.30000 0001 2168 5385Division of Health Services Research, Institute for Cancer Control, National Cancer Center, Tokyo, Japan
| | - Akira Kawai
- grid.272242.30000 0001 2168 5385Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo, Japan
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Ulanja MB, Beutler BD, Antwi-Amoabeng D, Governor SB, Rahman GA, Djankpa FT, Alese OB. Prognostic Factors and Survival in Gastrointestinal Extrapulmonary Small Cell Carcinoma: A Retrospective Cohort Study. Ann Surg Oncol 2022; 29:8250-8260. [PMID: 35978206 DOI: 10.1245/s10434-022-12395-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/28/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare, aggressive neuroendocrine tumor. Factors affecting survival, including the prognostic significance of primary tumor site, remain under investigation. METHODS Data from the surveillance, epidemiology, and end results (SEER) program were extracted to identify patients diagnosed with GI EPSCCa between 2000 and 2018. Cox proportional hazard models were used to assess prognostic factors based on primary tumor site. RESULTS A total of 1687 patients were included in the survival analysis. The distribution of the primary tumor location was as follows: 31.5% colorectum (CRC), 22.1% esophageal, 20.6% pancreatic, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Esophagogastric and SI EPSCCa were more common among Black individuals, whereas CRC, HB, and pancreatic EPSCCa were more common among White patients (p = 0.012). There were no racial differences in OS for GI EPSCCa. HB EPSCCa was associated with inferior OS compared with esophageal tumors (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.00-1.46; p = 0.048), and SI EPSCCa was associated with prolonged survival compared with esophageal EPSCCa (aHR 0.76, 95% CI 0.48-1.20; p = 0.237) but did not reach statistical significance. Surgical intervention and a treatment period after 2006 were associated with superior OS. CONCLUSIONS The prognosis for GI ESPCCa varies based on site. Chemotherapy, radiation, and surgical resection are associated with improved outcomes; however, the prognosis for patients with EPSCCa remains dismal. Prospective studies are needed to guide therapy for this aggressive tumor.
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Affiliation(s)
- Mark B Ulanja
- Christus Ochsner St. Patrick Hospital, Lake Charles, LA, USA.
| | - Bryce D Beutler
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | | | - Ganiyu A Rahman
- Department of Surgery, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Francis Tanam Djankpa
- Department of Physiology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Olatunji B Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
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Woo LT, Ding YF, Mao CY, Qian J, Zhang XM, Xu N. Long-term survival of gastric mixed neuroendocrine-non-neuroendocrine neoplasm: Two case reports. World J Clin Cases 2022; 10:7936-7943. [PMID: 36158478 PMCID: PMC9372867 DOI: 10.12998/wjcc.v10.i22.7936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 02/21/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which consists of neuroendocrine and non-neuroendocrine components, is quite rare. Until now, most data on gastric MiNEN come from clinical cases, without large-scale retrospective studies or controlled clinical trials. Consequently, no consensus regarding the origin, molecular characteristics, or appropriate treatment of MiNEN has been reached so far. We conducted chemotherapy of irinotecan plus cisplatin (IP regimen) and surgery in two patients with gastric MiNEN, which had never been used in treating this kind of tumor, leading to their long-term survival for more than 3 and 7 years, respectively.
CASE SUMMARY We present two patients (one male and one female) with gastric MiNEN, with the primary manifestation of recurrent upper abdominal pain. After they were referred to our hospital, a diagnosis of gastric MiNEN was defined with the help of CT scan, and histopathological and immunohistochemical examinations on the samples of gastrointestinal endoscopy or radical surgery. The male patient (case 1) were found to have metastases in the reginal lymph nodes and the left liver. He received four cycles of IP regimens first, then the gastrectomy and partial left liver resection, followed by additional two cycles of IP chemotherapy. The female patient (case 2) underwent a laparoscopic gastrectomy, and received six cycles of IP regimen. She was found to have metastatic lesions in the right lung 2 years after that, and underwent video-assisted thoracoscopic surgery (VATS) of the lower lobe of the right lung. The two patients have now survived for more than 3 years and 7 years, respectively, without any evidence of recurrence or metastases.
CONCLUSION IP regimen, combined with curative-intent surgery if feasible, could be considered as the priority in the choice of front-line chemotherapy for gastric MiNEN.
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Affiliation(s)
- Lun-Tao Woo
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Yong-Feng Ding
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Chen-Yu Mao
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Jiong Qian
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Xiu-Ming Zhang
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Nong Xu
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
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Luecke S, Fottner C, Lahner H, Jann H, Zolnowski D, Quietzsch D, Grabowski P, Cremer B, Maasberg S, Pape UF, Mueller HH, Gress TM, Rinke A. Treatment Approaches and Outcome of Patients with Neuroendocrine Neoplasia Grade 3 in German Real-World Clinical Practice. Cancers (Basel) 2022; 14:2718. [PMID: 35681701 PMCID: PMC9179270 DOI: 10.3390/cancers14112718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/20/2022] [Accepted: 05/25/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Neuroendocrine neoplasia grade 3 (NEN G3) represents a rare and heterogeneous cancer type with a poor prognosis. The aim of our study was to analyze real-world data from the German NET Registry with a focus on therapeutic and prognostic aspects. METHODS NEN G3 patients were identified within the German NET Registry. Demographic data and data on treatments and outcomes were retrieved. Univariate analyses were performed using the Kaplan-Meier-method. Multivariate analysis was performed using a Cox proportional hazard model. RESULTS Of 445 included patients, 318 (71.5%) were diagnosed at stage IV. Well-differentiated morphology (NET G3) was described in 31.7%, 60% of cases were classified as neuroendocrine carcinoma (NEC), and the median Ki67 value was 50%. First-line treatment comprised chemotherapy in 43.8%, with differences in the choice of regimen with regard to NET or NEC, and surgery in 41.6% of patients. Median overall survival for the entire cohort was 31 months. Stage, performance status and Ki67 were significant prognostic factors in multivariate analysis. CONCLUSIONS The survival data of our national registry compare favorably to population-based data, probably mainly because of a relatively low median Ki67 of 50%. Nevertheless, the best first- and second-line approaches for specific subgroups remain unclear, and an international effort to fill these gaps is needed.
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Affiliation(s)
- Simone Luecke
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
| | - Christian Fottner
- Department of Internal Medicine I, Endocrinology, University Hospital Mainz, 55131 Mainz, Germany;
| | - Harald Lahner
- Department of Endocrinology and Metabolism, University Hospital of Essen, 45147 Essen, Germany;
| | - Henning Jann
- Department of Gastroenterology and Hepatology, Campus Virchow Klinikum, University Medicine Charité, 10117 Berlin, Germany;
| | | | - Detlef Quietzsch
- Praxis Dr. med. habil. Diener, 09376 Oelsnitz/Erzgebirge, Germany;
| | - Patricia Grabowski
- Klinikum Havelhöhe, Campus Virchow Klinikum, Institute of Medical Immunology, MVZ Oncology, University Medicine Charité, 10117 Berlin, Germany;
| | - Birgit Cremer
- Department of Oncology, University Hospital of Cologne, 50923 Cologne, Germany;
| | - Sebastian Maasberg
- Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, Germany; (S.M.); (U.-F.P.)
| | - Ulrich-Frank Pape
- Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, Germany; (S.M.); (U.-F.P.)
| | - Hans-Helge Mueller
- Institute of Medical Biometry and Epidemiology, Philipps University Marburg, 35037 Marburg, Germany;
| | - Thomas Matthias Gress
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
| | - Anja Rinke
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
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Ohmoto A, Fujiwara Y, Horita N, Nakano K, Takahashi S. Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: a systematic review and meta-analysis. Discov Oncol 2022; 13:40. [PMID: 35635617 PMCID: PMC9151982 DOI: 10.1007/s12672-022-00499-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 05/18/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Platinum-doublet chemotherapy has been conventionally used for patients with advanced gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) but evidence of chemotherapy is based on studies with small sample sizes and remains scarce. Thus, we conducted a systematic review and meta-analysis to elucidate the efficacy of platinum-doublet chemotherapy for advanced GEP-NEC. METHODS We performed a database search in PubMed/MEDLINE and EMBASE. Eligible studies were prospective and retrospective studies documenting the efficacy of platinum plus etoposide (EP) and platinum plus irinotecan (IP) for advanced GEP-NEC. Overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were pooled and weighted using generic inverse variance in a random-effects meta-analysis model. RESULTS Nineteen studies including 1157 patients were identified. The ORR of the platinum-doublet regimen, EP, and IP was 49.1% (95% confidence interval [CI], 41.8-56.5), 44.4% (95% CI: 35.9-53.0), and 59.4% (95% CI: 48.0-70.8). The pooled median OS of the platinum-doublet regimen, EP, and IP was 12.9 months (95% CI:10.9-15.3), 12.9 months (95% CI: 10.8-15.4), and 12.9 months (95% CI: 6.0-27.8), and the pooled median PFS of the platinum-doublet regimen, EP, and IP was 5.4 months (95% CI: 4.5-6.4), 5.4 months (95% CI 4.5-6.5), and 4.0 months (95% CI: 1.4-11.7), respectively. CONCLUSION Considerable response rate and survival time of the platinum-doublet regimen for advanced GEP-NEC were observed. IP and EP regimens can be reasonably applicable and these results provide a reference for oncologists in deciding the suitable regimen for patients with advanced GEP-NEC.
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Affiliation(s)
- Akihiro Ohmoto
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 1358550, Japan.
| | - Yu Fujiwara
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, 281 First Avenue, New York, NY, 10003, USA.
| | - Nobuyuki Horita
- Chemotherapy Center, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Kenji Nakano
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 1358550, Japan
| | - Shunji Takahashi
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 1358550, Japan
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Que QY, Zhang LC, Bao JQ, Ling SB, Xu X. Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:397-408. [PMID: 35734618 PMCID: PMC9160682 DOI: 10.4240/wjgs.v14.i5.397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/19/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.
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Affiliation(s)
- Qing-Yang Que
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Lin-Cheng Zhang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Jia-Qi Bao
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Sun-Bin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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A single center's experience of the extrapulmonary neuroendocrine carcinomas. North Clin Istanb 2022; 9:35-40. [PMID: 35340315 PMCID: PMC8889205 DOI: 10.14744/nci.2021.47887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 01/14/2021] [Indexed: 11/20/2022] Open
Abstract
Objective Extrapulmonary neuroendocrine carcinoma (EP-NEC) is a rare tumor type, and a standard therapy for EP-NEC has not yet been established. The purpose of this research was to explore the overall survival (OS) and therapeutic effects of platinum-etoposide combination therapy in EP-NEC. Methods This retrospective study was conducted based on the medical records from January 2010 to March 2020. Eligible patients had been pathologically diagnosed with EP-NEC. Results Forty-seven patients were included in the study. About 72.3% (n=34) of the patients were diagnosed with metastatic disease at the first diagnosis. The most common primary tumor site was the stomach. The median progression-free survival (PFS) of the patient group, who received the combination of platinum/etoposide, was 5.83 months (95% CI 4.46-7.20), whereas the median OS of the patients, who were found to have metastatic disease at the first diagnosis, was 13.6 months (95% CI 9.01-18.18). There was no difference in PFS and OS between patients with and without liver metastasis. Conclusion The outcome of advanced EP-NECs with platinum/etoposide chemotherapy remains poor. Obviously, there is a need for new, more effective treatment options.
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Dhakre VW, Purushothaman G, Doctor N. Gallbladder Neuroendocrine Tumors: Is There a Need for a Specific Approach? Gastrointest Tumors 2022; 9:5-11. [PMID: 35528747 PMCID: PMC9021648 DOI: 10.1159/000520988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/15/2021] [Indexed: 10/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) of the gallbladder or the biliary tree are rare. Most of the current guidelines and protocols are derived from the experience of managing lung small cell neuroendocrine carcinoma or gastrointestinal NETs. But, the overall outcome of gallbladder NETs (GB-NETs) seems worse than similarly staged lung NETs and adenocarcinoma of the gallbladder. This may be due to its rarity and lack of literature for a focused approach toward its treatment. Hence, the need for a specifically designed approach might help improve results of treatment for these rare tumors. We share our experience of 2 patients with GB-NETs and their 5-year outcome.
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Affiliation(s)
- Vijay Waman Dhakre
- Department of Surgery, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India
| | - Govind Purushothaman
- Department of Surgical Gastroenterology & HPB Surgery, Jaslok Hospital and Research Centre, Mumbai, India
| | - Nilesh Doctor
- Department of Surgical Gastroenterology & HPB Surgery, Jaslok Hospital and Research Centre, Mumbai, India
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Levy S, Verbeek WH, Eskens FA, van den Berg JG, de Groot DJA, van Leerdam ME, Tesselaar ME. First-line everolimus and cisplatin in patients with advanced extrapulmonary neuroendocrine carcinoma: a nationwide phase 2 single-arm clinical trial. Ther Adv Med Oncol 2022; 14:17588359221077088. [PMID: 35251315 PMCID: PMC8891910 DOI: 10.1177/17588359221077088] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/12/2022] [Indexed: 11/23/2022] Open
Abstract
Background: Extrapulmonary neuroendocrine carcinoma (EP-NEC) are an aggressive subgroup of neuroendocrine neoplasms (NEN). Advanced EP-NEC is generally treated with platinum-based cytotoxic regimens, but progressive disease occurs rapidly, resulting in a poor prognosis. Genetic alterations in the mammalian target for rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for treatment with the mTOR-inhibitor everolimus. Methods: A prospective phase 2 single-arm study included patients with advanced EP-NEC from three Dutch NEN expertise centres between March 2016 and January 2020. Treatment consisted of cisplatin 75 mg/m2 every 3 weeks in combination with daily everolimus 7.5 mg for a maximum of six cycles, followed by maintenance everolimus until disease progression. Primary endpoint was disease control rate (DCR), defined as the sum of overall response rate (ORR) plus the rate of stable disease according to RECIST 1.1, assessed at 9-week intervals. Toxicity was evaluated according to CTCAE version 5.0. Results: Thirty-nine patients, with a median age of 64 years (range: 28–74), of whom 20 (51%) were male, were enrolled. DCR was 82.1% (95% confidence interval (CI): 66.4–92.4), with an ORR of 58.9% (CI: 42.1–74.4). Median duration of response was 6.4 (CI: 5.8–7.0) months and median progression-free survival was 6.0 (CI: 4.3–7.8) months. Three patients (8%) had durable responses lasting > 12 months. Median overall survival was 8.7 (CI: 7.8–9.6) months. Most common grade 3/4 toxicities were haematological (36%) and renal (21%). Conclusion: Everolimus in combination with cisplatin is an effective first-line treatment option for advanced EP-NEC, especially in highly selected patients. Trial registration: Clinicaltrials.gov, NCT02695459, https://clinicaltrials.gov/ct2/show/NCT02695459.
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Affiliation(s)
- Sonja Levy
- Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
| | - Wieke H.M. Verbeek
- Department of Gastroenterological Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Ferry A.L.M. Eskens
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - José G. van den Berg
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Derk Jan A. de Groot
- Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Monique E. van Leerdam
- Department of Gastroenterological Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Margot E.T. Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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Kartal İ. Childhood neuroendocrine tumors of the digestive system: A single center experience. Medicine (Baltimore) 2022; 101:e28795. [PMID: 35147110 PMCID: PMC8830841 DOI: 10.1097/md.0000000000028795] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 01/18/2022] [Indexed: 01/04/2023] Open
Abstract
The prevalence and incidence of neuroendocrine tumors (NETs) are increasing in the pediatric population. This increase can be associated with improved diagnostics and increased detection rates of the disease. We aimed to discuss the clinical and pathological characteristics of patients with this rare disease who were followed and treated at our center.The medical records of children (aged 0-18 years) with NETs of the digestive system, followed up and treated between 2007 and 2020 at Ondokuz Mayis University Faculty of Medicine, were reviewed.Overall, 16 patients (8 girls and 8 boys) were analyzed. Fifteen patients had NETs in the appendix; 14 of these had grade I NETs, and 1 had grade II NETs. No additional surgery was performed except for appendectomy. All patients were in complete remission at the last follow-up (median 38 months). The other patient, a 12-year-old girl, had a primary hepatic neuroendocrine carcinoma (grade III NET). Three cycles of neoadjuvant and adjuvant platinum-based chemotherapy were administered, and right hepatectomy was performed to remove the mass. The patient is being followed-up for approximately 3 years without disease recurrence.Most NETs are observed in adults, and most studies have focused on this population. Unlike adults, increasing awareness of the disease in the pediatric population (especially in cases of acute appendicitis), discovering therapeutic treatments, and sharing experiences are crucial for developing an optimal therapeutic approach for pediatric NETs.
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Nakano M, Shimada Y, Matsumoto Y, Saiki T, Zhou Q, Sasaki K, Moriyama M, Yoshihara K, Natsumeda M, Kuriyama Y, Takii Y, Watanabe G, Umezu H, Okuda S, Ikeuchi T, Wakai T, Saijo Y. Efficacy of BRAF inhibitor and anti-EGFR antibody in colorectal neuroendocrine carcinoma. Clin J Gastroenterol 2022; 15:413-418. [PMID: 35133626 DOI: 10.1007/s12328-022-01599-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 01/25/2022] [Indexed: 01/16/2023]
Abstract
Neuroendocrine neoplasms of the colon and rectum are colorectal epithelial neoplasms with neuroendocrine differentiation. A platinum regimen used for small cell lung cancer is the currently recommended chemotherapy for gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), regardless of the organ. The BRAF V600E mutation has been recently reported as a druggable driver mutation in colorectal NECs. In BRAF V600E mutant colorectal cancer, a combination of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody, with or without a MEK inhibitor, is recommended. Here, we report the case of 77-year-old man who had lymph node recurrence after surgery for primary ascending colonic NEC. Two cytotoxic regimens, cisplatin plus irinotecan and modified FOLFOX6, were administered as first- and second-line chemotherapies with no remarkable response observed. At this point, genetic analysis confirmed the tumor harbored a BRAF V600E mutation. Thus, a regimen of BRAF inhibitor plus anti-EGFR antibody was administered. After commencing this regimen, carcinoembryonic antigen levels decreased within normal range, and there was dramatic shrinkage of the lymph node metastases observed by chest and abdominal computed tomography scans. To our knowledge, this is the first reported case of a colorectal NEC responding to a BRAF inhibitor and anti-EGFR antibody.
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Affiliation(s)
- Mae Nakano
- Medical Genome Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.,Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 9518510, Japan
| | - Yoshifumi Shimada
- Medical Genome Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan. .,Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 9518510, Japan.
| | - Yoshifumi Matsumoto
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Takuro Saiki
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Qiliang Zhou
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Kenta Sasaki
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Masato Moriyama
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Kosuke Yoshihara
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Manabu Natsumeda
- Department of Neurosurgery, Brain Research Institute, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Yoko Kuriyama
- Medical Genome Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.,Center for Medical Genetics, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Yasumasa Takii
- Department of Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, Japan
| | - Gen Watanabe
- Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, Japan
| | - Hajime Umezu
- Department of Pathology, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Shujiro Okuda
- Center for Genomic Data Management, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.,Medical AI Center/Bioinformatics Laboratory, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, Japan
| | - Takeshi Ikeuchi
- Center for Medical Genetics, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Toshifumi Wakai
- Medical Genome Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.,Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 9518510, Japan
| | - Yasuo Saijo
- Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Japan
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Kim HJ, Lee KH, Shim HJ, Hwang EC, Choi YD, Bang H, Cho SH, Chung IJ, Hwang JE, Lee MA, Bae WK. Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma. Chonnam Med J 2022; 58:29-36. [PMID: 35169557 PMCID: PMC8813653 DOI: 10.4068/cmj.2022.58.1.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 11/25/2022] Open
Abstract
Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.
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Affiliation(s)
- Hyeon-Jong Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Kang Han Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyun Jeong Shim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Eu Chang Hwang
- Department of Urology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Yoo-Duk Choi
- Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyunjin Bang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Sang Hee Cho
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Ik-Joo Chung
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
- Immunotherapy Innovation Center, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Jun Eul Hwang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Woo Kyun Bae
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
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Zhang J, Cao Y, Zhang P, Zhang X, Li J, Zhou J, Wang X, Peng Z, Sun Y, Li J, Shen L, Lu M. Serum Biomarker Status with a Distinctive Pattern in Prognosis of Gastroenteropancreatic Neuroendocrine Carcinoma. Neuroendocrinology 2022; 112:733-743. [PMID: 34592743 PMCID: PMC9533446 DOI: 10.1159/000519948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 09/26/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Gastroenteropancreatic neuroendocrine carcinoma (GEPNEC) is a major research focus, but the application of biomarkers to guide its prognostication and management is unsatisfying. Clinical values of conventional serum biomarkers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) warrant scrutiny. METHODS Patients diagnosed with GEPNEC with baseline NSE, CEA, and CA199 levels provided in Peking University Cancer Hospital were retrospectively studied. Relationships between biomarkers and prognosis were investigated by the χ2 test, Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses. RESULTS A total of 640 GEPNEC patients were enrolled. NSE, CEA, and CA199 were elevated in 59.5%, 28.5%, and 21.3% of the population, respectively. Higher NSE had worse median overall survival (OS) (17.0 months vs. not reached, hazard ratio = 2.77 [2.06, 3.73], p < 0.001), and so did patients with higher CEA and CA199. Multivariable analysis confirmed that NSE and CA199 correlated with OS independently. Baseline NSE level and NSE remission predicted OS and the response of patients with first-line etoposide plus cisplatin (EP) treatment. Furthermore, we combined NSE/CEA/CA199 to segregate GEPNEC into novel subgroups, namely, adenocarcinoma-like NEC (ALN), neuroendocrine-like NEC (NLN), and triple-normal NEC (TNN). The groups shared distinctive clinicopathologic features and prognosis (21.0 months vs. 17.1 months vs. not reached, p < 0.001). The EP regimen remained the priority treatment option in NLN/TNN, while ALN was predisposed to "adenocarcinoma-like chemotherapy." CONCLUSIONS Elevation of NSE, CEA, or CA199 was common and independently indicates poor prognosis in GEPNEC patients. Serum biomarker-based subtypes suggest meaningful clinical implications and appropriate therapeutic approaches, illuminating promising ways to characterize the prognosis of GEPNEC.
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Affiliation(s)
- Jianwei Zhang
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Yanshuo Cao
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Panpan Zhang
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Xiaotian Zhang
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Jian Li
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Jun Zhou
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Xicheng Wang
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Zhi Peng
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Yu Sun
- Peking University Cancer Hospital and Institute, Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China
| | - Jie Li
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Lin Shen
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
| | - Ming Lu
- Peking University Cancer Hospital and Institute, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing, China), Beijing, China
- *Ming Lu,
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Li S, Niu M, Deng W, Li N, Wei C, Zhang C, Luo S. Efficacy of Chemotherapy versus Transcatheter Arterial Chemoembolization in Patients with Advanced Primary Hepatic Neuroendocrine Carcinoma and an Analysis of the Prognostic Factors: A Retrospective Study. Cancer Manag Res 2021; 13:9085-9093. [PMID: 34916851 PMCID: PMC8671721 DOI: 10.2147/cmar.s343572] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/01/2021] [Indexed: 12/11/2022] Open
Abstract
Background Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare liver tumor, and there is no clear therapeutic recommendation for patients with advanced PHNEC. This study aims to compare the efficacy of platinum-based chemotherapy (etoposide combined with cisplatin/carboplatin, EP/EC) and transcatheter arterial chemoembolization (TACE) in patients with advanced PHNEC, and to evaluate the relevant prognostic factors. Patients and Methods The clinical data of 41 patients with advanced PHNEC from June 2014 to October 2019 were retrospectively reviewed. Results At a median follow-up time of 13.9 months, the median overall survival (OS) was 14.8 months in the EP/EC group and 12.2 months in the TACE group (P = 0.040). The median progression-free survival (PFS) was 4.4 months and 2.7 months in the EP/EC group and the TACE group, respectively (P = 0.005). No significant differences in the overall response rate and disease control rate were observed between the EP/EC group and the TACE group (26.1% vs 11.1%, P = 0.429; 73.9% vs 44.4%, P = 0.055, respectively). A univariate analysis indicated that the Eastern Cooperative Oncology Group performance status (ECOG PS), Ki-67, tumor number, and treatment options were prognostic factors for OS. A multivariate analysis further showed that ECOG PS (P < 0.001), Ki-67 (P = 0.003), and treatment options (P = 0.022) were independent prognostic factors for OS. Conclusion Ki-67, ECOG PS, and treatment options were the independent prognostic factors for OS in patients with advanced PHNEC. EP/EC may be a better choice for patients with advanced PHNEC.
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Affiliation(s)
- Shuyi Li
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Mengke Niu
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, People's Republic of China
| | - Wenying Deng
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Ning Li
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Chen Wei
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Chi Zhang
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Suxia Luo
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
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50
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Bardasi C, Spallanzani A, Benatti S, Spada F, Laffi A, Antonuzzo L, Lavacchi D, Marconcini R, Ferrari M, Rimini M, Caputo F, Santini C, Cerma K, Casadei-Gardini A, Andrikou K, Salati M, Bertolini F, Fontana A, Dominici M, Luppi G, Gelsomino F. Irinotecan-based chemotherapy in extrapulmonary neuroendocrine carcinomas: survival and safety data from a multicentric Italian experience. Endocrine 2021; 74:707-713. [PMID: 34231124 DOI: 10.1007/s12020-021-02813-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 06/22/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE Neuroendocrine carcinomas (NECs) are a rare subgroup of neuroendocrine neoplasms that occasionally originate from gastro-entero-pancreatic (GEP) tract. Evidence of the effectiveness of chemotherapy is scarce. Platinum plus Etoposide regimens are currently the standard treatment in first-line, while little data are available on second-line treatments. The aim of this study is to evaluate the efficacy and safety of irinotecan (IRI)-based chemotherapy in a series of extrapulmonary NECs. METHODS Patients with NEC diagnosis treated at University Hospitals of Modena, Florence, Pisa, and European Institute of Oncology of Milan with an IRI-based regimen (FOLFIRI or XELIRI) after progression to a first-line platinum-based therapy were enrolled. Objective responses were assessed according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS Thirty-four patients, 16 males, and 18 females, median age of 59 years (range 32-77), with metastatic NEC were included. Twenty-seven patients had Ki-67 ≥ 55% and four patients Ki-67 of <55% (for three patients data were not available). The median number of treatment cycles of the IRI-based regimen was 7.5 (range 1-16). Six partial responses (17.6%) and 9 stable diseases (26.5%) were observed, with a disease control rate of 44.1%. Median PFS and OS were 4.4 and 5.9 months, respectively. Neutropenia, anemia, and nausea were the only G3-G4 toxicities reported. CONCLUSIONS Despite the relatively small sample size, IRI-based therapy demonstrated to be a valid option for patients with pretreated extrapulmonary NEC.
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Affiliation(s)
- Camilla Bardasi
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Andrea Spallanzani
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Stefania Benatti
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Milan, Italy
| | - Alice Laffi
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Milan, Italy
| | - Lorenzo Antonuzzo
- Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Daniele Lavacchi
- Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
| | | | - Marco Ferrari
- Unit of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | - Margherita Rimini
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Francesco Caputo
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Chiara Santini
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Krisida Cerma
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, University Vita-Salute, San Raffaele Hospital, IRCCS, Milan, Italy
| | - Kalliopi Andrikou
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Massimiliano Salati
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Federica Bertolini
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Annalisa Fontana
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Massimo Dominici
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Gabriele Luppi
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Fabio Gelsomino
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.
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