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Ma R, Li G, Ye Y, Liang L, Wang C, Zhou H, Zhang P, An L, Shi G, Chen Q, Xu H, Gao Z. Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei. Transl Oncol 2025; 53:102279. [PMID: 39929063 DOI: 10.1016/j.tranon.2025.102279] [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: 10/30/2024] [Accepted: 01/05/2025] [Indexed: 03/01/2025] Open
Abstract
INTRODUCTION Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics. METHODS Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS). RESULTS Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. MUC16-mutated patients had worse PFS (P = 0.016) and OS (P = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) > 1(P = 0.026) or alterations in TP53 (P = 0.006) or SMAD4 (P = 0.013) had significantly worse OS compared to those with a TMB < 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (P = 0.003) or alterations in TGFBR2 (P = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (P = 0.020), TP53 (P = 0.004), and MUC16 (P = 0.013) were identified as independent prognostic factors for OS, while HRD status (P = 0.003) was independent predictors for PFS in PMP. CONCLUSIONS The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies.
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Affiliation(s)
- Ruiqing Ma
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China; Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China.
| | - Guojun Li
- Thorgene Co., Ltd., Beijing, 100176, China.
| | - Yingjiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
| | - Lei Liang
- Department of Ultrasound, Aerospace Center Hospital, Beijing, China
| | - Chong Wang
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Haipeng Zhou
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Pu Zhang
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Lubiao An
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Guanjun Shi
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Qian Chen
- Thorgene Co., Ltd., Beijing, 100176, China.
| | - Hongbin Xu
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China.
| | - Zhidong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
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Mukherjee S, Vagha S, Mukherjee M. Various Markers of Neuroendocrine Tumor: A Narrative Review. Cureus 2024; 16:e67493. [PMID: 39314560 PMCID: PMC11417284 DOI: 10.7759/cureus.67493] [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: 07/26/2024] [Accepted: 08/21/2024] [Indexed: 09/25/2024] Open
Abstract
Neuroendocrine tumors (NETs) are uncommon tumors that develop from specialized endocrine cells. Thyroid medullary carcinoma, phaeochromocytomas, pituitary tumors, carcinoid, and gastroenteropancreatic NET are just a few examples of the diverse group known as NET. In recent times, they have garnered significant interest due to their ease of palliation and ability to reveal the long-term impact of the specific hormone raised. Neuroendocrine indicators, particularly chromogranin A, are very helpful in the diagnostic process. Accurate biomarkers that can be employed for NET diagnosis, prognosis and follow-up, therapy stratification, and treatment response evaluation are greatly needed. Due to the great diversity of neuroendocrine neoplasms, particular biomarkers must be developed in order to diagnose, treat, and identify them. The several NET biomarkers covered in this review will aid in the fight against this uncommon illness.
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Affiliation(s)
- Sreetama Mukherjee
- Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunita Vagha
- Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Jiang K, Cao F, Yin L, Hu Y, Zhao X, Huang X, Ma X, Li J, Lu M, Sun Y. Claudin 18.2 expression in digestive neuroendocrine neoplasms: a clinicopathological study. J Endocrinol Invest 2024; 47:1251-1260. [PMID: 38060154 DOI: 10.1007/s40618-023-02245-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 11/09/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs). METHODS Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining. RESULTS Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%. CONCLUSION The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.
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Affiliation(s)
- K Jiang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - F Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - L Yin
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Y Hu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - X Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - X Huang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - X Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - J Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - M Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Y Sun
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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Batty K, Taylor AM, Bernard EJ, Diakos CI, Clarke SJ, Guminski A, Baron-Hay S, Boyle F, Pavlakis N, Chan DL. Metastatic primary breast neuroendocrine neoplasms: a case series. Intern Med J 2023; 53:1813-1818. [PMID: 36314732 DOI: 10.1111/imj.15961] [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: 08/09/2022] [Accepted: 10/05/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Breast neuroendocrine neoplasms represent a rare subtype of breast cancer which have not been well studied or characterised, particularly in the metastatic setting. AIM To present clinicopathological characteristics, treatment and outcomes of a series of patients with metastatic neuroendocrine carcinoma of the breast and review the current literature. METHODS We performed a retrospective review to identify and describe patients with metastatic neuroendocrine carcinoma of the breast at our centre between 2011 and 2021. Medical records, pathology and imaging results were examined to evaluate the clinical and histopathological features as well as the treatment pathways and prognosis of these patients. RESULTS We present a series of seven female patients with metastatic neuroendocrine carcinoma of the breast, as defined by the World Health Organization classification, over a period of 10 years (2011-2021) from a single centre. Median age at diagnosis was 48 years (range 39-63). Six of seven tissue samples expressed synaptophysin and chromogranin and were also oestrogen and progesterone receptor positive; median Ki-67 index was 50% (range 20-90%). All seven patients had demonstrated avidity on 18 F-FDG PET imaging, and the six who underwent 68 Ga-DOTATATE PET all had significant avidity. Treatment modalities and sequencing varied, but all patients received chemotherapy during their disease course. Six patients received three or more lines of treatment. Median overall survival was 31.8 months (range 3.7-108.6). Median progression-free survival (PFS) with first-line therapy for metastatic disease was 5.8 months (range 1.8-37.8). CONCLUSIONS This series shows the use of multiple modalities in treating this disease, with different sequencing in different patients. Despite multiple modalities used in the first-line setting, first-line PFS remains short. Larger series and further molecular characterisation are required to aid clinicians in managing this condition and to guide optimal treatment sequencing to improve outcomes in this rare patient group.
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Affiliation(s)
- Kathleen Batty
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Amelia M Taylor
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Elizabeth J Bernard
- Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Connie I Diakos
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
| | - Stephen J Clarke
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
| | - Alexander Guminski
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Sally Baron-Hay
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Frances Boyle
- Patricia Ritchie Centre for Breast Cancer Research, Mater Hospital, North Sydney and University of Sydney, The Mater Hospital, Sydney, New South Wales, Australia
- University of Sydney, Sydney, Australia
| | - Nick Pavlakis
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
| | - David L Chan
- Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
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Abstract
Most pancreatic neuroendocrine neoplasms are slow-growing, and the patients may survive for many years, even after distant metastasis. The tumors usually display characteristic organoid growth patterns with typical neuroendocrine morphology. A smaller portion of the tumors follows a more precipitous clinical course. The classification has evolved from morphologic patterns to the current World Health Organization classification, with better-defined grading and prognostic criteria. Recent advances in molecular pathology have further improved our understanding of the pathogenesis of these tumors. Various issues and challenges remain, including the correct recognition of a neuroendocrine neoplasm, accurate classification and grading of the tumor, and differentiation from mimickers. This review focuses on the practical aspects during the workup of pancreatic neuroendocrine neoplasms and attempts to provide a general framework to help achieve an accurate diagnosis, classification, and grading.
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Saleh M, Bhosale PR, Yano M, Itani M, Elsayes AK, Halperin D, Bergsland EK, Morani AC. New frontiers in imaging including radiomics updates for pancreatic neuroendocrine neoplasms. Abdom Radiol (NY) 2022; 47:3078-3100. [PMID: 33095312 DOI: 10.1007/s00261-020-02833-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/07/2020] [Accepted: 10/12/2020] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To illustrate the applications of various imaging tools including conventional MDCT, MRI including DWI, CT & MRI radiomics, FDG & DOTATATE PET-CT for diagnosis, staging, grading, prognostication, treatment planning and assessing treatment response in cases of pancreatic neuroendocrine neoplasms (PNENs). BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are very diverse clinically & biologically. Their treatment and prognosis depend on staging and primary site, as well as histological grading, the importance of which is also reflected in the recently updated WHO classification of GEP NENs. Grade 3 poorly differentiated neuroendocrine carcinomas (NECs) are aggressive & nearly always advanced at diagnosis with poor prognosis; whereas Grades-1 and 2 well-differentiated neuroendocrine tumors (NETs) can be quite indolent. Grade 3 well-differentiated NETs represent a new category of neoplasm with an intermediate prognosis. Importantly, the evidence suggest grade heterogeneity can occur within a given tumor and even grade progression can occur over time. Emerging evidence suggests that several non-invasive qualitative and quantitative imaging features on CT, dual-energy CT (DECT), MRI, PET and somatostatin receptor imaging with new tracers, as well as texture analysis, may be useful to grade, prognosticate, and accurately stage primary NENs. Imaging features may also help to inform choice of treatment and follow these neoplasms post-treatment. CONCLUSION GEP NENs treatment and prognosis depend on the stage as well as histological grade of the tumor. Traditional ways of imaging evaluation for diagnosis and staging does not yet yield sufficient information to replace operative and histological evaluation. Recognition of important qualitative imaging features together with quantitative features and advanced imaging tools including functional imaging with DWI MRI, DOTATATE PET/CT, texture analysis with radiomics and radiogenomic features appear promising for more accurate staging, tumor risk stratification, guiding management and assessing treatment response.
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Affiliation(s)
- Mohammed Saleh
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, Phoenix, AZ, 77030, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Ahmed K Elsayes
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Daniel Halperin
- GI Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Emily K Bergsland
- University of California San Francisco, San Francisco, CA, 94143, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA.
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Cox T, O'Connell M, Leeuwenkamp O, Palimaka S, Reed N. Real-world comparison of healthcare resource utilization and costs of [ 177Lu]Lu-DOTA-TATE in patients with progressive neuroendocrine tumors in England: a matched cohort analysis using data from the hospital episode statistics dataset. Curr Med Res Opin 2022; 38:1305-1317. [PMID: 35418254 DOI: 10.1080/03007995.2022.2065146] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To explore the healthcare resource utilization (HCRU) and costs for patients with progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with [177Lu]Lu-DOTA-TATE and matched patients treated with somatostatin analogs (SSAs), chemotherapy, or targeted therapies. METHODS Hospital Episode Statistics (HES) dataset 2016-2018 was used to compare HCRU and costs between the two cohorts. The [177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET, a procedure code for imaging or SSAs, and a subsequent code for radionuclide therapy. The non-[177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET who had an increased frequency of SSAs or switched from SSAs to chemotherapy or targeted therapies. Cohorts were matched on propensity scores with sex, age at disease progression, and Charlson Comorbidity Index as parameters. Healthcare Resource Group codes were used for costing. RESULTS A total of 199 matched patients were included. The [177Lu]Lu-DOTA-TATE cohort had lower overall costs (£1,882,028 vs. £3,016,321; p < .0001), non-elective inpatient spells (289 vs. 611 days) and costs (£849,569 vs. £1,707,109; p < .0001 for both), Accident & Emergency costs (£41,978 vs. £62,480; p = .0013), and average length of stay for overall inpatient spells (14.2 vs. 23.3 days; p = .1092) compared with the non-[177Lu]Lu-DOTA-TATE cohort. CONCLUSIONS These analyses indicate significantly lower overall costs and HCRU for progressive GEP-NET patients treated with [177Lu]Lu-DOTA-TATE. Current research reveals that future real-world analyses would further benefit from using additional databases linked to the HES dataset such as the Clinical Practice Research Datalink and/or National Cancer Registration and Analysis Service database.
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Affiliation(s)
- Tony Cox
- Open Health, Marlow, United Kingdom
| | | | - Oscar Leeuwenkamp
- Advanced Accelerator Applications/A Novartis Company, Geneva, Switzerland
| | - Stefan Palimaka
- Advanced Accelerator Applications/A Novartis Company, London, United Kingdom
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O'Neill E, Cornelissen B. Know thy tumour: Biomarkers to improve treatment of molecular radionuclide therapy. Nucl Med Biol 2022; 108-109:44-53. [PMID: 35276447 DOI: 10.1016/j.nucmedbio.2022.02.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 02/15/2022] [Accepted: 02/22/2022] [Indexed: 10/18/2022]
Abstract
Molecular radionuclide therapy (MRT) is an effective treatment for both localised and disseminated tumours. Biomarkers can be used to identify potential subtypes of tumours that are known to respond better to standard MRT protocols. These enrolment-based biomarkers can further be used to develop dose-response relationships using image-based dosimetry within these defined subtypes. However, the biological identity of the cancers treated with MRT are commonly not well-defined, particularly for neuroendocrine neoplasms. The biological heterogeneity of such cancers has hindered the establishment of dose-responses and minimum tumour dose thresholds. Biomarkers could also be used to determine normal tissue MRT dose limits and permit greater injected doses of MRT in patients. An alternative approach is to understand the repair capacity limits of tumours using radiobiology-based biomarkers within and outside patient cohorts currently treated with MRT. It is hoped that by knowing more about tumours and how they respond to MRT, biomarkers can provide needed dimensionality to image-based biodosimetry to improve MRT with optimized protocols and personalised therapies.
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Affiliation(s)
- Edward O'Neill
- MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.
| | - Bart Cornelissen
- MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK; Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, the Netherlands.
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Haslerud T. SPECT/CT in Neuroendrocrine Tumours. CLINICAL APPLICATIONS OF SPECT-CT 2022:95-118. [DOI: 10.1007/978-3-030-65850-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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10
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Marini I, Sansovini M, Bongiovanni A, Nicolini S, Grassi I, Ranallo N, Monti M, DI Iorio V, Germanò L, Caroli P, Sarnelli A, Paganelli G, Severi S. Theragnostic in neuroendocrine tumors. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2021; 65:342-352. [PMID: 34881852 DOI: 10.23736/s1824-4785.21.03426-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of different neoplasms with the same ligand, is a typical nuclear medicine tool. Applied for years, is also pivotal in neuroendocrine tumors (NETs) where it has improved the diagnostic accuracy and the therapeutic efficacy with impact on patient's survival. Theragnostic also allows the identification of important prognostic factors such as tumor location and burden, presence of liver metastases and intensity of somatostatin receptors (SSTR) expression to consider in new and possibly combined studies to ameliorate patient's outcome. Moreover, the possibility to evaluate receptor expression even in non-NET malignancies has de facto widened the possible indications for PRRT. We believe that this innovative therapeutic approach will be implemented in next years by radiomics and biological tumors characterization to better address PRRT applications.
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Affiliation(s)
- Irene Marini
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Maddalena Sansovini
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Alberto Bongiovanni
- Osteoncology and Rare Tumors Center - CDO-TR, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Silvia Nicolini
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Ilaria Grassi
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Nicoletta Ranallo
- Osteoncology and Rare Tumors Center - CDO-TR, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Manuela Monti
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Valentina DI Iorio
- Unit of Oncological Pharmacy, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Luca Germanò
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Paola Caroli
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Anna Sarnelli
- Unit of Medical Physics, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Giovanni Paganelli
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy
| | - Stefano Severi
- Unit of Nuclear Medicine, IRCCS Istituto Romagnolo per lo Studio dei Tumori - IRST Dino Amadori, Meldola, Forlì-Cesena, Italy -
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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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Ciobanu OA, Martin S, Fica S. Perspectives on the diagnostic, predictive and prognostic markers of neuroendocrine neoplasms (Review). Exp Ther Med 2021; 22:1479. [PMID: 34765020 PMCID: PMC8576627 DOI: 10.3892/etm.2021.10914] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/23/2021] [Indexed: 12/15/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumors with different types of physiology and prognosis. Therefore, prognostic information, including morphological differentiation, grade, tumor stage and primary location, are invaluable and contribute to the formulation of treatment decisions. Biomarkers that are currently used, including chromogranin A (CgA), serotonin and neuron-specific enolase, are singular parameters that cannot be used to accurately predict variables associated with tumor growth, including proliferation, metabolic rate and metastatic potential. In addition, site-specific biomarkers, such as insulin and gastrin, cannot be applied to all types of NENs. The clinical application of broad-spectrum markers, as it is the case for CgA, remains controversial despite being widely used. Due to limitations of the currently available mono-analyte biomarkers, recent studies were conducted to explore novel parameters for NEN diagnosis, prognosis, therapy stratification and evaluation of treatment response. Identification of prognostic factors for predicting NEN outcome is a critical requirement for the planning of adequate clinical management. Advances in ‘liquid’ biopsies and genomic analysis techniques, including microRNA, circulating tumor DNA or circulating tumor cells and sophisticated biomathematical analysis techniques, such as NETest or molecular image-based biomarkers, are currently under investigation as potentially novel tools for the management of NENs in the future. Despite these recent findings yielding promising observations, further research is necessary. The present review therefore summarizes the existing knowledge and recent advancements in the exploration of biochemical markers for NENs, with focus on gastroenteropancreatic-neuroendocrine tumors.
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Affiliation(s)
- Oana Alexandra Ciobanu
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
| | - Sorina Martin
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
| | - Simona Fica
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
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13
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Mohib O, Papleux E, Remmelink M, Gottignies P, De Bels D. An ectopic Cushing's syndrome as a cause of severe refractory hypokalemia in the ICU. Acta Clin Belg 2021; 76:373-378. [PMID: 32089125 DOI: 10.1080/17843286.2020.1734162] [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: 10/24/2022]
Abstract
Background: Ectopic Cushing's syndrome is a very rare condition caused by an ACTH-secreting tumor outside the pituitary or adrenal glands, and the majority of these cases are encountered in the context of paraneoplastic syndromes. The ectopic source of ACTH secretion is not always obvious to detection and can be challenging. We report a rare case, in which a hidden ACTH-secreting carcinoid tumor of the lung caused a severe refractory hypokalemia, leading us to a race against time to locate the tumor.Case presentation: A 33-year-old young male was admitted to the ICU for the management of a severe hypokalemia, and complains from several months of depression, increased weight, disabling non-radiating dorsal lower back pain and refractory arterial hypertension. The physical examination immediately suggested a Cushing's syndrome. The 24-h cortisoluria confirmed hypercortisolism and the increased ACTH level was oriented towards ACTH-dependent Cushing's syndrome. Thereafter, a dexamethasone suppression test was negative, indicating in favor of ectopic ACTH secretion. The etiological assessment via imaging and isotopes revealed a solitary pulmonary nodule at the right lower lobe estimated at 18 mm, the resection and anatomopathological analysis of which led to the diagnosis of carcinoid pulmonary tumor, and resolved hypercortisolism and its complications.Conclusion: A delayed diagnosis of Cushing's syndrome result in a consequent morbi-mortality, mainly due to cardiovascular events. The optimal treatment for ectopic Cushing's syndrome is surgical resection, thus making the localization of the tumor a key element.
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Affiliation(s)
- Othmane Mohib
- Internal Medicine Department, Brugmann University Hospital, Brussels, Belgium
| | | | - Myriam Remmelink
- Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Philippe Gottignies
- Department of Emergency and Intensive Care, IRIS Hospitals South, Brussels, Belgium
| | - David De Bels
- Department of Intensive Care, Brugmann University Hospital, Brussels, Belgium
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14
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Karls S, Gold R, Kravets S, Wang Y, Cheng S, Perez K, Chan J, Jacene H. Correlation of 68Ga-DOTATATE uptake on PET/CT with pathologic features of cellular proliferation in neuroendocrine neoplasms. Ann Nucl Med 2021; 35:1066-1077. [PMID: 34146243 DOI: 10.1007/s12149-021-01642-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 06/08/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation. METHODS This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVmax of the most intense lesion and the most intense organ-matched lesion were determined. Demographics and pathology results for Ki-67 and MI were collected from the electronic medical record. Correlations and trends for correlations of SUVmax to Ki-67 and MI were performed using Kruskal-Wallis and Cuzick trend tests. RESULTS A trend for an association between SUVmax and Ki-67 grade was found; median SUVmax of Ki-67 < 3%, 3-20%, and > 20% was 35.2, 31.8, and 12.8 (p = 0.077), respectively. There was also a trend between SUVmax and Ki-67 categories in organ-matched lesions (p = 0.08). The median organ-matched SUVmax of MI < 2, 2-20, and > 20 lesions was 34.2, 18, and 21.7, respectively, (Cuzick trend test p = 0.066). The median SUVmax for small bowel, pancreatic, and other primary locations was 27.6, 46.9, and 9.3 (p < 0.01), respectively. CONCLUSIONS The association between 68Ga-DOTATATE SUVmax, histologic grade, and primary site of NEN demonstrates its potential use for prognostication, or potentially as a surrogate for histologic grading when biopsy is not possible.
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Affiliation(s)
- Shawn Karls
- Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Avenue, DL203, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Richard Gold
- St. Georges University, School of Medicine, St. George, Grenada
| | - Sasha Kravets
- Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Yating Wang
- Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
| | - SuChun Cheng
- Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Kimberly Perez
- Program in Neuroendocrine and Carcinoid Tumors, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Jennifer Chan
- Program in Neuroendocrine and Carcinoid Tumors, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Heather Jacene
- Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Avenue, DL203, Boston, MA, 02215, USA.
- Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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15
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Thongtan T, Deb A, Islam S, Nugent K. Upper gastrointestinal bleeding as the initial manifestation of gastroenteropancreatic neuroendocrine tumors. Proc AMIA Symp 2021; 34:618-619. [PMID: 34456491 DOI: 10.1080/08998280.2021.1913372] [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: 09/30/2022] Open
Abstract
A 78-year-old man presented with upper gastrointestinal bleeding, which was biopsy proven to be from a gastric neuroendocrine tumor. By the time of diagnosis, he developed liver metastasis and died 2 months later. Upper gastrointestinal bleeding is an uncommon feature in gastroenteropancreatic neuroendocrine tumor.
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Affiliation(s)
- Thanita Thongtan
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Anasua Deb
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Sameer Islam
- Division of Gastroenterology, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
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16
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Holmager P, Langer SW, Federspiel B, Willemoe GL, Garbyal RS, Melchior L, Klose M, Kjaer A, Hansen CP, Andreassen M, Knigge U. Increase of Ki-67 index and influence on mortality in patients with neuroendocrine neoplasms. J Neuroendocrinol 2021; 33:e13018. [PMID: 34414612 DOI: 10.1111/jne.13018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 12/11/2022]
Abstract
An increase in the Ki-67 index in neuroendocrine neoplasms over time in relation to prognosis has scarcely been investigated. We aimed to assess whether the Ki-67 index changed over time and also whether a change influenced prognosis. Second, we investigated the difference in the Ki-67 index between primary tumour and metastases. From 1 January 1995 to 31 December 2019, 108 consecutive patients with gastroenteropancreatic tumours were included. Patients were followed with regard to an increase in the Ki-67 index and all-cause mortality. Ki-67 determination of the primary tumour at diagnosis and at the time of radiological progression, including developed metastases, was performed. A significant increase in the Ki-67 index was defined as a doubling of the value at disease progression compared to the value at diagnosis. In addition, in 14 patients, the Ki-67 index of the primary tumour and present metastases at the time of diagnosis was investigated. At diagnosis, there were no differences in the Ki-67 index between primary tumours and metastases (P = .41). Sixty-five patients had a doubling of the Ki-67 index. The median Ki-67 index at the time of progression 17% (1%-90%) vs 5% (1%-60%) at the time of diagnosis (P = .006). A doubling of the Ki-67 index was independently associated with all-cause mortality (hazard ratio = 2.7 [1.3-6.3], P = 0.02), after adjustment for relevant co-variables including the Ki-67 index at baseline. Doubling of the Ki-67 index at the time of disease progression was associated with a significantly higher risk of all-cause mortality. We recommend that a Ki-67 index is obtained whenever disease progression is recorded by demonstrated progression because it may have impact on the choice of treatment.
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Affiliation(s)
- Pernille Holmager
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Seppo W Langer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Birgitte Federspiel
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Gro Linno Willemoe
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Rajendra Singh Garbyal
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Linea Melchior
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Marianne Klose
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Andreas Kjaer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Carsten Palnaes Hansen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Mikkel Andreassen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Abstract
OPINION STATEMENT Treatment recommendations for advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are based on uncontrolled, mainly retrospective data. Chemotherapy can offer palliative relief, but long-lasting complete responses or cures are rare. The European Neuroendocrine Tumour Society (ENETS) and European Society for Medical Oncology (ESMO) recommend platinum-based chemotherapy as first-line treatment. This has been the golden standard since the late 1980s and has been evaluated in mostly retrospective clinical studies. However, progression is inevitable for most patients. Unfortunately, data on effective second-line treatment options are scant, and ENETS and ESMO recommendations propose fluorouracil- or temozolomide-based chemotherapy schedules. As such, there is a huge unmet need for improved care. Improved knowledge on GEP-NEC biology may provide a pathway towards more effective interventions including chemotherapy, targeted gene therapy, peptide receptor radionuclide therapy, as well as immune checkpoint inhibitors. The review summarises this current state of the art as well as the most promising developments for systemic therapy in GEP-NEC patients.
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Abstract
Several studies have demonstrated the effectiveness of somatostatin receptor (SSTR)-targeted imaging for diagnosis, staging, evaluating the possibility of treatment with cold somatostatin analogs, as well peptide receptor radionuclide therapy (PRRT), and evaluation of treatment response. PET with 68Ga-labeled somatostatin analogs provides excellent sensitivity and specificity for diagnosing and staging neuroendocrine tumors (NETs). Metabolic imaging with PET with fludeoxyglucose 18F/computed tomography (CT) complements the molecular imaging with 68Ga-SSTR PET/CT toward a personalized therapy in NET patients. The documented response rate of PRRT in NET summing up complete response, partial response, minor response, and stable disease is 70% to 80%.
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Affiliation(s)
- Margarida Rodrigues
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria.
| | - Hanna Svirydenka
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
| | - Irene Virgolini
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria
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Evaluation of SSTR2 Expression in SI-NETs and Relation to Overall Survival after PRRT. Cancers (Basel) 2021; 13:cancers13092035. [PMID: 33922482 PMCID: PMC8122794 DOI: 10.3390/cancers13092035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/03/2021] [Accepted: 04/14/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Small intestinal neuroendocrine tumors (SI-NETs) are slow growing tumors expressing somatostatin receptors (SSTR), which are targeted in diagnostic and therapeutic methods. A fairly new treatment that targets SSTR2 is peptide receptor radionuclide therapy (PRRT), which prolongs survival for patients with metastasized NETs. However, the treatment is costly, and the effect is variable. Therefore, finding predictors for treatment response is warranted. The aim of this retrospective study was to immunohistochemically analyze the SSTR2 expression in SI-NETs, using a previously constructed tissue microarray, and to investigate if a high SSTR2 expression was correlated to overall survival (OS). Among 42 patients that had received PRRT, 10 had at least one tumor with low SSTR2 expression. The patients were grouped according to the SSTR2 expression (“High SSTR2” and “Low SSTR2”) in previously resected tumors. In contrast to the hypothesis of the study, patients with low SSTR2 expression had significantly longer OS after PRRT, compared with patients with high SSTR2 expression. Hence, the study suggests that low SSTR2 expression in resected tumors should not exclude SI-NET patients from receiving PRRT. Abstract (1) Purpose: Small intestinal neuroendocrine tumors (SI-NETs) often present with distant metastases at diagnosis. Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a systemic treatment that increases overall survival (OS) in SI-NET patients with stage IV disease. However, the treatment response after PRRT, which targets somatostatin receptor 2 (SSTR2), is variable and predictive factors have not been established. This exploratory study aims to evaluate if SSTR2 expression in SI-NETs could be used to predict OS after PRRT treatment. (2) Methods: Using a previously constructed Tissue Micro Array (TMA) we identified tissue samples from 42 patients that had received PRRT treatment during 2006–2017 at Sahlgrenska University hospital. Immunohistochemical expression of SSTR2, Ki-67 and neuroendocrine markers synaptophysin and Chromogranin A (CgA) were assessed. A retrospective estimation of 177Lu-DOTATATE uptake in 33 patients was performed. Data regarding OS and non-surgical treatment after PRRT were collected. Another subgroup of 34 patients with paired samples from 3 tumor sites (primary tumor, lymph node and liver metastases) was identified in the TMA. The SSTR2 expression was assessed in corresponding tissue samples (n = 102). (3) Results: The patients were grouped into Low SSTR2 or High SSTR2 groups based upon on levels of SSTR2 expression. There was no significant difference in 177Lu-DOTATATE uptake between the groups. The patients in the Low SSTR2 group had significantly longer OS after PRRT than the patients in the High SSTR2 group (p = 0.049). PRRT treated patients with low SSTR2 expression received less additional treatment compared with patients with high SSTR2 expression. SSTR2 expression did not vary between tumor sites but correlated within patients. (4) Conclusion: The results from the present study suggest that retrospective evaluation of SSTR2 expression in resected tumors cannot be used to predict OS after PRRT.
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Chen Y, Tu J, Zhou S, Fu J, Wang Q. Poorer prognosis for neuroendocrine carcinoma than signet ring cell cancer of the colon and rectum (CRC-NEC): a propensity score matching analysis of patients from the Surveillance, Epidemiology, and End Results (SEER) database. Int J Colorectal Dis 2021; 36:745-756. [PMID: 33415449 DOI: 10.1007/s00384-020-03809-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Colorectal neuroendocrine carcinomas (CRC-NECs) are rare, comprising < 1% of colorectal cancers. This study aimed to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes of CRC-NEC. METHODS We analysed the Surveillance, Epidemiology, and End Results (SEER) database to identify patients from 20 to 74 years old diagnosed with CRC-NEC or common CRC (non-NEC) during 2004-2013. Log-rank testing was conducted to assess survival differences. A competing-risks regression model was used to adjust for covariate effects in the propensity score-matched (PSM) cohort, and adjusted hazard ratios (HRs) were calculated for the raw and PSM cohorts. RESULTS We identified 67,484 patients (344 CRC-NEC and 67,140 non-NEC). Lymph node metastasis (LNM) was more common in CRC-NEC (75.29%, n = 259) than in non-NEC (51.53%, n = 34,600) (P < 0.001); 56.40% (n = 194) of CRC-NECs were located on the right side, while 18.31% (n = 63) were located on the left side, with a statistically significant difference in distribution (P < 0.001) compared to that in non-NEC CRC. Multivariate analysis indicated that a left-side location was an independent adverse prognostic factor for CRC-NEC (P = 0.043). CRC-NEC had the poorest cancer-specific survival (median CSS, 9.0 months) among assessed cancers, even poorer than that of signet ring cell cancer (median CSS, 24.0 months). However, both radical operation (P = 0.007) and chemotherapy (P = 0.008) were beneficial for CSS. CONCLUSION NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.
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Affiliation(s)
- Youwei Chen
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China
| | - Jiangfeng Tu
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China
| | - Shishi Zhou
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China
| | - Jianfei Fu
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China.
| | - Qinghua Wang
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, China.
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21
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Evers M, Rinke A, Rütz J, Ramaswamy A, Maurer E, Bartsch DK. Prognostic Factors in Curative Resected Locoregional Small Intestine Neuroendocrine Neoplasms. World J Surg 2021; 45:1109-1117. [PMID: 33416940 DOI: 10.1007/s00268-020-05884-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND Small intestinal neuroendocrine neoplasms (SI-NEN) are rare, and only about 40% of patients are diagnosed without distant metastases. Aim of the study was to identify prognostic factors in patients with potentially curative resected locoregional SI-NEN. METHODS Patients with curative resected locoregional SI-NEN (ENETS stages I-III) were retrieved from a prospective data base. Demographic, surgical and pathological data of patients with and without disease recurrence were retrospectively analyzed using univariate and multivariate analysis. RESULTS In a 20-year period, 65 of 203 (32%) patients with SI-NEN were operated for stages I-III disease. Thirty-eight (58.5%) patients were men, and the median age at surgery was 59 (range 37-87) years. After median follow-up of 65 months, 14 patients experienced disease relapse median 28.5 (range 6-122) months after initial surgery, of which 2 died due to their disease. Multivariate analysis revealed age ≥ 60 years (HR = 6.41, 95% CI 1.38-29.67, p = 0.017), tumor size ≥ 2 cm (HR = 26.54, 95% CI 4.46-157.62, p < 0.001), lymph node ratio > 0.5 (HR 7.18, 95% CI 1.74-29.74, p = 0.007) and multifocal tumor growth (HR = 6.98, 95% CI 1.66-29.39, p = 0.008) as independent negative prognostic factors and right hemicolectomy compared to segmental small bowel resection (HR = 0.04, 95% CI 0.01-0.24, p < 0.001) as independent protector against recurrence. CONCLUSION Patients with locoregional SI-NEN with an age ≥ 60 years, tumor size ≥ 2 cm, lymph node ratio > 0.5 and multiple small bowel tumor foci have an increased risk for recurrence and might benefit from adjuvant treatment. In contrast, right hemicolectomy of ileal SI-NEN seems to reduce the risk of recurrence.
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Affiliation(s)
- Maximilian Evers
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Johannes Rütz
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Annette Ramaswamy
- Department of Pathology, Philipps-University Marburg, Marburg, Germany
| | - Elisabeth Maurer
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany.
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22
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Benhaim L, Faron M, Hadoux J, Gelli M, Sourrouille I, Burtin P, Honoré C, Malka D, Leboulleux S, Ducreux M, Scoazec JY, Goere D, Baudin E. Long-Term Results after Surgical Resection of Peritoneal Metastasis from Neuroendocrine Tumors. Neuroendocrinology 2021; 111:599-608. [PMID: 32512564 DOI: 10.1159/000509220] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 06/08/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Peritoneal metastases from neuroendocrine tumors are associated with a bad prognosis. The objective of our study was to evaluate whether surgical resection could lead to prolonged survival in selected patients. This survival was compared to that of patients operated for liver metastasis. METHODS From our prospectively maintained database we included 88 patients who underwent the complete resection of peritoneal and/or liver metastasis between January 1995 and December 2016 in Gustave-Roussy. Three resection groups were compared: peritoneal metastasis alone, liver metastasis alone, and the combined resection of liver and peritoneal metastases. RESULTS The median peritoneal cancer index was 10 in the peritoneal group and 11 in the peritoneal + liver group. The 5-year overall survival was 81% (60-100) in the peritoneal group compared to 78% (65.2-92.8) in the liver group, and 72% (58.7-89.7) in the peritoneal + liver group (p = 0.71). The 3-year disease-free survival reached 26.9% (16.1-45.1) in the liver group, 12.5% (2.3-68.2) in the peritoneal group, and 32.4% (19.9-52.6) in the combined liver + peritoneal group (p = 0.45). In the univariate analysis, the prognosis factors for a longer survival were: small bowel primary tumor origin, low preoperative chromogranin A level, and tumor grade ≤1. CONCLUSION Despite a high recurrence rate, long-term overall survival can be achieved after the resection of peritoneal metastasis in selected patients. This survival is comparable to that of patients operated for liver metastasis only. Surgery should stand as a standard treatment for peritoneal metastases in patients with resectable disease.
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Affiliation(s)
- Léonor Benhaim
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France,
| | - Matthieu Faron
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
- Department of Biostatistics and Epidemiology, INSERM Unit 1018 CESP, Oncostat Team, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Julien Hadoux
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Maximiliano Gelli
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Isabelle Sourrouille
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Pascal Burtin
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Charles Honoré
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - David Malka
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Sophie Leboulleux
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Michel Ducreux
- Department of Gastro-enterology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Jean-Yves Scoazec
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
| | - Diane Goere
- Department of Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France
| | - Eric Baudin
- Department of Nuclear Medicine, Gustave Roussy Cancer Campus, Villejuif, France
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Muniraj T, Aslanian HR. Pancreatic Neuroendocrine Tumors. GERIATRIC GASTROENTEROLOGY 2021:1933-1951. [DOI: 10.1007/978-3-030-30192-7_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Aburjania Z, Whitt JD, Jang S, Nadkarni DH, Chen H, Rose JB, Velu SE, Jaskula-Sztul R. Synthetic Makaluvamine Analogs Decrease c-Kit Expression and Are Cytotoxic to Neuroendocrine Tumor Cells. Molecules 2020; 25:molecules25214940. [PMID: 33114525 PMCID: PMC7663375 DOI: 10.3390/molecules25214940] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/14/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022] Open
Abstract
In an effort to discover viable systemic chemotherapeutic agents for neuroendocrine tumors (NETs), we screened a small library of 18 drug-like compounds obtained from the Velu lab against pulmonary (H727) and thyroid (MZ-CRC-1 and TT) neuroendocrine tumor-derived cell lines. Two potent lead compounds (DHN-II-84 and DHN-III-14) identified from this screening were found to be analogs of the natural product makaluvamine. We further characterized the antitumor activities of these two compounds using pulmonary (H727), thyroid (MZ-CRC-1) and pancreatic (BON) neuroendocrine tumor cell lines. Flow cytometry showed a dose-dependent increase in apoptosis in all cell lines. Induction of apoptosis with these compounds was also supported by the decrease in myeloid cell leukemia-1 (MCL-1) and X-chromosome linked inhibitor of apoptosis (XIAP) detected by Western blot. Compound treatment decreased NET markers chromogranin A (CgA) and achaete-scute homolog 1 (ASCL1) in a dose-dependent manner. Moreover, the gene expression analysis showed that the compound treatment reduced c-Kit proto-oncogene expression in the NET cell lines. Induction of apoptosis could also have been caused by the inhibition of c-Kit expression, in addition to the known mechanisms such as damage of DNA by topoisomerase II inhibition for this class of compounds. In summary, makaluvamine analogs DHN-II-84 and DHN-III-14 induced apoptosis, decreased neuroendocrine tumor markers, and showed promising antitumor activity in pulmonary, thyroid, and pancreatic NET cell lines, and hold potential to be developed as an effective treatment to combat neuroendocrine tumors.
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Affiliation(s)
- Zviadi Aburjania
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
| | - Jason D. Whitt
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
| | - Samuel Jang
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
| | - Dwayaja H. Nadkarni
- Department of Chemistry, University of Alabama at Birmingham, 901 14th Street S., Birmingham, AL 35294, USA;
| | - Herbert Chen
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA
| | - J. Bart Rose
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
| | - Sadanandan E. Velu
- Department of Chemistry, University of Alabama at Birmingham, 901 14th Street S., Birmingham, AL 35294, USA;
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA
- Correspondence: (S.E.V.); (R.J.-S.); Tel.: +1-(205)-975-2478 (S.E.V.); +1-(205)-975-3507 (R.J.-S.); Fax: +1-(205)-934-2543 (S.E.V.); +1-(205)-934-0135 (R.J.-S.)
| | - Renata Jaskula-Sztul
- Department of Surgery, University of Alabama at Birmingham, 1824 6th Avenue S., Birmingham, AL 35233, USA; (Z.A.); (J.D.W.); (S.J.); (H.C.); (J.B.R.)
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USA
- Correspondence: (S.E.V.); (R.J.-S.); Tel.: +1-(205)-975-2478 (S.E.V.); +1-(205)-975-3507 (R.J.-S.); Fax: +1-(205)-934-2543 (S.E.V.); +1-(205)-934-0135 (R.J.-S.)
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Duan X, Zhao M, Zhang S, Xu Z, Mi L, Shi J, Ma X, Liu Y, Li N, Yin X, Han X, Han G, Wang J, Xu J, Yin F. Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs. Int J Colorectal Dis 2020; 35:1255-1264. [PMID: 32314191 DOI: 10.1007/s00384-020-03596-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/04/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.
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Affiliation(s)
- Xiaoling Duan
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Man Zhao
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Shenglei Zhang
- Department of Nephrology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Zhibin Xu
- Department of Endoscope Room, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, China
| | - Lili Mi
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Jianfei Shi
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Xiaoying Ma
- Department of Nephrology, Cangzhou Central Hospital, Xinhua Road, Cangzhou, 061000, Hebei, China
| | - Yueping Liu
- Department of Pathology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, China
| | - Ning Li
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Xiaolei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Xin Han
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Guangjie Han
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Jinfeng Wang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China
| | - Jinsheng Xu
- Department of Nephrology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China.
| | - Fei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050019, Hebei, People's Republic of China.
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Sun S, Wang W, He C. Development and Validation of Prognostic Nomograms for Patients with Duodenal Neuroendocrine Neoplasms. Med Sci Monit 2020; 26:e922613. [PMID: 32564052 PMCID: PMC7331477 DOI: 10.12659/msm.922613] [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: 11/22/2022] Open
Abstract
Background This study was designed to predict prognosis of patients with primary duodenal neuroendocrine neoplasms (D-NENs) by developing nomograms. Material/Methods Patients diagnosed with D-NENs between 1988 and 2015 were queried from the SEER database and a total of 965 appropriate cases were randomly separated into the training and validation sets. Kaplan-Meier analysis was used to generated survival curves, and the difference among the groups was assessed by the log-rank test. Independent prognostic indicators were acquired by Cox regression analysis, and were used to develop predictive overall survival (OS) and cancer-specific survival (CSS) nomograms. Harrell’s concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the efficacy of nomograms. Tumor stage was regarded as a benchmark in predicting prognostic compared with the nomograms built in this study. Results The C-index was 0.739 (0.690–0.788) and 0.859 (0.802–0.916) for OS and CSS nomograms, respectively. Calibration curves exhibited obvious consistency between the nomograms and the actual observations. In addition, C-index, AUC, and DCA were better than tumor stage in the evaluative performance of nomograms. Conclusions The nomograms were able to predict the 1-, 5-, and 10-year OS and CSS for D-NENs patients. The good performance of these nomograms suggest that they can be used for evaluating the prognosis of patients with D-NENs and can facilitate individualized treatment in clinical practice.
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Affiliation(s)
- Shenghong Sun
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China (mainland)
| | - Wei Wang
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China (mainland)
| | - Chiyi He
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China (mainland)
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Akaike T, Qazi J, Anderson A, Behnia FS, Shinohara MM, Akaike G, Hippe DS, Thomas H, Takagishi SR, Lachance K, Park SY, Tarabadkar ES, Iyer JG, Blom A, Parvathaneni U, Vesselle H, Nghiem P, Bhatia S. High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma. Br J Dermatol 2020; 184:319-327. [PMID: 32320473 DOI: 10.1111/bjd.19150] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.
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Affiliation(s)
- T Akaike
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - J Qazi
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - A Anderson
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - F S Behnia
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - M M Shinohara
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - G Akaike
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - D S Hippe
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - H Thomas
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - S R Takagishi
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - K Lachance
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - S Y Park
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - E S Tarabadkar
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - J G Iyer
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - A Blom
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - U Parvathaneni
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - H Vesselle
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - P Nghiem
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA, USA.,Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - S Bhatia
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA.,Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA
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Samanta STN, Mehta SPB, Patel TS, Jetly DH. Clinicopathological Study of 100 Cases of Neuroendocrine Neoplasms of the Gastroenteropancreatic System: A Tertiary Cancer Center Experience. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_217_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Abstract
Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is on the rise. Although the clinicopathologic characteristics of NENs have been previously reviewed in the literature, the data published in the Indian literature so far are sparse. This study aims to review the clinicopathological features of GEP-NENs, diagnosed at our institution, and that were classified and graded according to the World Health Organization 2010 classification system. Materials and Methods: One hundred patients with GEP-NENs presenting to our institute from August 2012 to May 2016 were analyzed retrospectively. Demographic data and tumor characteristics were expressed as number, percentage, and mean value. Tumor grade was correlated to metastasis through the Chi-square test. p < 0.05 was considered statistically significant. Results: Of the 100 cases studied, 58 were male and 42 were female. The most common primary site was the pancreas (n = 36), followed by the small intestine (n = 19), esophagus (n = 17), stomach (n = 15), colon (n = 6), rectum (n = 4), and appendix (n = 3). The incidence of neuroendocrine tumor (NET) Grade 1 (NET G1) was higher (n = 40) compared to NET Grade 2 (NET G2) (n = 25) and neuroendocrine carcinoma Grade 3 (NEC G3) (n = 35). Overall in these 100 cases, NET G1 tumors and NET G2 tumors were most common in the pancreas (n = 18/36) and (n = 13/36), respectively. NEC G3 tumors were most common in the esophagus (n = 16/17). The most common site of distant metastasis was the liver (n = 23/26). Conclusion: We elucidated the epidemiological and clinicopathological features of patients presenting to our institute with GEP-NENs.
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Affiliation(s)
| | | | - Trupti S Patel
- Department of Pathology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Dhaval H Jetly
- Department of Pathology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
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Lung MS, Hicks RJ, Pavlakis N, Link E, Jefford M, Thomson B, Wyld DK, Liauw W, Akhurst T, Kuru N, Michael M. The INTERNET STUDY: A phase II study of everolimus in patients with fluorodeoxyglucose ( 18 F) positron-emission tomography positive intermediate grade pancreatic neuroendocrine tumors. Asia Pac J Clin Oncol 2020; 16:150-157. [PMID: 32030887 DOI: 10.1111/ajco.13307] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 01/07/2020] [Indexed: 12/24/2022]
Abstract
AIMS This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) avidity. FDG-PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki-67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG-PET-avid G2 PNETs and prospectively evaluated progression-free survival (PFS) and response in the first-line setting. METHODS Patients with FDG-PET-avid G2 advanced PNET received everolimus 10 mg daily until disease progression. Patients were staged every 12 weeks with CT/MRI and FDG-PET and every 24 weeks with Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE, GaTate) PET. The primary endpoint was PFS at 6 months. Overall survival rate, PET/structural imaging response and toxicity were also measured. RESULTS Nine patients were accrued from December 2012 to February 2015. Median treatment duration was 13.8 months. The estimated PFS rate at 6 months was 78%. The best response on CT/MRI was stable disease in nine patients (100%) and partial response on FDG-PET in five patients (55.5%). Treatment-related adverse effects were consistent with previous studies of everolimus. CONCLUSION Everolimus is active with prolonged disease control in poor prognosis FDG-avid G2 PNETs. Treatment individualization based on functional imaging warrants further evaluation.
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Affiliation(s)
- Mei Sim Lung
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Rodney J Hicks
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia
| | - Emma Link
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.,Biostatistics and Clinical Trials Centre, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre Building, Melbourne, VIC, Australia
| | - Michael Jefford
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Benjamin Thomson
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,University of Melbourne Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - David K Wyld
- Department of Medical Oncology, Royal Brisbane and Women's Hospital, QLD, Australia.,School of Medicine, University of Queensland, QLD, Australia
| | - Winston Liauw
- Department of Medical Oncology, Cancer Care Centre, Kogarah, NSW, Australia
| | - Timothy Akhurst
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Narmatha Kuru
- Biostatistics and Clinical Trials Centre, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre Building, Melbourne, VIC, Australia
| | - Michael Michael
- Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
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Bukhari MH, Coppola D, Nasir A. Clinicopathologic analysis of primary gastroenteropancreatic poorly differentiated neuroendocrine carcinoma; A ten year retrospective study of 68 cases at Moffit Cancer Center. Pak J Med Sci 2019; 36:265-270. [PMID: 32063972 PMCID: PMC6994874 DOI: 10.12669/pjms.36.2.1336] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective: To assess clinicopathological characteristics of primary gastro-entero-pancreatic poorly differentiated neuroendocrine carcinomas (GEP-PDNECAs) and evaluate overall survival in patients treated with systemic platinum and etoposide therapy. Methods: A detailed retrospective review of clinico-pathologic data (1999-2009) on 68 consecutive adult patients with primary GEP-PDNECAs was carried out, from H Lee Moffit Cancer Center and Research Institute, Tampa, Florida; USA, based on electronic patient records, specialty consultation files, tumor registry, social security index and pathology archives. All available tumor slides were reviewed and subtyped by neuro-endocrine pathologists. Clinicopathologic data and patient survival were analyzed. Results: Of 68 patients 41 were males and 27 females with a mean age of 42 years (range: 25-76 years). Regarding the site of origin, 39 patients were of the colorectal location, 19 from the pancreas, 04 from small intestines, 03 from stomach and 03 were multi-focal from colon, small intestine and pancreas. Sixty three of 68 (93%) patients presented with lymph node/distant metastases. Of 68 tumors 37 (54%) were classified as small cell carcinoma (SCCA), 16 (24%) large cell carcinoma (LCCA), 5 (7%) mixed small and large cell (MSLCCA) and 10 (15%) poorly differentiated carcinoma with neuroendocrine features (PDCA-NEF). Neuroendocrine differentiation was confirmed by positivity for chromogranin in 38/65 (55%), synaptophysin in 62/67 (92%) and CD56 in 17/21 (81%) cases. One neuroendocrine marker was positive in 22/68 (32%), 2 in 40/68 (59%) and all 3 were positive in 9/68 (13%) cases. Fifty-eight of 68 (85%) patients were treated with platinum and etoposide. Overall patient survival at 1, 3 5 and 10 years was 85%, 40%, 16% and 1.5% respectively. Patient survival was independent of age (r= 0.1022), sex (r= -0.909) and histologic tumor subtype (r=0.1028) (p= 0.128) but was related to distant metastases (r=0.306; p=0.0383). Conclusions: GEP-PDNECA occurred in many part of the GI tract, most commonly in the colorectal region. Positivity of neuroendocrine markers was variable, which helped to confirm neuro-endocrine differentiation and to avoid under-diagnosis of GEP-PDNECA, especially in metastatic setting. Overall prognosis of GEP-PDNECA patients following platinum and etoposide therapy in our series was relatively favorable but remained poor in the presence of distant metastases.
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Affiliation(s)
- Mulazim Hussain Bukhari
- Prof. Mulazim Hussain Bukhari, MBBS, DCP, MPhil, FCPS, CHPE, PhD. Department of Pathology, UCMD, University of Lahore, Lahore, Pakistan
| | - Domenico Coppola
- Domenico Coppola, MD. Emeritus Professor of Inter-disciplinary Oncology, Department of Anatomic Pathology, H. Lee Moffitt Cancer Center Tampa, FL, USA
| | - Aejaz Nasir
- Aejaz Nasir, MD, MPhil, FCAP. Chief Pathologist, BJ's Diagnostic & Precision Oncology, Tampa, FL, USA
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Nehme F, Rowe K, Palko W, Tofteland N, Salyers W. Autoimmune metaplastic atrophic gastritis and association with neuroendocrine tumors of the stomach. Clin J Gastroenterol 2019; 13:299-307. [PMID: 31782113 DOI: 10.1007/s12328-019-01074-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/19/2019] [Indexed: 02/07/2023]
Abstract
Autoimmune metaplastic atrophic gastritis (AMAG) previously called type A chronic gastritis is an immune-mediated chronic inflammatory disease characterized by the immune-mediated destruction of gastric parietal cells in the fundus and body of the stomach. AMAG is an uncommon disease that often presents with hematological manifestations and may lead to the development of gastric carcinoids. AMAG can be reliably diagnosed by antibody assays, functional serology, and histology. The understanding of the disease process is essential for the detection and management of hematological complications and gastric lesions. The prevalence of AMAG is on the rise and subsequently gastric carcinoids. However, this association is not well recognized in clinical practice, and management and diagnosis of AMAG and gastric carcinoids remain suboptimal. In the current review, we will discuss the pathophysiology, diagnosis and management of AMAG. A special focus is given to the association between AMAG and gastric carcinoids. We will also review the management options of type 1 gastric carcinoids.
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Affiliation(s)
- Fredy Nehme
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City, 4800 Oak Street, Kansas, MO, 64112, USA.
| | - Kyle Rowe
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Dallas, TX, USA
| | - William Palko
- Department of Pathology, Kansas University School of Medicine, Wichita, KS, USA
| | - Nathan Tofteland
- Department of Gastroenterology and Hepatology, Kansas University School of Medicine, Wichita, KS, USA
| | - William Salyers
- Department of Gastroenterology and Hepatology, Kansas University School of Medicine, Wichita, KS, USA
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Basile ML, Kuga FS, Del Carlo Bernardi F. Comparation of the quantification of the proliferative index KI67 between eyeball and semi-automated digital analysis in gastro-intestinal neuroendrocrine tumors. SURGICAL AND EXPERIMENTAL PATHOLOGY 2019. [DOI: 10.1186/s42047-019-0045-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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Abstract
OBJECTIVES Gallium (Ga)-DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake. METHODS We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUVmax) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient. RESULTS Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0-2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5-10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26-34). There was a correlation between Ki-67 PI and SUVmax (r = -0.3, P = 0.018). CONCLUSIONS Our analysis demonstrates an inverse correlation between Ki-67 PI and SUVmax in NETs. Somatostatin receptor-PET provides additional information that can help guide management of NETs.
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Hamano Y, Moriwaki T, To K, Watahiki T, Yamada T, Sakashita S, Hyodo I. A Neuroendocrine Tumor of Unknown Primary Origin that Responded to Treatment Based on Tumor Grade Progression. Intern Med 2019; 58:1087-1091. [PMID: 30568142 PMCID: PMC6522411 DOI: 10.2169/internalmedicine.1809-18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
The standard chemotherapies for neuroendocrine tumors (NETs) are somatostatin analog (SSA) and targeted-agents for NET G1/G2 and platinum-based chemotherapy for neuroendocrine carcinoma (NEC), classified according to the WHO criteria of 2010. We report a case of NET, in which tumors were successfully treated with platinum-containing chemotherapy after remarkable progression with SSA. A 46-year-old man with multiple lymph nodes and liver metastases of unknown primary origin was diagnosed with NET G2 based on the examination of a biopsy specimen. His tumors were stable with SSA for a year, but rapidly became enlarged. A second biopsy revealed NEC. He received cisplatin plus etoposide, and his tumors showed a marked reduction in size.
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Affiliation(s)
- Yukako Hamano
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Toshikazu Moriwaki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Keii To
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Takahisa Watahiki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Takeshi Yamada
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Shingo Sakashita
- Department of Pathology, Faculty of Medicine, University of Tsukuba, Japan
| | - Ichinosuke Hyodo
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
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Komaç Ö, Bengi G, Sağol Ö, Akarsu M. C-reactive protein may be a prognostic factor for the whole gastroenteropancreatic neuroendocrine tumor group. World J Gastrointest Oncol 2019; 11:139-152. [PMID: 30788040 PMCID: PMC6379754 DOI: 10.4251/wjgo.v11.i2.139] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 08/24/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer (GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary. AIM To identify independent prognostic markers for the whole gastroenteropancreatic neuroendocrine tumor (GEP-NET) group. METHODS Ninety-three patients diagnosed with GEP-NETs within a specified period were included in this study. Patient data were retrospectively analyzed. The relationships between all independent variables and 5-year survival status calculated during the follow-up period (months) were assessed. In addition, the relationships between the independent variables were investigated. RESULTS When 5-year survival rate was compared, a statistically significant relationship between the age at diagnosis, male gender, tumor size, tumor stage, liver and/or distant metastasis, and tumor grade determined by the Ki-67 level and mitotic count, and the level of C-reactive protein (CRP), was observed. The mean survival (overall survival) of the study group was 102.5 ± 6.3 (SD) mo. The percentages of 1, 3 and 5-year survival were 90%, 72%, and 61%, respectively. In 63 of 93 patients, Ki-67 and the mitotic count determined the same grade. The Ki-67 levels in 29 patients and the mitotic count in only 1 patient were in the higher grade. The risk of death increased by 4% for every 1 year increase at the diagnosis age and was 2.0-fold higher for male patients, 3.0-fold higher for G3 according to the mitotic count, 3.7-fold higher for G3 according to the Ki-67 level, 12.7-fold higher for cases with tumor stage 3 or 4 by a 1 cm increase in the ratio of 9% in tumor size, and 6.1-fold higher for patients with liver metastasis for every 1 mg/dL increase in the ratio of 1.5% in CRP level. There was a significant difference between pancreatic and stomach NETs in favor of stomach tumors in terms of survival. CONCLUSION Tumor site, stage, grade and Ki-67 level affected patient survival, and it was observed that CRP affected disease progression (particularly if it was > 20 mg/dL). However, a relationship between surgical resection of the lesion and survival was not shown. Larger scale prospective studies are required to determine whether CRP level may be a poor prognostic factor for the entire GEP-NET group.
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Affiliation(s)
- Ömer Komaç
- Department of Internal Medicine, Dokuz Eylul University Faculty of Medicine, Izmir 35000, Turkey
| | - Göksel Bengi
- Department of Gastroenterology, Dokuz Eylul University Faculty of Medicine, Izmir 35000, Turkey
| | - Özgül Sağol
- Department of Pathology, Dokuz Eylul University Faculty of Medicine, Izmir 35000, Turkey
| | - Mesut Akarsu
- Department of Gastroenterology, Dokuz Eylul University Faculty of Medicine, Izmir 35000, Turkey
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Kim YI, Cho KG, Jang SJ. Comparison of dual-time point 18F-FDG PET/CT tumor-to-background ratio, intraoperative 5-aminolevulinic acid fluorescence scale, and Ki-67 index in high-grade glioma. Medicine (Baltimore) 2019; 98:e14397. [PMID: 30813140 PMCID: PMC6408082 DOI: 10.1097/md.0000000000014397] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The aim of this study was to compare preoperative dual-time point F-fluorodeoxyglucose (FDG) uptake pattern with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in high-grade gliomas. In addition, we assessed for possible associations with a pathologic parameter (Ki-67 index).Thirty-one patients with high-grade glioma (M:F = 19:12, mean age = 60.6 ± 11.2 years) who underwent dual-time point F-FDG positron emission tomography (PET)/computed tomography (CT) scan before surgery were retrospectively enrolled; 5-ALA was applied to the surgical field of all these patients and its fluorescence intensity was evaluated during surgery. Measured F-FDG PET/CT parameters were maximum and peak tumor-to-background ratio (maxTBR and peakTBR) at base (-base) and delayed (-delay) scan. The intensity of 5-ALA fluorescence was graded on a scale of three (grade I as no or mild intensity, grade II as moderate intensity, and grade III as strong intensity).Seven of the patients had WHO grade III brain tumors and 24 had WHO grade IV tumors (mean tumor size = 4.8 ± 1.8 cm). MaxTBR-delay and peakTBR-delay showed significantly higher values than maxTBR-base and peakTBR-base, respectively (all P < .001). Among the F-FDG PET/CT parameters, only maxTBR-delay demonstrated significance according to grade of 5-ALA (P = .030), and maxTBR-delay gradually decreased as the fluorescence intensity increased. Also, maxTBR-delay and peakTBR-delay showed significant positive correlation with Ki-67 index (P = .011 and .009, respectively).Delayed F-FDG uptake on PET/CT images could reflect proliferation in high-grade glioma, and it has a complementary role with 5-ALA fluorescence.
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Affiliation(s)
- Yong-il Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Kyung Gi Cho
- Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam
| | - Su Jin Jang
- Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
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Yu X, Gu J, Wu H, Fu D, Li J, Jin C. Resection of Liver Metastases: A Treatment Provides a Long-Term Survival Benefit for Patients with Advanced Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. JOURNAL OF ONCOLOGY 2018; 2018:6273947. [PMID: 30538745 PMCID: PMC6261248 DOI: 10.1155/2018/6273947] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 10/24/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients. METHODS A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software. RESULTS A total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity. CONCLUSIONS Liver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.
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Affiliation(s)
- Xinzhe Yu
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center. 270 Dong-An Rd, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jichun Gu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Haoxuan Wu
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center. 270 Dong-An Rd, Shanghai 200032, China
| | - Deliang Fu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Ji Li
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Chen Jin
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China
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Abstract
Appendiceal neuroendocrine neoplasms are uncommon, mostly discovered coincidentally during appendectomy. They usually show a benign clinical course and appendectomy alone is curative. However, some cases may harbor malignant potential; therefore, additional/prophylactic operations, such as right hemicolectomy, are offered. Current international guidelines are based on heterogeneous and retrospective series. Thus, there is lack of robust evidence, mainly in terms of accurate factors, that could identify patients at risk, requiring more extensive surgical treatment. In this article, we highlight controversies in the epidemiology, workup assessment, and management algorithms of appendiceal neuroendocrine neoplasms, but also to explore future developments and advances.
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Affiliation(s)
- Michail Galanopoulos
- Department of Gastroenterology, Evangelismos Hospital, 45-47 Ipsilantou Street, Athens 105 52, Greece
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, 8 South, Pond Street, London NW3 2QG, UK.
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Genç CG, Klümpen HJ, Denecke T, Wiedenmann B, Pavel M. Successful treatment of high-grade pancreatic neuroendocrine neoplasms with everolimus. Acta Oncol 2018; 57:686-688. [PMID: 29126357 DOI: 10.1080/0284186x.2017.1398410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- Cansu G. Genç
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands
| | - Timm Denecke
- Klinik für Radiologie, Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Bertram Wiedenmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Marianne Pavel
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Nucl Med Commun 2018; 38:593-600. [PMID: 28471845 DOI: 10.1097/mnm.0000000000000685] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity. PATIENTS AND METHODS We retrospectively analysed patient, tumour and treatment characteristics, end-of-treatment outcome, time to progression and toxicity in 79 consecutive patients treated with Lu-DOTATATE who had progressive NET according to Response Evaluation Criteria in Solid Tumours criteria. Follow-up time was 12-40 months. Study of Kaplan-Meier plots, analysis of time to progression and multiple regression analysis of factors predictive of time to progression were performed. RESULTS At end-of-treatment radiological restaging, 13% of patients were found to have partial response and 64% to have stable disease; 23% of patients progressed through treatment. Overall, 47% of patients demonstrated a reduction in chromogranin A levels. The overall estimated median time to progression from the start of treatment was 28 months for the entire cohort and 31, 30 and 5 months for those with partial response, stable disease and progressive disease, respectively. On multivariate regression analysis, higher grade of tumour was found to be significantly associated with shorter progression-free survival. Three patients experienced grade 1 haematotoxicity, five grade 1 nephrotoxicity and one grade 2 nephrotoxicity. CONCLUSION Early outcomes of patients treated with Lu-DOTATATE are similar to those in previously published series in terms of end-of-treatment efficacy and toxicity. This provides further evidence that this is a safe and efficacious form of treatment for patients with progressive metastatic neuroendocrine tumours.
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Zandee WT, de Herder WW. The Evolution of Neuroendocrine Tumor Treatment Reflected by ENETS Guidelines. Neuroendocrinology 2018; 106:357-365. [PMID: 29320780 PMCID: PMC6067804 DOI: 10.1159/000486096] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 12/05/2017] [Indexed: 12/11/2022]
Abstract
In 2016, the third version of guidelines for the diagnosis and treatment of neuroendocrine tumors (NETs) has been published by the European Neuroendocrine Tumor Society (ENETS). These guidelines reflect the progress in treatment of NETs, and by comparing the newest guidelines with the first guidelines of 2001, this progress can be clearly recognized. Diagnostic accuracy has been increased by the introduction of PET-CT with Ga-labelled somatostatin analogs, and multiple new treatments and treatment schedules have been developed, like peptide receptor radiotherapy with radiolabeled somatostatin analogs, or targeted therapies. Evidence and indications for these therapies are discussed in the ENETS guidelines. In this review, we aim to show the progress in NET diagnosis and treatment on the basis of the advances in the guidelines, but also to discuss the unsolved questions and unmet needs which still remain.
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Affiliation(s)
- Wouter T. Zandee
- *Wouter T. Zandee, MD, Department of Internal Medicine, Endocrinology Sector, Erasmus Medical Center, ‘s-Gravendijkwal 230, NL–3015 CE Rotterdam (The Netherlands), E-Mail
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Laskiewicz L, Jamshed S, Gong Y, Ainechi S, LaFemina J, Wang X. The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors. Cancer Cytopathol 2017; 126:170-178. [PMID: 29266776 DOI: 10.1002/cncy.21956] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 11/10/2017] [Accepted: 11/13/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND There has been much controversy regarding the accuracy of grading pancreatic neuroendocrine tumors (PNETs) on fine-needle aspiration (FNA) biopsy. The objectives of this study were to evaluate whether grading according to the fraction of Ki-67-positive tumor cells (the Ki-67 proliferation index) on material from endoscopic ultrasound-guided FNA biopsies correlated with grading on surgical resection specimens and to evaluate the minimum amount of FNA material needed. METHODS A case series of 27 PNETs with FNA biopsies and corresponding surgical resection specimens at the authors' institution were evaluated. Tumors were graded on FNA and surgical specimens with an evaluation of Ki-67 index according to 2010 World Health Organization criteria. Chart reviews were conducted to evaluate recurrence or clinical progression in patients who were being managed conservatively with observation. RESULTS The evaluation of grading between FNA and tumor resection specimens revealed that 22 of 26 FNA specimens (84.6%) had Ki-67 results comparable to those in the corresponding surgical resection specimens, thus allowing for accurate grading. Correct FNA diagnosis with the ability to distinguish between grade 1 and 2 tumors had a positive predictive value of 88.9%, with 72.7% sensitivity, 93.3% specificity, and a P value of .00081. In addition, 24 of 26 cases contained less than 2000 cells, of which 20 were correctly graded on FNA material. Seven of 26 FNA samples had less than 1000 cells, of which 6 were correctly graded, including 2 that had only 50 cells. CONCLUSIONS The current results exhibit good correlation between FNA grade and final grade on surgical resection specimens using Ki-67 index, even in samples with less than the recommended total cell count. Therefore, grading of PNETs on FNA with the Ki-67 proliferation index should be assessed and is a practical parameter to report to clinicians. Cancer Cytopathol 2018;126:170-8. © 2017 American Cancer Society.
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Affiliation(s)
- Lisa Laskiewicz
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Sarah Jamshed
- Department of Pathology, UMass Medical School and UMass Memorial Hospital, Worcester, Massachusetts
| | - Yuna Gong
- Department of Pathology, Keck School of Medicine at the University of Southern California (USC) and Keck Hospital of USC, Los Angeles, California
| | - Sanaz Ainechi
- Department of Pathology, UMass Medical School and UMass Memorial Hospital, Worcester, Massachusetts
| | - Jennifer LaFemina
- Department of Surgical Oncology, UMass Medical School and UMass Memorial Hospital, Worcester, Massachusetts
| | - Xiaofei Wang
- Department of Pathology, UMass Medical School and UMass Memorial Hospital, Worcester, Massachusetts
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Ramirez RA, Chauhan A, Gimenez J, Thomas KEH, Kokodis I, Voros BA. Management of pulmonary neuroendocrine tumors. Rev Endocr Metab Disord 2017; 18:433-442. [PMID: 28868578 DOI: 10.1007/s11154-017-9429-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Neuroendocrine tumors (NETs) of the lung are divided into 4 major types: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC) or typical carcinoid (TC). Each classification has distinctly different treatment paradigms, making an accurate initial diagnosis essential. The inconsistent clinical presentation of this disease, however, makes this difficult. The objective of this manuscript is to detail the diagnosis and management of the well differentiated pulmonary carcinoid (PC) tumors. A multidisciplinary approach to work up and treatment should be utilized for each patient. A multimodal radiological work-up is used for diagnosis, with contrast enhanced CT predominantly utilized and functional imaging techniques. A definitive diagnosis is based on tissue findings. Surgical management remains the mainstay of therapy and can be curative. In those with advanced disease, medical treatments consist of somatostatin analog (SSA) therapy, targeted therapy, chemotherapy or peptide receptor radionuclide therapy. SSAs are the standard of care in those with metastatic NETs, using either Octreotide long acting repeatable (LAR) or lanreotide as reasonable options, despite a scarcity of prospective data in PCs. Targeted therapies consist of everolimus which is approved for use in PCs, with various studies showing mixed results with other targeted agents. Additionally, radionuclide therapy may be used and has been shown to increase survival and to reduce symptoms in some studies. Prospective trials are needed to determine other strategies that may be beneficial in PCs as well as sequencing of therapy. Successful diagnosis and optimal treatment relies on a multidisciplinary approach in patients with lung NETs. Clinical trials should be used in appropriate patients.
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Affiliation(s)
- Robert A Ramirez
- Ochsner Medical Center - Kenner, 200 West Esplanade Ave, Suite 200, Kenner, LA, 70065, USA.
| | - Aman Chauhan
- University of Kentucky Medical Center, Lexington, KY, 40536, USA
| | - Juan Gimenez
- Ochsner Medical Center - Kenner, 200 West Esplanade Ave, Suite 200, Kenner, LA, 70065, USA
| | - Katharine E H Thomas
- Ochsner Medical Center - Kenner, 200 West Esplanade Ave, Suite 200, Kenner, LA, 70065, USA
| | - Ioni Kokodis
- Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, 70121, USA
| | - Brianne A Voros
- Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA
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Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors. Pancreas 2017; 46:1359-1365. [PMID: 29040195 DOI: 10.1097/mpa.0000000000000923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the concordance in grade assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C). METHODS Resected gastroenteropancreatic neuroendocrine tumors were graded based on MC, KPI, and PHH3C. Concordance was determined using a weighted κ statistic. Median survival across each grade category was determined using Kaplan-Meier methods. RESULTS Of the 110 patients, the majority had gastrointestinal primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were 29% of cases for KPI versus MC (κW = 0.26), 32% for PHH3C versus MC (κW = 0.34), and 32% for PHH3C versus KPI (κW = 0.37). There was fair agreement between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to upgrade tumors. The proportion alive at 3 and 5 years was not significantly different for patients with grade 1 versus grade 2 tumors. CONCLUSIONS The concordance between KPI and MC was fair. Phosphohistone H3 count tended to upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors were associated with similar survival regardless of grading method. The overall relevance of the current cutoff values used in grading neuroendocrine tumors may need to be revisited.
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Papatsimpas G, Samaras I, Theodosiou P, Papacharalampous K, Maragkouli E, Papadopoulos NV, Tsapakidis K, Litos I, Sogka E, Kostopoulou E, Koukoulis GK. A Case of Cervical Carcinoid and Review of the Literature. Case Rep Oncol 2017; 10:737-742. [PMID: 28878659 PMCID: PMC5582492 DOI: 10.1159/000479498] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 07/13/2017] [Indexed: 01/06/2023] Open
Abstract
Uterine cervix carcinoids are distinct neuroendocrine cervical tumors, representing a comparatively small percentage of them. These well-differentiated neoplasms are far less prevalent than small- and large-cell carcinomas, characterized by a more favorable biological course. We report a case of a 43-year-old woman with a nonmetastatic cervical carcinoid, managed with radical hysterectomy. She still remains free of disease. Scant reports in the literature prohibit any reliable prediction of cervical carcinoid prognosis. Thus, prompt identification of the disease and subsequent therapeutic intervention could alter the final outcome.
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Affiliation(s)
| | - Ioannis Samaras
- Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece
| | | | - Konstantina Papacharalampous
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessalia, Larissa, Greece
| | - Eleni Maragkouli
- Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece
| | | | | | - Ioannis Litos
- Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece
| | - Eleni Sogka
- Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece
| | - Evanthia Kostopoulou
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessalia, Larissa, Greece
| | - Georgios K Koukoulis
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessalia, Larissa, Greece
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Allison DB, McCuiston A, VandenBussche CJ. The presence of neuroendocrine features generates a broad differential diagnosis in the fine-needle aspiration of bone and soft tissue neoplasms. J Am Soc Cytopathol 2017; 6:185-193. [PMID: 31043241 DOI: 10.1016/j.jasc.2017.06.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 06/01/2017] [Accepted: 06/01/2017] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Biopsy of bone and soft tissue (BST) lesions occasionally yields neoplasms with neuroendocrine (NE) features. We identify a differential diagnosis for neoplasms containing NE features when encountered on fine-needle aspiration (FNA) of BST masses. MATERIALS AND METHODS The cytopathology archives of the Johns Hopkins Hospital were searched for any BST FNA specimen diagnosed as a neoplasm with NE features or in which NE immunohistochemical (IHC) markers were ordered. Specimen diagnoses were reviewed and specimens were excluded if neuroendocrine features were not considered at the time of original diagnosis. RESULTS A total of 179 specimens met the inclusion criteria. Of these, 64 (36%) and 115 (64%) neoplasms were primary and metastatic, respectively. A total of 29 distinct entities were identified. Sixteen were entities with established NE differentiation and 13 were entities not typically regarded as having an NE origin. The most commonly encountered neoplasms included small cell carcinoma of all primary locations (38), Ewing sarcoma (37), medullary thyroid carcinoma (24), Merkel cell carcinoma (23), and paraganglioma (10). NE IHC markers were ordered in 45% of cases; 86% were positive by at least one NE marker. Entities with established NE differentiation were more likely to be positive for NE IHC than those not typically regarded as having NE differentiation (100% and 59%, respectively). CONCLUSIONS A variety of BST lesions-including neoplasms not typically thought to have neuroendocrine differentiation-can possess NE cytomorphologic features and/or NE IHC marker positivity. The patient's clinical presentation and history can help narrow the differential diagnosis.
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Affiliation(s)
- Derek B Allison
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Austin McCuiston
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Enzler T, Fojo T. Long-acting somatostatin analogues in the treatment of unresectable/metastatic neuroendocrine tumors. Semin Oncol 2017; 44:141-156. [PMID: 28923213 DOI: 10.1053/j.seminoncol.2017.07.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Neuroendocrine tumors (NETs) are a relatively rare and heterogeneous group of neoplasms with an annual incidence of ~35 cases per 100,000 people in the United States. The updated World Health Organization (WHO) classification system of gastroenteropancreatic (GEP)-NETs categorizes these tumors according to site of origin, clinical syndrome, and degree of differentiation. Well-differentiated NETs arising from the gastrointestinal tract or lungs (formerly known as carcinoid tumors) are often indolent and slow-growing. In contrast, poorly differentiated neuroendocrine carcinomas (NECs) are aggressive and have a poor prognosis. Due to their insidious onset, most NETs are diagnosed at an advanced stage and a curative approach is not possible. In these patients, medical therapy is limited to disease control, including relief of symptoms that arise from overproduction of peptide hormones by the tumors. Somatostatin analogues (SSAs) have remained the mainstay of symptoms control. In addition to symptoms control, clinical data also support an anti-proliferative effect of SSAs in patients with well- to moderately differentiated NETs. Long-acting SSAs have greatly facilitated their use. This review will focus on two long-acting SSAs, octreotide LAR and lanreotide, and their use in the clinical setting. Information necessary to assess their relative merits is summarized. We conclude these two therapies are interchangeable making value a very important consideration in their use.
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Affiliation(s)
- Thomas Enzler
- Department of Medicine, Division of Hematology Oncology, Columbia University, New York, NY
| | - Tito Fojo
- Department of Medicine, Division of Hematology Oncology, Columbia University, New York, NY; James J. Peter VAMC, Bronx, NY.
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Mesenteric Tumor Deposits in Midgut Small Intestinal Neuroendocrine Tumors Are a Stronger Indicator Than Lymph Node Metastasis for Liver Metastasis and Poor Prognosis. Am J Surg Pathol 2017; 41:128-133. [PMID: 27684993 DOI: 10.1097/pas.0000000000000751] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Mesenteric tumor deposits (MTDs) are not included in the American Joint Committee on Cancer (AJCC) staging system for midgut small intestinal neuroendocrine tumors (NETs). We examined the prognostic significance of MTDs associated with midgut NETs. Hematoxylin and eosin slides from 132 resected jejunal/ileal NETs were reviewed for AJCC tumor stage, lymph node (LN) metastasis, MTDs, and hepatic metastases. MTDs were defined as discrete irregular mesenteric tumor nodules discontinuous from the primary tumor. Clinical or pathologic evidence of metastases and survival data were abstracted from electronic medical records. The cohort included 72 male and 60 female patients with a median age of 60 years. LN metastasis, MTDs, and liver metastasis were present in 80%, 68%, and 58% of patients, respectively. Female sex and presence of MTDs were independent predictors of liver metastasis. The odds ratio for hepatic metastasis in the presence of MTDs was 16.68 (95% confidence interval [CI], 4.66-59.73) and 0.81 (95% CI, 0.20-3.26) for LN metastasis. Age, MTDs, and hepatic metastasis were associated with disease-specific survival (DSS) in univariate analysis. Primary tumor histologic grade, pT3/T4 stage, and LN metastasis were not associated with DSS. Multivariate analysis of liver metastasis-free survival stratified by tumor grade showed that MTDs were associated with adverse outcomes. The hazard ratio for MTDs was 4.58 (95% CI, 1.89-11.11), compared with 0.98 (95% CI, 0.47-2.05) for LN metastasis. MTDs, but not LN metastasis, in midgut NETs are a strong predictor for hepatic metastasis and are associated with poor DSS.
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McMullen T, Al-Jahdali A, de Gara C, Ghosh S, McEwan A, Schiller D. A population-based study of outcomes in patients with gastrointestinal neuroendocrine tumours. Can J Surg 2017; 60:192-197. [PMID: 28327275 DOI: 10.1503/cjs.007616] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are heterogeneous, with varying presentations and treatment options. To our knowledge, there are no randomized and few long-term studies of patient outcomes. The role of surgical and medical therapy for local, regional and metastatic disease continues to be evaluated in the literature. METHODS We conducted a population-based search of the provincial cancer registry to identify patients with gastrointestinal NETs from the stomach, small intestine, colon and rectum diagnosed between 1990 and 2005 and assessed their outcomes. RESULTS We examined clinicopathological information on the outcomes of 530 patients with gastrointestinal NETs. The overall incidence of NETs increased from 11 per million to 19 per million during the study period. Advancing stage and patient age were associated with poor overall or disease-specific outcomes. Surgery, both curative and palliative, was associated with decreased risk of overall (hazard ratio [HR] 0.5, p < 0.001) and disease-specific (HR 0.5, p < 0.001) death. The biggest benefit was observed in patients with distant disease, in whom 5-year disease-specific survival for R0 resections was nearly double that for patients with macroscopic residual disease (92% v. 48%, p = 0.009). Older age was associated with poor 5-year overall and disease-specific survival (p < 0.001). CONCLUSION There has been a significant increase in incidence of gastrointestinal NETs, and advancing patient age, but not sex, is linked to poor outcomes in terms of overall and disease-specific survival. Surgery, both curative and palliative, was associated with decreased risk of overall and disease-specific death. Compared with patients with residual macroscopic disease, patients with distant disease were nearly twice as likely to survive 5 years if they had R0 resections. The use of radioisotope therapy and long-acting octreotide therapy was also associated with improved outcomes overall.
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Affiliation(s)
- Todd McMullen
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
| | - Akram Al-Jahdali
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
| | - Christopher de Gara
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
| | - Sunita Ghosh
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
| | - Alexander McEwan
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
| | - Daniel Schiller
- From the Division of General Surgery, University of Alberta, Edmonton, Alta. (McMullen, de Gara, Schiller); the Division of Pediatric Surgery, University of Dammam, Saudi Arabia (Al-Jahdali); the Department of Biostatistics and Epidemiology, Cross Cancer Institute, Edmonton, Alta. (Ghosh); and the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alta. (McEwan)
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Landau M, Wisniewski S, Davison J. Jejunoileal Neuroendocrine Tumors Complicated by Intestinal Ischemic Necrosis Are Associated With Worse Overall Survival. Arch Pathol Lab Med 2017; 140:461-6. [PMID: 27128303 DOI: 10.5858/arpa.2015-0105-oa] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT -Jejunoileal neuroendocrine tumors (JINETs) are slow-growing, malignant tumors that are often associated with protracted survival, despite their frequent presentation at an advanced stage. A subset of JINETs is complicated by intestinal ischemic necrosis (IIN), which leads to their initial clinical presentation. OBJECTIVE -To assess the effect of IIN on overall survival in patients with JINETs. DESIGN -Ten JINETs with IIN during a 14-year period and a control group of 52 JINETs without IIN were identified retrospectively. The hematoxylin-eosin slides and gross descriptions were reviewed, and pathologic features were assessed. Overall survival was compared between the 2 groups using the Kaplan Meier method and Cox proportional hazards model. RESULTS -At 1 year postresection, only 40% (4 of 10) of the patients with IIN were alive, whereas 94% (49 of 52) of those without IIN were alive (P < .001). Patients with IIN were significantly older than those without IIN (median, 83 years versus 65.5 years, P = .001). By univariate Cox proportional hazards regression, IIN was associated with a 4.30-fold increased risk of death (95% confidence interval 1.75-10.56; P = .001). When controlling for age, advanced stage (stage III or IV), tumor grade, and synchronous carcinoma in a multivariate analysis, IIN showed a trend toward prognostic significance (2.31-fold increased risk of death; 95% confidence interval, 0.85-6.27; P = .10). CONCLUSIONS -The pathologic identification of tumor-associated IIN portends a worse overall survival among patients with JINETs.
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Affiliation(s)
| | | | - Jon Davison
- From the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Landau and Davison); and the Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh (Dr Wisniewski)
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