Kosmas Daskalakis, Marina Tsoli, Göran Wallin, Angelika Kogut, Raj Srirajaskanthan, Christopher Harlow, Georgios Giovos, Martin O Weickert, Beata Kos-Kudla, Gregory Kaltsas
{"title":"修改后的组织病理学分级可优化小肠神经内分泌肿瘤的生存预后","authors":"Kosmas Daskalakis, Marina Tsoli, Göran Wallin, Angelika Kogut, Raj Srirajaskanthan, Christopher Harlow, Georgios Giovos, Martin O Weickert, Beata Kos-Kudla, Gregory Kaltsas","doi":"10.1210/clinem/dgae111","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>One of the major prognostic indices in neuroendocrine tumors (NETs) is Ki67 proliferation index.</p><p><strong>Objective: </strong>To identify optimal grading Ki67 cutoffs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs).</p><p><strong>Methods: </strong>Multicenter retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at 5 European referral centers with a mean (±SD) follow-up time of 51.5 (±52.9) months, measuring rates of overall survival (OS) and event-free survival (EFS).</p><p><strong>Results: </strong>Median age at baseline was 62.3 (range, 17-90) years; 252 (45.7%) patients were female. All SI-NETs were well-differentiated, with 326 being grade 1 (G1; 59.2%), 169 G2 (30.7%), and 8 G3 (1.5), while 48 tumors were unspecified grade (8.7%). The median Ki67 was 2% (range, 1%-70%). At baseline, 247 (44.8%) patients had distant metastases (stage IV), 217 locoregional disease (41.1%; stage III), while 29 (7.1%) and 25 (4.5%) presented at stages II and I, respectively. Median OS was 214.7 (95% CI, 152.7-276.6) months and median EFS was 79.8 (68.2-91.5) months. In multivariable Cox-regression OS analysis, the proposed modified histopathological Ki67 grading system (Ki67 5%-10% group: HR = 2.2 [95% CI, 1.15-4.31], P = .018 and Ki67 ≥ 10% group: HR = 5.11 [2.87-9.09], P < .001), age (HR = 1.07 [1.04-1.09], P < .001), Charlson Comorbidity Index (HR = 1.08 [1-1.16], P = .028), and TNM stage (HR = 1.79 [1.05-3.06], P = .034) were independent predictors for death. Pertinent EFS analysis confirmed the proposed modified histopathological Ki67 grading system (Ki67 ≥ 10% group: HR = 4.01 [2.6-6.37], P < .001) and age (HR = 1.04 [1.02-1.05], P < .001) as independent predictors for recurrence, progression, and/or death.</p><p><strong>Conclusion: </strong>Ki67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki67 cutoffs of 5% and 10% could be superior to predict differences in SI-NET patient survival outcomes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2222-e2230"},"PeriodicalIF":5.0000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570380/pdf/","citationCount":"0","resultStr":"{\"title\":\"Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumors.\",\"authors\":\"Kosmas Daskalakis, Marina Tsoli, Göran Wallin, Angelika Kogut, Raj Srirajaskanthan, Christopher Harlow, Georgios Giovos, Martin O Weickert, Beata Kos-Kudla, Gregory Kaltsas\",\"doi\":\"10.1210/clinem/dgae111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>One of the major prognostic indices in neuroendocrine tumors (NETs) is Ki67 proliferation index.</p><p><strong>Objective: </strong>To identify optimal grading Ki67 cutoffs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs).</p><p><strong>Methods: </strong>Multicenter retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at 5 European referral centers with a mean (±SD) follow-up time of 51.5 (±52.9) months, measuring rates of overall survival (OS) and event-free survival (EFS).</p><p><strong>Results: </strong>Median age at baseline was 62.3 (range, 17-90) years; 252 (45.7%) patients were female. All SI-NETs were well-differentiated, with 326 being grade 1 (G1; 59.2%), 169 G2 (30.7%), and 8 G3 (1.5), while 48 tumors were unspecified grade (8.7%). The median Ki67 was 2% (range, 1%-70%). At baseline, 247 (44.8%) patients had distant metastases (stage IV), 217 locoregional disease (41.1%; stage III), while 29 (7.1%) and 25 (4.5%) presented at stages II and I, respectively. Median OS was 214.7 (95% CI, 152.7-276.6) months and median EFS was 79.8 (68.2-91.5) months. In multivariable Cox-regression OS analysis, the proposed modified histopathological Ki67 grading system (Ki67 5%-10% group: HR = 2.2 [95% CI, 1.15-4.31], P = .018 and Ki67 ≥ 10% group: HR = 5.11 [2.87-9.09], P < .001), age (HR = 1.07 [1.04-1.09], P < .001), Charlson Comorbidity Index (HR = 1.08 [1-1.16], P = .028), and TNM stage (HR = 1.79 [1.05-3.06], P = .034) were independent predictors for death. Pertinent EFS analysis confirmed the proposed modified histopathological Ki67 grading system (Ki67 ≥ 10% group: HR = 4.01 [2.6-6.37], P < .001) and age (HR = 1.04 [1.02-1.05], P < .001) as independent predictors for recurrence, progression, and/or death.</p><p><strong>Conclusion: </strong>Ki67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki67 cutoffs of 5% and 10% could be superior to predict differences in SI-NET patient survival outcomes.</p>\",\"PeriodicalId\":50238,\"journal\":{\"name\":\"Journal of Clinical Endocrinology & Metabolism\",\"volume\":\" \",\"pages\":\"e2222-e2230\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570380/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Endocrinology & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1210/clinem/dgae111\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Endocrinology & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/clinem/dgae111","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumors.
Context: One of the major prognostic indices in neuroendocrine tumors (NETs) is Ki67 proliferation index.
Objective: To identify optimal grading Ki67 cutoffs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs).
Methods: Multicenter retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at 5 European referral centers with a mean (±SD) follow-up time of 51.5 (±52.9) months, measuring rates of overall survival (OS) and event-free survival (EFS).
Results: Median age at baseline was 62.3 (range, 17-90) years; 252 (45.7%) patients were female. All SI-NETs were well-differentiated, with 326 being grade 1 (G1; 59.2%), 169 G2 (30.7%), and 8 G3 (1.5), while 48 tumors were unspecified grade (8.7%). The median Ki67 was 2% (range, 1%-70%). At baseline, 247 (44.8%) patients had distant metastases (stage IV), 217 locoregional disease (41.1%; stage III), while 29 (7.1%) and 25 (4.5%) presented at stages II and I, respectively. Median OS was 214.7 (95% CI, 152.7-276.6) months and median EFS was 79.8 (68.2-91.5) months. In multivariable Cox-regression OS analysis, the proposed modified histopathological Ki67 grading system (Ki67 5%-10% group: HR = 2.2 [95% CI, 1.15-4.31], P = .018 and Ki67 ≥ 10% group: HR = 5.11 [2.87-9.09], P < .001), age (HR = 1.07 [1.04-1.09], P < .001), Charlson Comorbidity Index (HR = 1.08 [1-1.16], P = .028), and TNM stage (HR = 1.79 [1.05-3.06], P = .034) were independent predictors for death. Pertinent EFS analysis confirmed the proposed modified histopathological Ki67 grading system (Ki67 ≥ 10% group: HR = 4.01 [2.6-6.37], P < .001) and age (HR = 1.04 [1.02-1.05], P < .001) as independent predictors for recurrence, progression, and/or death.
Conclusion: Ki67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki67 cutoffs of 5% and 10% could be superior to predict differences in SI-NET patient survival outcomes.
期刊介绍：
The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.
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