Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumors.

IF 5 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Clinical Endocrinology & Metabolism Pub Date : 2024-11-18 DOI:10.1210/clinem/dgae111

Kosmas Daskalakis, Marina Tsoli, Göran Wallin, Angelika Kogut, Raj Srirajaskanthan, Christopher Harlow, Georgios Giovos, Martin O Weickert, Beata Kos-Kudla, Gregory Kaltsas

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Abstract

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.

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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

背景：Ki67增殖指数是神经内分泌肿瘤（NET）的主要预后指标之一：目的：确定Ki-67的最佳分级临界值，以划定小肠NET（SI-NET）患者预后的差异：多中心回顾性队列分析：1993年至2021年在欧洲5个转诊中心确诊的551例SI-NET患者，平均（±SD）随访时间为51.5（±52.9）个月：主要结果指标：总生存率和无事件生存率（OS和EFS）：基线年龄中位数为62.3岁（17-90岁）；252名（45.7%）患者为女性。所有SI-NET均为分化良好的肿瘤，其中326例为1级（G1；59.2%），169例为2级（30.7%），仅8例为3级（1.5%），48例未明确分级（8.7%）。Ki67 中位数为 2%（范围：1-70%）。247名患者（44.8%）在基线时有远处转移（IV期），217名患者有局部病变（41.1%；III期），而29名患者（7.1%）和25名患者（4.5%）分别处于II期和I期。中位OS为214.7（95%CI：152.7-276.6）个月，中位EFS为79.8（95%CI：68.2-91.5）个月。在多变量Cox回归OS分析中，提出的改良组织病理学Ki67分级系统（K67:5-10%组：HR=2.2，95%CI:1.15-4.31；P=0.018；K67≥10%组：HR=5.11，95%CI：2.87-9.09；p结论：Ki-67增殖指数是预测OS和EFS的强有力的独立指标。采用Ki-67临界值为5%和10%的改良组织病理学分级系统可以更好地预测SI-NET患者生存结果的差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Endocrinology & Metabolism 医学-内分泌学与代谢

CiteScore

11.40

自引率

5.20%

发文量

673

审稿时长

1 months

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.