Increment in KI-67 proliferation indices over time is associated with worse survival outcomes in small-intestinal neuroendocrine tumours

Kosmas Daskalakis; Marina Tsoli; Goran Wallin; Angelika Kogut; Rajaventhan Srirajaskanthan; Christopher Harlow; Georgios Giovos; Martin Weickert; Kudla Beata Kos; Gregory Kaltsas

doi:10.1530/endoabs.99.P104

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Endocrine Abstracts (2024) 99 P104 | DOI: 10.1530/endoabs.99.P104

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

Increment in KI-67 proliferation indices over time is associated with worse survival outcomes in small-intestinal neuroendocrine tumours

Kosmas Daskalakis ^1,2 , Marina Tsoli ³ , Göran Wallin ² , Angelika Kogut ⁴ , Rajaventhan Srirajaskanthan ⁵ , Christopher Harlow ⁵ , Georgios Giovos ⁶ , Martin Weickert ⁶ , Beata Kos Kudla ⁷ & Gregory Kaltsas ³

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Author affiliations

¹General Hospital of Athens Korgialeneio - Benakeio Hellenic Red Cross, Athina, Greece; ²Örebro University, Department of Surgery, Faculty of Medicine and Health, Örebro, Sweden; ³National and Kapodistrian University of Athens, Endocrine Oncology Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, Athens, Greece; ⁴Medical University of Silesia, Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Katowice, Poland; ⁵King’s College Hospital, London; ⁶University Hospital Coventry & Warwickshire, Coventry; ⁷Medical University of Silesia, Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Katowice

Introduction: A change in the biological behaviour of Small-Intestinal Neuroendocrine Tumours (SiNETs), as reflected by an increase in the Ki-67 proliferation index may occur over time. The purpose of this study was to evaluate longitudinal changes in Ki-67 indices of SiNETs and assess the impact of these in overall survival (OS).

Patients and methods: We screened 551 patients with SI-NETs diagnosed from 1993, through 2021, identified using the SI-NET databases from five European referral centres. Only patients with well-differentiated tumours and available baseline tumour samples, as well as follow-up re-biopsies were included. Pathology reports were reviewed with regard to tumour histopathology and Ki-67 indices. To avoid immortal time bias, baseline for survival estimates was defined as the date of re-biopsy.

Results: We included 47 patients. Median Ki-67 index at SI-NET diagnosis was 2% (range 0.5-15%). Twenty-seven patients had grade 1 (G1) tumours (57.4%), and 20 G2 (42.6%). Mean time to re-biopsy was 48.8 months (SD: +/-162.5). At re-biopsy, the median change in Ki-67 index (absolute value; follow-up minus time of diagnosis) was 1% (range -10 to +38%). An increase in Ki-67 occurred in 20 patients (42.6%); in 11 patients the change in Ki-67 resulted in progression to higher tumour grade. The patients with an increment in Ki-67≥1%, with or without grade progression had a median OS of 46 months compared to 53.7 months in patients with stable or decreasing Ki-67 (hazard ratio 3.26, 95% CI: 1.11-9.58, P=0.031).

Conclusion: Increment in Ki-67 indices over time was observed in approximately 40% of SiNETs included in this study and was linked with worse survival outcomes. Further studies on molecular pathways with sequential biopsies at disease progression are necessary to shed light on the mechanisms that render a neoplasm more aggressive during the disease course.