MODIFIED HISTOPATHOLOGICAL GRADING OPTIMIZES PREDICTION OF SURVIVAL OUTCOMES IN SMALL INTESTINAL NEUROENDOCRINE TUMOURS.

AUTHORS:
K. Daskalakis (Örebro, Sweden) , M. Tsoli (Athens, Greece) , G. Wallin (Örebro, Sweden) , A. Kogut (Katowice, Poland) , R. Srirajaskanthan (London, United Kingdom) , G. Giovos (London, United Kingdom) , M.O. Weickert (London, United Kingdom) , B. Kos-Kudla (Katowice, Poland) , G. Kaltsas (Athens, Greece)
Background:
We aimed to identify optimal grading Ki-67 cut-offs to delineate differences in prognosis of patients with small intestinal neuroendocrine tumours (SI-NETs) in terms of overall- and event-free survival rates.
Methods:
We included 551 patients with SI-NETs diagnosed from June 15th, 1993, through March 8th, 2021, identified using the SI-NET databases from five European referral centres.
Results:
Median age at baseline was 62.3(17-90) years; 252 patients were women(45.7%). All tumours were well-differentiated; 326 were G1 tumours(59.2%), 169 G2(30.7%), only 8 G3(1.5%), while 48 tumours were of unspecified grade(8.7%). The median Ki67 was 2%(1-70%). 247 patients(44.8%) had distant metastases at baseline (stage IV), 217 locoregional disease(41.1%; stage III), whereas 29(7.1%) and 25(4.5%) presented at stages II and I, respectively. Within a mean(SD) follow-up of 51.5(52.9) months, 94 patients(17.1%) died, whereas overall 188 experienced disease recurrence, progression and/or death(34.1%). The median OS was 214.7(95%CI: 152.7-276.6) months and the median EFS was 79.8(95%CI: 68.2-91.5) months, respectively. In multivariable Cox-regression OS analysis, age (HR=1.07, 95%CI: 1.04-1.09; p<0.001), Charlson Comorbidity Index(HR=1.1, 95%CI: 1.03-1.17; p=0.006) and the proposed modified histopathological Ki67 grading system(K67:5-10% group:HR=2.4, 95%CI: 1.3-4.5; p=0.007 and K67≥10% group: HR=5.1, 95%CI: 2.9-9.2; p<0.001) were independent predictors for death. Pertinent EFS analysis, confirmed age(HR=1.04, 95%CI: 1.02-1.05;p<0.001) and the proposed modified histopathological Ki67 grading system(K67≥10% group:HR=4; 95%CI:2.5-6.2;p<0.001) as independent predictors for recurrence, progression and/or death.
Conclusions:
Ki-67 proliferation index is an independent predictor of EFS and OS. A modified site-specific histopathological grading system applying Ki-67 cut-offs of 5% and 10% seems more optimal to predict differences in SI-NET patient prognosis.