Can Ki-67 predict radiotherapy response in neuroendocrine tumors? Retrospective analysis of a monocentric series of patients

Dario Zerini, Marco Rotondi, Stefania Volpe, Eleonora Pisa, Emanuele Frigo, Cristiana Pedone, Michele Flospergher, Vincenzo Bagnardi, Samuele Frassoni, Cristiana Iuliana Fodor, Francesca Spada, Nicola Fazio, Daniela Alterio, Barbara Alicja Jereczek-Fossa

The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity. Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment. Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses. No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.