Low Ki-67 Positive Index is a Prognostic Factor for Better Survival Outcomes of Patients treated with Intracavitary Cisplatin-Fibrin

Abstract Background Novel therapeutic approaches are needed for patients with pleural mesothelioma (PM), an aggressive cancer driven by asbestos exposure. Our phase II clinical trial for localized chemotherapy with cisplatin-fibrin after surgery (INFLuenCe – Meso) investigated safety and efficacy of this novel approach. Aims To identify biomarkers associated with outcomes for future application in patient selection. Methods We collected tumor tissues at surgery, before start of localized treatment, from all patients enrolled (n=23). FFPE tissues were immunohistochemically stained for p21 (cisplatin resistance) and Ki-67 (proliferation). Using Qupath software, we classified tumor cells from stroma. Number of positive cells (%) were automatically counted from 1,050 - 208,751 tumor cells/slide. For P21, we also differentiated weak (1), moderate (2) and strong (3) staining. Thus, we also acquired H-score (sum of intensity x % positive cells). The association between marker expression and clinical parameters and disease outcomes including progression free survival (PFS) and overall survival (OS) was analysed by SPSS software. Results Ki-67 staining index (%) ranged from 1.2 - 44 (median 12.4). P21 staining index and H–score (range (median)) are 0 - 96 (21) and 0 - 225 (32), respectively. High Ki-67 labelling index was significantly associated with shorter PFS (p=0.001, median (95% CI): 26.6 (11.7 - 41.6) vs 8.6 (6.8 -10.4) months) and OS (p<0.001, 39 (27.2–50.9) vs 16 (12.3–19.6) months). There was no association between clinical parameters and Ki-67 or p21 staining. P21 staining index and H-score showed no association with disease outcomes. Conclusions Although a small patient cohort, Ki-67 showed significant association with disease outcomes for patients receiving localized cisplatin-fibrin. We are currently assessing Ki-67 in tissues collected at diagnosis to confirm the association with survival prior to therapy. Ki-67 may be useful for the selection of patients for this treatment regimen.