Implementing Indiana regimen salvage high-dose chemotherapy in relapsed germ cell tumors in Slovakia.

642 Background: Salvage chemotherapy for relapsed testicular germ cell tumors (GCT) remains controversial, however, large retrospective series show higher cure rates with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) compared to conventional dose chemotherapy (CDCT). Successful implementation of HDCT salvage treatment in high-volume centers is an important step towards achieving optimal cure rates in relapsed GCTs. Methods: 22 relapsed GCT patients were treated at National Cancer Institute in Slovakia with first (41%), second (54%) and third line (5%) salvage HDCT between 2014 and 2024. Median age at 1 st HDCT cycle was 33 years (range 21-55). Of the 22 patients, 3 (14%) had pure seminoma, 3 (14%) had primary mediastinal non-seminoma (PMNSGCT), 10 (45%) patients had cisplatin resistant disease, 7 (32%) and 15 (68%) of patients received 1 and 2 cycles of HDCT, respectively, 5 (23%) received maintenance oral etoposide and 6 (27%) had post-HDCT surgery. Indiana regimen consisted of 750mg/m2 etoposide and 700mg/m2 of carboplatin given on days -5,-4,-3 followed by PBSCT on day 0. Of 22 patients, 3 have received single dose CarboPEC (carboplatin, etoposide, cyclophosphamide) regimen in 2014 and 2015. Results: Median time between two cycles was 43 days (range 26-89) showing decreasing trend over the last years. 2-year PFS and OS were 40% (95% CI 0.19-0.61) and 34% (95% CI 0.13-0.55) and 5-year PFS and OS were 32% (95% CI 0.1-0.54) and 27% (0.06-0.48). Kaplan-Meier analysis produced inaccurate outcomes due to small sample size, currently 32% of patients is alive and disease-free. Predictors of unfavorable outcome were non-seminoma, NPMGCT, 1 cycle of HDCT, CarboPEC regimen and platinum resistant disease. Patients who underwent post-HDCT surgical resection had longer OS compared to patients unable to undergo surgery HR 4,85 (95% CI 1,69-13,9), p = 0.01 Patients receiving pre-HDCT bridging CDCT regimens had significantly worse OS compared to patients going directly to HDCT, HR 0 (95% CI 0-0), 5 year OS 19% vs 100%, p = 0.05. 10% of patients with cisplatin resistant disease is surviving beyond 5 years. There was one (4.5%) treatment-related death due to septic shock. Conclusions: HDCT is an effective salvage option in heavily pretreated relapsed GCTs. Our study suffers from weakness associated with small number of patients and selection biases. However, increasing expertise and timely delivery of HDCT results in cures in relapsed GCTs including cisplatin resistant subgroup.