The study was approved by the institutional ethics committee.
Therapy
Written informed consent was obtained from all children or their guardians prior to instituting therapy. All patients were risk stratified after initial investigations and underwent surgery, chemotherapy or a combination of both. The risk stratification and treatment schema is shown in Figure 2. The chemotherapy regimen that was employed was PEb, consisting of Inj.Bleomycin (15 IU/m2) on day 1, Inj. Etoposide (100mg/m2) and Inj. Cisplatin (20mg/m2) on day 1-5, given every 21 days. Completely excised teratomas and stage I gonadal GCTs did not receive any additional therapy and were kept under observation only. Patients with intermediate risk tumors received 4 cycles of PEb following surgical excision, whereas high-risk patients received 6 cycles. In children with underlying renal dysfunction or obstructive uropathy, Carboplatin (560mg/m2; AUC 7.5) instead of Cisplatin was administered with no modification in doses of the other 2 agents. After normalization of renal dysfunction,patients were switched back to Cisplatin-based regimen on the physician’s discretion.
Assessment of chemotherapy related toxicity
All children had periodic complete blood counts to monitor hematologic toxicities. Renal function was assessed by monitoring of renal function tests (BUN/Creatinine) and Tc99-DTPA scintigraphy scan (GFR scan) done only in children who had deranged renal function tests. Brainstem Evoked Response Audiometry (BERA) in young infants and Pure Tone Audiometry (PTA) in older children monitored audiological status, wherever possible. Once in remission after completion of treatment, tumor markers were done three monthly for the first 12 months, 4 monthly for the next 12 months, 6 monthly in the third year and annually thereafter. Imaging was only done to look for relapse was done in symptomatic patients or if tumor markers were elevated on surveillance. Patients with normal tumor markers at presentation (non-secretory GCTs) had periodic regional imaging during follow-up.
Statistical Methods
The cohort was evaluated for both event free survival (EFS) and overall survival(OS). EFS was measured from the date of commencing therapy until the date of the occurrence of the first event, which was designated as relapse or progression or death. If no event occurred, then the date of the last follow-up was used as a censored observation. OS was measured from the date of registration until the date of death. In surviving patients, the date of the last follow-up was used as a censored observation. For survival analysis, all patients were censored at the date of last follow-up OR date of telephonic contact as on 25th May 2020.
EFS and OS were computed using Kaplan-Meier analysis. Statistical significance of possible prognostic factors was compared using log-rank test. Multivariate analysis using Cox proportional hazards model was performed to identify risk factors and a risk model. IBM SPSS® Statistics ver. 26 was used to compute all statistical data.