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.