Conventional Salvage Chemotherapy Without Stem Cell Rescue for Relapsed or Refractory Extracranial Germ Cell Tumors: Insights From the Tertiary Cancer Center in a Developing Country

Background Evidence regarding outcomes and prognostic determinants of extracranial relapsed or refractory germ cell tumors (GCTs) in children remains scarce. The present study evaluates remission rates and survival outcomes of pediatric relapsed or refractory GCTs managed with conventional salvage chemotherapy regimens, without the use of stem cell rescue, at a single tertiary cancer centre in a developing country. Methods This retrospective cohort study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2011 to December 2022. Patients aged ≤18 years with histologically confirmed extracranial GCTs who received definitive treatment, or presented with relapsed/progressive disease after prior chemotherapy, were included. Demographic, clinical, treatment, and outcome data were extracted from electronic records. Event-free survival (EFS) and overall survival (OS) were calculated from initiation of salvage chemotherapy. Results Out of 283 patients treated, 51 (18%) with relapsed (n=41, 14.5%) or refractory (n=10, 3.5%) extracranial GCTs were analyzed. The cohort included 25 males (49%) and 26 females (51%), with a median age of 8 years (IQR: 3.0-12.0). Primary tumors were gonadal in 33 (64.7%) and extragonadal in 18 (35.3%) patients. Yolk sac histology was most frequent (n=27, 52.9%), and 24 (47.1%) patients had high-risk disease. Vinblastine, ifosfamide and cisplatin/vinblastine, ifosfamide, carboplatin (VeIP/VeIC) was the commonest salvage regimen (54.9%). At median follow-up of 32 months, 26 (51.0%) were alive without disease, and 14 (27.5%) had died. Five-year OS and EFS were 72.5% and 50%. High-risk disease independently predicted higher mortality (HR: 12.27, 95% CI: 1.51-99.6; p=0.019). Conclusions Salvage chemotherapy regimens provide an effective option for children with relapsed or refractory extracranial GCTs in settings where high-dose chemotherapy and autologous stem cell transplant are not readily available.