Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center.

Data on the outcome and prognostic indicators in extracranial relapsed/refractory germ cell tumors (rel/ref-GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel/ref-GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world.

Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III-IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine-ifosfamide-cisplatin/carboplatin or paclitaxel-ifosfamide-cisplatin/carboplatin, or cisplatin/carboplatin-etoposide-bleomycin. Local therapy was either surgery and/or radiotherapy.

The analyzable cohort comprised 50 patients (44 = rel-GCTs; 6 = ref-GCTs) with a median age of 3.8 years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5 months. At a median follow-up of 60 months, the 5-year event-free survival (EFS) and overall survival (OS) of the entire cohort (n = 50) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (n = 38), 5-year-EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5-year EFS: 64% vs. 23% vs. 0%; p = .009). LR and IR tumors did better compared to HR (5-year EFS: 81.5% vs. 49.3% vs. 6.5%; p = .002). Patients with normalization of tumor markers after two cycles had a superior EFS (57.6% vs. 0%; p < .001). Relapsed tumors fared better than primary refractory GCTs (5-year EFS: 48.6% vs. 0%; p < .001).

Primary refractory GCTs, extragonadal rel-GCTs, and rel/ref-GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel/ref-testicular GCTs had the best chance of salvage despite a second recurrence (5-year EFS and OS: 28.60% and 42.90%, respectively).

Pediatric blood & cancer. 2023 Jan 16 [Epub ahead of print]

Subramaniam Ramanathan, Maya Prasad, Tushar Vora, Cheriyalinkal Parambil Badira, Seema Kembhavi, Mukta Ramadwar, Nehal Khanna, Siddhartha Laskar, Mary Ann Muckaden, Sajid Qureshi, Shripad Banavali, Girish Chinnaswamy

Department of Paediatric Oncology, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, Tyne and Wear, UK., Department of Paediatric Oncology, Tata Memorial hospital, Mumbai, Maharashtra, India., Department of Paediatric Oncology, SickKids Hospital, Toronto, Ontario, Canada., Department of Radiology, Mackay Hospital and Health Services, Mackay, Queensland, Australia., Homi Bhabha National Institute, Mumbai, Maharashtra, India.