Abstract Background Central nervous system non-germinomatous germ cell tumors (NGGCT) are rare and aggressive malignancies with inferior outcomes compared with germinomas. In low- and middle-income countries (LMICs), limitations in diagnostic, surgical, and supportive care resources may further affect treatment delivery and survival. Multicenter real-world data from LMIC settings remain scarce. Objectives To describe treatment strategies and evaluate survival outcomes of pediatric CNS NGGCT treated in an LMIC context, with emphasis on treatment-related morbidity, and timing of mortality. Methods Retrospective multicenter cohort study including pediatric patients with CNS NGGCT treated at eight Mexican hospitals (2013-2025). Clinical characteristics, histology, tumor markers, treatment modalities, treatment-related complications, and outcomes were analyzed. Overall survival (OS) and EFS were estimated using Kaplan–Meier. Results A total of 39 patients were included. Median age at diagnosis was 10.2 years, 76.9% were male. Histologic subtypes included choriocarcinoma(28.2%), yolk sac tumor(23.7%), mixed germ cell tumors(23.7%), immature teratoma(7.9%), and embryonal carcinoma(2.6%). Only 16.2% had no marker elevation, 35.1% showed concurrent AFP and β-hCG elevation; mean AFP level: 1,488.1ng/mL. Primary sites were suprasellar (46.2%), pineal (41.0%), and bifocal (7.7%). Most patients presented with localized disease (87.2%). Diagnosis was established by imaging and/or tumor markers(61.5%), surgical resection(28.2%), and biopsy(10%). Combined modality treatment predominated, 54.1% receiving chemotherapy followed by radiotherapy; 2.7% received radiotherapy alone. Chemotherapy regimens included alternating carboplatin/etoposide with ifosfamide/etoposide (46.7%), ICE (20%), and carboplatin/etoposide, PEI, or PEB/JEB(6.7% each). 4-6 chemotherapy cycles were administered in 63.3% of patients. Radiotherapy strategies included CSI (40%), WVI (25%), and WB in (15%). Treatment-related morbidity was substantial: 73.3% required inpatient management, 60% experienced chemotherapy delays, 25.6% developed surgical infectious complications. Residual tumor after chemotherapy was observed in 15 patients (2 mature teratoma and 1 viable tumor). 1- and 10-year OS were 58.1% and 54.2%, respectively, while 1- and 10-year EFS were 54.4% and 42.6%, indicating that most mortality occurred early during treatment. Residual tumor after chemotherapy was strongly associated with inferior EFS (5-year EFS 13.6% vs. 68.4%; p 0.001; HR 3.5). Conclusions In this multicenter LMIC cohort outcomes remain inferior to those reported in contemporary cooperative group trials. The minimal difference between 1- and 10-year survival highlights that deaths predominantly occur during early treatment phases. In contrast, COG ACNS1123 and SIOP NGGCT studies have demonstrated improved survival through risk-adapted multimodal therapy, treatment standardization, and optimized supportive care. These findings underscore the need to harmonize treatment strategies, and improve supportive care infrastructure in LMIC settings to reduce early mortality.
Rivera et al. (Tue,) studied this question.
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