Safety and efficacy of concurrent carboplatin during full‐dose craniospinal irradiation for high‐risk/metastatic medulloblastoma in a resource‐limited setting

Abstract

Purpose To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high‐risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm2 or leptomeningeal metastases. Methods This single‐arm combined prospective (2005–2011) and retrospective (2011–2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high‐risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m2) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy. Results All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment‐related toxicity. Grade 3–4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony‐stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment‐related deaths during the concurrent chemo‐radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy‐related complications. At a median follow‐up of 82 months, the 5‐year Kaplan–Meier estimates of progression‐free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival. Conclusion Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high‐risk/metastatic medulloblastoma.

Current Strategies for Management of Medulloblastoma

“…Lower survivals globally from low-and middle-income countries are due to the limitation of resources [ 10 , 11 ]. These outcomes are not insurmountable, however, as reported, India has shown 5-year 62% survival for high-risk disease, similar to those reported in North America and Europe [ 12 , 13 ]. Relapsed medulloblastoma is often incurable [ 14 , 15 , 16 , 17 , 18 ].…”

How Can Genomic Innovations in Pediatric Brain Tumors Transform Outcomes in Low- and Middle-Income Countries?

“…Only four published works appear to satisfy this requirement, and only one of them was published after the year 2010. [32][33][34][35] There are no publications describing clinical trials in the LMIC setting of biologic agents commonly in use in HICs for pediatric brain tumors (vascular endothelial growth factor inhibitors, V600E-mutated BRAF inhibitors, MEK inhibitors, smoothing inhibitors, and cell cycle checkpoint inhibitors). There are, however, some excellent reports describing the utility of molecular subtyping in predicting the outcomes of medulloblastoma 19,36,37 and at least one report demonstrating the feasibility of high-dose chemotherapy for infants with brain tumors.…”

“…Only four published works appear to satisfy this requirement, and only one of them was published after the year 2010. 32 - 35 …”

Global metabolomics study on the pathogenesis of pediatric medulloblastoma via UPLC- Q/E-MS/MS

“…However, the mechanism of medulloblastoma is still unknown. More importantly, the deficiency of reliable clinical diagnosis biomarker makes the diagnosis specifically relying on the imaging examination, like magnetic resonance imaging and computerized tomography [ 32 , 33 ]. Highly accurate biomarkers could be helpful for early pre-diagnosis in the regular peripheral blood-based biochemical screening.…”