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EMBR-17. DE-INTENSIFICATION OF RADIOTHERAPY IN RIGOROUSLY DEFINED LOW-RISK WNT-SUBGROUP MEDULLOBLASTOMA IS ASSOCIATED WITH UNACCEPTABLY HIGH RISK OF NEURAXIAL FAILURE: RESULTS FROM THE PROSPECTIVE FOR-WNT STUDY

Authors :
Nazia Bano
Maya Prasad
Neelam Shirsat
Rahul Krishnatry
Archya Dasgupta
Abhishek Chatterjee
Rakesh Jalali
Jayant Godasastri
Tejpal Gupta
Sridhar Epari
Aliasgar Moiyadi
Shizan Pervez
Farnaz Shaikh
Ayushi Sahay
Girish Chinnaswamy
Prakash Shetty
Source :
Neuro-Oncology
Publication Year :
2021
Publisher :
Oxford University Press (OUP), 2021.

Abstract

Background Medulloblastoma is a heterogenous disease comprising four molecular subgroups (WNT, SHH, Group 3, and Group 4) with varying outcomes. Excellent long-term survival (>90%) has prompted de-intensification of therapy in WNT-subgroup medulloblastoma globally. FOR-WNT is one such prospective study (CTRI/2017/12/010767) testing the hypothesis that focal conformal radiotherapy (RT) (54Gy/30 fractions/6-weeks) with avoidance of upfront craniospinal irradiation (CSI) followed by standard adjuvant chemotherapy significantly reduces RT-related late toxicity without unduly compromising survival in low-risk WNT-subgroup medulloblastoma (residual tumor Methods Patients with low-risk WNT-subgroup medulloblastoma were enrolled after written informed consent/assent. To ensure patient safety, stopping rules were devised according to group-sequential method. Results Between July 2017 till Feb 2019, seven children of WNT-pathway medulloblastoma were treated with focal conformal RT followed by 6-cycles of adjuvant chemotherapy (cisplatin, cyclophosphamide, and vincristine). One child succumbed to acute renal failure during chemotherapy, while the other 6 patients completed all 6-cycles as planned. Three children were detected with neuraxial failure (supratentorial brain and/or spine) without synchronous local recurrence in the treated tumor-bed on surveillance neuro-imaging between 1.5–2 years from index diagnosis following which the study was terminated prematurely. All 3 children with relapse were treated with salvage CSI (35Gy/21 fractions) with (conformal avoidance of previously treated tumor-bed) plus boost irradiation (10.8-18Gy/6–10 fractions) of metastatic deposits resulting in complete/near complete response and are alive with controlled disease. The other 3 children have not shown any evidence of relapse for over 2-years from index diagnosis and remain on active clinico-radiological surveillance. Conclusion In rigorously defined low-risk WNT-subgroup medulloblastoma, avoidance of upfront CSI is associated with unacceptably high risk of neuraxial failure. A successor study (FOR-WNT 2) incorporating low-dose CSI (18Gy/10 fractions) with similar tumor-bed dose and adjuvant systemic chemotherapy is currently underway.

Details

ISSN :
15235866 and 15228517
Volume :
23
Database :
OpenAIRE
Journal :
Neuro-Oncology
Accession number :
edsair.doi.dedup.....f8f50d5e2cea1d7ff52fc243bcb90fb5
Full Text :
https://doi.org/10.1093/neuonc/noab090.035