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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
- 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.
- Subjects :
- Medulloblastoma
Oncology
Cancer Research
medicine.medical_specialty
business.industry
Adjuvant chemotherapy
medicine.medical_treatment
Complete remission
Wnt signaling pathway
medicine.disease
Chemotherapy regimen
Molecular conformation
Embryonal Tumors
Radiation therapy
Pharmaceutical Adjuvants
Internal medicine
AcademicSubjects/MED00300
Medicine
AcademicSubjects/MED00310
Neurology (clinical)
business
Subjects
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