Omission of Upfront Craniospinal Irradiation in Patients with Low-Risk WNT-Pathway Medulloblastoma Is Associated with Unacceptably High Risk of Neuraxial Failure.
Clin Cancer Res
; 28(19): 4180-4185, 2022 10 03.
Article
de En
| MEDLINE
| ID: mdl-35653134
ABSTRACT
PURPOSE:
Medulloblastoma is a heterogenous disease comprising four molecular subgroups wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, respectively. Excellent long-term outcomes have prompted deintensification of therapy in WNT-pathway medulloblastoma. We assessed the safety of avoiding upfront craniospinal irradiation (CSI) in children with low-risk WNT-pathway medulloblastoma. PATIENTS ANDMETHODS:
Children with low-risk WNT-pathway medulloblastoma were treated with postoperative focal conformal radiotherapy, avoiding upfront CSI, followed by six cycles of adjuvant systemic chemotherapy. A group-sequential design (triangular test) with predefined stopping rules if the rate of relapse exceeded 15% at 2 years was incorporated to ensure the safety of study participants.RESULTS:
7 children with low-risk WNT-pathway medulloblastoma were accrued after written informed consent/assent and treated as per protocol. One child died of neutropenic sepsis and multiorgan dysfunction during chemotherapy. Three children were detected with neuraxial failure (supratentorial brain and/or spine) on surveillance neuro-imaging within 2 years from index diagnosis, leading to premature study termination. At relapse, children were treated with salvage CSI plus boost irradiation of metastatic deposits followed by second-line chemotherapy. Two of them continue to be in remission (32 and 26 months after first relapse), while one child developed a second relapse, necessitating further systemic chemotherapy and craniospinal reirradiation, resulting in excellent clinico-radiologic response. At a median follow-up of 42 months, the 2-year Kaplan-Meier estimates of event-free survival, recurrence-free survival, and overall survival were 42.9%, 50%, and 85.7% respectively.CONCLUSIONS:
Omission of upfront CSI in low-risk WNT-pathway medulloblastoma is associated with an unacceptably high risk of neuraxial failure. See related commentary by Remke and Ramaswamy, p. 4161.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du cervelet
/
Irradiation craniospinale
/
Médulloblastome
Type d'étude:
Etiology_studies
/
Guideline
/
Risk_factors_studies
Limites:
Child
/
Humans
Langue:
En
Journal:
Clin Cancer Res
Sujet du journal:
NEOPLASIAS
Année:
2022
Type de document:
Article
Pays d'affiliation:
Inde