Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping
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To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB).
Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively.
A total of 28 patients (median age 18 years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4 MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5 months (range 24–98 months) with median cumulative biologically effective dose of 117 Gy (range 78–132 Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24 months (range 6–84 months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18 years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes.
Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.
KeywordsRecurrent medulloblastoma Salvage re-irradiation Molecular subgrouping
No source of funding was involved in this retrospective study.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
- 2.Khanna V, Achey R, Oostrom Q, Block-Beach H, Kruchko C, Barnholtz-Sloan JS et al (2017) Incidence and survival trends for medulloblastoma in the United States from 2001 to 2013. J Neurooncol 135(Suppl 10):1–9Google Scholar
- 5.Kunder R, Jalali R, Sridhar E, Moiyadi A, Goel N, Goel A et al (2013) Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas. Neuro-Oncology 15(12):1644–1651CrossRefGoogle Scholar
- 9.Michalski JM, Janss A, Vezina G, Gajjar A, Pollack I, Merchant TE et al (2016) Results of COG ACNS0331: a phase III trial of involved-field radiation therapy (IFRT) and low-dose craniospinal irradiation (LDCSI) with chemotherapy in average-risk medulloblastoma: a report from the Children’s Oncology Group. Int J Radiat Oncol Biol Phys 96(Issue_2, Supplement S1-S268):e1–e717Google Scholar
- 10.Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE et al (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7(10):813–820CrossRefGoogle Scholar
- 15.Dasgupta A, Gupta T, Sridhar E, Shirsat N, Krishnatry R, Goda JS et al (2019) Pediatric patients with SHH medulloblastoma fail differently as compared with adults: possible implications for treatment modifications. J Pediatr Hematol Oncol (in press)Google Scholar
- 17.Bode U, Zimmermann M, Moser O, Rutkowski S, Warmuth-Metz M, Pietsch T et al (2014) Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial. J Neurooncol 120(3):635–642CrossRefGoogle Scholar