Radiation-Induced Neurooncological Outcomes

Radiation-induced neurooncological outcomes encompass the spectrum of secondary central nervous system malignancies that arise as a late complication of cranial or craniospinal radiotherapy. Although radiotherapy remains a cornerstone of treatment for primary brain tumours and certain paediatric malignancies, a subset of survivors develop radiation-induced gliomas (RIGs), high-grade gliomas or diffuse intrinsic pontine gliomas years to decades after initial exposure. These tumours typically exhibit a prolonged latency period, aggressive clinical behaviour and poor prognosis. At the histopathological level they are often IDH-wildtype and H3-wildtype, with recurrent genomic alterations such as PDGFRA amplification and CDKN2A/B deletion. Molecular profiling has demonstrated distinct epigenetic and transcriptomic signatures compared with their de novo counterparts, implicating radiation-induced DNA damage and repair pathway disruption in tumourigenesis. Clinically, these secondary neoplasms pose challenges in diagnosis—frequently masquerading as recurrence of the primary disease—and in management, where resection, reirradiation and systemic therapy must be balanced against the risks of cumulative toxicity. Advances in genomic and methylation profiling have begun to inform targeted therapy approaches, offering hope for improved outcomes in this vulnerable patient population.

Research from Nature Portfolio

Recent clinical and molecular characterisations of radiation-induced gliomas have quantified patient risk and defined prognostic molecular markers. A cohort study of post-radiotherapy survivors established a 1.6 % risk at ten years, identifying PDGFRA amplification and CDKN2A/B deletion as hallmarks associated with dismal median survival of seven months. Paediatric RIGs have been stratified into stem-like and pro-inflammatory subgroups via DNA methylation profiling, revealing chromothripsis-driven extrachromosomal amplification of receptor tyrosine kinases and distinctive immune-related transcriptional programmes. Comprehensive epigenetic and expression analyses of RIGs emerging after treatment for medulloblastoma and leukaemia further confirmed the absence of hotspot H3 and IDH mutations, consolidating a unifying molecular signature that may guide diagnostic and therapeutic decisions.

Radiation-Induced Neurooncological Outcomes publication trend

The graph below shows the total number of articles in radiation-induced neurooncological outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Radiation-induced glioma: A high-grade glial neoplasm that arises in a previously irradiated field, distinct from a recurrence of the primary tumour.
Latency period: The interval between initial radiotherapy exposure and the clinical onset of a secondary neoplasm.
DNA methylation profiling: A genome-wide assay to assess cytosine methylation patterns that classify tumours into molecular subtypes.
PDGFRA amplification: Increase in copy number of the platelet-derived growth factor receptor A gene, driving cell proliferation.
CDKN2A/B deletion: Loss of tumour suppressor genes encoding cell cycle regulators p16INK4a and p15INK4b, facilitating unchecked cell division.

References

1. Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting. Acta Neuropathologica Communications (2023).
2. Clinical and molecular study of radiation-induced gliomas. Scientific Reports (2024).
3. Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma. Nature Communications (2021).
4. Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B. Nature Communications (2021).
5. Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry. Acta Neuropathologica Communications (2018).
6. Assessment of therapeutic outcome and role of reirradiation in patients with radiation-induced glioma. Radiation Oncology (2022).