KEY POINTS
- The report describes a 20-year-old woman with 22q11.2 deletion syndrome and localized WHO grade 4 pineoblastoma. After subtotal resection, residual enhancing disease measured 2.1 × 2.4 × 1.3 cm, with negative spinal imaging and CSF cytology.
- She received guideline-concordant proton craniospinal irradiation to 36 Gy(RBE) in 20 fractions, with weekly vincristine, followed by a sequential primary-site boost to 54 Gy(RBE) in 30 total fractions. Acute toxicity was limited to mild fatigue, dermatitis, nausea and appetite loss.
- Maintenance cisplatin, vincristine and cyclophosphamide followed according to ACNS0332, although persistent thrombocytopenia led to discontinuation after five of six planned cycles.
- Approximately nine months after radiotherapy, MRI showed new enhancement involving the resection cavity, cerebellar structures, pons and corpus callosum, accompanied by tremor, weakness and facial paresthesia. Symptoms progressed to multiple cranial neuropathies, gait ataxia, aspiration and severe brainstem/cerebellar dysfunction.
- The process remained refractory despite dexamethasone up to 4 mg three times daily and biweekly bevacizumab. Salvage laser interstitial thermal therapy also failed to provide meaningful clinical or radiographic improvement; biopsy obtained during the procedure demonstrated necrosis and reactive changes without recurrent tumor.
- The severity was unusual: contemporary proton series report brainstem necrosis at approximately 1–2%, while the largest photon CSI series cited by the authors reported a five-year incidence around 3.7%. The case therefore prompted consideration of an underlying host-specific radiosensitivity rather than a straightforward planning failure.
- A potential DNA-repair mechanism is proposed around ZNF280A, which supports homologous-recombination repair of double-strand breaks. Importantly, however, this patient's proximal 22q11.2 deletion did not actually delete ZNF280A or its immediate promoter; indirect effects on its expression are speculative. The authors therefore do not recommend withholding curative RT, but suggest breakpoint characterization, conservative achievable OAR constraints and explicit toxicity counseling in similar patients.
CLINICAL TAKEAWAY
This case should not establish 22q11.2 deletion syndrome as a contraindication to radiation, and the authors specifically argue against withholding potentially curative CSI on current evidence. It does, however, provide a biologically plausible safety signal that unusual germline DNA-repair backgrounds may justify more detailed genetic characterization and especially conservative normal-tissue planning.