Case Presentation

The patient was, at the time of the initial diagnosis of GBM, a 51-year-old male with minimal medical comorbidities and a history notable for medulloblastoma of the cerebellum diagnosed and treated 7 years prior (Figure 1). The medulloblastoma was of the sonic hedgehog (SHH) molecular subtype and was treated with surgical resection, craniospinal radiotherapy and adjuvant chemotherapy (without concurrent chemotherapy). He was initially prescribed craniospinal irradiation (CSI) to a dose of 3600 cGy in 18 fractions, but after a second opinion at an outside institution, he ultimately opted for reduced-dose CSI (described in some recent reports) due to concerns regarding cognitive effects. ^{Reference Moxon-Emre, Bouffet and Taylor6} He received CSI to a dose of 2340 cGy in 13 fractions, followed by a posterior fossa boost of 3060 cGy in 17 fractions, for a total dose of 5400 cGy to the posterior fossa. He subsequently received adjuvant temozolomide, etoposide, vincristine, cyclophosphamide and carboplatin chemotherapy. The patient then had a short-interval development of multicentric malignant glioma with MET mutation necessitating the use of SRS.

Figure 1. Medulloblastoma prior to resection and treatment.

On surveillance imaging, a new (since brain MRI with and without contrast 10 months prior) 2.5 cm × 1.5 cm, contrast-enhancing, centrally necrotic, right superior cerebellar vermis lesion was seen and attributed to either tumour progression vs. radiation necrosis (Figure 2). He received 6 cycles of bevacizumab, after which the lesion markedly regressed.

Figure 2. Contrast-enhanced T1-weighted magnetic resonance (left) and FLAIR images (right) demonstrating right cerebellar vermian lesion (tumour progression vs. radiation necrosis).

Subsequent MRI neuroimaging demonstrated a non-enhancing left cerebellar peduncular lesion (Figure 3). Lumbar puncture revealed rare, small malignant cells, and recurrent medulloblastoma was suspected. Stereotactic biopsy was performed, and pathology demonstrated a low-grade glioma of astrocyte origin with a somatic MET mutation and no IDH mutation. No germline mutation was identified in this patient’s glioma. He was then treated with temozolomide (5 total cycles), irinotecan, crizotinib and lomustine.

Figure 3. Contrast-enhanced T1-weighted magnetic resonance (left) and FLAIR images (right) demonstrating a left cerebellar peduncular lesion, positive for the MET mutation.

Six months after the non-enhancing left cerebellar lesion was identified and 11 months after the enhancing right cerebellar lesion was seen, surveillance brain MRI showed regression of the non-enhancing left cerebellar peduncle lesion and stability of the right cerebellar vermian lesion. In the interval, however, a new right temporal lobe contrast-enhancing mass had developed. Given his recent diagnosis of astrocytoma and the aggressive appearance and behaviour of this new lesion, he opted for definitive radiotherapy without a biopsy or resection. The patient was simulated on a GE Discovery RT CT. The VMAT treatment plan was created in the Varian Eclipse treatment planning system (v16.1, Varian Medical Systems, Palo Alto, CA) using the Acuros XB algorithm for a Varian TrueBeam STx C-arm linac equipped with a high-definition multileaf collimator. The new tumour was treated with linear accelerator (LINAC)-based fractionated stereotactic/IMRT to a dose of 30 Gy in 5 fractions over 1 week (Figure 4), with concurrent temozolomide chemotherapy and 2 cycles of bevacizumab. The right optic nerve, right optic tract, optic chiasm and right cochlea received mean doses of 1152 cGy, 2093 cGy, 1022 cGy and 1066 cGy, respectively.

Figure 4. IMRT targeting right temporal lesion–Clinical Target Volume (CTV) highlighted above.

Subsequent imaging showed an interval decrease in the size of the right temporal lesion with improved mass effect (Figure 5) and the development of a new left cerebellar hemispheric lesion, which was resected. Pathology revealed IDH wildtype, high-grade cerebellar glioma. He then underwent a subsequent GKRS dose of 27 Gy in 3 fractions to the surgical cavity margin (Figure 6). GKRS was performed using Esprit (Elekta Instrument AB, Stockholm, Sweden), and dosimetry parameters are summarised in Table 1. The brainstem received a composite dose of 84.2 Gy and a composite D0.035cc of 82.2 Gy. The patient was noted to be awake, alert and orientated to person, place and time on subsequent patient visits following completion of GKRS. At the time of the last follow-up, one year after completion of GKRS, the patient had not developed any symptomatic radiation necrosis or neuroimaging changes reflective of treatment toxicity.

Figure 5. Interval decrease in right temporal lobe FLAIR signal change following linear accelerator (LINAC)-based stereotactic IMRT.

Figure 6. Gamma knife stereotactic radiosurgery (GKRS) plan highlighting isodose distributions (27 Gy, 24 Gy, 20 Gy and 18 Gy).

Table 1. Gamma knife stereotactic radiosurgery dosimetry parameters

Recommendation

This case highlights multiple considerations in the management of RIMG following prior craniospinal irradiation for medulloblastoma, which poses treatment challenges. Stereotactic radiosurgery is an effective treatment modality, particularly in reducing the integral dose of radiation in patients who have undergone prior craniospinal irradiation. Radiation oncologists must be cognisant of the implications of a glial tumour’s molecular profile, particularly the MET mutation, which may have contributed to this patient’s short interval RIMG following prior definitive treatment of adult medulloblastoma.