Efficacy and toxicity of bimodal radiotherapy in WHO grade 2 meningiomas following subtotal resection with carbon ion boost: prospective phase 2 MARCIE trial
Maximilian Y Deng, Sybren L N Maas, Felix Hinz, Christian P Karger, Philipp Sievers, Tanja Eichkorn, Eva Meixner, Philipp Hoegen-Sassmannshausen, Juliane Hörner-Rieber, Jonathan W Lischalk, Katharina Seidensaal, Denise Bernhardt, Christine Jungk, Andreas Unterberg, Antje Wick, Wolfgang Wick, Andreas von Deimling, Felix Sahm, Stephanie Combs, Klaus Herfarth, Jürgen Debus, Laila König- Cancer Research
- Neurology (clinical)
- Oncology
Abstract
Background
Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing the radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5).
Methods
A total of 33 patients were enrolled from July 2012 until July 2020. Study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). Primary endpoint was the 3-year progression-free survival (PFS) , and secondary endpoints included overall survival, safety and treatment toxicities.
Results
With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7% and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly-located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in one patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients.
Conclusions
Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve an superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.