Abstract

AbstractPurpose:To report preliminary results of re-irradiation with proton therapy (PT) in large-volume recurrent glioblastoma (rGBM).Matherial/Methods:Between January and December 2015 ten patients (pts) with rGBM were re-irradiated with PT. All pts were previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant TMZ for 1–20 cycles (median, 7). Seven pts were re-irradiated at first relapse/progression. Four patients were re-irradiated after partial tumor resection. Median age and Karnofsky performance status at re-irradiation were 57 years (range, 41–68) and 80%, (range, 70–100), respectively. Median time between prior radiotherapy and PT was 9 months (range, 5–24). Target definition was based on CT, MR, and 18F-DOPA PET imaging. GTV included any area of contrast enhancement after contrast medium administration plus any pathological PET uptake regions. CTV was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. CTV was expanded by 4 mm to create PTV. Median PTV volume was 90 cc (range, 46–231). All pts received 36 GyRBE in 18 fractions. Four pts also received concomitant temozolomide (75 mg/m2/die, 7 days/week). All pts were treated with active beam scanning PT using 2–3 fields with single field optimization technique.Results:All pts completed the treatment without breaks. Registered acute side effects (according to Common Terminology Criteria for Adverse Events version 4.0 - CTCAE) include grade 1–2 skin erythema, alopecia, fatigue, conjunctivitis, concentration impairment, dysphasia, and headache. There were no grade 3 or higher toxicities. One patient developed grade 1 neutropenia. Five pts started PT under steroids (2–7 mg/daily); two of them reduced the dose during PT, while three kept the same steroids dose. None of remaining pts needed steroids therapy. Registered late side effects (according to CTCAE version 4.0) include grade 1–2 alopecia, fatigue, concentration impairment, and dysphasia. During follow-up two pts (20%) developed radionecrosis (diagnosed at imaging) with mild symptoms controlled with steroids. There were no grade 3 or higher toxicities. The median progression-free survival (PFS) was 6.4 months, while the 3-, 6- and 9-month PFS rates were 80%, 67% and 22%, respectively. Median overall survival (OS) after PT was not achieved, while the 6- and 12-month survival after PT rates were 100% and 60%, respectively.Conclusion:PT re-irradiation of large-volume rGBM showed to be feasible and safe even with concomitant chemotherapy administration. Despite the small number of patients and the retrospective nature of the study PFS and OS rates were promising and deserve further evaluation in a larger pts sample.

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