Table 1.

Reports on toxicity potentially attributed to the RBE effect.

First Author [reference]	Tumor site; cohort size	Observations
Harrabi [19]	Meningioma, low grade glioma; 430 patients (276 protons, 154 photons)	Correlation of MRI findings (minimum follow-up 12 months) with LET and RBE distributions Cumulative incidence of necrosis after proton beam therapy: 3.3% No correlation with technique, number of beams, dose, concomitant chemotherapy Significant association with periventricular border and distal edge of SOPB
Zhang [60]	Nasopharyngeal carcinoma; 75 patients (61 protons, 14 IMRT)	Incidence temporal lobe necrosis (TLN) at 5.6 years: 7% for IMRT versus 14.8% in PBT; median interval 34 months (9–82 months). Asian race is the only clinical risk-factor for TLN. RBE estimated 1.12–1.25
Merchant [29]	Craniopharyngioma; 97 proton patients (subset of NCT01419067) and 101 photon patients	Incidence of necrosis 2.68% (± SE 1.89%) for protons versus 1.98% (± SE 1.39%) for photons; permanent neurological deficits 4.15% (± SE 2.38%) versus 2.97% (± SE 1.70%)