Radiation-induced secondary malignancies are a significant, yet uncommon cause 
of morbidity and mortality among cancer survivors. Secondary malignancy risk is 
dependent upon multiple factors including patient age, the biological and 
genetic predisposition of the individual, the volume and location of tissue 
irradiated, and the dose of radiation received. Proton therapy (PRT) is an 
advanced particle therapy with unique dosimetric properties resulting in reduced 
entrance dose and minimal to no exit dose when compared with standard photon 
radiation therapy. Multiple dosimetric studies in varying cancer subtypes have 
demonstrated that PRT enables the delivery of adequate target volume coverage 
with reduced integral dose delivered to surrounding tissues, and modeling 
studies taking into account dosimetry and radiation cell biology have estimated 
a significantly reduced risk of radiation-induced secondary malignancy with PRT. 
Clinical data are emerging supporting the lower incidence of secondary 
malignancies after PRT compared with historical photon data, though longer 
follow-up in proton treated cohorts is awaited. This article reviews the current 
dosimetric and clinical literature evaluating the incidence of and risk factors 
associated with radiation-induced secondary malignancy following PRT.