Proton Beam Radiation-Induced Skull Base Malignancy

Background Proton beam therapy is gaining increased use as a number of centers offering this treatment rapidly proliferate in the United States. The surge in its popularity stems from the theoretical benefit of an improved dose curve. Charged particles deposit low doses of radiation proximal to the target volume with rapid fall off distal to the target. Decreased levels of out of field radiation make the technology especially appealing in skull base tumors where high conformality is needed to avoid damage to delicate neural structures and prevent the induction of devastating secondary intracranial malignancies. Prior modeling of the risk for secondary malignancy in proton therapy compares favorably to photons but often does not account for charged particles ability to create neutron scatter, which can be highly carcinogenic. Additionally, if adaptive replanning is not instituted, fractionated protons may be delivered to nontarget volumes as the tumor response changes the location of the target volume. Currently, no long-term clinical data exists for proton therapy, which reveals true rates of secondary malignancy. The first cohort of patients treated with proton beam are currently reaching the follow-up time period at which radiation-induced malignancies typically appear, making this question particularly important.

Objective To present one of the first cases of proton therapy-induced malignancy after uneventful 12-year follow-up.

Case Patient was an 18-year-old man who initially presented with left-sided hearing loss and was found to have a large 5.5-cm low-grade papillary adenocarcinoma consistent with an endolymphatic sac tumor. Petrosectomy was performed with near total resection. Small remnants remained encasing the carotid and the patient was referred to outside facility for proton beam therapy. Patient had uneventful follow-up for 12 years until small 6 mm enhancement was noted. Patient was scheduled for repeat MRI, however, represented with new-onset ataxia and headache within 3 months and was found to have a massive 5 cm enhancing tumor of the left cerebellum with vasogenic edema and mass effect on the midbrain and fourth ventricle. He was taken for resection with pathologic finding of glioblastoma multiforme.

Conclusion Rates of secondary malignancy after proton therapy remain controversial with limited clinical data available. This case highlights the coming of age of a cohort of previously irradiated patients treated with this relatively young technology. Future evaluation with long-term follow-up is needed to accurately assess the safety of proton beam therapy and rates of secondary malignancy.