Long-Term Follow-up of Patients Treated at a Single Institution Using a Passively Scattered Proton Beam; Observations Around the Occurrence of Second Malignancies.

Purpose: To investigate the occurrence of second malignancies resulting from the secondary radiation from a passively scattered proton beam.

Methods And Materials: A cohort of patients with long-term follow-up was defined. All were treated at the same institution with the same proton delivery system, consisting of a 200 MeV fixed, horizontal, passively scattered beam combined with a robotic chair. This setup allows for stereotactic positioning and permits fractionated treatments. The majority of patients underwent cranial or intracranial stereotactic radiation therapy. Patients with previous photon therapy or a follow-up of 24 months or less were excluded. For out-of-field secondary malignancies (SMs), the observed incidence in the study population was compared to the risk of developing a malignancy in the general population, taking patient sex into account.

Results: From September 1993 to May 2016, a total of 524 patients received proton beam therapy, and 322 patients could be evaluated for this study (164 female and 158 male). Age ranged from 2 to 85 years, with a median of 40 years. Follow-up ranged from 25 to 276 months, with a median of 150 months (12.5 years). During the study observation period, 7 patients had out-of-field new malignant disease. Three female patients developed a malignancy, compared with an expected incidence of 4.09 (standardized incidence ratio, 0.73 [95% confidence interval, 0.24-2.27]); 4 male patients developed a malignancy, versus an expected incidence of 3.99 (standardized incidence ratio, 1.00 [95% confidence interval, 0.38-2.67]). New intracranial disease developed in 9 patients: 8 meningiomas and 1 carcinoma.

Conclusions: For out-of-field SMs, no increased risk of developing a variety of malignancies was observed. For in-field SMs, only 1 malignant histology was noted 15 years after the original proton therapy. No SM was observed in children and young adults.