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Simple Summary  A variety of therapies are available for the treatment of retinoblastomas. Nevertheless, despite exhaustion of all therapeutic methods, refractory or recurrent courses of the disease occur. In eyes with a function worthy of preservation radiation therapy may become unavoidable. Proton beam therapy, compared to conventional photon-based radiotherapy, is a highly conformal form of radiation therapy with a high biological effectiveness with a simultaneously reduced probability of radiation-related side-effects and induction of secondary primary malignancies. The aim of our retrospective study was to evaluate the efficacy of proton beam therapy as rescue therapy in 15 heavily pretreated retinoblastoma eyes. In our retrospective series of a highly negatively selected patient population, we were able to preserve 60% of the eyes with a manageable side effect profile. A cataract, as the most common long-term complication, was evident in 44.4% of the preserved eyes. There was no in-field second tumor manifestation during follow-up, therefore the preliminary data of this study and series published by others suggest that the risk is significantly lower after proton beam therapy compared to conventional external beam radiation therapy using photons.    Abstract  Despite the increased risk of subsequent primary tumors (SPTs) external beam radiation (EBRT) may be the only therapeutic option to preserve a retinoblastoma eye. Due to their physical properties, proton beam therapy (PBT) offers the possibility to use the effectiveness of EBRT in tumor treatment and to decisively reduce the treatment-related morbidity. We report our experiences of PBT as rescue therapy in a retrospectively studied cohort of 15 advanced retinoblastoma eyes as final option for eye-preserving therapy. The average age at the initiation of PBT was 35 (14–97) months, mean follow-up was 22 (2–46) months. Prior to PBT, all eyes were treated with systemic chemotherapy and a mean number of 7.1 additional treatments. Indication for PBT was non-feasibility of intra-arterial chemotherapy (IAC) in 10 eyes, tumor recurrence after IAC in another 3 eyes and diffuse infiltrating retinoblastoma in 2 eyes. Six eyes (40%) were enucleated after a mean time interval of 4.8 (1–8) months. Cataract formation was the most common complication affecting 44.4% of the preserved eyes, yet 77.8% achieved a visual acuity of >20/200. Two of the 15 children treated developed metastatic disease during follow-up, resulting in a 13.3% metastasis rate. PBT is a useful treatment modality as a rescue therapy in retinoblastoma eyes with an eye-preserving rate of 60%. As patients are at lifetime risk of SPTs consistent monitoring is mandatory.

Feasibility of Proton Beam Therapy as a Rescue Therapy in Heavily Pre-Treated Retinoblastoma Eyes