Systematic review
Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation

https://doi.org/10.1016/j.radonc.2017.08.005Get rights and content

Abstract

Reirradiation (reRT) for locoregional recurrences poses unique challenges and risks; re-treatment using proton beam radiotherapy (PBT) could prove advantageous. Assessing clinical outcomes and toxicity profiles, this systematic review comprehensively evaluated available evidence regarding PBT reRT. Fourteen original investigations across central nervous system (CNS) (n = 6), head/neck (H&N) (n = 4), lung (n = 2), and gastrointestinal (n = 2) malignancies were analyzed. PBT for recurrent uveal melanoma achieved 5-year eye retention of 55%; for chordomas, reRT afforded a 2-year local control and overall survival (OS) of 85% and 80%, respectively. Multiple PBT reRT studies for adult gliomas illustrate no grade ≥3 toxicities. Two pediatric CNS tumor studies demonstrated the safety and efficacy of reRT, with one total grade 3 toxicity and achievement of longer-term OS. PBT for H&N malignancies shows appropriate local/locoregional control and favorable toxicity profiles versus historical photon-based methods, including low (9–10%) rates of feeding tube placement. PBT for recurrent lung cancer can achieve favorable survival with expected toxicities/complications of reRT, especially with concurrent chemotherapy and centrally located recurrences. Lastly, PBT reRT in gastrointestinal malignancies induced very few high-grade complications. Hence, based on the limited existing data, PBT is a notably safe reRT modality for effective salvage of recurrent disease. Institutional experiences must continue to be reported: dosimetric correlations, late toxicities, and advanced PBT techniques.

Section snippets

Materials and methods

This systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [16]. Eligibility criteria included published work in English evaluating proton RT for neoplasms that have undergone an initial course of RT, with reRT being performed in the setting of recurrent disease or second primary tumor in the initial RT field. Relevant endpoints to be considered for each disease site were any types of adverse events and/or complications,

Ocular

Table 1 illustrates details regarding PBT reRT for ocular, adult central nervous system (CNS), and pediatric CNS neoplasms. In an evaluation of re-PBT for 31 patients with recurrent uveal melanoma at Harvard University [17], the median time to reRT was 36 months, and nearly all patients were re-treated with a full dose of 70 Gray-equivalent (GyE). Most patients had initially received 70 GyE. At 5 years, the rate of local recurrence (LR) was 31%, with a 5-year eye retention rate of 55%. Of the

Discussion

This is the first systematic review to date comprehensively assessing the safety and efficacy of PBT for re-irradiation, a high-risk circumstance for which advanced technologies such as PBT may have substantial utility. Literature to date, while encouraging, is limited, and reporting of further experiences and correlations with toxicities and outcomes is needed.

Among the diverse constellation of CNS malignancies, PBT displays appropriate safety profiles in the reRT setting. Although outcomes of

Conflicts of interest

All authors declare that conflicts of interest do not exist.

Funding

There were no funding sources for this work.

Ethics

This work did not involve patients.

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