Pencil‐beam scanning for pediatric rhabdomyosarcoma: Promise and precautions

Abstract

Despite the proliferation of proton therapy centers worldwide, questions regarding the true benefit and safety of the modality remain. At present, a multitude of dosimetric studies clearly demonstrate that proton therapy has the ability to reduce dose to critical structures in the head and neck and other rhabdomyosarcoma (RMS) sites, 1-3 but useful clinical data demonstrating a meaningful benefit in light of this dosimetric advantage are sparse. This is in part due to the scarcity of large proton cohorts with long-term follow-up, as well as the absence of comparable photon toxicity data from recent cooperative group trials and single-institution studies utilizing modern photon techniques. MGH also published a retrospective subset analysis of 24 embryonal PM-RMS patients treated with passive scatter protons, looking at the correlation between LF and response to induction chemotherapy. 8 In this study, the LF rate for the entire cohort was 37%, raising concerns about the potential for an increased risk of local or marginal failures with protons, due to the rapid dose fall off and high sensitivity to anatomy changes. Close examination of the study patients found that all local recurrences were within the high radiation dose region without marginal failures, and no differences in target coverage were observed between local control (LC) and LF patients. The authors did find a strong correlation between response to induction chemotherapy and LF, with 100% LC in patients achieving a complete or partial response prior to radiation versus 46% LC in those with no response or progressive disease. In the MGH study, the objective response rate to induction chemotherapy (tumor reduction of >50%) was 42%, significantly lower than the 81% and 85% seen in the COG IRS-IV and D9803 studies, and the authors felt that the higher rate of LF seen was likely attributable to this poorer chemotherapeutic response. 9,10 Ultimately, the current study by Weber et al. suggests that LF rates utilizing PBS for PM-RMS are acceptable. In this issue ofThe potential benefit of proton therapy rests in the expected reduction in late toxicity. Weber et al. reported four occurrences of grade 3 late toxicities in three patients (8%), including three cataracts and one instance of hearing loss. There were no grade 4 or 5 late toxicities. The total incidence of grade 1 or 2 toxicities was 18% for endocrinopathies, 20% for facial hypoplasia, and 8% for visual complications. Similarly, in the prospective proton study from MGH and MDACC, there were two occurrences of grade 3 late toxicity (chronic otitis and retinopathy) and no grade 4 or 5 late toxicity in 21 evaluable patients with PM-RMS. 11The rates of grade 1 or 2 toxicity for endocrinopathies (14%), facial hypoplasia (10%), hearing (10%), and vision (5%) were also quite low.Direct comparison of these results to modern photon cohorts using IMRT is difficult, as most published photon series are small, retrospective in nature, and generally have included orbital patients in the toxicity rates. 6,7,12 Simil...