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Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far. (C) 2018 Elsevier B.V. All rights reserved.

To report disease control, survival and treatment-associated toxicity with the use of proton therapy (PRT) for re-irradiation of intracranial ependymoma.Twenty patients underwent 33 PRT re-irradiation courses for recurrent or metastatic lesions between June 2004 and February 2015 at Massachusetts General Hospital.The majority of patients were female (60%), with infratentorial tumors (90%), anaplastic histology (55%), and initially received 55.8 GyRBE (52.2-59.4) involved field (IF) PRT. First failure was local (55%), distant (30%) or both (15%) at a median time of 23.9 months (9.9-98.5) from first treatment. Salvage therapy included re-resection (75%), chemotherapy (60%) and IFPRT (70%) to a median dose 50.4 GyRBE (35-55.8) in the majority of patients. The median follow-up was 37.8 months (5.5-138.0). Three year OS and PFS are 78.6% (95% CI 67.6-89.6) and 28.1% (95% CI 15.6-40.6), respectively. Longer OS was significantly associated with surgical resection of recurrent disease (HR 9.19, 95% CI 1.27-66.44, p=0.028). The pattern of second failure after re-irradiation was directly related to the pattern of first failure (p0.01). Three of 14 patients (21.4%) locally re-treated experienced grade 2 radiation-associated treatment change.Proton therapy appears safe and efficacious for the re-treatment of recurrent intracranial ependymoma.

Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors.HRQoL data were prospectively collected on PRT-treated patients aged 2-18 treated at Massachusetts General Hospital (MGH). Cross-sectional PedsQL data from XRT treated Lucile Packard Children's Hospital (LPCH) patients provided the comparison data.Parent proxy HRQoL scores were reported at 3 years for the PRT cohort (PRT-C) and 2.9 years (median) for the XRT cohort (XRT-C). The total core HRQoL score for the PRT-C, XRT-C, and normative population differed from one another and was 75.9, 65.4 and 80.9 respectively (p=0.002; p=0.024; p0.001). The PRT-C scored 10.3 and 10.5 points higher than the XRT-C in the physical (PhSD) and psychosocial (PsSD) summary domains of the total core score (TCS, p=0.015; p=0.001). The PRT-C showed no difference in PhSD compared with the normative population, but scored 6.1 points less in the PsSD (p=0.003). Compared to healthy controls, the XRT-C scored lower in all domains (p0.001).The HRQoL of pediatric brain tumor survivors treated with PRT compare favorably to those treated with XRT and similar to healthy controls in the PhSD.

Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects.Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans.Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for HN (p0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p0.01), and 3.5 times higher for orbit (p0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients.Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available.

Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.