PURPOSE Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. METHODS AND MATERIALS Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at XXXXX from 2003–2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4–103) for x-CSI patients and 26 months (range 11–63) for p-CSI. RESULTS p-CSI patients lost less weight than x-CSI patients (1.2%, versus 5.8%; p=0.004), and less p-CSI patients had greater than 5% weight loss compared to x-CSI (16% versus 64%; p=0.004). p-CSI patients experienced less grade 2 nausea and vomiting compared to x-CSI (26% versus 71%; p=0.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, p=<0.001). p-CSI patients had a smaller reduction in peripheral white blood cells (WBC), hemoglobin and platelets compared to x-CSI (WBC 46% versus 55%, p=0.04; hemoglobin 88% versus 97%, p=0.009; platelets 48% versus 65%, p=0.05). Mean vertebral doses were significantly associated with reductions in blood counts. CONCLUSIONS This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including less acute gastrointestinal and hematologic toxicities.

Significant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker.

Purpose To examine a relationship between serum transforming growth factor beta-1 (TGF-β1) values and radiation induced fibrosis (RIF). Methods We conducted a prospective analysis of development of RIF in 38 women with AJCC Stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via interstitial brachytherapy (IBAPBI). An ELISA (Quantikine ®, R&D, MN) immunoassay was used to measure serum TGF-β1 pre-surgery, pre- IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, non-treated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess radiation-induced fibrosis (RIF). Results Median time to follow-up for 38 patients is 44 months (range, 5 – 59 months). RIF is graded by the TCM scale as 0, 1, 2 and 3 in 5/20 (25%), 6/20 (30%), 5/20 (25%) and 4/20 (20%) patients, respectively. ΔTCM ≥6mm (moderate-to-severe RIF) is statistically different from ΔTCM ≤3mm (none-to-mild RIF) (p<0.05). Mean serum TGF-β1 values are significantly higher in patients pre-surgery than disease-free controls in: a) all cancer patients (30,201 ± 5,889 pg/ml, p=0.02), b) patients with any type of RIF (32,273 ± 5,016 pg/ml, p<0.0001) and c) women with moderate-to-severe RIF (34,462 ± 4,713 pg/ml, p<0.0001). The post-IBAPBI mean serum TGF-β1 is 21,915pg/ml in patients with ΔTCM ≥6mm (moderate-severe RIF). This is significantly higher than the mean serum TGF-β1, 14,940pg/ml, in patients with ΔTCM ≤3mm (p = 0.036). In patients who develop moderate-to-severe RIF, pre-IAPBI mean TGF-β1 values are also predictive of this sequela (17,885 ± 3,952 pg/ml, p=0.007). Conclusions TGF-β1 levels correlate with development of moderate-to-severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for development of moderate-to-severe RIF after IBAPBI

This large series of patients treated with p-CSI confirms low rates of acute toxicity, consistent with dosimetric models. Vertebral body-sparing p-CSI is feasible and should be considered as a way to reduce acute gastrointestinal and hematologic toxicity in adults requiring CSI.

We found that mean TVB dose and low-dose parameters (V-V) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group *T.H.B. and C.B. are co-first authors † N.C. and A.D.B. are co-senior authors Cancer Therapy and Prevention compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.What's new? While head and neck squamous cell carcinoma that are caused by human papillomavirus can be treated relatively well, virusnegative tumors have a poor prognosis. In this large multi-institutional study, the authors found that cisplatin-and carboplatin-based regimens-in concurrent chemoradiotherapy-were superior to antibody-based therapies, with carboplatinbased regimens representing a more tolerable alternative for patients with virus-negative tumors.

About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.

As our understanding of normal brain tissue tolerance and radiation technology have improved, central nervous system (CNS) re-irradiation has garnered more attention; whereas, in the past there had been hesitancy due to late toxicity concerns, particularly radionecrosis (RN). There is minimal prospective data evaluating repeat radiation in recurrent gliomas. In this review, the rationale for and different approaches to re-irradiation will be discussed, and the biology and clinical impact of late CNS toxicity will be reviewed.