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We conducted a prospective, in silico imaging clinical trial to evaluate the feasibility and potential dosimetric benefits of computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of locally advanced pancreatic cancer (LAPC).Eight patients with LAPC received five additional CBCTs on the ETHOS system before or after their standard of care radiotherapy treatment. Initial plans were created based on their initial simulation anatomy (PCT-STAR was feasible in silico for LAPC and improved OAR and/or target dosimetry in 100% of fractions. Use of the PCT-STAR for the treatment of LAPC cancer proved feasible and was dosimetrically superior to non-adapted CT-stereotactic body radiotherapy.

A kV imager coupled to a novel, ring-gantry radiotherapy system offers improved on-board kV-cone-beam computed tomography (CBCT) acquisition time (17-40 seconds) and image quality, which may improve CT radiotherapy image-guidance and enable online adaptive radiotherapy. We evaluated whether inter-observer contour variability over various anatomic structures was non-inferior using a novel ring gantry kV-CBCT (RG-CBCT) imager as compared to diagnostic-quality simulation CT (simCT).Seven patients undergoing radiotherapy were imaged with the RG-CBCT system at breath hold (BH) and/or free breathing (FB) for various disease sites on a prospective imaging study. Anatomy was independently contoured by seven radiation oncologists on: 1. SimCT 2. Standard C-arm kV-CBCT (CA-CBCT), and 3. Novel RG-CBCT at FB and BH. Inter-observer contour variability was evaluated by computing simultaneous truth and performance level estimation (STAPLE) consensus contours, then computing average symmetric surface distance (ASSD) and Dice similarity coefficient (DSC) between individual raters and consensus contours for comparison across image types.Across 7 patients, 18 organs-at-risk (OARs) were evaluated on 27 image sets. Both BH and FB RG-CBCT were non-inferior to simCT for inter-observer delineation variability across all OARs and patients by ASSD analysis (p 0.001), whereas CA-CBCT was not (p = 0.923). RG-CBCT (FB and BH) also remained non-inferior for abdomen and breast subsites compared to simCT on ASSD analysis (p 0.025). On DSC comparison, neither RG-CBCT nor CA-CBCT were non-inferior to simCT for all sites (p 0.025).Inter-observer ability to delineate OARs using novel RG-CBCT images was non-inferior to simCT by the ASSD criterion but not DSC criterion.

Purpose Optimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC. Methods/Materials Patients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3–5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival. Results A total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7–52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3–60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed. Conclusions Salvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.

Preclinical studies have suggested that radiation therapy (RT) enhances antitumor immune response and can act synergistically when administered with immunotherapy. However, this effect in melanoma brain metastasis is not well studied. We aim to explore the clinical effect of combining RT and immunotherapy in patients with melanoma brain metastasis (MBM).Patients with MBM between 2011 and 2013 were obtained from the National Cancer Database. Patients who did not have identifiable sites of metastasis and who did not receive RT for the treatment of their MBM were excluded. Patients were separated into cohorts that received immunotherapy versus patients who did not. Univariable and multivariable analyses were performed using Cox model to determine predictors of OS. Kaplan-Meier method was used to compare OS. Univariable and multivariable analyses using logistic regression model were used to determine the factors predictive for the use of immunotherapy. Propensity score analysis was used to account for differences in baseline patient characteristics between the RT and RT + immunotherapy groups. Significance was defined as a P value ≤ 0.05.A total of 1104 patients were identified: 912 received RT alone and 192 received RT plus immunotherapy. The median follow-up time was 6.4 (0.1-56.8) months. Patients with extracranial disease (OR 1.603, 95% CI 1.146-2.243, P = 0.006), and patients receiving SRS (OR 1.955, 95% CI 1.410-2.711, P 0.001) as compared to WBRT, had a higher likelihood of being treated with immunotherapy. The utilization of immunotherapy had nearly doubled between 2011 and 2013 (12.9-22.8%). On multivariable analysis, factors associated with superior OS were younger age, lower medical comorbidities, lack of extracranial disease, and treatment with immunotherapy and SRS. The median OS was 11.1 (8.9-13.4) months in RT plus immunotherapy vs. 6.2 (5.6-6.8) months in RT alone (P 0.001), which remained significant after propensity score matching.An increase in trend for the use of immunotherapy was noted, however, an overwhelming majority of the patients with this disease are still treated without immunotherapy. Addition of immunotherapy to RT is associated with improved OS in MBM. Given the selection biases that are inherent in this analysis, prospective trials investigating the combination of RT, especially SRS and immunotherapy are warranted.

Purpose Explore the patterns of use of extracranial radiation therapy (RT) in metastatic melanoma patients receiving immunotherapy, its potential association with OS, the impact of the site and timing of RT on clinical outcomes when combined with immunotherapy. Materials and methods Patients with extracranial metastatic melanoma who received immunotherapy with or without extracranial RT from 2004 to 2013 were obtained from the National Cancer Database. Multivariable Cox regression analysis was used to evaluate factors associated with overall survival (OS). Subset analyses comparing outcomes in patients receiving RT to bone metastases versus soft tissue metastases were also performed. OS was compared using the Kaplan–Meier and log-rank statistics. Results A total of 1675 patients were identified: 1387 received immunotherapy alone and 288 received immunotherapy plus RT. An increase in the utilization of RT as well as SBRT was noted over time. The rate of RT use was 11.5% (0% with SBRT) in 2004 and gradually rose to 19.8% (27.0% with SBRT) in 2013 (P = 0.04). The median OS was 15.4 vs. 19.4 months in the immunotherapy plus RT and immunotherapy alone groups, respectively (P = 0.02). However, on multivariable analysis, RT was not associated with worse OS. The poor OS in the RT group was confined to the patients who received RT to bone metastases, but not in patients who received RT to soft tissue metastases. In subset analyses of patients irradiated to soft tissue, RT administered at least 30 days before immunotherapy was associated with a higher OS than RT administered within 30 days or 30 days after immunotherapy: median 26.1 months vs. 16.0 months (P = 0.009) vs. 15.4 months (P = 0.004), respectively. Conclusions This study demonstrates that extracranial RT plays an increasing role in the management of metastatic melanoma patients in the era of immunotherapy. The site and the timing of RT may have important interaction with immunotherapy, and need to be carefully considered in future clinical trials.

Background and purpose Patients with multiple primary lung cancers (MPLC) present a therapeutic dilemma, particularly when they are at high risk for surgical resection. We evaluated the role of stereotactic body radiation therapy (SBRT) in the treatment of MPLC. Materials and methods A prospective thoracic SBRT registry was explored for patients with either synchronous or metachronous MPLC treated with SBRT for one or both of their tumors. Sixty-three patients were identified and clinical data were analyzed. Results Fifteen patients had synchronous lesions and 48 patients had metachronous lesions. Seventy-six lesions were treated with SBRT. Median follow-up was 24months for living patients. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort was 15.5 and 20months, respectively. Patients with metachronous MPLC had a significantly higher 2year PFS (53.3% vs. 0%, p =0.0466) compared to patients with synchronous MPLC. Likewise, 2year OS was also superior for patients with metachronous versus synchronous MPLC (68.1% vs. 27.5%, p =0.0014). Six tumors (7.9%) recurred within the radiation field. There were no grade ⩾3 toxicities. Conclusions SBRT for patients with MPLC appears to be a safe and effective local treatment alternative to surgery, particularly for medically inoperable patients. Patients with metachronous MPLC have encouraging survival rates, and thus local therapy appears justified. However, patients with synchronous MPLC have poor OS and PFS despite having excellent local control, and thus the utility of local therapy in this population requires further study.