Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI. METHODS: Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression. RESULTS: 213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated "possibly" related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE. CONCLUSION: This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

Combined Stereotactic Body Radiation Therapy and Immune Checkpoint Inhibition for Liver Metastases: Safety and Outcomes in a Pooled Analysis of 3 Phase 1 Trials.

PURPOSE: Stereotactic body radiation therapy (SBRT) safely and effectively controls liver metastases (LMs), but its safety and efficacy when combined with immune checkpoint inhibitors (ICIs) are not well characterized. This analysis of 3 phase 1 trials of combination SBRT and ICI evaluates whether LM-SBRT increases the risk for hepatotoxicity when combined with ICI and explores efficacy endpoints. METHODS AND MATERIALS: Data were analyzed from 3 phase 1 trials of combination SBRT and ICI for patients with metastatic solid tumors conducted between 2016 and 2020. ICI was administered per trial protocol with LM-SBRT delivered to 45 Gy in 3 fractions with mean liver dose <16 Gy and ≥700 cc of normal liver spared 17.1 Gy. Hepatic adverse events (HAEs) were defined as hepatic failure, autoimmune hepatitis, or elevation of aspartate transaminase, alanine transaminase, bilirubin, or alkaline phosphatase using Common Terminology Criteria for Adverse Events version 4.0. Cumulative incidence of HAEs and local failure were modeled with death as a competing risk. Competing risk regression was performed using Fine-Gray modeling. Survival was estimated via the Kaplan-Meier method. RESULTS: Two hundred patients were analyzed, including 81 patients with LM, 57 of whom received LM-SBRT. The 12-month rate of any grade ≥2 HAE was 11% and 10% in LM-SBRT and non-LM-SBRT patients, respectively non-significant (NS). Radiographic evidence for liver disease and dual-agent ICI was significantly associated with HAEs on univariable and multivariable analysis, but liver dose metrics were not. Patients with LM had significantly worse progression-free and overall survival compared with those without, and local failure of treated LM was significantly higher than for treated extrahepatic metastases (28% vs 4% at 12 months, P < .001). CONCLUSIONS: Combination LM-SBRT and ICI did not significantly increase the risk for HAEs compared with ICI without LM-SBRT, suggesting hepatotoxicity is largely driven by factors other than liver radiation therapy, such as choice of ICI. LM is associated with worse overall survival and local control outcomes.

Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases.

BACKGROUNDWe previously demonstrated the safety of stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) in patients with advanced solid tumors. This phase I clinical trial was expanded to study the safety of partial tumor irradiation (partial-Rx). We assessed irradiated local failure (LF) and clinical outcomes with correlations to biomarkers including CD8+ T cell radiomics score (RS) and circulating cytokines.METHODSPatients received SBRT to 2-4 metastases and pembrolizumab for up to 7 days after SBRT. Tumors measuring up to 65 cc received the full radiation dose (complete-Rx), whereas tumors measuring more than 65 cc received partial-Rx. Landmark analysis was used to assess the relationship between tumor response and overall survival (OS). Multivariable analysis was performed for RS and circulating cytokines.RESULTSIn the combined (expansion plus original) cohort, 97 patients (219 metastases) were analyzed and received SBRT+P. Forty-six (47%) patients received at least 1 partial-Rx treatment. There were 7 (7.2%)dose-limiting toxicities (DLTs). 1-year LF was 7.6% overall, and 13.3% and 5.4% for partial-Rx and complete-Rx tumors, respectively (HR 2.32, 95% CI 0.90-5.97, P = 0.08). The overall, unirradiated, and irradiated objective response rates were 22%, 12%, and 34%, respectively. Irradiated tumor response to SBRT+P was associated with prolonged OS; 1-year OS was 71% (responders), 42% (mixed-responders), and 0% (nonresponders) (P < 0.01). High-RS was significantly associated with improved LF, progression-free survival (PFS), and OS. Elevated circulating IL-8 was independently associated with inferior PFS and OS.CONCLUSIONSBRT+P is safe in patients with large, advanced solid tumors. Additional studies are warranted to assess noninferiority of complete versus partial irradiation of tumors in the setting of immunotherapy.TRIAL REGISTRATIONClinicaltrials.gov NCT02608385FUNDINGMerck Investigator Studies Program; Hillman Fellows for Innovative Cancer Research Program; NIH grants UM1CA186690-06, P50CA254865-01A1, P30CA047904-32, and R01DE031729-01A1.

Increased Utilization of Stereotactic Body Radiotherapy is Associated with Decreased Disparities and Improved Survival for Early-Stage NSCLC.

INTRODUCTION: We sought to determine if increased use of stereotactic body radiation therapy (SBRT) was associated with decreased disparities in the receipt of definitive treatment for early-stage non-small cell lung cancer (NSCLC). METHODS: The National Cancer Database (NCDB) was utilized to determine the proportion of patients with NSCLC receiving surgery, SBRT, or no definitive treatment for clinical cT1-2aN0M0 NSCLC from 2004-2017. Univariable and multivariable logistic regressions were used. Age-adjusted mortality rates were calculated using the Surveillance, Epidemiology, and End Result (SEER) database. RESULTS: From 2004 to 2017, the proportion of early-stage NSCLC undergoing no definitive treatment declined from 22% to 10.5% (P<.001), while the proportion receiving SBRT increased from 1% (0.9%-1.3%) to 22% (21.4%-22.3%; P<.001). Among Whites, the proportion undergoing no definitive treatment decreased from 21% to 10% (P<.001), as compared to Blacks, which had a higher decrease, of 32% to 15% (P<.001). The proportion of Blacks receiving SBRT increased from 1% (0.3%-1.7%) to 22% (20.8%-23.5%) (P<.001). Between 2011 and 2017 likelihood of Blacksreceiving curative therapy increased compared to Whites [OR: 0.55 (0.48-0.64) to 0.70 (0.62-0.79; P<.001]. Furthermore, the age-adjusted mortality rate of early-stage NSCLC decreased from 4.3 (4.0-4.5) in 2004 to 0.8 (0.7-0.9) in 2017 (P<.001). CONCLUSIONS: Increased utilization of SBRT significantly increased the proportion of patients receiving curative therapy for early-stage NSCLC and was associated with an improvement in mortality.  Furthermore, the use of SBRT reduced previously seen disparities in receipt of treatment between Whites and Blacks. SBRT was also associated with decreased mortality from early-stage NSCLC.

Predictors of Pneumonitis in Combined Thoracic Stereotactic Body Radiation Therapy and Immunotherapy.

PURPOSE: Thoracic stereotactic body radiation therapy (SBRT) is associated with high rates of local control but carries a risk of pneumonitis. Immunotherapy is a standard treatment for patients with metastatic disease but can also cause pneumonitis. To evaluate the feasibility and safety of thoracic SBRT with systemic immunotherapy, clinical outcomes of patients treated with immune checkpoint blockade (ICB) and SBRT on prospective trials were reviewed. METHODS AND MATERIALS: Three consecutive phase 1 trials of combination SBRT and ICB conducted between 2016 to 2020 for widely metastatic solid tumors were reviewed. The protocols mandated adherence to NRG BR001/BR002 organs at risk constraints, resulting in <100% coverage of some target volumes. ICB was administered either sequentially (within 7 days after completion of SBRT) or concurrently (before or at the start of SBRT), depending on protocol. End points included pneumonitis, dose-volume constraints, local failure, and overall survival. The cumulative incidence estimator and Kaplan-Meier method were used. RESULTS: In the study, 123 patients met eligibility with 311 metastases irradiated. The most common histologies included non-small cell lung cancer (33%) and colorectal cancer (12%). Median follow-up was 12 months. The overall rate of grade 3+ pneumonitis was 8.1%; 1-year local failure was 3.6%. Established dosimetric parameters were significantly associated with the development of pneumonitis (P < .05). In most patients, the lungs were not challenged with high doses of radiation, defined as receiving ≥75% of the maximum for a given lung dose-volume constraint. Patients who were challenged were not found to have a significantly higher risk of pneumonitis. CONCLUSIONS: In the largest series of thoracic SBRT and immunotherapy, local control was excellent with acceptable toxicity and support the conclusion that established dose-volume constraints for the lung are safe. However, these results highlight the potential value in reporting of organs at risk being challenged with doses approaching protocol specified limits.

Decreased overall survival in patients with locally advanced head and neck cancer receiving definitive radiotherapy and concurrent cetuximab: National Cancer Database analysis.

BACKGROUND: Recently, randomized trials have questioned the efficacy of cetuximab-based bioradiotherapy compared to chemoradiation for patients with squamous cell carcinoma of the oropharynx, larynx, and hypopharynx (HNSCC). We compared the OS of patients treated with radiotherapy alone (RTonly), chemoradiotherapy (chemoRT), and bioradiotherapy (cetuxRT). METHODS: Patients with stage III-IVB HNSCC treated with RTonly, chemoRT, or cetuxRT were identified in the National Cancer Database. OS was estimated using Cox proportional hazards. Analyses were conducted on the overall cohort and propensity matched cohorts. RESULTS: 31 014 patients were treated with RTonly (22%), chemoRT (72%), or cetuxRT (6%) from 2013 to 2016. The 2-year OS was 69% for RTonly, 79% for chemoRT, and 66% for cetuxRT (p < 0.001). In the overall and propensity-matched cohorts, chemoRT and RTonly were associated with improved OS as compared to cetuxRT (p ≤ 0.001). CONCLUSION: Compared to chemoRT or RTonly, cetuxRT is associated with decreased OS for patients with HNSCC, suggesting minimal benefit of bioradiotherapy in this population.

Impact of anatomic site of distant metastasis on survival in salivary gland cancers.

BACKGROUND: As exemplified in patients with adenoid cystic carcinoma (ACC), metastatic salivary gland cancers display heterogenous behavior. Although anatomic site of metastasis has been suggested to be prognostic for survival in this population, this is not adequately characterized in the current literature. METHODS: Using the National Cancer Database (NCDB), patients with newly diagnosed metastatic salivary gland cancers with distant metastasis to a single organ were identified. RESULTS: Eight hundred and fifty-eight patients (n = 284 bone-only, n = 322 lung-only, n = 252 other-site-only) were identified. Anatomic site of distant metastasis was not associated with survival in the cohort as a whole; however, on pre-planned subgroup analysis, lung-only metastasis, relative to bone-only metastasis, was the only factor associated with improved survival in patients with ACC (HR: 0.52, 95%CI: 0.30-0.93, p = 0.029). CONCLUSIONS: Anatomic site of metastasis is strongly associated with survival in patients with metastatic ACC and should be considered in future studies aiming to optimize therapy in this population.

Patterns of Care and Survival Outcomes for Odontogenic Cancers.

OBJECTIVES: Our understanding of odontogenic cancers is limited primarily to case studies given the rarity of these head and neck neoplasms. Using the National Cancer Database, we report the treatment patterns and survival outcomes for one of the largest cohorts of patients with odontogenic cancers. METHODS: Patients with odontogenic tumors who did not have metastatic disease and received at least part of their care at the reporting facility were included. Patient and treatment variables were assessed using logistic regression. Survival was assessed using Cox proportional hazard models. RESULTS: We identified 437 patients with odontogenic cancers, the majority of which had malignant ameloblastoma (n = 203) or odontogenic carcinoma (n = 217). Median follow-up was 44.8 months. On multivariate analysis, improved survival was associated with age <57 years (Hazard ratios [HR] 0.44, P = .012), lower comorbidity scores (HR 0.40, P = .008), surgical resection (HR 0.08, P < .001) and absence of lymph node metastasis (HR 0.23, P < .001). The 5-year overall survival was 87.1% for debulking surgery, 88.6% for radical resection and 26.6% for no surgical resection (P < .001). Lymph node metastases were associated with tumor size ≥5 cm (P = .006), malignant odontogenic histology (P = .025), and moderate/poor differentiation (P < .001). CONCLUSION: In this large series of odontogenic cancers, any type of surgical resection was associated with improved survival. Lymph node metastases, although infrequent, were associated with significantly worse survival. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 131:E1496-E1502, 2021.

Patient and physician reported toxicity with two-fraction definitive high-dose-rate prostate brachytherapy: the impact of implant interval.

PURPOSE: High-dose-rate (HDR) brachytherapy is an effective method of treating localized prostate cancer. There are limited data on the relationship between implant interval and outcomes. This study aims to assess if the implant interval between HDR treatments has an impact on patient-reported health-related quality of life (QOL) and physician-graded toxicity in men treated for localized prostate cancer. MATERIAL AND METHODS: Patients were treated with HDR brachytherapy as monotherapy with 27 Gy in 2 fractions, given over two implants, performed 1-2 weeks apart. Patients were dichotomized into one-week and two-week cohorts. Patient-reported EPIC-26 genitourinary (GU), gastrointestinal (GI), and sexual QOL were assessed. Linear regression, chi-squared testing, and generalized linear mixed effect models were used to assess the differences in patient characteristics, patient-reported QOL, and physician-graded toxicity. RESULTS: Outcomes of 122 patients were analyzed. Median follow-up was 18 months. Patient-reported GU and GI QOL worsened after treatment with a return towards baseline over time, while patient-reported sexual QOL worsened after treatment, but did not return towards baseline. There were no differences in patient-reported health related QOL as a function of implant interval. Maximum physician-graded GU, GI, and sexual toxicity rates of grade 2 or 3 were 68%, 3%, and 53%, respectively. There was no difference in rates of grade 2 or 3 toxicity as a function of implants interval. CONCLUSIONS: HDR brachytherapy for prostate cancer is a well-tolerated treatment. The interval between treatments is not associated with differences in patient-reported QOL or physician-graded toxicities.

A Validated T Cell Radiomics Score Is Associated With Clinical Outcomes Following Multisite SBRT and Pembrolizumab.

PURPOSE: Combining immune checkpoint blockade (ICB) with stereotactic body radiation therapy (SBRT) may improve the local response to radiation and the systemic response to immunotherapy. However, no prognostic markers exist to identify patients likely to benefit from combined therapy. The degree of T cell-mediated immunity, which can be quantified with radiomics using computed tomography (CT) imaging, is predictive of immunotherapy response. Herein we investigated whether a validated T cell radiomics score (RS) is correlated with clinical outcomes after multisite SBRT and pembrolizumab (SBRT + P). METHODS AND MATERIALS: The RS was quantified for 68 patients with metastatic treatment-refractory adult solid tumors who received SBRT (30-50 Gy, 3-5 fractions) and pembrolizumab ≤7 days after SBRT. RS was calculated using 8 variables, including 5 radiomics features extracted from pretreatment CT scans. At a prespecified cutoff of the 25th percentile, we assessed the association between RS and clinical outcomes. The Kaplan-Meier method was used to estimate survival outcomes. The prognostic effect of RS was assessed via logistic regression or Cox proportional hazards models. In an exploratory analysis, RS was also analyzed as a continuous variable. RESULTS: One hundred thirty-nine tumors were analyzed. At the 25th percentile cutoff, high-RS patients were more likely to exhibit irradiated tumor responses to SBRT + P (odds ratio [OR] 10.2; 95% confidence interval [CI], 1.76-59.17; P = .012). High-RS was associated with improved TMC compared with low-RS tumors (hazard ratio [HR] 0.18; 95% CI, 0.04-0.74; P = .018). Furthermore, high-RS patients had improved PFS (HR 0.47, 95% CI, 0.26-0.85; P = .013) and OS (HR 0.39, 95% CI, 0.20-0.75; P = .005). As a continuous variable, higher RS was associated with improved PFS (HR 0.12, 95% CI, 0.03-0.51; P = .004) but did not reach statistical significance for TMC (HR 0.36, 95% CI, 0.02-7.02; P = .502) or OS (HR 0.28, 95% CI, 0.05-1.55; P = .144). CONCLUSIONS: We demonstrated the clinical validity of RS (at the 25th percentile cutoff) as a prognostic biomarker in patients treated with SBRT + P. Future validation of the prognostic value of RS in larger similarly treated patient cohorts is warranted.

Proceedings of the ASTRO-RSNA Oligometastatic Disease Research Workshop.

PURPOSE: On June 13 to 14, 2019, the American Society for Radiation Oncology and the Radiological Society of North America convened a workshop on the treatment of oligometastatic disease in Washington, DC. The workshop was initiated for several reasons. First, oligometastatic disease is of increasing academic and community interest and has been identified by the American Society for Radiation Oncology membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease, making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal noninvasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state. METHODS AND MATERIALS: The workshop was organized into 2 keynote addresses, 6 scientific sessions, and 3 group discussions during an end-of-workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer 3 critical questions: (1) Can we refine the clinical and biological definitions of oligometastatic disease; (2) how can we better treat oligometastatic disease; and (3) what clinical trials are needed? RESULTS: Here, we present the proceedings of the workshop. CONCLUSIONS: The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact.

Utilizing the TrueBeam Advanced Imaging Package to monitor intrafraction motion with periodic kV imaging and automatic marker detection during VMAT prostate treatments.

BACKGROUND: Fiducial markers are frequently used before treatment for image-guided patient setup in radiation therapy (RT), but can also be used during treatment for image-guided intrafraction motion detection. This report describes our implementation of automatic marker detection with periodic kV imaging (TrueBeam v2.5) to monitor and correct intrafraction motion during prostate RT. METHODS: We evaluated the reproducibility and accuracy of software fiducial detection using a phantom with 3 implanted fiducial markers. Clinical implementation for patients with intraprostatic fiducials receiving volumetric modulated arc therapy (VMAT) utilized periodic on-board kV imaging with 10 s intervals during treatment delivery. For each image, the software automatically identified fiducial locations and determined whether their distance relative to planned locations were within a 3 mm tolerance. Motion was corrected if either ≥2 fiducials in a single image or ≥1 fiducial in sequential images were out of tolerance. RESULTS: Phantom studies demonstrated poorer performance of linear fiducials compared to collapsible fiducials, and wide variability to accurately detect fiducials across eight software settings. For any given setting, results were relatively reproducible and precise to ~0.5 mm. Across 17 patients treated with a median of 20 fractions, the software recommended a shift in 44% of fractions, and a shift was actually implemented after visual confirmation of movement greater than the 3 mm threshold in 20% of fractions. Adjustment of our approach led to improved accuracy for the latter (n = 7) patient subset. On average, table repositioning added 3.0 ± 0.3 min to patient time on table. Periodic kV imaging increased skin dose by an estimated 1 cGy per treatment arc. CONCLUSIONS: Periodic kV imaging with automatic detection of motion during VMAT prostate treatments is commercially available, and can be successfully implemented to mitigate effects of intrafraction motion with careful attention to software settings.

Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis.

Early stage glottic cancer has traditionally been treated with 3D conformal radiotherapy (3DCRT). However, intensity-modulated radiotherapy (IMRT) has been recently adopted as an alternative to decrease toxicity. Here, we compared the usage and outcomes of IMRT and 3DCRT for patients with early stage squamous cell carcinoma (SCC) of the glottic larynx. Using the National Cancer Database, we identified patients with Stage I-II SCC of the glottis who received 55-75 Gy using IMRT (n = 1623) or 3DCRT (n = 2696). Median follow up was 42 months with a 5-year overall survival (OS) of 72%. Using a nominal logistic regression, race, ethnicity, year of diagnosis and fraction size were associated with the receipt of IMRT (p < 0.05). Using Kaplan-Meier methods and Cox proportional hazards models as well as a propensity matched cohort, there was no difference in OS for patients who received IMRT versus 3DCRT (hazard ratio (HR), 1.08; 95% confidence interval (95% CI), 0.93-1.26; p = 0.302). However, there was a survival benefit for patients receiving slight hypofractionation as compared to conventional fractionation (HR, 0.78; 95% CI, 0.69-0.92; p = 0.003). IMRT was associated with similar survival as 3DCRT, supporting the implementation of this potentially less toxic modality without compromising survival.

Transitioning From a Low-Dose-Rate to a High-Dose-Rate Prostate Brachytherapy Program: Comparing Initial Dosimetry and Improving Workflow Efficiency Through Targeted Interventions.

PURPOSE: We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency. METHODS AND MATERIALS: We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography-based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time. RESULTS: The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR (P = .28). HDR mean V100 and V95 were higher (P < .0001), but mean V200 and V150 were lower (P < .0001). HDR rectum V100 and D1cc were lower (P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001). CONCLUSIONS: We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

Bladder-Preserving Therapy Patterns of Care: A Survey of US Radiation Oncologists.

PURPOSE: Clinical trials have demonstrated the efficacy of bladder-preserving chemoradiation therapy (BPT) in muscle-invasive bladder cancer but have differed in the radiation therapy dose/fractionations, radiation therapy targets, and concurrent chemotherapy regimens used. No data exist on the technical and practical approaches actually used in clinical practice throughout the United States when delivering BPT. We performed a survey to explore radiation oncologists' practice patterns. METHODS AND MATERIALS: We conducted an electronic survey of US radiation oncologists regarding the management of patients with cT2-3N0M0 transitional cell muscle-invasive bladder cancer. The instrument included questions regarding the types of patients treated with BPT, as well as several aspects of treatment delivery. Descriptive statistics were reported for all responses. Pearson χ2 tests were used for univariate analysis. RESULTS: In total, 277 physicians completed our survey. Most respondents (58%) stated that they only treated 1 to 3 patients in the prior year. Seventy-four percent of respondents primarily treated patients deemed unfit for cystectomy, while only 28% saw patients prior to cystectomy for consultation to discuss BPT. The majority of radiation oncologists used conventional fractionation (91%) instead of hypofractionation (7.6%), but more variability existed for radiation therapy targets. Sixty percent used a small pelvis field, 29% used a whole-pelvis field, and 12% treated the bladder only. There was increased use of hypofractionation (29%) and bladder-only radiation therapy (34%) in patients who were not candidates for cystectomy or chemotherapy (P<.001). Cisplatin-based concurrent chemotherapy was most commonly preferred (89%). In non-cisplatin candidates, most respondents preferred 5-fluorouracil plus mitomycin C (32%) or carboplatin (32%). Intensity modulated radiation therapy use and midtreatment cystoscopic re-evaluation were variable, while hyperfractionation use was low. CONCLUSIONS: Our study describes radiation oncologists' practice patterns for patients undergoing BPT. Although there are areas of consistency, variability exists in many technical and practical aspects of treatment delivery. Further research and education are needed to determine the optimal radiation therapy target, dose/fractionation, and concurrent chemotherapy regimen.

Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy.

BACKGROUND: The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle-invasive bladder cancer (MIBC). METHODS: Patients aged ≥80 years with cT2-4, N0-3, M0 transitional cell MIBC who were treated with curative RT (60-70 Gray) or CCRT were identified in the National Cancer Data Base. Univariable and multivariable frailty survival analyses, as well as 1-to-1 propensity score matching, were used to isolate the association between CCRT and OS. RESULTS: A total of 1369 patients who were treated with RT from 2004 through 2013 met eligibility criteria: 739 patients (54%) received RT alone and 630 patients (46%) received CCRT. The median age of the patients was 84 years (range, 80-90 years). The median follow-up was 21 months. The 2-year OS rate was 48%. When comparing CCRT with RT alone, the 2-year OS rate was 56% versus 42% (P<.0001), respectively. Multivariable analysis demonstrated that CCRT (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.65-0.84 [P<.0001]) and a higher RT dose (HR, 0.78; 95% CI, 0.67-0.90 [P<.001]) were associated with improved OS. T4 disease was associated with worse OS (HR, 1.42; 95% CI, 1.15-1.76 [P = .001]). After using 1-to-1 propensity score matching, there remained an OS benefit for the use of CCRT (HR, 0.77; 95% CI, 0.67-0.90 [P<.001]). CONCLUSIONS: CCRT is associated with improved OS compared with the use of RT alone in elderly patients with MIBC, independent of Charlson-Deyo comorbidity score, suggesting that CCRT should be used in this population. Cancer 2017;123:3524-31. © 2017 American Cancer Society.

Observer Evaluation of a Metal Artifact Reduction Algorithm Applied to Head and Neck Cone Beam Computed Tomographic Images.

PURPOSE AND OBJECTIVES: To quantify, through an observer study, the reduction in metal artifacts on cone beam computed tomographic (CBCT) images using a projection-interpolation algorithm, on images containing metal artifacts from dental fillings and implants in patients treated for head and neck (H&N) cancer. METHODS AND MATERIALS: An interpolation-substitution algorithm was applied to H&N CBCT images containing metal artifacts from dental fillings and implants. Image quality with respect to metal artifacts was evaluated subjectively and objectively. First, 6 independent radiation oncologists were asked to rank randomly sorted blinded images (before and after metal artifact reduction) using a 5-point rating scale (1 = severe artifacts; 5 = no artifacts). Second, the standard deviation of different regions of interest (ROI) within each image was calculated and compared with the mean rating scores. RESULTS: The interpolation-substitution technique successfully reduced metal artifacts in 70% of the cases. From a total of 60 images from 15 H&N cancer patients undergoing image guided radiation therapy, the mean rating score on the uncorrected images was 2.3 ± 1.1, versus 3.3 ± 1.0 for the corrected images. The mean difference in ranking score between uncorrected and corrected images was 1.0 (95% confidence interval: 0.9-1.2, P<.05). The standard deviation of each ROI significantly decreased after artifact reduction (P<.01). Moreover, a negative correlation between the mean rating score for each image and the standard deviation of the oral cavity and bilateral cheeks was observed. CONCLUSION: The interpolation-substitution algorithm is efficient and effective for reducing metal artifacts caused by dental fillings and implants on CBCT images, as demonstrated by the statistically significant increase in observer image quality ranking and by the decrease in ROI standard deviation between uncorrected and corrected images.

Metal Artifact Reduction in Cone-Beam Computed Tomography for Head and Neck Radiotherapy.

PURPOSE: To evaluate a method for reducing metal artifacts, arising from dental fillings, on cone-beam computed tomography images. MATERIALS AND METHODS: A projection interpolation algorithm is applied to cone-beam computed tomography images containing metal artifacts from dental fillings. This technique involves identifying metal regions in individual cone-beam computed tomography projections and interpolating the surrounding values to remove the metal from the projection data. Axial cone-beam computed tomography images are then reconstructed, resulting in a reduction in the streak artifacts produced by the metal. Both phantom and patient imaging data are used to evaluate this technique. RESULTS: The interpolation substitution technique successfully reduced metal artifacts in all cases. Corrected images had fewer or no streak artifacts compared to their noncorrected counterparts. Quantitatively, regions of interest containing the artifacts showed reduced variance in the corrected images versus the uncorrected images. Average pixel values in regions of interest around the metal object were also closer in value to nonmetal regions after artifact reduction. Artifact correction tended to perform better on patient images with less complex metal objects versus those with multiple large dental fillings. CONCLUSION: The interpolation substitution is potentially an efficient and effective technique for reducing metal artifacts caused by dental fillings on cone-beam computed tomography image. This technique may be effective in reducing such artifacts in patients with head and neck cancer receiving daily image-guided radiotherapy.

Shaping colloids for self-assembly.

The creation of a new material often starts from the design of its constituent building blocks at a smaller scale. From macromolecules to colloidal architectures, to granular systems, the interactions between basic units of matter can dictate the macroscopic behaviour of the resulting engineered material and even regulate its genesis. Information can be imparted to the building units by altering their physical and chemical properties. In particular, the shape of building blocks has a fundamental role at the colloidal scale, as it can govern the self-organization of particles into hierarchical structures and ultimately into the desired material. Herein we report a simple and general approach to generate an entire zoo of new anisotropic colloids. Our method is based on a controlled deformation of multiphase colloidal particles that can be selectively liquified, polymerized, dissolved and functionalized in bulk. We further demonstrate control over the particle functionalization and coating by realizing patchy and Janus colloids.