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Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways.

PURPOSE: Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them. METHODS: The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non–facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population. RESULTS: Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, P < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, P < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, P < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, P = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, P = .02). CONCLUSION: Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.

Càncer de pròstata; Teràpia de privació d'andrògens Cáncer de próstata; Terapia de privación de andrógenos Prostate cancer; Androgen-deprivation therapy PURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT. Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020).

Introduction. Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. Methods. An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. Results. The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. Conclusion. Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.

Purpose Though utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics. Methods The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non‐facility‐based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT). Results In total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58–26.05, p

Purpose/Objective(s) Preventing malnutrition during chemoradiation (CRT) for head and neck cancer (HNC) is crucial for treatment adherence, minimizing treatment-related complications, and maximizing quality of life (QOL). We sought to assess patient-reported QOL outcomes after integrating exclusive liquid meal replacement with Soylent, a novel meal replacement agent, in patients with HNC undergoing CRT. Materials/Methods Patients undergoing definitive or adjuvant concurrent CRT for locally advanced HNC enrolled on our single-institution, prospective phase II protocol evaluating nutritional replacement with Soylent. Patients who reached 5% body weight loss during CRT were transitioned to Soylent meal replacement for all nutritional needs. Patients who reached 10% body weight loss were recommended for gastrostomy tube placement. The University of Washington QOL (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaires were used to assess patient-reported QOL prior to the receipt of CRT (baseline), as well as at 1, 3, 6, 12, and 18 months following conclusion of CRT. Higher scores indicated better QOL for both assessments. Paired t-test or Wilcoxon signed-rank test was applied to assess whether differences between scores at each time point and baseline exist. Multiple testing was addressed via Benjamini-Hochberg procedure with a false discovery rate threshold of 0.2. Results Of the 41 patients who completed evaluable QOL surveys, 33/41 (80%) reached the 5% weight loss threshold and 32/33 (97%) were transitioned to Soylent. Subsequently, 11/33 (33%) on Soylent reached the 10% weight loss threshold, but only 1/11 (9%) received a gastrostomy tube. The nadirs for overall and health-related UW-QOL were reached at 1 month and rebounded to exceed baseline by 6 months. The mean overall UW-QOL score was 71 at baseline compared with 62, 69, 77, 73, and 80 at 1, 3, 6, 12, and 18 months, respectively. Comparing individual UW-QOL domains from baseline to 18 months, significant differences were found in only two domains. Saliva scores decreased from 91 to 73 (adjusted P = 0.02) whereas anxiety scores increased from 51 to 81 (adjusted P = 0.11). FACT-H&N survey scores were reduced from 32 at baseline to 20 at 1 month (adjusted P 0.57 for all). Conclusion This study's results reveal encouraging QOL outcomes from exclusive liquid meal replacement with Soylent, which appear potentially comparable with QOL outcomes from contemporary de-escalation trials in HNC pending further direct comparison. Soylent liquid meal replacement with aggressive dietary monitoring appears to be a promising approach for maximizing patient-reported QOL after conventional, concurrent CRT.

CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low–dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.

Context The use, common findings, and impact of modern molecular positron emission tomography (PET)/computed tomography (CT) imaging prior to salvage radiation therapy (RT) in men with biochemical recurrence after radical prostatectomy (RP) have not been evaluated comprehensively. Objective We performed a scoping systematic review of the literature assessing detection rates, detection patterns, changes in management, as well as changes in patient outcome resulting from molecular PET/CT imaging using three molecular tracers: 18F-fluciclovine, 8Ga prostate-specific membrane antigen (PSMA)-11, and 18F-DCFPyL. Evidence acquisition A computerized bibliographic search of the Medline/PubMed database was carried out from inception to October 1, 2020. We included published reports and abstracts evaluating the utility of 1Fluciclovine, 68Ga-PSMA-11, and 18F-DCFPyL PET in the detection of recurrent disease in the post-RP, pre–salvage RT setting. Outcomes of interest were extracted and tabulated, and existing evidence was synthesized qualitatively. Evidence synthesis A total of 45 studies were included in our qualitative synthesis. Detection rates were high across most studies, and there was often a clear relationship between prostate-specific antigen (PSA) level and positive imaging findings. Though limited randomized data are available, there appears to be increased sensitivity with the use of PSMA ligands compared with fluciclovine at low PSA values. Most studies have shown that only one-third to one-half of patients with detected lesions have lesions in the prostatic fossa alone. Management changes occur in nearly 50% of patients undergoing molecular imaging, and biochemical response in patients who undergo molecular PET-based RT planning appears to be statistically superior to the response in patients who undergo conventional imaging -based RT planning alone. High biochemical responses from molecular PET–based salvage RT, ranging from 45% to 94%, did not appear to come at the expense of increased genitourinary or gastrointestinal toxicity. The presence or absence of avid lesions appears to be a strong prognostic factor. Conclusions Molecular PET/CT imaging in the post-RP, pre–salvage RT setting often triggers management changes that result from detecting lesions in locations not typically included in consensus-driven postoperative RT fields. Ongoing trials will assess the benefit of PSMA PET in guiding salvage RT following RP and determine its impact on long-term outcomes. Patient summary We reviewed and reported detection rates, detection patterns, and changes in management resulting from molecular positron emission tomography/computed tomography imaging in men with biochemically recurrent prostate cancer following radical prostatectomy. Prior to the receipt of salvage radiation therapy, molecular tracers targeting prostate-specific membrane antigen appear to be especially sensitive at identifying the place where prostate cancer has come back after surgery, which can help radiation oncologists better target the recurrent disease and potentially improve the rates of cure from prostate cancer in this setting. Future studies will determine whether these imaging tools will change cure rates and side effects, but early results are promising.

"Near miss" events are valuable low-cost learning opportunities in radiation oncology as they do not result in patient harm and are more pervasive than adverse events that do. Near misses vary depending on the presence of a latent error of behavior or process, and the presence of an enabling condition predisposing the patient to harm. These nuanced distinctions across near miss types can elicit different cognitive biases affecting the recognition of near misses as learning opportunities. We define near miss types in radiation oncology and explore the differential perceptions among radiation oncology staff.Six event types were defined based on attributes of latent error and enabling conditions: "hit," "potential hit," "almost happened," "fortuitous catch," "could have happened," and "process-based catch." These events were illustrated with an example of a patient receiving pacemaker cardiac clearance before radiation treatment. A survey assessing (1) success versus failure of an event and (2) willingness to report the event was administered to a radiation oncology department using the pacemaker example. Mean scores for each near miss type were compared.Ninety-five staff members (74%) completed the survey. Perceived success scores and willing-to-report scores significantly differed by near miss type (P = .042 for success ratings; P.0001 for willingness to report). "Could have happened" events were viewed as less successful and were more likely to be reported than "almost happened" events (P.0001).Cognitive biases appear to influence whether and how near miss types are recognized as report-worthy. Education of near miss types and engaging staff for quality improvement may improve recognition.

Purpose Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response. Methods and Materials Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology. Gene expression was evaluated using polymerase chain reaction arrays. In vivo tumor growth delay was used to evaluate the effects of MTA on radiosensitivity. Results Targeting of SP1 with small interfering RNA or MTA sensitized A549 and UM-UC-3 to irradiation, with no effect on the BJ radiation response. MTA did not alter γH2AX foci formation after irradiation in tumor cells but did enhance mitotic catastrophe. Treatment with MTA suppressed transcription of genes involved in cell death. MTA administration to mice bearing A549 and UM-UC-3 xenografts enhanced radiation-induced tumor growth delay. Conclusions These results support SP1 as a target for radiation sensitization and confirm MTA as a radiation sensitizer in human tumor models.

Purpose Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. Methods and Materials All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network risk groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. Results From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P P P =.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). Conclusions In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.

Extramammary Paget disease (EMPD) is an intraepithelial adenocarcinoma characterized by epithelial infiltration of large atypical cells with prominent nuclei.1 The disease process is hypothesized to originate in the apocrine sweat glands in the anogenital region. It is often diagnosed in postmenopausal women and most commonly affects the vulva, perianal skin, and axilla but can sometimes be associated with invasive visceral or adnexal adenocarcinoma.2 Standard therapy for EMPD is wide local excision. However, many of the elderly patients affected by EMPD may be medically unfit for aggressive surgery. Radiotherapy is rarely used, and there is a paucity of reports detailing the efficacy of electron beam radiotherapy for exceptionally large EMPD lesions.

Breast conservation therapy (BCT) for early-stage breast cancer involves lumpectomy followed by whole breast radiotherapy, which can involve either standard fractionation (SRT) or accelerated fractionation (ART). This systematic review and meta-analysis was performed to determine whether any benefit exists for ART or SRT. We searched MEDLINE (1966–2014), all seven databases of the Cochrane Library (1968–2014), EMBASE (1974–2014), clinicaltrials.gov, ISRCTN, WHO ICTRP, and meeting abstracts in the Web of Science Core Collection (1900–2014). RCTs comparing SRT to ART among women undergoing BCT with stage T1–T2 and/or N1 breast cancer or carcinoma in situ were included. Follow-up was 30 days for acute toxicity, or three years for disease control and late toxicity. 13 trials with 8189 participants were included. No differences were observed in local failure (n = 7 trials; RR 0.97; 95% CI 0.78–1.19, I 2 = 0%), locoregional failure, (n = 8 trials; RR 0.86; 95% CI 0.63–1.16, I 2 = 0%), or survival (n = 4 trials; RR 1.00; 95% CI 0.85–1.17, I 2 = 0%). ART was associated with significantly less acute toxicity (n = 5 trials; RR 0.36; 95% CI 0.21–0.62, I 2 = 20%), but no difference in late cosmesis (RR 0.95; 95% CI 0.81–1.12, I 2 = 54%). ART use does not reduce disease control or worsen long-term cosmetic outcome, and may decrease the risk of acute radiation toxicity as compared to SRT.

Hepatoid adenocarcinoma (HAC) is a rare tumor that typically originates in gastrointestinal tissue, such as the stomach, but can also occasionally originate in the lung. The majority of HACs express α-fetoprotein (AFP) on tumor cells, and serum AFP can be used as a marker of response to treatment or disease progression. HAC has a poor prognosis, although early diagnosis and aggressive treatment can result in long-term survival. To the best of our knowledge, this is the first reported case of HAC metastasizing to the tonsil. Irradiation using intensity-modulated radiation therapy (IMRT) to 30 Gray (Gy) achieved a significant, and durable tumor response. IMRT can be considered for local control of HAC at other metastatic sites of disease.

296 Background: Patients’ treatment-related acute and late toxicities are essential clinical data, yet this information is widely dispersed among notes in the EHR. This lack of structure impedes clinician ability to efficiently and comprehensively integrate toxicity information into clinical management. We aimed to consolidate toxicity data to improve clinician efficiency in accessing this information, and to evaluate the utility of this tool in radiation oncology. Methods: We developed an auto-updating flowsheet view (“Synopsis”) in the Epic EHR that longitudinally integrates physician-graded CTCAE toxicity selected using a SmartForm embedded in EHR notes. Physicians timed themselves performing 4 tasks to assess acute and post-treatment toxicity information for patients seen in follow-up, alternating with vs. without use of Synopsis. Wilcoxon Rank-Sum testing compared recorded task times with and without Synopsis. A survey was sent to physicians regarding qualitative utility of Synopsis. Results: Six physicians reviewed 98 patients seen in follow-up (49 with Synopsis, 49 without Synopsis) at median 8.1 months (Synopsis) and 6.5 months (no Synopsis) since completion of radiation (p = 0.88). Use of Synopsis was associated with significantly faster assessment of: overall toxicity history (median 50 vs. 93 seconds, p = 0.0007), highest acute toxicity during treatment (median 19 vs. 40 seconds, p = 0.0002), highest post-treatment toxicity (11 vs. 65 seconds, p < 0.0001), and longitudinal review of a single symptom (8 vs. 61 seconds, p < 0.0001). Among 10 physician survey respondents, 100% reported that Synopsis improved efficiency and 30% reported it led to a change in management. All physicians felt it was important to understand a patient’s toxicity history, but 80% reported that time required with the note-based EHR structure was prohibitive; with use of Synopsis, 90% reported that this task was now feasible. Specific domains most improved included ability to: identify high-grade toxicities (100%), contextualize new symptoms (80%), summarize treatment-related toxicity (80%), navigate in the EHR to a time of high-grade toxicity (60%), evaluate the success of an intervention (30%), and decide whether to discuss a reported new symptom (30%). Conclusions: A centralized toxicity view in the EHR improves clinician efficiency in evaluating longitudinal toxicity data and enhances clinician ability to comprehensively integrate toxicity information into patient care.

Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Key Points Question What is the sex distribution of industry payments in radiation oncology? Findings In this cross-sectional study involving 4483 radiation oncologists, the proportion of radiation oncologists who received at least 1 industry payment in 2016 was substantially lower among female physicians (61.4%) than their male counterparts (70.4%). Across all payment types, female radiation oncologists received a smaller percentage of the total industry funding than their corresponding representation in these categories. Meaning Distribution of corporate payments appears to show sex disparity in industry relationships among radiation oncologists; further investigation is needed to increase parity., Importance Industry relationships are an important measure of professional advancement; however, the association between physician sex and industry payments in radiation oncology has not been described. Objective To update the trends in the sex distribution of industry payments in radiation oncology. Design, Setting, and Participants This retrospective cross-sectional study was conducted between July 1, 2018, and August 31, 2018. It used the publicly available Centers for Medicare & Medicaid Services (CMS) Open Payments program and CMS Physician and Other Supplier Public Use File databases to obtain 2016 industry payment data for US radiation oncologists who reported receiving industry funding in that year (n = 3052). Total monetary value, number of payments, and median payment amounts were determined for each sex in the following categories: research, consulting, honoraria, industry grants, royalty or license, and services other than consulting. Main Outcomes and Measures Industry payment amounts among 3052 radiation oncologists who reported receiving payments in 2016; association of median payment with the types of payment by sex. Results Of the total 4483 radiation oncologists who practiced in 2016, 1164 (25.9%) were female and 3319 (74.0%) were male. Industry payments were distributed among 3052 radiation oncologists (68.1%), of whom 715 (23.4%) were female and 2337 (76.6%) were male. The proportion of female radiation oncologists who received at least 1 industry payment was 61.4% (715 of 1164), whereas the proportion of their male counterparts was 70.4% (2337 of 3319). Across all payment types, female radiation oncologists received a smaller percentage of total industry funding than the percentage of female physicians represented in each category. The median payment value was smaller for female radiation oncologists in consulting (–$1000; 95% CI, −$1966.67 to $100.63; P = .005) and honoraria (–$500; 95% CI, −$1071.43 to $0; P = .007). This trend was also observed in research payments, but was not statistically significant (–$135.02; 95% CI, −$476.93 to $6.88; P = .08). Of the $1 347 509 royalty or license payments made to 72 physicians, none was for female radiation oncologists. Conclusions and Relevance Distribution of industry payments appears to show sex disparity in industry relationships among radiation oncologists; this observation warrants further investigation to determine the underlying reasons and provide avenues for increased parity., This cross-sectional study uses the 2016 self-reported industry payment data from the Centers for Medicare & Medicaid Services (CMS) Open Payments and CMS Physician and Other Supplier Public Use File databases to investigate trends in funding distribution by sex among radiation oncologists.

Purpose This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. Methods and Materials Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. Results Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 ( P P =.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. Conclusions The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

Background Definitive surgical and radiation therapy (RT) treatments are evolving rapidly for stage I non-small cell lung cancer (NSCLC). We hypothesized that utilization of definitive therapies increased between 2000 and 2010 and that survival improved for stage I NSCLC patients over the same time period. Secondary objectives were determining trends in patterns of care and predictors of utilization. Methods Population-based, observational, comparative effectiveness study used Surveillance, Epidemiology, and End Results-18 data from 2000 to 2010. The main outcome measure was 2-year risk of death for stage I NSCLC. Results Between 2000 and 2010, 40,589 patients (62%) underwent surgery, 10,048 (15%) received RT, 2,130 (3%) received both surgery and RT, and 11,537 (18%) received neither surgery nor RT. Annually, the odds of receiving either definitive RT or undergoing surgery increased relative to the odds of receiving no treatment (odds ratio [OR] radiation 1.04, 95% confidence interval [CI]: 1.03 to 1.05; OR surgery 1.05, 95% CI: 1.04 to 1.05). Among surgical patients, the proportion of sublobar resections steadily increased from 12.9% to 17.9%. For all patients, the 2-year risk of death decreased by 3.5% each year (hazard ratio [HR] 0.965, 95% CI: 0.962 to 0.969), driven primarily by improved survival for surgical (annualized HR 0.959, 95% CI: 0.954 to 0.964) and RT (annualized HR 0.942, 95% CI: 0.935 to 0.949) patients. Conclusions Between 2000 and 2010, stage I NSCLC patients were more likely to receive definitive treatment with either surgery or RT, leading to a decline in the number of untreated patients. Survival also improved substantially for stage I NSCLC patients, with the largest survival improvements observed in patients undergoing definitive RT.

Radiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive complication of therapeutic irradiation of the thorax. It has been suggested that senescence of type II pneumocytes (AECIIs), an alveolar stem cell, plays a role in the development of RIPF through loss of replicative reserve and via senescent AECII-driven release of proinflammatory and profibrotic cytokines. Within this context, we hypothesized that arachidonate 12-lipoxygenase (12-LOX) is a critical mediator of AECII senescence and RIPF. Treatment of wild-type AECIIs with 12S-hydroxyeicosateraenoic acid (12S-HETE), a downstream product of 12-LOX, was sufficient to induce senescence in a NADPH oxidase 4 (NOX4)-dependent manner. Mice deficient in 12-LOX exhibited reduced AECII senescence, pulmonary collagen accumulation and accumulation of alternatively activated (M2) macrophages after thoracic irradiation (5 × 6 Gy) compared to wild-type mice. Conditioned media from irradiated or 12S-HETE-treated primary pneumocytes contained elevated levels of IL-4 and IL-13 compared to untreated pneumocytes. Primary macrophages treated with conditioned media from irradiated AECII demonstrated preferential M2 type polarization when AECIIs were derived from wild-type mice compared to 12-LOX-deficient mice. Together, these data identified 12-LOX as a critical component of RIPF and a therapeutic target for radiation-induced lung injury.

Importance Although physician sex is known to influence salary even after controlling for productivity, sex-based differences in clinical activity and reimbursement among radiation oncologists are poorly understood. Objectives To evaluate differences by sex in productivity, breadth of practice, and payments and to characterize Medicare reimbursement by sex among similarly productive groups of radiation oncologists. Design, Setting, and Participants A retrospective cohort study was conducted using the January 1 to December 31, 2016, Centers for Medicare & Medicaid Services Physician and Other Supplier Public Use File (POSPUF) to identify charge and payment information for individual radiation oncologists. Clinicians were part of a population-based sample of US radiation oncologists who bill Medicare in both non–facility-based (NFB) and facility-based (FB) practice settings. Analysis was conducted from June 5 to 25, 2018. Main Outcomes and Measures Outcome measurements included physician productivity (measured by number of Medicare charges), physician payments (reported as total Medicare payments as well as mean payments per charge submitted and per beneficiary treated), and physician breadth of practice (measured by number of unique Medicare billing codes) in NFB and FB settings. Results A total of 4393 radiation oncologists (1133 women and 3260 men) were included in the POSPUF in 2016. Compared with their male counterparts, female physicians in the NFB setting submitted a mean of 1051 fewer charges (95% CI, –1458 to –644; P, This population-based cohort study uses the Centers for Medicare & Medicaid Services Physician and Other Supplier Public Use File to evaluate sex differences among radiation oncologists in productivity, breadth of practice, and payments and to characterize Medicare reimbursement by sex among similar groups of radiation oncologists., Key Points Question How do clinical activities and Medicare payments to radiation oncologists vary by sex? Findings This population-based cohort study of the Centers for Medicare & Medicaid Services Physician and Other Supplier Public Use File database demonstrated that regardless of practice setting, female radiation oncologists submitted significantly fewer charges, billed using significantly fewer unique codes, and collected significantly less Medicare reimbursement than did male radiation oncologists; in the non–facility-based setting, women also collected significantly less per charge submitted and per beneficiary treated. Among similarly productive radiation oncologists, women still collected significantly less Medicare reimbursement than did men. Meaning The findings suggest that female sex is associated with decreased Medicare reimbursement, and further research is required to understand the mechanisms and potential sex-based barriers to economic advancement within radiation oncology.

Introduction: Over time there have been changes in consensus therapy for out of hospital cardiac arrest (OOHCA), including changes in BLS-ACLS, and recently targeted temperature management. There has been only limited success, however, in determining the effect of specific interventions on neurological outcome using randomized clinical trials (RCT’s) and registries. Hypothesis: The control groups in OOHCA RCT’s can be utilized to identify the presence or absence of potential trends in neurological outcome related to secular changes in care. Methods: Comprehensive online search for RCT’s in OOHCA with n > 50 in control group, and reporting neurological outcome, 1960 to present. Extraction of demographic and outcome variables. Analysis, fraction of resuscitated patients with good neurological outcome (GNO), defined as CPC 1 or 2 as a function of year. Results: n=32 usable RCTS were identified, all since 1985. No significant trends in the fraction of patients with GNO were identified (Figure). There was relatively large variability. Outcomes in the epoch since the promulgation of hypothermia have not changed overall. However, since about 2012 there have been a handful of RCT’s with relatively high fraction of patients with GNO compared to historical norms. Limitations: Retrospective methodology and background regional differences limits significance and applicability, hypothesis generating only. Conclusion: Between 1985 and the present, there were no trends in GNO rates in the control groups of RCTs, possibly indicating lack of efficacy or toxicity with respect to therapies experiencing changing patterns of utilization, or an offsetting change in substrate.

Introduction: Ionizing radiation (IR) is commonly used in the treatment of thoracic malignancies. Exposure of adjacent normal lung may result in lung injury and fibrosis. Recently, we reported that accelerated senescence of type II pneumocytes, the alveolar stem cell, results in parynchymal depletion and precedes pulmonary fibrosis. Arachidonate 12-lipoxygenase (12-LOX) oxidizes arachidonic acid to form 12-Hydroxyeicosatetraeonic acid (12-HETE), a pro-inflammatory mediator. Increased expression of ALOX-12 has previously been associated with aging. We hypothesized that mice deficient in ALOX-12 would be resistant to IR induced fibrosis and senescence. Methods: C57/Bl6J (WT) and Alox12 homozygous knockout (Alox12-KO) mice (n>3 per group) were exposed to thoracic IR (0Gy, 5Gy, 17.5Gy, 5×5Gy, or 6×5Gy). Fibrotic foci were identified with aniline blue staining of fixed lung sections. Levels of 12-LOX mRNA and protein were assessed in WT lungs after IR with microarray, quantitative PCR, and western blotting. In vitro studies with primary murine pneumocyte cultures and A549 cells included staining for senescence associated β-galactosidase activity and western blotting for NOX4, p21, and PML following IR and 12-HETE treatment. Results: A significant increase in 12-LOX mRNA and protein was observed in murine lungs exposed to fibrogenic doses of IR (17.5 Gy, 5×5 Gy and 5×6 Gy) compared to low dose IR (5 Gy) or controls (0 Gy). 12-LOX deficiency significantly reduced fibrotic foci in murine lungs receiving fibrogenic doses of thoracic IR (6×5 Gy) at 18 weeks. Treatment of murine primary pneumocytes with 12-HETE (1 and 150 nM) increased the rate of pneumocyte senescence (2.1 fold). Treatment of murine primary pneumocytes with 12-HETE increased the expression of NOX4 (a mediator of superoxide generation), p21, and PML (senescence markers), paralleling increases observed after IR. Similarly, human type II pneumocyte A549 cells exhibited increased 12-LOX expression in β-galactosidase-stained senescent cells at 3 days after IR. Conclusion: These studies identify 12-LOX as a critical mediator in radiation lung fibrosis and type II pneumocyte senescence. 12-LOX may serve as a novel therapeutic target in mitigating IR-induced lung fibrosis. Citation Format: Eun Joo Chung, Luca F. Valle, Ayla O. White, Deborah E. Citrin. Arachidonate 12-lipoxygenase contributes to radiation-induced type II pneumocyte senescence and fibrosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3049.