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PURPOSE Cisplatin is widely used and highly ototoxic, but patient-reported functional impairment because of cisplatin-related hearing loss (HL) and tinnitus has not been comprehensively evaluated. PATIENTS AND METHODS Testicular cancer survivors (TCS) given first-line cisplatin-based chemotherapy completed validated questionnaires, including the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Primary Function Questionnaire (TPFQ), each of which quantifies toxicity-specific functional impairment. Spearman correlations evaluated associations between HL and tinnitus severity and level of functional handicap quantified with the HHIA and TPFQ, respectively. Associations between HL or tinnitus and five prespecified adverse health outcomes (cognitive dysfunction, fatigue, depression, anxiety, and overall health) were evaluated. RESULTS HL and tinnitus affected 137 (56.4%) and 147 (60.5%) of 243 TCS, respectively. Hearing aids were used by 10% TCS (14/137). Of TCS with HL, 35.8% reported clinically significant functional impairment. Severe HHIA-assessed functional impairment was associated with cognitive dysfunction (odds ratio [OR], 10.62; P < .001), fatigue (OR, 5.48; P = .003), and worse overall health (OR, 0.19; P = .012). Significant relationships existed between HL severity and HHIA score, and tinnitus severity and TPFQ score ( P < .0001 each). TCS with either greater hearing difficulty or more severe tinnitus were more likely to report cognitive dysfunction (OR, 5.52; P = .002; and OR, 2.56; P = .05), fatigue (OR, 6.18; P < .001; and OR, 4.04; P < .001), depression (OR, 3.93; P < .01; and OR, 3.83; P < .01), and lower overall health (OR, 0.39; P = .03; and OR, 0.46; P = .02, respectively). CONCLUSION One in three TCS with HL report clinically significant functional impairment. Follow-up of cisplatin-treated survivors should include routine assessment for HL and tinnitus. Use of the HHIA and TPFQ permit risk stratification and referral to audiologists as needed, since HL adversely affects functional status and is the single largest modifiable risk factor for cognitive decline and dementia in the general population.

BackgroundAlthough clinical features of multi-parametric magnetic resonance imaging (mpMRI) have been associated with biochemical recurrence in localized prostate cancer, such features are subject to inter-observer variability.ObjectiveTo evaluate whether the volume of the dominant intraprostatic lesion (DIL), as provided by a deep learning segmentation algorithm, could provide prognostic information for patients treated with definitive radiation therapy (RT).Design, Setting, and ParticipantsRetrospective study of 438 patients with localized prostate cancer who underwent an endorectal coil, high B-value, 3-Tesla mpMRI and were treated with RT between 2010 and 2017.InterventionRT.Outcome Measurements and Statistical AnalysisBiochemical recurrence and metastasis risk, assessed with a cause-specific Cox regression and time-dependent receiver operating characteristic analysis.Results and LimitationsThe artificial intelligence (AI) model identified DILs with an area under the receiver operating characteristic curve (AUROC) of 0.827 at the patient level. For the 233 patients with available PI-RADS scores, with a median follow-up of 5.6 years, AI-defined DIL volume was significantly associated with biochemical failure (adjusted hazard ratio 1.54, 95% confidence interval 1.09-2.17, p=0.014) after adjustment for PI-RADS score. Among all 438 patients with a median follow-up of 6.9 years, the AUROC for predicting 7-year biochemical failure for AI volume (0.790) was similar to that for an expanded National Comprehensive Cancer Network (NCCN+) category (p=0.17). The AUROC for predicting 7-year metastasis for AI volume trended towards being higher compared to NCCN+ categories (0.854 vs 0.769, p=0.06).ConclusionsA deep learning algorithm could identify the DIL with good performance. AI-defined DIL volume may be able to provide prognostic information independent of the NCCN+ risk group or other radiologic factors for patients with localized prostate cancer treated with RT.

Purpose: To study associations between single nucleotide polymorphisms (SNP) in Ribonuclease L (RNASEL), a gene implicated in inflammation and prostate cancer risk, and outcomes after radiation therapy.Experimental Design: We followed participants in the prospective US Health Professionals Follow-Up Study treated with radiation therapy for early-stage prostate cancer. Three SNPs were genotyped based on previously determined functional and biological significance. We used multivariable Cox proportional hazards models to assess per-allele associations with the primary outcome defined as time to a composite endpoint including development of lethal prostate cancer or biochemical recurrence.Results: We followed 434 patients treated with radiation therapy for a median of 9 years. On multivariate analysis, the rs12757998 variant allele was associated with significantly decreased risk of the composite endpoint [HR: 0.65; 95% confidence interval (CI), 0.45–0.94%; P = 0.02] driven by decreased biochemical recurrence (HR: 0.60; 95% CI, 0.40–0.89%; P = 0.01) and men treated with external beam (HR: 0.58; 95% CI, 0.36–0.93%; P = 0.02). In contrast, in 516 men from the same cohort treated with radical prostatectomy, we found no significant impact of this variant on outcome. Furthermore, the rs12757998 variant allele significantly modified the association between androgen deprivation therapy and outcomes after radiation therapy (p-interaction = 0.02).Conclusion: We show an association between RNASEL SNP rs12757998 and outcome after radiation therapy for prostate cancer. This SNP is associated with increased circulating C-reactive protein and interleukin-6, suggesting a potential role for inflammation in the response to radiation. If validated, genetic predictors of outcome may help inform prostate cancer management. Clin Cancer Res; 19(6); 1612–9. ©2013 AACR.

PDF file - 54K, Univariate associations with time to composite outcome

Supplementary Table 2

PDF file, 143K, Characteristics for all men and by ERG-overexpression status among 90 men diagnosed with prostate cancer during transurethral resection of the prostate (TURP)a, PHS and HPFS cohorts 1982-2011.

Supplementary Table 3

XLS file, 43K, List of studies reviewed for but excluded from the meta-analysis.

PDF file - 51K, Time to event stratified by genotype for men who reached the composite outcome. Boxplots show the interquartile range (boxes) and outliers (whiskers).

PDF file - 49K, Participant Flow Diagram

PDF file, 130K, Selection process for the study inclusion in the meta-analysis.

PDF file - 46K

Supplementary Methods, Tables, and Figures

Purpose: Squamous cell carcinoma of the anal canal (ASCC) accounts for 2% to 4% of gastrointestinal malignancies in the United States and is increasing in incidence; however, genomic features of ASCC are incompletely characterized. Primary treatment of ASCC involves concurrent chemotherapy and radiation (CRT), but the mutational landscape of resistance to CRT is unknown. Here, we aim to compare mutational features of ASCC in the pre- and post-CRT setting.Experimental Design: We perform whole-exome sequencing of primary (n = 31) and recurrent (n = 30) ASCCs and correlate findings with clinical data. We compare genomic features of matched pre- and post-CRT tumors to identify genomic features of CRT response. Finally, we investigate the mutational underpinnings of an extraordinary ASCC response to immunotherapy.Results: We find that both primary and recurrent ASCC tumors harbor mutations in genes, such as PIK3CA and FBXW7, that are also mutated in other HPV-associated cancers. Overall mutational burden was not significantly different in pre- versus post-CRT tumors, and several examples of shared clonal driver mutations were identified. In two cases, clonally related pre- and post-CRT tumors harbored distinct oncogenic driver mutations in the same cancer gene (KRAS or FBXW7). A patient with recurrent disease achieved an exceptional response to anti-programmed death (PD-1) therapy, and genomic dissection revealed high mutational burden and predicted neoantigen load.Conclusions: We perform comprehensive mutational analysis of ASCC and characterize mutational features associated with CRT. Although many primary and recurrent tumors share driver events, we identify several unique examples of clonal evolution in response to treatment. Clin Cancer Res; 23(12); 3214–22. ©2016 AACR.

Background: Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear.Methods: Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes.Results: The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78–1.26] or lethal disease (HR, 0.93; 95% CI, 0.61–1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis [risk ratio (RR)≥T3 vs. T2, 1.23; 95% CI, 1.16–1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86–1.17) or lethal disease (RR, 0.99; 95% CI, 0.47–2.09).Conclusions: These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy.Impact: This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(9); 1497–509. ©2012 AACR.

Background Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. Methods A cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. Results For 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P Conclusions Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

Deficits in speech understanding constitute one of the most severe consequences of hearing loss. Here we investigate the clinical and genetic risk factors for symmetric deterioration of speech recognition thresholds (SRT) among cancer survivors treated with cisplatin.SRT was measured using spondaic words and calculating the mean of measurements for both ears with symmetric SRT values. For clinical associations, SRT-based hearing disability (SHD) was defined as SRT≥15 dB hearing loss and clinical variables were derived from the study dataset. Genotyped blood samples were used for GWAS with rank-based inverse normal transformed SRT values as the response variable. Age was used as a covariate in association analyses.SHD was inversely associated with self-reported health (p = 0.004). Current smoking (p = 0.002), years of smoking (p = 0.02), BMI (p 0.001), and peripheral motor neuropathy (p = 0.003) were positively associated with SHD, while physical activity was inversely associated with SHD (p = 0.005). In contrast, cumulative cisplatin dose, peripheral sensory neuropathy, hypertension, and hypercholesterolemia were not associated with SHD. Although no genetic variants had an association p value 5 × 10Current results improve our understanding of risk factors for SRT deterioration in cancer survivors. Higher BMI, lower physical activity, and smoking are associated with SHD. Larger samples would allow for expansion of the current findings on the genetic architecture of SRT.

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men.Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA]20 ng/mL or cT1c, biopsy Gleason 8, PSA10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups.Patients with unfavorable intermediate-risk (n = 31,381) and favorable high-risk (n = 10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n = 30,260) or very high-risk (n = 7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P.001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P.001).Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision‐making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS‐CoV‐2–positive patients with cancer., This commentary describes the ethical rationale and implementation details for a novel, multidisciplinary, treatment prioritization committee that makes treatment decisions regarding patients with cancer who are positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This consistent, ethical, and transparent process could be adapted to any oncology department in which there is risk disparity between physician decision makers and the frontline staff who are implementing these decisions.

To provide new information on factors associated with discrepancies between patient-reported and audiometrically defined hearing loss (HL) in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT) and to comprehensively investigate risk factors associated with audiometrically defined HL.A total of 1410 testicular cancer survivors (TCS) ≥6 months post-CBCT underwent comprehensive audiometric assessments (0.25 to 12 kHz) and completed questionnaires. HL severity was defined using American Speech-Language-Hearing Association criteria. Multivariable multinomial regression identified factors associated with discrepancies between patient-reported and audiometrically defined HL and multivariable ordinal regression evaluated factors associated with the latter.Overall, 34.8% of TCS self-reported HL. Among TCS without tinnitus, those with audiometrically defined HL at only extended high frequencies (EHFs) (10 to 12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25 to 8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically defined HL (8.1%) [odds ratio (OR) = 2.48; 95% confidence interval (CI), 1.31 to 4.68; and OR = 3.49; 95% CI, 1.89 to 6.44, respectively]. Older age (OR = 1.09; 95% CI, 1.07 to 1.11, p0.0001), absence of prior noise exposure (OR = 1.40; 95% CI, 1.06 to 1.84, p = 0.02), mixed/conductive HL (OR = 2.01; 95% CI, 1.34 to 3.02, p = 0.0007), no hearing aid use (OR = 5.64; 95% CI, 1.84 to 17.32, p = 0.003), and lower education (OR = 2.12; 95% CI, 1.23 to 3.67, p = 0.007 for high school or less education versus postgraduate education) were associated with greater underestimation of audiometrically defined HL severity, while tinnitus was associated with greater overestimation (OR = 4.65; 95% CI, 2.64 to 8.20 for a little tinnitus, OR = 5.87; 95% CI, 2.65 to 13.04 for quite a bit tinnitus, and OR = 10.57; 95% CI, 4.91 to 22.79 for very much tinnitus p0.0001). Older age (OR = 1.13; 95% CI, 1.12 to 1.15, p0.0001), cumulative cisplatin dose (300 mg/m2, OR = 1.47; 95% CI, 1.21 to 1.80, p = 0.0001), and hypertension (OR = 1.80; 95% CI, 1.28 to 2.52, p = 0.0007) were associated with greater American Speech-Language-Hearing Association-defined HL severity, whereas postgraduate education (OR = 0.58; 95% CI, 0.40 to 0.85, p = 0.005) was associated with less severe HL.Discrepancies between patient-reported and audiometrically defined HL after CBCT are due to several factors. For survivors who self-report HL but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments should be considered.

PURPOSE: In recent years, the American Society for Radiation Oncology (ASTRO) has received requests for a standard list of data elements from other societies, database architects, Electronic Health Record vendors and, most recently, the pharmaceutical industry. These requests point to a growing interest in capturing radiation oncology data within registries and for quality measurement, interoperability initiatives, and research. Identifying a short and consistent list will lead to improved care coordination, a reduction in data entry by practice staff, and a more complete view of the holistic approach required for cancer treatment.METHODS AND MATERIALS: The task force formulated recommendations based on analysis from radiation specific data elements currently in use in registries, accreditation programs, incident learning systems, and electronic health records. The draft manuscript was peer reviewed by 8 reviewers and ASTRO legal counsel and was revised accordingly and posted on the ASTRO website for public comment in April 2019 for 2 weeks. The final document was approved by the ASTRO Board of Directors in June 2019.

BACKGROUND Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend

e24089 Background: Cisplatin is one of the most used cytotoxic drugs worldwide, but few studies have comprehensively evaluated CIS-TINN in adult-onset cancer survivors. It is critical to identify survivors with high degrees of handicap and related risk factors, as tinnitus (TINN) is strongly related to adverse health outcomes (AHO) including reduced quality of life, and poorer physical and mental health. Methods: Eligible cisplatin-treated testicular cancer survivors (TCS) (aged < 60 y at diagnosis) completed comprehensive, validated health surveys, including the 20-item Tinnitus Primary Function Questionnaire (TPFQ). TPFQ assesses the 4 main TINN-impaired domains (see Table), each with a response metric of 0% (no interference) to 100% interference by TINN, with final impairment groupings of 0-16% (none/minimal), 17-42% (mild/moderate), and 43-100% (significant). TPFQ measures were compared by 2-sided signed-rank tests. Multinomial logistic regression models (adjusted for age, income, education, yrs since therapy, cisplatin dose, BMI, smoking, hypertension, and hearing loss (HL)) tested for associations with TINN severity. Results are shown as OR [95% CI], p-value. Results: Among 213 TCS [median age 46 y (IQR: 38-52 y); median time since therapy: 10.6 y (IQR: 6.8-16.6 y)], the most common AHOs were CIS-TINN (60%), and HL (60%). For TCS with CIS-TINN, the mean degree of reported interference across all TPFQ domains was 21% (median: 15, IQR: 3-33). TCS with CIS-TINN reported significantly greater interference with emotion (median: 22, range 5-40) than with concentration (median 13, IQR: 1.0-37, p = .004), hearing (median: 10, IQR: 0-30, p < .001), and sleep (median: 2.4, IQR: 0-21, p < .001). Conclusions: Following cisplatin chemotherapy, CIS-TINN is a leading AHO and often reported with HL and reduced quality of life. Severe CIS-TINN was associated with greater handicap on the TPFQ as well as with depression, cognitive dysfunction, and hearing aid use. Overall, however, TCS with CIS-TINN and HL reported underutilization of hearing aids.[Table: see text]

12080 Background: No study has systematically evaluated the impact of AHOs on PROMIS-validated measures of physical and mental health in TCS. Patient-reported outcomes are increasingly recognized as crucial in TCS follow-up, given their young age at diagnosis and high cure rates. Methods: Eligible TCS (age < 60 yr at diagnosis, given first-line cisplatin-based chemotherapy (CHEM)) completed comprehensive health surveys, prescription drug usage, and PROMIS global physical health and global mental health measures. PROMIS scores were compared to US subpopulation norms for similar-age men. 2017-2018 NHANES data were compared with select survey responses. Linear regression examined the relationship between individual AHOs (pain, obesity, cisplatin-induced peripheral neuropathy (CIPN)), cisplatin-related AHOs (CIPN, hearing loss, vertigo, tinnitus, renal disease), cardiovascular (CVD) AHOs (7 AHO), and all AHOs taken together (24 AHOs), with PROMIS global physical and mental health measures. Regression models were adjusted for age, cisplatin dose, time since CHEM, education, income, smoking, and alcohol. Results: Among 213 TCS (median age at evaluation: 46 yr; IQR: 38-52 yr; median time since CHEM completion: 10.6 yr; IQR: 6.8-16.6 yr), the most common AHOs were tinnitus (60%), self-reported hearing loss (60%), CIPN (55%), and Raynaud Phenomenon (43%). The median number of AHOs was 5 (IQR: 3-7), and 12% of TCS had ≥10 AHOs. Only 1.4% of TCS had no AHOs. Compared to NHANES men without cancer, controlling for age, education, and race, fewer TCS currently smoked (3% vs. 22%; P

12120 Background: Cisplatin is one of the most commonly used ototoxic drugs, but no study has quantified the handicap imposed by CIHL in U.S. adult-onset cancer survivors. Identification of survivors with high degrees of handicap and related risk factors is vital, as hearing loss (HL) in the general population is strongly related to adverse health outcomes, including cognitive decline, dementia, and poor mental health and social well-being. Methods: Eligible testicular cancer survivors (TCS) (age < 60 y at diagnosis, given first line cisplatin) completed comprehensive health surveys, including the validated 25-item Hearing Handicap Inventory for Adults (HHIA). HHIA quantifies emotional (13 items) and social difficulties (12 items) related to HL; for each scale (0-100%), based on their responses, TCS were grouped into 3 handicap levels: 0-16% (none/minimal), 17-42% (mild/moderate), and 43-100% (significant) following HHIA recommendations. A Spearman correlation evaluated the associations between increasing HL severity and HHIA group. The association between HL and reported cognitive dysfunction was evaluated by a logistic regression analysis adjusted for age, income, education, yrs since therapy, cisplatin dose, BMI, smoking, and hypertension, with results presented as OR[CI], p-value. Results: Among 213 TCS [median age at evaluation, 46 y (IQR: 38-52 y); median time since cisplatin completion, 10.6 y (IQR: 6.8-16.6 y)], CIHL was reported by 127 TCS (60%). Of TCS with CIHL, 31% reported some degree of related handicap (for total HHIA scale: 13% TCS and 18% TCS reporting mild/moderate and significant handicap, respectively). HL severity was significantly correlated with handicap level in all domains (social, ρ = 0.85, p

PURPOSE/OBJECTIVE(S) Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes. MATERIALS/METHODS We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5. RESULTS A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics. CONCLUSION Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

PURPOSE/OBJECTIVE(S) Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). Relative SM probabilities following stereotactic body radiotherapy (SBRT) or moderately hypofractionated radiation (HF-IMRT) remain unknown. We hypothesized that the probability of SM following SBRT or HF-IMRT would differ compared with conventionally fractionated intensity modulated radiotherapy (CF-IMRT). MATERIALS/METHODS Cohort analysis of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up compared SM probability amongst men receiving either radical prostatectomy (RP), CF-IMRT, HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models. Sensitivity analyses were conducted to evaluate differences in SM stratified by year of treatment and follow up length. Propensity score-adjusted pairwise assessments of modalities were also performed. RESULTS For 303,432 patients, median follow-up was 9.08 years (IQR 7.01 - 11.21), and median age was 64 years (IQR 58-69). Crude rates of SM by treatment modality were: 5.2% for RP, 8.9% for CF-IMRT, 7.7% for HF-IMRT, 7.9% for BT, and 5.3% for SBRT. Adjusted odds ratios (AOR) for development of SM (referent: RP) were: CF-IMRT vs. RP 1.20 (95% CI 1.14-1.25, P < 0.001), HF-IMRT vs. RP 1.25 (95% CI 1.01-1.55, P = 0.045), BT vs. RP 1.11 (95% CI 1.07-1.16, P < 0.001), and SBRT vs. RP 0.95 (95% CI 0.81-1.12, P = 0.567). Sensitivity analyses confirmed higher probability of SM comparing CF-IMRT to RP (P < 0.01 for all) and no statistically significant difference comparing SBRT to RP at all year and follow-up length groupings (P = NS for all). On propensity score-adjusted analysis, SBRT was associated with lower probability of SM compared to CF-IMRT (AOR 0.78, 95% CI 0.66-0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95% CI 0.73-1.03, P = 0.102). CONCLUSION Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy, but not stereotactic body radiotherapy, were associated with increased probability of a second malignancy compared to radical prostatectomy. Our findings underscore the need for assessment of second malignancy risk in prospective studies of SBRT.

Purpose: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for oligometastatic prostate cancer. We sought to characterize prostate specific antigen (PSA) response and progression-free survival (PFS) after SBRT among men who have progressed on ARSI therapy in the oligometastatic castration-resistant setting. Methods and Materials: A single-institution retrospective analysis was performed for men with ARSI-resistant, oligometastatic, castrate-resistant prostate cancer (omCRPC). Intervention consisted of SBRT. PSA reduction greater than 50% and median PFS (PSA or radiographic progression) as determined by routine care comprised outcome measurements. Cox regression analysis was used to determine factors influencing PFS. Results: Thirty-five men with ARSI-resistant omCRPC and 65 lesions treated with SBRT were followed for a median of 17.2 months. In 63% of men PSA reduction greater than 50% was achieved. Median PFS was 9.0 months. Incomplete ablation (defined as the presence of untreated lesions after SBRT or receipt of prior palliative radiation therapy doses) was associated with worse PFS (hazard ratio 4.21 [1.74-10.19]; P < .01). For a subgroup of 22 men with complete ablation of metastatic sites with SBRT, the median PFS was 13.1 months. One-year overall survival was 93.1% (95% confidence interval, 84.4-100). Conclusions: SBRT may augment the efficacy of ARSI in omCRPC, provided that all lesions receive ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.

Purpose Clinical trials assessing evaluation prostate stereotactic body radiation therapy (SBRT) have used a wide range of allowed doses to the intraprostatic urethra, but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. The goal of this study was to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. Methods and Materials The MEDLINE (PubMed) database was searched for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Logistic regression and weighted Pearson correlation models were used to assess associations between urinary toxicity rates and MUDM. Results Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (equivalent dose in 2 Gy fractions [EQD2]: 69-141.75 Gy; α/β = 3 Gy). The median follow-up ranged from 3 to 67 months (median, 32 months). On logistic regression analysis, the MUDM EQD2 was significantly associated with multiple urinary toxicity endpoints, including acute grade (G) 2+ (odds ratio [OR], 1.02; P Conclusions Radiation dose to the urethra correlates closely with urinary toxicity in patients with prostate cancer treated with SBRT. Attention should be paid to the urethral dose when delivering prostate SBRT to high doses, and approaches for urethral dose reduction warrant further investigation.

Background: This study examined sociodemographic factors, cisplatin-related adverse health outcomes (AHO), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in testicular cancer survivors (TCS). Methods: A total of 1,802 TCS who completed cisplatin-based chemotherapy ≥12 months previously completed questionnaires regarding sociodemographic features and cisplatin-related AHOs [hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), and kidney disease]. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. No cisplatin-related AHOs were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. In the multivariable model, higher CBMPt scores were significantly associated with medication use for anxiety and/or depression (P < 0.0001). In addition, tinnitus (P = 0.0009), PSN (P = 0.02), and having health insurance (P = 0.05) were significantly associated with greater use of these medications, whereas being employed (P = 0.0005) and vigorous physical activity (P = 0.01) were significantly associated with diminished use. Conclusions: TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression, and conversely, those who were employed and physically active tended to have reduced use of these medications. Impact: Healthcare providers should encourage TCS to increase physical activity to improve both physical and mental health. Rehabilitation programs should assess work-related skills and provide career development counseling/training.

Purpose The role of multimodality therapy (MMT) in the treatment of Gleason 8–10 prostate cancer remains controversial. We sought to evaluate factors associated with MMT utilization for primary radical prostatectomy (RP) and primary radiation therapy (RT). Methods and Materials From the National Cancer Database, we conducted a retrospective review of 81,528 men with National Cancer Center Network Gleason 8–10 prostate cancer diagnosed between 2004 and 2015, who underwent (1) primary RP with or without early postoperative external beam RT (EBRT) or (2) primary RT (androgen deprivation therapy + EBRT) with or without brachytherapy (BT) boost. Using multivariable logistic regression models, we evaluated factors associated with the utilization of MMT, defined as early postoperative EBRT for primary RP or BT boost for primary RT. Results For primary RP, the percentages of men who underwent MMT for Gleason 8 and 9–10 disease were 12.2% and 24.1%, respectively. On multivariable logistic regression, men with Gleason 9–10 were more likely to undergo MMT (odds ratio 1.03 [1.02, 1.04]), although adverse pathologic features such as T3b-4 (1.24 [1.23, 1.25]) disease demonstrated the strongest associations. For primary RT, the percentages of men who underwent BT boost for Gleason 8 and 9–10 disease were 11.8% and 9.8%, respectively. On multivariable logistic regression, men with Gleason 9–10 disease were less likely to receive BT boost (0.99 [0.98, 0.99]). Conclusions Men with more aggressive Gleason 9 disease were more likely to undergo MMT if they underwent primary RP but not primary RT. Further blood-based or imaging biomarkers may aid in identifying optimal candidates for MMT, especially for primary RT.

Background While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8–10 (Grade Group 4–5) prostate cancer (PCa), it has been hypothesized that Gleason 9–10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. Objective To examine the association between ADT and OS for Gleason 8 versus Gleason 9–10 PCa. Design, setting, and participants A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8–10 PCa who received EBRT. Data were collected from 2004 to 2012. Intervention ADT. Outcome measurements and statistical analysis Cox proportional hazards regression was used to examine the association between ADT and OS. Results and limitations Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9–10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70–0.87, p Conclusions In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9–10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9–10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings. Patient summary In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9–10 (Grade Group 5) prostate cancer. We found that Gleason 9–10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.

BackgroundFew data exist on the relationship of cisplatin-related adverse health outcomes (AHOs) with disability, unemployment, and self-reported health (SRH) among testicular cancer survivors (TCS).MethodsA total of 1815 TCS at least 1 year postchemotherapy underwent clinical examination and completed questionnaires. Treatment data were abstracted from medical records. A cumulative burden of morbidity score (CBMPt) encompassed the number and severity of platinum-related AHOs (peripheral sensory neuropathy [PSN], hearing loss, tinnitus, renal disease). Multivariable regression assessed the association of AHOs and CBMPt with employment status and SRH, adjusting for sociodemographic and clinical characteristics. Unemployment was compared with a male normative population of similar age, race, and ethnicity.ResultsAlmost 1 in 10 TCS was out of work (2.4%, disability leave; 6.8%, unemployed) at a median age of 37 years (median follow-up = 4 years). PSN (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 1.01 to 8.26, grade 3 vs 0, P = .048), renal dysfunction defined by estimated glomerular filtration rate (OR = 12.1, 95% CI = 2.06 to 70.8, grade 2 vs 0, P = .01), pain (OR = 10.6, 95% CI = 4.40 to 25.40, grade 2 or 3 vs 0, P ConclusionsOur findings have important implications regarding treatment-associated productivity losses and socioeconomic costs in this young population. Survivorship care strategies should include inquiries about disability and unemployment status, with efforts made to assist affected TCS in returning to the workforce.

Clinical pathways increase compliance with treatment guidelines, improve outcomes, and reduce costs. Guidelines recommend single fraction radiation therapy (SFRT) for palliation of uncomplicated bone metastases, but implementation is variable. We examined the effects of a pathway tool on SFRT rates in an academic radiation oncology practice.Using published literature, clinical guidelines, and expert input, we designed a clinical pathway for bone metastases radiation therapy displayed on a Web-based electronic interface. In March 2016, the pathway launched on a palliative radiation service at the Dana Farber/Brigham and Women's Cancer Center main campus and at affiliated community sites. Providers were surveyed pre- and postimplementation to assess expectations and elicit feedback. Rates of pathway utilization, compliance with SFRT recommendations, and reasons for noncompliance were assessed.The final pathway includes 20 endpoints and several validated prognostic scoring systems. It was used in 38% of 723 bone metastases radiation prescriptions, with appropriate SFRT rates rising from 18% before implementation to 48% after launch (P.01). Major reasons for rejecting recommendations included disagreement with life expectancy prognostication and patient convenience. The pathway increased physicians' confidence regarding compliance with treatment guidelines and made it easier to find well-supported treatment recommendations. Workflow disruptions and the inability to handle nuanced situations emerged as limitations.Our experience demonstrates the utility of clinical pathway decision support for bone metastases radiation in complex academic settings. Next steps include increasing the pathway's ease of use, refining the pathway's prognostic abilities, and measuring cost savings related to the pathway.

Background Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes. Methods There were 83,804 patients with 2 malignancies, diagnosed 12 to 60 months apart, from 1973-2006 from the Surveillance, Epidemiology, and End Results database. Patients were identified as newly divorced if married at their first diagnosis and single/divorced at their second. Multivariable logistic regression and competing-risks regression were used to analyze the association of becoming newly divorced or newly married with cancer-specific outcomes from the second malignancy, including advanced diagnosis (T4 or N1 or M1), receipt of treatment, and cancer-specific survival. Results Four percent became newly divorced and 3.4% became newly married. Compared with long-term married, newly divorced patients were most likely to be diagnosed with advanced disease (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI], 1.19-1.43), followed by long-term divorced (AOR 1.18; 95% CI, 1.11-1.25), and were least likely to receive curative treatment (AOR 0.74; 95% CI, 0.67-0.81). Newly divorced patients had the worst cancer-specific survival (adjusted hazard ratio [AHR] 1.17; 95% CI, 1.05-1.30, P = .005), followed by long-term divorced (AHR 1.08; 95% CI, 1.01-1.16, P = .032), while newly married patients had similar cancer-specific survival to long-term married (AHR 0.96; 95% CI, 0.85-1.08, P = .46). Conclusion Recent divorce, which represents an acute disruption of a patient's social support network, was associated with the worst cancer outcomes, followed by long-term divorce. Clinicians should consider recent divorce as a risk factor for worse cancer outcomes, and encourage appropriate screening, treatment, and access to social and financial supports for recently divorced patients.

Background Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. Objective To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. Design, setting, and participants Using the National Cancer Data Base (2004–2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. Outcome measures and statistical analysis We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. Results and limitations Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=–2.7, 95% confidence interval [CI]: –4.4, –1.1, p =0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio=0.36, 95% CI: 0.12, 1.14, p =0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: –0.7, +2.2, p =0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p =0.36). Limitations include the lack of full treatment details and cancer-specific survival information. Conclusions Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. Patient summary We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus observation for both seminomatous and nonseminomatous germ cell tumors.

Purpose/objective(s) The use of ablative stereotactic body radiation therapy (SBRT) in pancreatic cancer is constrained by nearby radiation-sensitive organs. Magnetic resonance (MR)-guided adaptive radiation therapy (SMART) is an innovation that offers superior anatomical imaging during treatment allowing for daily plan adaptation based on the volumetric images prior to each treatment. We report results of a prospective phase 1 trial (NCT04115254) assessing feasibility of SMART and describe early outcomes of patients with pancreatic cancer. Secondary objectives included analysis of 90-day toxicity, local control, and patient-reported outcomes (PROMs) in patients undergoing SMART. Materials/methods In this prospective IRB approved study, patient eligibility criteria included: biopsy-proven diagnosis of pancreatic cancer, eligibility for SBRT, and ability to undergo and tolerate MRI imaging. Patients were ineligible if they had prior abdominal radiation, active ulcerative disease, or tumor invasion of the stomach, duodenum or bowel on endoscopy. Patients were monitored for acute and late grade ≥ 3 toxicity. PROMs included the FACT-HEP and PROMIS Physical and Mental Health batteries and were completed at baseline and during follow-up. Feasibility was defined as 1) enrolling patients and delivering SMART on the MR-Linac; 2) assessing tumor using MR guidance before, during and after MR-guided treatment and 3) generating adaptive plans. Results All 10 patients successfully completed SMART, receiving 40 Gy in 5 fractions with 48 of 50 fractions requiring adaptation to meet target or critical organ-at-risk metrics. The median follow up was 10.49 months (range 5.00 - 11.38). The median age was 72 (range 55 - 89), 60% were female, and 80% were white. Disease stages included 30% T1-T2, 10% T3, and 60% T4 disease, as well as 30% N0, 60% N1, 10% N2 disease, and 80% M0, 10% MX, and 10% M1. 90% of patients had other medical comorbidities. ECOG performance status was 0-1 in 90% of patients. There were no acute or late grade ≥ 3 treatment related toxicities. There were no local recurrences. The 6-month survival rate was 90% (95% CI 47.3-98.5) with two deaths due to progressive disease. The median change between baseline and follow-up within 6 months of treatment was -0.5 on FACT-HEP, -2.5 on PROMIS Physical, and -4.7 on PROMIS Mental Health (table 1). Conclusion We successfully demonstrated the feasibility and safety of SMART with daily adaptation in patients with pancreatic cancer. PROMs highlight that patients tolerated treatment well with minimal toxicity. Further investigation in dose escalation in pancreatic cancer is warranted.

PURPOSE/OBJECTIVE(S) Beams-eye view (BEV) imaging during radiation therapy can be used for real-time localization of the treatment target. However, clinical implementation is limited by the poor performance of current electronic portal imaging devices (EPIDs). A novel multilayer imager (MLI), consisting of four stacked conventional flat-panel imagers, was recently shown to have 5.7 times the detective quantum efficiency and nearly 2 times the contrast-to-noise ratio of a conventional EPID. In the current study, we compare the MLI against a single layer imager for the application of fiducial tracking during liver SBRT procedures. The hypothesis is that the MLI will provide more accurate and efficient fiducial tracking. MATERIALS/METHODS The prototype MLI was installed in the standard MV imager housing on a clinical LINAC, replacing the conventional EPID. The MV imager arm was extended during volumetric modulated arc therapy (VMAT) SBRT treatments for passive data acquisition. Six patients with liver metastases receiving SBRT in 3-5 fractions (900-1200 cGy/fx) were studied. Data was acquired for two fractions of each treatment course, one fraction with the MLI using all 4 layers and one with the MLI using the top layer only. Automatic fiducial localization was performed using a modification of a previously published algorithm. Truth data was derived using external surrogate respiratory traces combined with manual tracking. Results for 4- and 1-layer modes were compared against truth data to determine tracking accuracy and efficiency. Tracking and noise improvements were assessed for any correlation. RESULTS Between 2771 to 6505 image frames were acquired for each patient, with roughly half of each corresponding to acquisition in 1-layer mode and the other half 4-layer mode. Tracking accuracy with the 1-layer imager returned a root mean square error (RMSE) of 2.1 mm compared to 4-layer RMSE of 1.5 mm, a statistically significant (P < 0.001) improvement of 0.6 mm. Successful tracking efficiency with 4 layers improved to 82.8% versus 58.4% for the 1-layer mode, a relative improvement of 41.8% (P < 0.001). There was a strong correlation (r = 0.913) between the increase in successfully tracked frames and reduction in noise when using the 4-layer mode. CONCLUSION Noise reduction and increased MV photon detection efficiency achieved by utilizing a multi-layer MV imager results in improved fiducial tracking for liver SBRT treatments. Future BEV clinical applications may be improved by pursuing similar noise reduction and photon detection enhancement strategies.

PURPOSE/OBJECTIVE(S) Dose escalated stereotactic body radiotherapy (SBRT) may improve both local control and overall survival for patients with pancreatic cancer. However, escalated dose cannot be routinely offered because of the risk of injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents an innovation that may achieve safer delivery of ablative doses and improve outcomes. The goal of the present study is to identify specific dosimetric gains that can be achieved with MR-guided adaptive pancreatic SBRT and describe acute clinical outcomes. MATERIALS/METHODS We performed a single institution IRB approved retrospective analysis of 37 consecutive pancreatic cancer patients treated with 40 Gy in 5 fractions with SMART on a MR-linear accelerator using a light inspiration breath hold. The adaptive workflow starts with an "original" plan which is then adapted daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured pre-treatment anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and meet critical organ-at-risk (OAR) metrics, including stomach, duodenum, large bowel and small bowel V33 < 1cc. Acute GI toxicity rates were assessed according to CTCAE v5. RESULTS The median age of our cohort was 71 (range 35-87) with 23/37 (62%) patients having locally advanced disease and 14/37 (38%) having borderline resectable disease. Adaptive planning was used in all cases with a prescription goal of 40 Gy in 5 fractions prescribed to 90% of the target volume. The median CTV was 80.5 cc (range, 10-180cc) and the PTV was a 3mm expansion. Adaptive planning was required in 156/185 fractions to meet either the stomach (63.8%), duodenum (33.5%), large bowel (12.4%) or small bowel (11.4%) V33 < 1cc metric. Of the plans adapted for OAR sparing, 90 plans required adaptation for one gastrointestinal organ, 50 plans for two, 10 plans for three and 1 plan for four. For predicted plans exceeding the V33 < 1cc metric, the median V33 for duodenum was 2.475cc (range: 1.01-10.68cc), stomach was 2.67cc (range: 1.01-8.21cc), small bowel was 2.71cc (range: 1.14-9.54cc) and large bowel was 1.93cc (range: 1.05-8.36cc). All re-optimized plans met the V33 < 1cc metric. No local failure or acute grade 3 toxicities were observed with a median follow-up of 6 months (range 3-15). CONCLUSION Online adaptive re-optimization was necessary for the majority of fractions and improved plan dosimetry was achieved specifically for duodenum, stomach, large and small bowel, achieving low rates of acute toxicity. The clinical benefits of MR-guided adaptive pancreatic SBRT for dose escalation warrant further investigation.

Purpose/objective(s) To characterize the representation of various demographic groups, including gender, age, primary language, race, ethnicity, marital status, religion and country of origin, in a department-wide clinical database and biobanking study. Materials/methods A total of 10,114 patients who presented for radiotherapy planning between Oct 14, 2016 and Mar 15, 2020 were identified using an institutional resource. Among those deemed eligible for the study by treating clinicians, 3421 patients were consented. Self-reported demographics data were obtained from a research patient data registry. Associations between the consent status and the demographic characteristics were analyzed using logistic regression models, and the odds ratios adjusted for other covariates (OR) with 95% confidence interval (CI) were reported. The Cochran-Mantel-Haenszel (CMH) and Breslow-Day tests were used to assess potential interactions between language and ethnicity and marital status and gender and to evaluate confounding effects of ethnicity and gender. Results After excluding participants 18 years and under or those with incomplete demographics data, a total of 9,388 patients were included in the analysis. Among these, 3,276 were consented. Consent rates to the study varied significantly across all demographic groups except for country of origin. Men were more likely than women to enroll in the study (OR, 1.29; 95% CI, 1.18-1.42; P Conclusion Women, the elderly, non-English speakers, racial and ethnic minorities, single, and religious individuals showed lower consent rates to the study compared to men, younger, English speakers, Whites, married, and non-religious patients. These results demonstrate demographic disparities that could influence the results of future research performed using this departmental biobanking database resource, and identify areas for improvement.