Prevalence, trends, and characteristics of trials investigating local therapy in contemporary phase 3 clinical cancer research.

BACKGROUND: Although most patients with cancer are treated with local therapy (LT), the proportion of late-phase clinical trials investigating local therapeutic interventions is unknown. The purpose of this study was to determine the proportion, characteristics, and trends of phase 3 cancer clinical trials assessing the therapeutic value of LT over time. METHODS: This was a cross-sectional analysis of interventional randomized controlled trials in oncology published from 2002 through 2020 and registered on ClinicalTrials.gov. Trends and characteristics of LT trials were compared to all other trials. RESULTS: Of 1877 trials screened, 794 trials enrolling 584,347 patients met inclusion criteria. A total of 27 trials (3%) included a primary randomization assessing LT compared with 767 trials (97%) investigating systemic therapy or supportive care. Annual increase in the number of LT trials (slope [m] = 0.28; 95% confidence interval [CI], 0.15-0.39; p < .001) was outpaced by the increase of trials testing systemic therapy or supportive care (m = 7.57; 95% CI, 6.03-9.11; p < .001). LT trials were more often sponsored by cooperative groups (22 of 27 [81%] vs. 211 of 767 [28%]; p < .001) and less often sponsored by industry (5 of 27 [19%] vs. 609 of 767 [79%]; p < .001). LT trials were more likely to use overall survival as primary end point compared to other trials (13 of 27 [48%] vs. 199 of 767 [26%]; p = .01). CONCLUSIONS: In contemporary late-phase oncology research, LT trials are increasingly under-represented, under-funded, and evaluate more challenging end points compared to other modalities. These findings strongly argue for greater resource allocation and funding mechanisms for LT clinical trials. PLAIN LANGUAGE SUMMARY: Most people who have cancer receive treatments directed at the site of their cancer, such as surgery or radiation. We do not know, however, how many trials test surgery or radiation compared to drug treatments (that go all over the body). We reviewed trials testing the most researched strategies (phase 3) completed between 2002 and 2020. Only 27 trials tested local treatments like surgery or radiation compared to 767 trials testing other treatments. Our study has important implications for funding research and understanding cancer research priorities.

Health-related quality of life in adolescents and young adults with cancer who received radiation therapy: a scoping review.

PURPOSE: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT. METHODS: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review (n = 19), articles that met eligibility criteria were analyzed. RESULTS: Six studies were analyzed. Two studies included AYAs actively receiving treatment and all included patients in survivorship; time between diagnosis and HRQOL data collection ranged from 3 to > 20 years. Physical and mental health were commonly assessed (6/6 studies) with social health assessed in three studies. AYA-relevant HRQOL needs were rarely assessed: fertility (1/6 studies), financial hardship (1/6), body image (0/6), spirituality (0/6), and sexual health (0/6). No study compared HRQOL between patients actively receiving RT and those post-treatment. None of the studies collected HRQOL data longitudinally. CONCLUSION: HRQOL data in AYAs receiving RT is limited. Future studies examining longitudinal, clinician- vs. patient-reported, and AYA-relevant HRQOL are needed to better understand the unique needs in this population.

Financial toxicity impact on younger versus older adults with cancer in the setting of care delivery.

BACKGROUND: Young adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39 years old) (YAs), other working-age adults (40-64 years old), and older adults (≥65 years old) receiving cancer care. METHODS: A total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution. RESULTS: YAs (median age, 31.5 years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P < .001 in all multivariable models). Compared with older adults, younger age adults demonstrated worse material hardship (median scores, 3.70 vs 4.80 vs 1.30 for YAs, other working-age, and older adults, respectively; P < .001), coping resource depletion (4.50 vs 3.40 vs 0.80; P < .001), and psychological burden (6.50 vs 7.00 vs 1.00; P < .001). Fifty percent of YAs had severe overall FT versus 40.7% of other working-age adults and 9.6% of older adults (P < .001). CONCLUSIONS: Younger age adults with cancer bore disproportionate FT. Interventions to address unmet needs are critical components for addressing FT in this population.

Ablative liver radiotherapy for unresected intrahepatic cholangiocarcinoma: Patterns of care and survival in the United States.

BACKGROUND: Single-institution studies have shown the oncologic benefit of ablative liver radiotherapy (A-RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of A-RT across the United States and its associated outcomes are unknown. METHODS: We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A-RT for receipt of biologically effective doses (BED10 ) ≥ 80.5 Gy and conventional RT (Conv-RT) for lower doses. Associations with A-RT use and overall survival were identified using logistic and Cox regressions, respectively. RESULTS: Of 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv-RT (median BED10 , 53 Gy; median, 20 fractions) and 27% A-RT (median BED10 , 100 Gy; median, 5 fractions). Use of A-RT increased from 5% in 2004 to 48% in 2018 (Ptrend < .001). With a median follow-up of 52.3 months, median survival estimates for Conv-RT and A-RT were 12.8 and 23.7 months (P < .001), respectively. On multivariable analysis, stage III and IV disease correlated with a higher risk of death, whereas chemotherapy and A-RT correlated with a lower risk. CONCLUSIONS: Although A-RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A-RT is associated with longer survival versus Conv-RT. LAY SUMMARY: Bile duct cancer is a rare, deadly disease that often presents at advanced stages. Single-institution retrospective studies have demonstrated that use of high-dose radiotherapy may be associated with longer survival, but larger studies have not been conducted. We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high-dose radiotherapy lived longer than those who received lower doses. Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes.

Long-term survival following definitive radiation therapy for recurrence or oligometastases in gynecological malignancies: A landmark analysis.

OBJECTIVE: Radiation therapy (RT) may improve outcomes for patients with oligometastatic cancer. We sought to determine if there are long-term survivors treated with definitive RT for recurrent or oligometastatic gynecological cancer (ROMGC), and to evaluate the clinical and disease characteristics of these patients. METHODS: We performed a landmark analysis in 48 patients with ROMGC who survived for ≥5 years following definitive RT of their metastasis. Patient characteristics were extracted from the medical record. DFS was modeled using the Kaplan-Meier method. RESULTS: This cohort included 20 patients (42%) with ovarian cancer, 16 (33%) with endometrial cancer, 11 (23%) with cervical cancer, and one (2%) with vaginal cancer. The sites of ROMGC were the pelvic (46%), para-aortic (44%), supraclavicular (7%), mediastinal (4%), axillary (4%) lymph nodes and the lung (5.5%). Median total RT dose and fractionation were 62.1 Gy and 2.1 Gy/fraction; one patient was treated with SBRT. 32 patients (67%) received chemoradiation; these patients had higher rates of median DFS than those treated with RT alone (93 vs. 34 months, P = 0.05). At median follow-up of 11.7 years, 11 (23%) patients had progression of disease. 20 (42%) patients had died, 9 (19%) died from non-gynecologic cancer and 8 (17%) from gynecologic cancer (three were unknown). 25 (52%) patients were alive and disease-free (10 initially had endometrial cancer [63% of these patients], eight had cervical cancer [73%], six had ovarian cancer [30%], one had vaginal cancer [100%]). CONCLUSIONS: Long-term survival is possible for patients treated with definitive RT for ROMG, however randomized data are needed to identify which patients derive the most benefit.

HIV, cancer, and coping: The cumulative burden of a cancer diagnosis among people living with HIV.

OBJECTIVES: People living with HIV (PLWH) have increased risk for cancer and worse cancer-specific survival. We explored the emotional burden of cancer and HIV as a potential driver of cancer mortality. RESEARCH APPROACH: Semi-structured qualitative interviews with PLWH and cancer. PARTICIPANTS: 27 PLWH who had either completed cancer treatment, were currently undergoing treatment, or experienced challenges in completing treatment. METHODOLOGICAL APPROACH: An inductive qualitative approach using the constant comparative method. FINDINGS: Participants drew strong parallels between being diagnosed with HIV and cancer. Many described HIV-related stigma that hindered social support. Cancer treatment side effects were a major challenge, impacting treatment adherence for both cancer and HIV. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: There is a need for convenient, affordable, and visible services to support PLHIV as they navigate cancer care. Services should be tailored to the unique needs of this population by addressing HIV-related stigma, building social support, and fostering resilience.

The impact of the Patient Protection and Affordable Care Act on insurance coverage and cancer-directed treatment in HIV-infected patients with cancer in the United States.

BACKGROUND: To the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act (ACA) on people living with HIV and cancer (PLWHC), who have lower cancer treatment rates and worse cancer outcomes. To investigate this research gap, the authors examined the effects of the ACA on insurance coverage and receipt of cancer treatment among PLWHC in the United States. METHODS: HIV-infected individuals aged 18 to 64 years old with cancer diagnosed between 2011 and 2015 were identified in the National Cancer Data Base. Health insurance coverage and cancer treatment receipt were compared before and after implementation of the ACA in non-Medicaid expansion and Medicaid expansion states using difference-in-differences analysis. RESULTS: Of the 4794 PLWHC analyzed, approximately 49% resided in nonexpansion states and were more often uninsured (16.7% vs 4.2%), nonwhite (65.2% vs 60.2%), and of low income (36.3% vs 26.9%) compared with those in Medicaid expansion states. After 2014, the percentage of uninsured individuals decreased in expansion states (from 4.9% to 3%; P = .01) and nonexpansion states (from 17.6% to 14.6%; P = .06), possibly due to increased Medicaid coverage in expansion states (from 36.9% to 39.2%) and increased private insurance coverage in nonexpansion states (from 29.5% to 34.7%). There was no significant difference in cancer treatment receipt noted between Medicaid expansion and nonexpansion states. However, the percentage of PLWHC treated at academic facilities increased significantly only in expansion states (from 40.2% to 46.7% [P < .0001]; difference-in-differences analysis: 7.2 percentage points [P = .02]). CONCLUSIONS: The implementation of the ACA was associated with improved insurance coverage among PLWHC. Lack of insurance still is common in non-Medicaid expansion states. Patients with minority or low socioeconomic status more often resided in nonexpansion states, thereby highlighting the need for further insurance expansion.

Exclusion of Men from Randomized Phase III Breast Cancer Clinical Trials.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

Cancer disparities in people with HIV: A systematic review of screening for non-AIDS-defining malignancies.

BACKGROUND: People with HIV (PWHIV) have improved survival because of the advent of antiretroviral therapy. Consequently, PWHIV experience higher rates of non-acquired immunodeficiency syndrome-defining malignancies (NADMs). Previous studies have demonstrated worsened cancer-specific survival in PWHIV, partly because of advanced cancer stage at diagnosis. The objective of the current systematic review was to evaluate screening disparities for NADMs among PWHIV. METHODS: The PubMed, Cochrane, EMBASE, and ClinicalTrials.gov databases were searched from January 1, 1996 through April 10, 2018 to identify studies related to screening disparities for NADMs among PWHIV. Eligibility criteria included any study performed in a high-income country that compared screening for NADMs by HIV status. After title/abstract screening and full-text review, articles that met eligibility criteria were analyzed. RESULTS: Of 613 unique articles identified through the search, 9 studies were analyzed. Three studies addressed breast cancer screening, 4 addressed colorectal cancer screening, and 2 addressed prostate cancer screening. Five of the reviewed studies demonstrated that PWHIV were less likely to receive indicated cancer screenings compared with the general population, whereas 3 indicated that screening proportions were higher among PWHIV, and 1 demonstrated that screening proportions were comparable. In most of the studies, PWHIV who had regular access to health care were more likely to undergo cancer screening. CONCLUSIONS: The available evidence does not uniformly confirm that PWHIV are less likely to receive cancer screening. Social determinants of health (insurance status, access to health care, education, income level) were associated with the receipt of appropriate cancer screening, suggesting that these barriers need to be addressed to improve cancer screening in PWHIV.

Gender and the Receipt of the Association of Residents in Radiation Oncology Educator of the Year Award.

Purpose: We hypothesized that there may be a gender disparity in the receipt of the Association of Residents in Radiation Oncology (ARRO) Educator of the Year Award and sought to elucidate factors that contribute to differences in award receipt. Methods and Materials: Using a database provided by the American Society for Radiation Oncology, award recipients were identified from 2010 to 2022. Publicly available websites were accessed to obtain data regarding gender, years since residency graduation, percentage of female faculty, size of residency program, and program director designation. A 1-sample Z-test was used to assess whether the proportion of female ARRO award winners, defined as the proportion of female radiation oncology faculty members in the nominating universities that year, was significantly less than the population average. Secondary analyses used univariable binary logistic regression to identify global associations between gender, year since gradation, or program size. Results: The lowest proportion of female awardees occurred in 2013 (14.3%) and the greatest proportion in 2022 (30.6%). Compared with the proportion of female faculty members in nominating programs for the respective year, there were significantly fewer female awardees in 2010 (18% female awardees vs 32% female faculty members; P = .02) and 2013 (14% female awardees vs 31% female faculty members; P = .01). There was a statistically significant increase in female awardees during the study period (P < .01). On logistic regression analysis, large program size (≥10 residents) (odds ratio [OR], 6.86; 95% CI, 2.71-23.1; P < .001) and medium program size (5-9 residents) (OR, 4.05; 95% CI, 1.60-13.7; P < .001) were associated with a greater proportion of female awardees compared with small program size (1-4 residents). There was no association between awardee gender and years since graduation. Conclusions: A gender disparity was present in the receipt of ARRO Educator Awards. Residency chiefs, program directors, and chairs should work to ensure that a diverse slate of faculty is considered annually for the ARRO Educator Award.

Random Forest Modeling of Acute Toxicity in Anal Cancer: Effects of Peritoneal Cavity Contouring Approaches on Model Performance.

PURPOSE: Our purpose was to analyze the effect on gastrointestinal (GI) toxicity models when their dose-volume metrics predictors are derived from segmentations of the peritoneal cavity after different contouring approaches. METHODS AND MATERIALS: A random forest machine learning approach was used to predict acute grade ≥3 GI toxicity from dose-volume metrics and clinicopathologic factors for 246 patients (toxicity incidence = 9.5%) treated with definitive chemoradiation for squamous cell carcinoma of the anus. Three types of random forest models were constructed based on different bowel bag segmentation approaches: (1) physician-delineated after Radiation Therapy Oncology Group (RTOG) guidelines, (2) autosegmented by a deep learning model (nnU-Net) following RTOG guidelines, and (3) autosegmented but spanning the entire bowel space. Each model type was evaluated using repeated cross-validation (100 iterations; 50%/50% training/test split). The performance of the models was assessed using area under the precision-recall curve (AUPRC) and the receiver operating characteristic curve (AUROCC), as well as optimal F1 score. RESULTS: When following RTOG guidelines, the models based on the nnU-Net auto segmentations (mean values: AUROCC, 0.71 ± 0.07; AUPRC, 0.42 ± 0.09; F1 score, 0.46 ± 0.08) significantly outperformed (P < .001) those based on the physician-delineated contours (mean values: AUROCC, 0.67 ± 0.07; AUPRC, 0.34 ± 0.08; F1 score, 0.36 ± 0.07). When spanning the entire bowel space, the performance of the autosegmentation models improved considerably (mean values: AUROCC, 0.87 ± 0.05; AUPRC, 0.70 ± 0.09; F1 score, 0.68 ± 0.09). CONCLUSIONS: Random forest models were superior at predicting acute grade ≥3 GI toxicity when based on RTOG-defined bowel bag autosegmentations rather than physician-delineated contours. Models based on autosegmentations spanning the entire bowel space show further considerable improvement in model performance. The results of this study should be further validated using an external data set.

Daily Vaginal Dilator Use During Radiation for Women With Squamous Cell Carcinoma of the Anus: Vaginal Wall Dosimetry and Patient-Reported Sexual Function.

PURPOSE: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW), and anterior vaginal wall (AVW), and patient-reported long-term sexual function. METHODS AND MATERIALS: We included women with SCCA who received definitive, intensity-modulated radiation therapy-based CRT. Women who were alive without evidence of disease received a patient-reported outcome survey, which included the Female Sexual Function Index (FSFI). We identified factors associated with FSFI, such as radiation dose to the VW and AVW using linear regression models and used Youden index analysis to estimate a dose cutoff to predict sexual dysfunction. RESULTS: Three hundred thirty-nine consecutively treated women were included in the analysis; 285 (84.1%) were treated with a daily VD. Of 184 women alive without disease, 90 patients (49%) completed the FSFI, and 51 (56.7%) were sexually active with valid FSFI scores. All received therapy with a daily VD. Forty-one women (80%) had sexual dysfunction. Univariate analysis showed higher dose to 50% (D50%) of the AVW correlated with worse FSFI (ß -.262; P = .043), worse desire FSFI subscore (ß -.056; P = .003), and worse pain FSFI subscore (ß -.084; P = .009). Younger age correlated with worse pain FSFI subscale (ß .067; P = .026). Age (ß .070; P = .013) and AVW D50% (ß -.087; P = .009) were significant on multivariable analysis. AVW D50% >48 Gy predicted increased risk of sexual dysfunction. CONCLUSIONS: Daily VD use is safe and well tolerated during CRT for SCCA. Using a VD during treatment to displace the AVW may reduce the risk for sexual dysfunction. Limiting the AVW D50% <48 Gy may further reduce the risk but additional data are needed to validate this constraint.

Comparing long-term sexual dysfunction across different uterine cancer treatment modalities.

INTRODUCTION: The objective of this study was to assess differences in long-term sexual and menopausal side effects after uterine cancer treatment among treatment modalities. METHODS AND MATERIALS: This is a cross-sectional study that examined women treated for uterine cancer from 2006-2018. Eligible women included those who underwent a hysterectomy/bilateral salpino-oophorectemy alone (HS), with brachytherapy (BT), or with external beam radiation therapy (EBRT). A noncancer cohort of women who underwent a hysterectomy/BSO for benign indications were also identified (non-CA). To compare outcomes, we utilized a shortened form of the female sexual function index (FSFI) and the menopause survey, which consists of 3 subscales: hot flashes, vaginal symptoms, and urinary symptoms. Demographic, comorbidity, and other treatment variables were collected. Survey totals were compared across cohorts using ANOVA tests and logistic regression. RESULTS: A total of 284 women completed the Menopause Survey (Non-CA 64, HS 60, BT 69, EBRT 91); 116 women reported sexual activity in the last 4 weeks and completed the FSFI (NC 32, HS 21, BT 31, EBRT 32). The mean FSFI score for the entire cohort was 11.4 (SD 4.16), which indicates poor sexual function. There was no significant difference between any cohort in the overall FSFI score (p = 0.708) or in any of the FSFI subscales (all p > 0.05). On univariate analysis, BT was associated with fewer menopausal hot flashes and vaginal symptoms compared to the non-CA cohort (p < 0.05), which did not persist on multivariable analysis. CONCLUSION: There was no significant difference in sexual dysfunction or menopausal symptoms in those treated for uterine cancer with or without adjuvant radiation. Most patients reported poor sexual function.

Applicant and Program Director Perceptions of Second Look Events During the 2023 Radiation Oncology Residency Match.

Purpose: Virtual radiation oncology (RO) residency interviews may impair applicant and program evaluation. Second look events (SLEs) exist; however, the frequency, nature, and implications are unknown. We surveyed applicants and program directors (PDs) to characterize the 2023 RO Match SLEs and assess perspectives. Method and Materials: An online, anonymous survey was distributed to 2023 RO Match applicants and American College of Graduate Medical Education-accredited RO PDs post-Match. Number and percentage are reported as response per question. Likert-type scores (1, strongly agree; 5, strongly disagree) are reported as median, IQR. Results: Responses were received from 51 of 246 applicants (21%) and 52 of 88 PDs (59%). Forty applicants (87%) were offered in-person and virtual SLEs; 20 (51%) and 17 (44%) applicants were invited to 1 to 3 and 4 to 6 events, respectively. Most invited applicants attended none (21, 54%). Applicants reported that all (21, 54%) or some (16, 41%) programs communicated intentions to finalize rank order lists (ROLs) before SLEs. Most applicants (29, 74%) agreed that SLEs were optional without ROL consequences (median, 2, IQR 1-3). Applicants declined in-person SLEs due to city/facility indifference (10, 43%), finances (10, 43%), and logistics (9, 39%). Most (12, 86%) in-person SLE attendees agreed that SLEs influenced their ROL (median, 2, IQR 1-2). Nineteen PDs (40%) reported offering SLEs, with 18 of 19 being in-person. PDs who did not offer SLEs cited ethical concerns (13, 45%) and institutional policies (11, 38%). All PDs reported that SLEs were optional, and 18 of 19 explained that the SLE would be without ROL consequences. SLEs mostly occurred in February before (11, 58%) and after (15, 79%) ROL submission. Conclusions: In-person SLEs occurred during Match 2023. All PDs considered SLEs optional which was trusted by most applicants. Attendance at in-person SLEs influenced applicants' ROLs; however, finances and logistics impaired applicant attendance. Further work is needed to appreciate SLE implications and ensure equitable residency recruitment.

The value of patient-reported outcomes to predict for symptom burden and health-related quality of life after chemoradiation for cervical cancer: A prospective study.

PURPOSE: Cervical cancer patients undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected patient-reported outcomes(PROs) to determine characteristics predictive of poor treatment experience. METHODS: Between 2021-2023, we prospectively collected PROs from cervical cancer patients undergoing definitive chemoradiation. EORTC-QLQ-C30 and EORTC-QLQ-CX24 were completed at baseline(BL) and at the end of treatment(EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, disease-specific factors, and baseline financial toxicity, depression, social function, and emotional function. ROC analysis provided appropriate predictive cut-off values. Univariable(UVA) and multivariable(MVA) linear regression analyses were performed. RESULTS: Fourty-nine patients completed BL and EOT questionnaires. Median age was 43 (range, 18-85). Most patients (59%) had stage III disease. Baseline financial toxicity ≥66.7, depression ≥66.7, social function ≤50 and emotional function ≤58 on the EORTC linear transformed scale of 0-100 were significant predictors for poor treatment experience (p≤0.04) based on ROC analysis. On MVA poor BL social function was associated with reduced EOT HRQOL (ß-9.3,_95%CI_-16.1_to_-2.6,_p<0.008), decreased physical function (ß-24.4,_95%CI_-36.3_to_-12.6,_p<0.001), and high symptom burden_(ß26.9,_95%CI_17.5_to_36.3,_p<0.001). Earlier disease stage predicted for decreased symptom burden_(ß-6.7,_95%CI_-13.1_to_-0.3,_p=0.039). BL financial toxicity was a significant predictor on UVA (p=0.001-0.044) and showed a significant interaction term on MVA (p=0.024-0.041) for all three domains of poor treatment experience. Demographic and treatment-related factors were not predictive. CONCLUSION: Cervical cancer patients with poor baseline social function or high financial toxicity were at-risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.

Disease site specialization in the academic radiation oncology workforce: Evidence of gender differences.

PURPOSE: As some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of woman representation of all specialties, and no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO). METHODS AND MATERIALS: Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. Chi-square analyses were conducted to assess differences between proportions of women faculty treating each disease site. RESULTS: Of 1,337 ARO faculty, 408 (30.5%) were identified as women. Breast, gynecology, and pediatrics had the largest proportions of women faculty (all>40%, P<0.001). A majority (53%, P<0.001) of women ARO faculty treated breast. Genitourinary (GU), thoracic, and head and neck had the smallest proportions of women faculty (all<25%, P<0.001). Women ARO faculty were twice as likely to treat breast and gynecological malignancies compared to men (risk ratio [RR] with 95% confidence interval [CI]: 2.01 [1.75-2.50], P<0.001 and RR [CI]: 2.06 [1.72-2.79], P<0.001, respectively). Men ARO faculty were three times more likely to treat GU cancer as compared to women faculty (RR [CI]: 0.40 [0.34-0.48], P<0.001). There was no difference in the mean number of disease sites treated between women and men ARO faculty (2.63 vs. 2.53, P=0.29). CONCLUSION: Gender differences in disease site specialization were observed in ARO. Future research into the drivers of disease site selection should be explored.

Deep learning-based automatic segmentation of cardiac substructures for lung cancers.

PURPOSE: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures. MATERIALS AND METHODS: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. The auto-segmented contours were evaluated by comparing them with manually drawn contours in terms of Dice similarity coefficient (DSC) and dose metrics extracted from clinical plans. An independent dataset of 42 patients was used for subjective evaluation of the auto-segmentation model by 4 physicians. RESULTS: The average DSCs were 0.95 (+/- 0.01) for the whole heart, 0.91 (+/- 0.02) for 4 chambers, 0.86 (+/- 0.09) for 6 great vessels, 0.81 (+/- 0.09) for 4 valves, and 0.60 (+/- 0.14) for 4 coronary arteries. The average absolute errors in mean/max doses to all substructures were 1.04 (+/- 1.99) Gy and 2.20 (+/- 4.37) Gy. The subjective evaluation revealed that 94% of the auto-segmented contours were clinically acceptable. CONCLUSION: We demonstrated the effectiveness of our nnU-Net model for delineating cardiac substructures, including coronary arteries. Our results indicate that this model has promise for studies regarding radiation dose to cardiac substructures.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.