Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials.

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

The Perceived Usability of Virtual Visits Among Black Adults' Receiving Oncology Care: A Qualitative Analysis.

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.

Organ-aware CBCT enhancement via dual path learning for prostate cancer treatment.

BACKGROUND: Cone-beam computed tomography (CBCT) plays a crucial role in the intensity modulated radiotherapy (IMRT) of prostate cancer. However, poor image contrast and fuzzy organ boundaries pose challenges to precise targeting for dose delivery and plan reoptimization for adaptive therapy. PURPOSE: In this work, we aim to enhance pelvic CBCT images by translating them to high-quality CT images with a particular focus on the anatomical structures important for radiotherapy. METHODS: We develop a novel dual-path learning framework, covering both global and local information, for organ-aware enhancement of the prostate, bladder and rectum. The global path learns coarse inter-modality translation at the image level. The local path learns organ-aware translation at the regional level. This dual-path learning architecture can serve as a plug-and-play module adaptable to other medical image-to-image translation frameworks. RESULTS: We evaluated the performance of the proposed method both quantitatively and qualitatively. The training dataset consists of unpaired 40 CBCT and 40 CT scans, the validation dataset consists of 5 paired CBCT-CT scans, and the testing dataset consists of 10 paired CBCT-CT scans. The peak signal-to-noise ratio (PSNR) between enhanced CBCT and reference CT images is 27.22 ± 1.79, and the structural similarity (SSIM) between enhanced CBCT and the reference CT images is 0.71 ± 0.03. We also compared our method with state-of-the-art image-to-image translation methods, where our method achieves the best performance. Moreover, the statistical analysis confirms that the improvements achieved by our method are statistically significant. CONCLUSIONS: The proposed method demonstrates its superiority in enhancing pelvic CBCT images, especially at the organ level, compared to relevant methods.

Sociodemographic Inequities in Telemedicine Use Among US Patients Initiating Treatment in Community Cancer Centers During the Ongoing COVID-19 Pandemic, 2020-2022.

PURPOSE: Although telemedicine was seen as a way to improve cancer care during the coronavirus disease (COVID-19) pandemic, there is limited information regarding inequities in its uptake. This study assessed sociodemographic factors associated with telemedicine use among patients initiating treatment for 20 common cancers. METHODS: This retrospective cohort study used deidentified electronic health record-derived patient data from a nationwide network of community cancer practices, linked to area-level Census information. We included adults (age 18 years and older) who initiated first-line systemic cancer treatment between March 2020 and December 2022 (follow-up through March 2023). Exposures include race/ethnicity, insurance status, and area-level social determinants of health (eg, block group socioeconomic status [SES]). The outcome was telemedicine use within 90 days after treatment initiation. Associations were examined using logistic regression models adjusted for age, sex, performance status, stage, and cancer type. RESULTS: This study included 36,993 patients (48.6% women; median age, 69 years), of whom 15.1% used telemedicine services. Black (12.2%; odds ratio [OR], 0.78 [95% CI, 0.70 to 0.88]) and uninsured (9.2%; OR, 0.59 [95% CI, 0.48 to 0.73]) patients were less likely to use telemedicine services than their White and well-insured counterparts (14.5% and 15.0%, respectively). Patients in rural (9.7%; OR, 0.54 [95% CI, 0.46 to 0.57]), suburban (11.8%; OR, 0.67 [95% CI, 0.61 to 0.74]), and low SES areas (9.9%; OR, 0.39 [95% CI, 0.35 to 0.43]) were less also likely to use telemedicine than their counterparts in urban (16.6%) or high SES (21.6%) areas. CONCLUSION: Nearly one sixth of patients initiating cancer treatment during the pandemic used telemedicine, but there were substantial inequities. The proliferation of telemedicine may perpetuate cancer care inequities if marginalized populations do not have equitable access.

Considerations for pooling real-world data as a comparator cohort to a single arm trial: a simulation study on assessment of heterogeneity.

BACKGROUND: Novel precision medicine therapeutics target increasingly granular, genomically-defined populations. Rare sub-groups make it challenging to study within a clinical trial or single real-world data (RWD) source; therefore, pooling from disparate sources of RWD may be required for feasibility. Heterogeneity assessment for pooled data is particularly complex when contrasting a pooled real-world comparator cohort (rwCC) with a single-arm clinical trial (SAT), because the individual comparisons are not independent as all compare a rwCC to the same SAT. Our objective was to develop a methodological framework for pooling RWD focused on the rwCC use case, and simulate novel approaches of heterogeneity assessment, especially for small datasets. METHODS: We present a framework with the following steps: pre-specification, assessment of dataset eligibility, and outcome analyses (including assessment of outcome heterogeneity). We then simulated heterogeneity assessments for a binary response outcome in a SAT compared to two rwCCs, using standard methods for meta-analysis, and an Adjusted Cochran's Q test, and directly comparing the individual participant data (IPD) from the rwCCs. RESULTS: We found identical power to detect a true difference for the adjusted Cochran's Q test and the IPD method, with both approaches superior to a standard Cochran's Q test. When assessing the impact of heterogeneity in the null scenario of no difference between the SAT and rwCCs, a lack of statistical power led to Type 1 error inflation. Similarly, in the alternative scenario of a true difference between SAT and rwCCs, we found substantial Type 2 error, with underpowered heterogeneity testing leading to underestimation of the treatment effect. CONCLUSIONS: We developed a methodological framework for pooling RWD sources in the context of designing a rwCC for a SAT. When testing for heterogeneity during this process, the adjusted Cochran's Q test matches the statistical power of IPD heterogeneity testing. Limitations of quantitative heterogeneity testing in protecting against Type 1 or Type 2 error indicate these tests are best used descriptively, and after careful selection of datasets based on clinical/data considerations. We hope these findings will facilitate the rigorous pooling of RWD to unlock insights to benefit oncology patients.

Racial and Ethnic Inequities in US Oncology Clinical Trial Participation From 2017 to 2022.

Importance: There is increasing recognition from regulatory agencies that racial and ethnic representation in clinical trials is inadequate and linked to health inequities. The extent of racial inequities in clinical trial participation is unclear because prior studies have synthesized enrollment data from published trials, which often do not report participant race and ethnicity. Objective: To evaluate racial and ethnic inequities in oncology clinical trial participation in a contemporary cohort of patients with cancer before and during the COVID-19 pandemic. Design, Setting, and Participants: This cohort study used a nationwide electronic health record-derived deidentified database, which includes data for approximately 280 US cancer clinics (approximately 800 sites of care). The study included Latinx, non-Latinx Black (hereinafter, Black), and non-Latinx White (reference; hereinafter, White) patients aged 18 years or older who had been diagnosed with advanced non-small cell lung cancer, metastatic colorectal cancer, metastatic breast cancer, multiple myeloma, or metastatic pancreatic cancer between January 1, 2017, and June 30, 2022 (follow-up through December 31, 2022). Data analysis was performed between August 1, 2022, and February 7, 2023. Exposures: Electronic health record-documented race and ethnicity. Main Outcomes and Measures: The main outcome was oncology trial participation (ie, receipt of a clinical study drug). Stratified cause-specific hazard models were used to estimate adjusted hazard ratios (HRs) and 95% CIs for likelihood of participation. Participation was assessed overall, by cancer type, and by period of diagnosis (2017-2019 vs 2020-2022). Results: Of the 50 411 patients in this study, 28 878 (57.3%) were women and 21 533 (42.7%) were men. Black and Latinx patients were younger than White patients, with a median age of 65 (IQR, 57-72), 64 (IQR, 54-73), and 68 (IQR, 60-76) years, respectively. Oncology trial participation was lower among Black patients (307 of 6912 [4.4%]) and Latinx patients (166 of 3973 [4.2%]) relative to White patients (2858 of 39 526 [7.2%]) over the entire study period. Inequities in participation were observed across the 5 cancer types studied, with notably large inequities observed among Black patients (HR, 0.54 [95% CI, 0.36-0.81]) and Latinx patients (HR, 0.46 [95% CI, 0.27-0.77]) with metastatic pancreatic cancer. Moreover, inequities between Black and White patients in terms of participation widened among those diagnosed in the COVID-19 era (2020-2022: HR, 0.49 [95% CI, 0.40-0.60] vs 1.00 [95% CI, 0.93-1.09]) relative to those diagnosed before the pandemic (2017-2019: HR, 0.61 [95% CI, 0.53-0.70] vs 1 [reference]). Conclusions and Relevance: The findings of this cohort study suggest that oncology trial participation was lower among Black and Latinx patients relative to White patients across all 5 cancer types examined. These findings, including potentially widening inequities in the COVID-19 era, support the need for regulatory guidance to improve enrollment of participants from historically excluded racial and ethnic populations in clinical trials.

Associations With Virtual Visit Use Among Patients Receiving Radiation Therapy.

Purpose: The objective of this study was to test for patient characteristics associated with virtual versus office visits among radiation oncology patients. Methods and Materials: Using the electronic health record, we extracted encounter data and corresponding patient information for the 6 months before and 6 months of COVID-19-enabled virtual visits (October 1, 2019, to March 22, 2020 vs March 23, 2020, to September 1, 2020) at a National Cancer Institute-Designated Cancer Center. Encounters during COVID-19 were categorized as in-person or virtual visits. We compared patient demographic variables including race, age, sex, marital status, preferred language, insurance status, and tumor type during the pre-COVID-19 period as a baseline versus during the COVID-19 period. Multivariable analyses examined associations between these variables and virtual visit use. Results: We analyzed 4974 total encounters (2287 before COVID-19 and 2687 during COVID-19) for 3960 unique patients. All (100%) pre-COVID-19 encounters were in-person. During COVID-19, 21% of encounters were via virtual visits. There were no differences identified in pre- versus during-COVID-19 patient characteristics. However, we found significant differences in patient characteristics for in-person versus virtual encounters during COVID-19. On multivariable analysis, virtual visit use was less common among patients who were Black versus White (odds ratio [OR], 0.75; 95% CI, 0.57-0.99; P = .044) and not married versus married (OR, 0.76; 95% CI, 0.59-0.98; P = .037). Patients with head and neck (OR, 0.63; 95% CI, 0.41-0.97; P = .034), breast (OR, 0.36; 95% CI, 0.21-0.62; P ≤ .001), gastrointestinal/abdominal (OR, 0.31; 95% CI, 0.15-0.63; P = .001), or hematologic malignancy (OR, 0.20; 95% CI, 0.04-0.95; P = .043) diagnoses were less likely to be scheduled for virtual visits relative to patients with genitourinary malignancy. No Spanish-speaking patients engaged in a virtual visit. We did not identify differences in the insurance status or sex of patients scheduled for virtual visits. Conclusions: We found significant differences in virtual visit use by patient sociodemographic and clinical characteristics. Further investigation into implications of differential virtual visit use including social and structural determinants and subsequent clinical outcomes is indicated.

Bladder only versus bladder plus pelvic lymph node chemoradiation for muscle-invasive bladder cancer.

BACKGROUND: Bladder-sparing chemoradiation therapy (CRT) is a definitive first-line treatment for muscle-invasive bladder cancer. The optimal radiotherapy target volume, either bladder-only (BO) or bladder plus pelvic lymph nodes (BPN), remains unclear. METHODS: We identified 2,104 patients in the National Cancer Database with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with CRT following maximal transurethral resection of bladder tumor from 2004 to 2016. The exposure of interest was BO vs. BPN treatment volume. The primary outcome was overall survival (OS), compared between groups using Kaplan-Meier and multivariable Cox proportional hazards. Sensitivity analysis tested an interaction term for clinical T stage (T2 vs. T3-4) and radiation modality (3-dimensional conformal radiotherapy vs. intensity modulated radiotherapy or proton therapy). Annual use of BO vs. BPN from 2004 to 2016 was compared using Cochran-Armitage test. RESULTS: A total of 578 patients were treated with BO and 1,526 patients treated with BPN CRT. There was a significant increase in BPN use from 2004 to 2016 (66.9%-76.8%, P < 0.0001). With a median follow-up of 6.2 years, there was no survival difference between groups: 5- and 10-year OS 27.4% (95% CI 23.4%-31.4%) in the BO group vs. 31.9% (95% CI 29.3%-34.6%) in the BPN group, and 13.1% (95% CI 9.7%-17.1%) in the BO group vs. 13.2% (95% CI 10.6%-16.0%) in the BPN group, respectively (log-rank P = 0.10). On multivariable analysis, there was no significant association between BPN and OS (adjusted HR 0.90, 95% CI 0.81-1.02, P = 0.09). On sensitivity analysis, we found no differential effect by T stage or radiation modality. CONCLUSION: Use of pelvic lymph node radiation has risen in the US but may not impact long-term survival outcomes for patients with node-negative muscle-invasive bladder cancer (MIBC). Optimizing radiation treatment volumes for CRT for MIBC will be important to study under prospective trials, such as the SWOG/NRG 1806.

Improving Diversity in Clinical Trials by Using Real-world Data to Define Eligibility Criteria.

This Viewpoint discusses the need for thoughtful, modernized eligibility criteria with equity prioritization in clinical trials.

Exposure to US Cancer Drugs With Lack of Confirmed Benefit After US Food and Drug Administration Accelerated Approval.

This cross-sectional study evaluates patient exposure to oncology drugs withdrawn from the US Food and Drug Administration (FDA) Accelerated Approval program.

Prospective 5-Year Analysis of the United States Radiation Oncology Job Market Using the ASTRO Career Center Website.

PURPOSE: We provide 5-year results of prospectively collected radiation oncology (RO) job opportunities and a longitudinal assessment of RO graduate numbers within the United States. METHODS AND MATERIALS: Full-time domestic RO job opportunities were collected and categorized using the American Society for Radiation Oncology (ASTRO) Career Center from July 1, 2016 to June 30, 2021. A chi-square test was used to compare regional job availability by city size and position type. The corresponding number of graduating United States (US) RO residents (2017-2021) was collected. US census and Medicare database resources were used as comparators for population and workforce estimates. Pearson's correlation coefficients were used to examine changes in data over time and a 2-tailed t test was used to assess for statistical significance. RESULTS: Over the 5-year study period, 819 unique job offers were posted, compared with 935 RO graduates (0.88 total jobs-to-graduates ratio). Most jobs were nonacademic (57.6%), located in populated areas >1 million (57.1%; median: 1.57M), with the largest proportion of jobs seen in the South region (32.4%). One-third of academic jobs were located at satellites. Regional differences were seen between academic versus nonacademic job availability (P < .01), with the highest proportion of academic jobs seen in the Northeast (60.3%) and the lowest in the Midwest (34.5%). Differences between regions were also observed for jobs in areas >1 million versus ≤1 million (P < .01), with the most jobs in areas >1 million seen in the West (64.6%) and the least in the South (51.3%). Regional job availability over time did not differ by position type (academic vs nonacademic) or population area size (P = .11 and P = .27, respectively). Annual graduate numbers increased with time (P = .02), with the highest percentage of graduates trained in the South (30.8%). Regional distribution of jobs versus graduates significantly differed (P < .01) with the lowest jobs-to-graduates ratio observed in the Northeast (0.67) and highest ratio in the West (1.07). Regional RO workforce estimates based on the 4336 radiation oncologists who were Medicare providers in 2020 were compared with total jobs and graduates by region with no difference observed between the distributions of the workforce and jobs (P = .39), but comparisons between the workforce and graduates were proportionally different (P < .01). The number of total jobs (vs graduates) per 10 million population in the Northeast, South, Midwest, and West were 30.2 (45.1), 21.0 (22.7), 30.6 (33.4), and 22.6 (21.2), respectively. CONCLUSIONS: This multiyear quantitative assessment of the RO job market and graduates identified fewer job opportunities than graduates overall in most regions, most notably in the Northeast. Regional differences were seen between available job type (academic vs nonacademic) and population size (>1 million vs ≤1 million). The findings are worrisome for trainee oversupply and geographic maldistribution. The number and distribution of RO trainees and residency programs across the US should be evaluated to minimize job market imbalance for future graduates, promote workforce stability, and continue to meet the future societal needs of patients with cancer.

Dynamic Cross-Task Representation Adaptation for Clinical Targets Co-Segmentation in CT Image-Guided Post-Prostatectomy Radiotherapy.

Adjuvant and salvage radiotherapy after radical prostatectomy requires precise delineations of prostate bed (PB), i.e., the clinical target volume, and surrounding organs at risk (OARs) to optimize radiotherapy planning. Segmenting PB is particularly challenging even for clinicians, e.g., from the planning computed tomography (CT) images, as it is an invisible/virtual target after the operative removal of the cancerous prostate gland. Very recently, a few deep learning-based methods have been proposed to automatically contour non-contrast PB by leveraging its spatial reliance on adjacent OARs (i.e., the bladder and rectum) with much more clear boundaries, mimicking the clinical workflow of experienced clinicians. Although achieving state-of-the-art results from both the clinical and technical aspects, these existing methods improperly ignore the gap between the hierarchical feature representations needed for segmenting those fundamentally different clinical targets (i.e., PB and OARs), which in turn limits their delineation accuracy. This paper proposes an asymmetric multi-task network integrating dynamic cross-task representation adaptation (i.e., DyAdapt) for accurate and efficient co-segmentation of PB and OARs in one-pass from CT images. In the learning-to-learn framework, the DyAdapt modules adaptively transfer the hierarchical feature representations from the source task of OARs segmentation to match up with the target (and more challenging) task of PB segmentation, conditioned on the dynamic inter-task associations learned from the learning states of the feed-forward path. On a real-patient dataset, our method led to state-of-the-art results of PB and OARs co-segmentation. Code is available at https://github.com/ladderlab-xjtu/DyAdapt.

Unsealed Source: Scope of Practice for Radiopharmaceuticals Among United States Radiation Oncologists.

Purpose: Our purpose was to determine the utilization of and barriers to implementation of radiopharmaceutical therapy (RPT) among U.S. radiation oncologists. Methods and Materials: An anonymous, voluntary 21-item survey directed toward attending radiation oncologists was distributed via social media platforms (Twitter, LinkedIn, Facebook, Student Doctor Network). Questions assessed practice characteristics, specific RPT prescribing patterns, RPT prescribing interest, and perceived barriers to RPT implementation. Nonparametric χ2 test was used for correlation statistics. Results: Of the 142 respondents, 131 (92.3%) practiced in the United States and were included for this analysis. Respondents were well balanced in terms of practicing region, population size served, practice setting, and years in practice. Forty-eight percent (n = 63) reported prescribing at least 1 RPT. An additional 7% (n = 8) participate in RPT administration without billing themselves. Among those that actively prescribed RPT, the mean cumulative cases per month was 4.2 (range, 1-5). The most commonly prescribed radionuclides were radium-223 (40%; mean 2.8 cases/mo), iodine-131 (18%; mean 2.3 cases/mo), yttrium-90 (13%; mean 3.4 cases/mo), "other" (8%), samarium-153 (6%; mean 1.0 cases/mo), and strontrium-89 and phosphorous-32 (2% each; mean 1.8 and 0.4 cases/mo, respectively). Of those who answered "other," lutetium-177 dotatate was most commonly prescribed (8%). No significant (P < .05) association was noted between practice type, practice location, years of practice, or practice volume with utilization of any RPTs. Most radiation oncologists (56%, n = 74) responded they would like to actively prescribe more RPT, although 27% (n = 35) were indifferent, and 17% (n = 22) said they would not like to prescribe more RPT. Perceived barriers to implementation were varied but broadly categorized into treatment infrastructure (44%, n = 57), interspecialty relations (41%, n = 53), lack of training (23%, n = 30), and financial considerations (16%, n = 21). Conclusions: Among surveyed U.S. radiation oncologists, a significant number reported prescribing at least 1 RPT. The majority expressed interest in prescribing additional RPT. Wide-ranging barriers to implementation exist, most commonly interspecialty relations, treatment infrastructure, lack of training, and financial considerations.

High Dose "HDR-Like" Prostate SBRT: PSA 10-Year Results From a Mature, Multi-Institutional Clinical Trial.

Purpose/Objectives: Although ample intermediate-term prostate stereotactic body radiotherapy (SBRT) outcomes have been reported, 10-year results remain relatively sparse. Materials/Methods: Eighteen institutions enrolled 259 low- and intermediate-risk patients. Median follow-up is 5.5 years, with 66 patients followed ≥ 10 years. This SBRT regimen specifically emulated an existing HDR brachytherapy dose schedule and isodose morphology, prescribed to 38 Gy/4 fractions, delivered daily by robotic SBRT, mandating > 150% dose escalation in the peripheral zone. Androgen deprivation therapy was not allowed, and a hydrogel spacer was not available at that time. Results: Median pre-SBRT PSA 5.12 ng/mL decreased to 0.1 ng/mL by 3.5 years, with further decrease to a nadir of < 0.1 ng/mL by 7 years, maintained through 10 years. Ten-year freedom from biochemical recurrence measured 100% for low-risk, 84.3% for favorable intermediate risk (FIR), and 68.4% for unfavorable intermediate (UIR) cases. Multivariable analysis revealed that the UIR group bifurcated into two distinct prognostic subgroups. Those so classified by having Gleason score 4 + 3 and/or clinical stage T2 (versus T1b/T1c) had a significantly poorer 10 year freedom from biochemical recurrence rate, 54.8% if either or both factors were present, while UIR patients without these specific factors had a 94.4% 10-year freedom from biochemical recurrence rate. The cumulative incidence of grade 2 GU toxicity modestly increased over time - 16.3% at 5 years increased to 19.2% at 10 years-- while the incidence of grade 3+ GU and GI toxicity remained low and stable to 10 years - 2.6% and 0%, respectively. The grade 2 GI toxicity incidence also remained low and stable to 10 years - 4.1% with no further events after year 5. Conclusion: This HDR-like SBRT regimen prescribing 38 Gy/4 fractions but delivering much higher intraprostatic doses on a daily basis is safe and effective. This treatment achieves a median PSA nadir of <0.1 ng/mL and provides high long-term disease control rates without ADT except for a subgroup of unfavorable intermediate-risk patients.

Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor.

PURPOSE: Management paradigms now allow for systemic targeted drugs before central nervous system (CNS)-directed radiation therapy (RT) in selected asymptomatic patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). We aimed to quantify how novel targeted agents with improved CNS activity, such as second-generation anaplastic lymphoma kinase (ALK) inhibitors (eg, alectinib), might affect the role of CNS-directed RT. METHODS AND MATERIALS: This retrospective, observational, real-world, patterns-of-care study used a nationwide, electronic, health record-derived, de-identified, longitudinal database. A random sample of patients with ALK+ advanced NSCLC and BM on first-line ALK-inhibitor monotherapy between January 1, 2014 and August 31, 2019 were included. Using an index date of the first instance of BM, the outcome was brain-directed local treatment within 4 months. Trends over time were reported and tested using multivariable modified Poisson regression with robust error variance, including an indicator during or after 2017 (when alectinib was approved). RESULTS: Of the 352 included patients, 146 had BM. In addition, 104 patients received CNS-directed local therapy, and 42 did not. The majority of patients (89.4%) were treated with RT alone. Of those receiving RT, stereotactic radiosurgery monotherapy was the most common (53%), followed by whole brain RT alone (39%). On multivariable analysis, patients who had their first BM during or after 2017 had a decreased rate of receiving local BM treatment versus those before 2017 with an adjusted incidence rate ratio of 0.63 (95% confidence interval [CI], 0.41-0.95; P = .026). We found no change in the proportion of BM treated with whole brain RT during or after 2017 versus before (adjusted incidence rate ratio: 0.70; 95% CI: 0.24-2.06; P = .517). CONCLUSIONS: We found decreasing use of CNS-directed RT in patients with NSCLC with new BM on first-line ALK inhibitors. Clinical outcomes for these patients require continued investigation, because physicians may become increasingly comfortable deferring upfront local therapy for BM in lieu of novel targeted agents with improved CNS activity.

Financial Toxicity as an End Point in Prospective Clinical Trials Involving Radiation Therapy.

Prior research, predominately retrospective, has increased awareness that patients with cancer are at elevated risk for financial toxicity (FT). Radiation therapy (RT) can be particularly disruptive due to weeks of daily treatments. Yet, FT in patients receiving RT is less studied, and the extent to which FT has been incorporated as an end point in prospective clinical trials involving RT is unknown. Clinicaltrials.gov was queried to identify all observational or interventional studies from 2001 to 2020 wherein RT was administered for cancer. Studies with primary, secondary, or exploratory FT end points were identified through keyword search. For trials incorporating FT outcomes, pertinent study characteristics were collected. Detailed information regarding FT measures was recorded. Descriptive statistics, including frequency counts and proportions, were performed. The overall rate of inclusion of FT end points was calculated, and rates over 5-year intervals were compared using the χ2 test (α = 0.05). Overall, 10,550 studies involving RT were identified, of which 88 reported FT end points (0.8%). Included FT end points were typically secondary (78%), with just 15 studies (17%), including primary end points. Notably, only 19 studies (22%) reported a standalone FT end point. The majority measured FT as part of a larger quality of life (QoL) questionnaire. The rate of inclusion of FT end points significantly increased over time from 0.1% from 2001 to 2005 to 1.5% from 2016 to 2020, (P < .0001). FT is a major stressor for patients with cancer, yet even after a relative increase over time, the absolute rate of inclusion of FT end points remains low among RT-based trials. When included, FT outcomes were typically a single question within a QoL assessment not validated as a standalone measure of FT, preventing meaningful study and inference. To characterize and mitigate this burden more accurately, future prospective studies should include FT end points with greater frequency.