Radiation Oncology Clinical Trials Research Articles

Dummy run for planning of isotoxic dose-escalated radiation therapy for glioblastoma used in the PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06)

BackgroundThe PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. MethodsA suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). ResultsMedian DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1–391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5–142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00–0.69) and the right lacrimal gland (median 0.59, range 0.42–0.78). ConclusionsThe deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registrationNCT05871021

Abstract A078: Exploring the unexplored: Clinical trial investigator perspectives of disparities in racial/ethnic minority participation in oncology clinical trials

Abstract Purpose: Thirty years after the NIH Revitalization Act, racial/ethnic minority (REM) patients continue to be underrepresented in oncology clinical trials with disproportionately low rates of participation compared to non-Hispanic whites. Health system, patient, and medical provider factors contribute to this disparity. However, little is known about clinical trial investigator perspectives of REM participation in oncology clinical trials and their contribution to this disparity. To our knowledge there are no published quantitative studies that have investigated this important and actionable topic. Methods: We conducted a cross-sectional, anonymous, pilot survey of medical, radiation, and surgical oncology clinical trial investigators at a large academic center. Over a 5-week period, 107 individuals received a survey. The survey assessed 6 domains regarding disparities in REM participation in clinical trials: investigator knowledge, attitudes, and prior training on the topic, self-efficacy and motivation for improvement in addressing known disparities, and perceived barriers to REM participation in clinical trials. Modified, previously validated items were used when possible. Results: Of 60 respondents (56% response rate), 33 were male (55%). Thirty-six identified as non-Hispanic white (60%), 16 as Asian (27%), 1 as Hispanic/Latinx (2%), and 7 as other/prefer not to state (11%). Respondents included 49 medical (82%), 7 surgical (11%), and 4 radiation oncologists (7%). Average time as a clinical trial investigator was 14 years (2-40). Respondents opened an average of 2 clinical trials as primary investigator in the past year (0-10). A majority (83%) strongly agreed disparities exist in REM clinical trial participation and that the resulting lack of diversity is problematic (75%). However, only 34% strongly agreed they consider ways to achieve racial/ethnic diversity among trial participants when designing clinical trials, or ways to specifically enroll REM patients (28%). Respondents most commonly cited patient rather than health system factors as barriers to REM participation in clinical trials. Notably, nearly half (45%) agreed that lack of REM participation is a problem they cannot directly address. A majority (83%) endorsed wanting to improve their consideration of barriers to REM participation as they design clinical trials and wanted help to improve (86%). Conclusion: Our results suggest there is awareness among clinical trial investigators at our academic center of disparities in REM participation in oncology clinical trials and the problem this poses to cancer care. There is also a pervasive view that primary barriers to REM participation are patient factors, and investigators do not feel they can directly address these. Nonetheless, there is motivation among investigators to improve in their ability to consider barriers to REM participation as they design clinical trials. Interventions that improve investigators’ self-efficacy for addressing barriers to REM participation in clinical trials, especially patient level barriers, are needed. Citation Format: Natalie P. Bransky, Anne M. Walling, John A. Glaspy, Maria Garcia-Jimenez. Exploring the unexplored: Clinical trial investigator perspectives of disparities in racial/ethnic minority participation in oncology clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A078.

INNV-03. INSTITUTION SPECIFIC CLINICAL TRIAL MATCHING WEB APPLICATION FOR CENTRAL NERVOUS SYSTEM METASTASES

Abstract BACKGROUND Current clinical trials evaluating treatment options for patients with brain metastases are tailored to a number of clinical factors, including type of underlying cancer, number of brain metastases, size and volume of brain metastasis, prior treatment, and genomic characterization. A multidisciplinary brain metastasis tumor board was established at our institution in January 2023. Subsequently, an institution specific clinical trial matching web application was developed in-house to screen and match subjects for trials accruing at our institution. METHODS We reviewed our institution’s list of phase III surgical, radiation, and medical oncology clinical trials specific for brain metastasis to identify the most discriminating inclusion criteria that can be used as a basis for branching and differentiation. These disease specific trials were then individually assessed according to these criteria and these results were populated in a common separated value (CSV) file. RESULTS A web application was created using Python for analysis of the CSV and incorporating branching logic. HTML, CSS, and JavaScript were used for building the webpage interface. The web application is hosted on our institutional server and can be utilized to search available clinical trials for each patient being presented during tumor board. CONCLUSION We developed an institution specific web application that can be used to screen patients for various clinical trials. By developing this application and hosting it internally, we are able to edit the components at our discretion. The methodology for this web-build can be applied to other disease sites or institutions. This web application is useful for screening our institution’s clinical trial portfolio to identify potential gaps, and can also be used to avoid competing trials. This web application significantly reduces the time to identify protocol eligibility and has increased clinical trial enrollment.

Characteristics of chief investigators and principal investigators in Australian and New Zealand radiation oncology clinical trials.

Globally, the research community is coming to realise the need for diversity, equity and inclusion (DEI) amongst research teams and leadership. Diverse teams reduce homogeneous 'group think', propagate innovation, propound support for broader more representative research and facilitate the recruitment of patients from diverse backgrounds. Given the above, this study aims to retrospectively examine the characteristics of chief investigators (CI) and principal investigators (PI) in past and present Australian and New Zealand radiation oncology clinical trials. Data on CI and PI characteristics were attained from the Trans Tasman Radiation Oncology Group (TROG) website as well as archived master database files provided by the TROG Scientific Committee. Data included CI and PI discipline, clinical trial activation date, institution type (private vs. public) and geographical location if in Australia. Australian and New Zealand health practitioner registration agency websites were used to determine the registered sex of the CIs and PIs and their years of experience. One hundred and twenty TROG clinical trials have been initiated by 134 CIs from 1989 to 2022 and 463 TROG clinical trials have been opened by 465 PIs at their respective institutions from 2000 to 2022. Most TROG trial investigators have been radiation oncologists and those with over 10 years of experience. Only one in five trials and one in three trials have been led by female PIs and CIs, respectively. Investigators have largely been affiliated with public institutions, with only one in 100 CIs and one in eight PIs being affiliated with the private sector. TROG members from regional and rural areas in Australia have not been engaged as investigators, with all CIs and most PIs affiliated with metropolitan institutions. This study highlights the gaps in diversity amongst CIs and PIs in TROG clinical trials. Further unpacking and understanding of issues related to CI and PI diversity are important to inform initiatives to improve researcher, leadership and patient diversity in future TROG clinical trials.

Racial and Ethnic Demographic Reporting in Phase 2 Proton Therapy Clinical Trials: A Review.

Equitable inclusion of racial and ethnic participation in clinical trials is crucial to improving disparities in health care, especially for historically marginalized populations. Our study aims to describe the racial and ethnic demographics of patients enrolled in published phase 2 clinical trials involving proton therapy in the United States. Published manuscripts were identified in PubMed, Embase, World of Science, and Cochrane. Phase 2 trials evaluating proton therapy for US patients were included. For each article in the study, data were collected comprising authors, title, and publication year, and clinical trial numbers were verified. Additional data included tumor site, primary institution, sample size, reported race/ethnicity, and raw number/percentile of race/ethnicity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used. Overall, 970 titles were identified; 636 remained after duplicate screening, and 75 full-text articles were assessed. We identified 38 eligible manuscripts for inclusion comprising 2648 patients. Only 15 (39%) of the publications reported race/ethnicity. Of these, 8 (21%) and 10 (26%) documented Hispanic or Black trial participants, respectively; however, only 6 (16%) documented trial participation for both Hispanic and Black patients. Of the 1409 patients with a documented race/ethnicity, 89.0% (n = 1254) were non-Hispanic white, 5.3% (n = 75) were Black, and 2.2% (n = 31) were Hispanic. Other and unknown race/ethnicity comprised the remaining patients (3.5%; n = 49). We identified underreporting of demographic data in published phase 2 proton therapy trials, which unfortunately mirrored underreporting for cancer drug clinical trials. We also noted dramatic Black and Hispanic patient underrepresentation across the trials in which race and ethnicity are reported. Findings highlight the urgent need to identify and address barriers to proton therapy trials for Black and Hispanic patients ensuring clinical trials in radiation oncology are representative of the patients seen in clinical practice.

Quality improvements in radiation oncology clinical trials.

Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use of artificial intelligence in treatment planning. Informatics technology has improved, and departments have become geographically transparent integrated through informatics bridges creating an economy of scale for the planning and execution of advanced technology radiation therapy. This serves to provide consistency in department habits and improve quality of patient care. Improvements in normal tissue sparing have further improved tolerance of treatment and allowed radiation oncologists to increase both daily and total dose to target. Radiation oncologists need to define a priori dose volume constraints to normal tissue as well as define how image guidance will be applied to each radiation treatment. These process improvements have enhanced the utility of radiation therapy in patient care and have made radiation therapy an attractive option for care in multiple primary disease settings. In this chapter we review how these changes have been applied to clinical practice and incorporated into clinical trials. We will discuss how the changes in clinical practice have improved the quality of clinical trials in radiation therapy. We will also identify what gaps remain and need to be addressed to offer further improvements in radiation oncology clinical trials and patient care.

Hypofractionation in Breast Cancer Radiotherapy Across World Bank Income Groups: Results of an International Survey.

Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use. An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models. One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively. Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.

A Systematic Review Evaluating Racial and Ethnic Demographic Reporting for Patients Enrolled on Prospective Phase II Clinical Trials of Proton Therapy

<h3>Purpose/Objective(s)</h3> Equitable inclusion of racial and ethnic participation in clinical trials is crucial to improving disparities in healthcare, especially for historically marginalized populations. However, a recent review noted a prevalence in underreporting of racial and ethnic demographics in published studies, with Hispanic and Black representation recorded in 10% and 38.2% of cancer drug clinical trials and representing 3.1% and 6.1% of trial participants. Proton therapy relies on clinical investigations to guide treatment protocols; yet, few publications have investigated their demographic composition. We aimed to describe the racial and ethnic demographics of patients enrolled on published phase II U.S. clinical trials involving proton therapy. <h3>Materials/Methods</h3> Published manuscripts were identified in PubMed, Embase, World of Science, and Cochrane. Phase II trials evaluating proton therapy for patients in the United States were included. For each article included, data were collected on authors, title, and publication year; clinical trial numbers were verified. Additional data included tumor site, primary institution, sample size, reported race/ethnicity data, and raw number/percentile of race/ethnicity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used for reporting. <h3>Results</h3> Overall, 970 titles were identified; 636 remained after duplicate screening; and 75 full-text articles were assessed. Ultimately, we identified 38 eligible manuscripts for inclusion with a total 2,648 patients. Only 15 (39%) of the publications reported race/ethnicity. Of these 38, 8 (21%) and 10 (26%) documented Hispanic or Black representation of trial participants, respectively. Moreover, 6 (16%) documented both Hispanic and Black representation in trial participants. Of 1,409 patients with documented race/ethnicity, 89.0% (n=1,254) were non-Hispanic white, 5.3% (n=75) were Black, and 2.2% (n=31) were Hispanic. Other and unknown race/ethnicity comprised the remaining patients (3.5%; n=49). <h3>Conclusion</h3> In this analysis, we identified underreporting of demographic data in published phase II proton therapy trials, unfortunately mirroring underreporting for cancer drug clinical trials. We also note dramatic Black and Hispanic underrepresentation across the trials in which race and ethnicity are reported. Findings highlight the urgent need to identify and address barriers to proton therapy trials for Black and Hispanic patients so that clinical trials in radiation oncology are representative of patients seen in clinical practice.

Factors that Influence a Woman's Decision to Enroll in Breast Cancer Clinical Trials – Implications on How to Improve Minority Enrollment and Retention

<h3>Purpose/Objective(s)</h3> Black women with breast cancer often present with more advanced and aggressive disease when compared to White women, resulting in a relative increased risk of mortality. Despite this disparity, Black women remain severely underrepresented in breast cancer clinical trials. We aimed to characterize the important psychosocial factors that influence a woman's decision to enroll in a radiation oncology clinical trial. <h3>Materials/Methods</h3> With IRB approval, a questionnaire adapted from two pre-validated surveys investigating psychosocial factors influencing clinical trial enrollment was administered to women with curable breast cancer treated with radiation therapy at four different sites within a university medical system where all patients are screened for clinical trial eligibility and offered enrollment. Eligible participants were administered the survey during a single follow-up visit. Chi-square tests and a Mann-Whitney U test were used to assess associations or differences between the populations. <h3>Results</h3> From August 2020-February 2022, 148 women completed the survey, the majority of which were located at community sites (77%) and were diagnosed with early-stage disease (I:57%; II:32%). Over half (58%) of the women were employed, had some collegiate-level education (82%) and the median income of the entire cohort was $98,845. Thirty-six women (24.3%) self-identified as being Black. When compared to non-Black (predominantly White, 70%) patients, Black women had a lower median income (p<0.001) and a lower median Charlson Comorbidity Index (CCI; p=0.024). On the survey, Black women reported they were less likely to have been asked to participate in a clinical trial (p=0.005), were more likely to agree with statements regarding research harming minorities (p<0.001), hiding information from participants (p=0.024) or research providing unwanted health information (p<0.001). In this patient population, religious beliefs have an important influence in Black women choosing to participate in a clinical trial when compared to White women (p=0.002). <h3>Conclusion</h3> This data suggests a level of distrust among Black women against research that may hinder enrollment into clinical trials. We are further characterizing these important factors through focus groups, with a goal of designing interventions to help with clinical trial recruitment, particularly in patients of color.

Characteristics of Chief Investigators of Radiation Oncology Clinical Trials in Australia and New Zealand

<h3>Purpose/Objective(s)</h3> The Chief Investigator (CI) is the individual responsible for the overall development, conduct and reporting of a clinical trial.¹ Research demonstrates that diverse teams – composed of individuals of varying genders, cultures, ethnicities, training, and expertise – tend to outperform a homogenous group of highest performing individuals due to their collective problem-solving and cognitive diversity.^2,3 Furthermore, having diverse individuals in clinical leadership roles can, via the flow-on effect, enhance recruitment of diverse trial investigators and participants.⁴ Given the value of realizing diversity in clinical trials, this study aims to retrospectively examine characteristics of CIs in past, present, and proposed Trans Tasman Radiation Oncology (TROG) clinical trials. <h3>Materials/Methods</h3> Data on CI characteristics were attained from the TROG website as well as archived files provided by the TROG scientific committee. Data included CCI discipline, experience (number of years post-fellowship), sex and institution (private vs public, metro vs regional). Descriptive statistics was employed to elucidate the data obtained. <h3>Results</h3> 118 TROG clinical trials have been led by 132 CIs since 1989. Less than 5% of studies had some missing CI data. Of 132 CIs, 86.4% (n = 114) were radiation oncologists (ROs), 9.9% (n = 12) were medical oncologists (MOs) and 3.0% (n = 4) were physicists. At the time in which they were appointed as a CI, 19.4% (n=25) had less than 5 years of experience post-fellowship, 31% (n=40) had between 5-10 years of experience post-fellowship and 49.6% (n=64) had more than 10 years of experience post-fellowship. There was a total of 26 female CIs (19.7%) and 105 male CIs (79.5%). The proportion of female CIs has trended upwards since the initiation of TROG trials; 1980-1989 (0%; n = 0), 1990-19999 (3.7%; n=1), 2000-2009 (25.6%; n = 11), 2010-2019 (27.5%; n=14), 2020-2029 (0% out of 6 initiated trials). In instances where there has been more than 1 CI assigned to a particular clinical trial (n = 17), female and male co-investigators made up 41.1% (n = 7), male only co-investigators made up 58.8% (n = 10) and female only co-investigators made up 0% (n=0). Trials have been conducted more often in the public (98.4%; n=122) compared to private setting (1.6%; n=2) and in metropolitan areas (82.9%, n=102) compared to regional areas (17.1%, n = 21). <h3>Conclusion</h3> Of 132 CIs who has led TROG clinical trials since 1989, most were ROs, those who have had over 10 years of experience (80.6%) and male (79.5%). Most CIs were affiliated with large public centers located in metropolitan areas. Further research is required to unpack and address the underlying reasons for the trends identified in this study such that optimal diversity amongst CIs can be achieved.

Quality of Life and Cognitive Function Evaluations and Interventions for Patients with Brain Metastases in the Radiation Oncology Clinic.

Simple SummaryBrain metastases (BMs) are the most common brain malignancy and are projected to increase in incidence over the coming decades. Historically, brain metastasis studies have focused on improving survival outcomes, but recently, the importance of evaluating health-related quality of life (HRQOL) and cognitive function has gained recognition. Although there is a myriad of validated HRQOL and cognitive assessments available in the radiation oncology clinic, there is an urgent need to identify tools tailored to patients with BMs and to adopt a uniform set of tests that measure HRQOL and cognition. This review presents various assessments for measuring HRQOL and cognitive function, current recommendations to improve standardization, and treatments known to preserve HRQOL and cognitive function.Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments in the radiation oncology clinic, but there is a lack of consensus regarding how to incorporate them in modern clinical practice. Herein, we present validated assessments for BM patients, current recommendations for future clinical studies, and treatment advances that have improved HRQOL and cognitive outcomes for BM patients.

Analyzing factors associated with clinical trial publication in radiation oncology

Clinical trials are considered the gold standard of clinical research and are sought in the medical literature for the goal of providing quality care. To identify factors associated with successful or unsuccessful publication of clinical trials in radiation oncology, data on trial characteristics were collected from the National Institutes of Health database on clinicaltrials.gov. To assess studies that had adequate time to accrue, trials between 2000 and 2005 were extracted by filtering for “radiation oncology”. Studies were excluded if they were incomplete, observational, Phase 4, or lacked sufficient method descriptions. Included studies underwent independent samples t-tests and Pearson Chi-Square bivariate analyses. 538 studies were candidates for analysis of clinical trial characteristics. United States (US) origin, multi-center sites, government funding, Phase III status, and randomized allocation were factors associated with increased publication rate. The number of study arms, study length, and number of participants were significantly greater in published trials. The review's results demonstrate potential barriers or facilitators to publication, and they suggest that publication status may be influenced by geographic, financial, and temporal characteristics of clinical trials. Understanding trial background factors that may impact publication improve data visibility and clinical advancements for all.

Implementation Strategies to Increase Clinical Trial Enrollment in a Community-Academic Partnership and Impact on Hispanic Representation: An Interrupted Time Series Analysis.

Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

Unnatural Selection? An Analysis of the Factors Associated with Unpublished Prospective Clinical Research in Radiation Oncology

<h3>Purpose/Objective(s)</h3> Factors associated with successful publication of clinical trials in radiation oncology have not yet been identified. We investigated whether publication bias was associated with factors such as funding source, size, phase of trial, study length, randomized design, and trial origin. <h3>Materials/Methods</h3> Clinical trials between 2000-2005 were extracted by filtering for "radiation oncology" using the National Institutes of Health database, clinicaltrials.gov. The dates were chosen to select for studies that had adequate time to accrue. Studies were excluded if they were incomplete, observational, Phase 4, or lacked sufficient descriptions of their methods. Included studies underwent independent samples <b>t-</b>tests and bivariate analyses to evaluate for publication status using the Pearson Chi-Square test through JMP. <h3>Results</h3> 538 studies were candidates for analysis. Multi-center trial sites, government funding, Phase III status, and randomized allocation were factors independently associated with increased likelihood of publication. The average number of study arms, lengths of the study in years, and number of participants were all significantly greater in trials that achieved publication. <h3>Conclusion</h3> The results of the review demonstrate publication bias. Less than half of the completed clinical trials in radiation oncology from 2000-2005 were published; Phase III status, multi-center sites, non-industry funding, randomized allocation larger participant pools, and a longer study duration all contributed to successful publication of those trials. Ascertaining facilitative and inhibitory factors to publication may facilitate transparency in medical literature and thereby improve clinical advancements and the scientific discovery process.

Enhancing Enrollment of Patients to Radiation Oncology Clinical Trials Across a Multi-Institutional Community-Academic Partnership: An Interrupted Time Series Analysis

<h3>Purpose/Objective(s)</h3> Although clinical trial enrollment is critical to development of new cancer therapies, < 5% of cancer patients in the United States enroll onto trials. Participation is particularly low among underrepresented minority groups, who comprise < 20% of enrollments. Community-academic partnerships have the potential to improve patient access to clinical trials, as most patients are treated for cancer in the community. In 2017, our tertiary cancer center began opening investigator-initiated clinical trials in radiation oncology in our community partner sites. This study evaluates demographics of patients enrolled, the effectiveness of strategies to address potential barriers to enrollment, and variation among physician enrollers. <h3>Materials/Methods</h3> All patients enrolled on radiation oncology therapeutic clinical trials at community-based partner sites from Q2 2018 – Q1 2021 were included in this analysis. Guided by Expert Recommendation for Implementing Change (ERIC), strategies to increase trial enrollment were implemented prior to Q2 2020, and included: 1) altered incentive structure (per-patient cost paid to partner site, leaderboards), 2) building a coalition of physicians in metastatic disease, and 3) practice facilitation. An interrupted time series analysis included a two-tailed student's t-test to compare mean trial enrollments per quarter pre- and post-implementation. Protocol deviations were assessed in quality assurance (QA) review. <h3>Results</h3> Among 52 total patients enrolled in community-based, partner sites, 28 (54%) identify as Black or Hispanic. The number of clinical trials open to enrollment pre- and post-implementation was 5 vs. 8, respectively, while the number of patients enrolled was 6 vs. 46, respectively, representing an overall increase in mean number of quarterly patient enrollments from 1 to 11 (<i>P</i> < 0.02). The patient enrollment trend (slope) also increased from -0.1 to 6.5 pre- and post-implementation. In the post-implementation period, the greatest number of enrollments occurred among patients treated for metastatic disease (n = 28). Among 49 radiation oncologists, 7 (14%) enrolled at least one patient, and total enrollments per physician ranged from 0-24. QA review revealed that patient-reported outcomes (PROs) were available only in English, resulting in missing data for secondary endpoints in 3 patients with Spanish as their preferred language. <h3>Conclusion</h3> These implementation strategies were associated with increased therapeutic trial enrollment in community-based partner sites. With high variation in enrollment between physicians and prior research suggesting limited impact of site-level financial incentives, qualitative research will further investigate non-financial incentives and other facilitators to clinical trial enrollment within community-academic partnerships. Over-representation of minority patients further supports the benefit of enrolling patients on clinical trials in the community-based setting.

Surgery versus SABR for early-stage lung cancer-time to call it a draw?

Randomised controlled trials comparing surgery with non-surgical treatment for cancer have been notoriously difficult to complete, owing to challenges in both equipoise and preference in patients and providers alike. 1 Nguyen TK Nguyen EK Warner A Louie AV Palma DA Failed randomized clinical trials in radiation oncology: what can we learn?. Int J Radiat Oncol Biol Phys. 2018; 101: 1018-1024 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar Debate on the relative merit of stereotactic ablative radiotherapy (SABR) versus surgery for early-stage non-small-cell lung cancer (NSCLC) is no exception. Prospective randomised controlled trials designed to identify a so-called winner between surgery and SABR have not been able to accrue, and the pooled analysis from the prematurely closed original STARS and ROSEL studies has been a lightning rod for discussion among thoracic oncologists. 2 Jones DR Do we know bad science when we see it?. J Thorac Cardiovasc Surg. 2015; 150: 472-473 Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar Even with other comparative effectiveness studies attempting to adjust for confounding, inherent limitations engender polarising opinions. 3 Chen H Laba JM Boldt RG et al. Stereotactic ablative radiation therapy versus surgery in early lung cancer: a meta-analysis of propensity score studies. Int J Radiat Oncol Biol Phys. 2018; 101: 186-194 Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgeryLong-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Full-Text PDF

RadOnc Tables: An Online Resource for Commentary and Summaries of Key Clinical Trials

The RadOnc Tables key studies sheet and App aim to be a rapid online reference for key clinical trials in radiation oncology for a wide range of users, adapting features that are not possible in a physical book: continually up-to-date, updated in realtime, with fast usability, and crowd-sourcing of knowledge.

Phase III Radiation Oncology Clinical Trials: A Snapshot of the Last Two Decades

Modern radiation therapy is an integral modality in the treatment of cancer, yet data on the current state of Phase III radiation therapy trials remains scarce. We sought to characterize the landscape of radiation oncology phase III clinical trials in the last two decades. We searched ClinicalTrials.gov for phase III randomized controlled trials (RCTs) between 2003 and 2018. Randomized, multi-arm trials assessing a therapeutic intervention in adult cancer patients were included. Trials where radiation therapy was a main intervention were identified and grouped according to specific disease subsites and other trial information. Differences in trial factors between radiotherapy and other oncologic interventional trials were analyzed. Out of the 600 phase III RCTs identified, 15 trials were solely radiation therapy trials (2.5%). By disease subsite, we identified 3 (20%) breast cancer trials, 2 (13.3%) gastrointestinal cancer trials, 2 (13.3%) genitourinary cancer trials, 2 (13.3%) colorectal cancer trials, and 2 (13.3%) head and neck cancer trials. Radiation trials were less likely to be industry funded when compared to other oncological trials (20.0% vs 79.3% respectively, p<0.001). Furthermore, 73.3% of radiation trials had cooperative group sponsorship (vs 30.3% for other oncologic trials, p<0.001). Radiotherapy trials had less restrictions on including healthier patients (ECOG score 0 to 1) when compared to trials of systemic therapy (p<0.001). Even though radiation therapy is currently recognized as an integral modality in treating cancer patients, radiation therapy trials remain scarce and largely underfunded. Lastly, while cooperative groups seem to play an important role in radiation therapy trials, stakeholders are encouraged to assess and address ways to increase quality radiotherapy research.

How to Improve Enrollment Onto GI Radiation Oncology Clinical Trials: Lessons Learned From a Brachytherapy Trial for Newly Diagnosed Locally Advanced Pancreatic Cancer

How to Improve Enrollment Onto GI Radiation Oncology Clinical Trials: Lessons Learned From a Brachytherapy Trial for Newly Diagnosed Locally Advanced Pancreatic Cancer

Health-Related Quality of Life and Patient-Reported Outcomes in Radiation Oncology Clinical Trials.

The importance of assessing health-related quality of life (HRQoL) and patient-reported outcomes (PROs) is now well recognized as an essential measure when evaluating the effectiveness of new cancer therapies. Quality of life measures provide for a multi-dimensional understanding of the impact of cancer treatment on measures ranging from functional, psychological, and social aspects of a patient's health. Patient-reported outcomes provide for an assessment of physical and functional symptoms that are directly elicited from patients. Collection of PROs and HRQoL data has been shown to not only be feasible but also provide for reliable measures that correlate with established outcomes measures better than clinician-scored toxicities. The importance of HRQoL measures has been emphasized by both patients and clinicians, as well as policy makers and regulatory bodies. Given the benefits associated with measuring HRQoL and PROs in oncology clinical trials, it is increasingly important to establish methods to effectively incorporate PROs and HRQoL measures into routine clinical practice.