Trials In Radiation Oncology Research Articles

Evaluation of clinical trials addressing supportive care measures for management of acute and chronic radiation toxicities.

Radiation therapy can cause acute and long-term side effects despite advances in treatment delivery techniques. While significant research has been conducted to prevent the occurrence of toxicity, there is a need for evidence-based supportive care measures to manage radiation side effects. This analysis aims to examine the current state of supportive care trials in radiation oncology and identify areas that require further study. A Clinicaltrials.gov search was conducted using the term "radiation toxicity" to identify registered trials with a primary endpoint of toxicity management. These studies were further classified as supportive care interventions or toxicity prevention. Study details were evaluated for all supportive care trials. Of the thirty-eight supportive care trials identified, most were observational/uncategorized (50%), in phase III (28.9%), or phase II (13.2%). Head and neck (42.1%), genitourinary (18.4%), and breast (13.2%) were the most studied disease sites. Xerostomia (23.7%), mucositis (18.4%), and dermatitis (18.4%) were the most evaluated toxicities. Medication-based (28.9%), procedures (28.9%), and topical agents (21.1%) were the most common interventions. Thirty-two studies included patient-reported outcomes (PROs; 84.2%), of which seventeen trials (53.1%) had PROs as a primary endpoint. Only a small portion of supportive care trials generate high-level evidence to evaluate interventions with patient-reported endpoints. More supportive care trials are needed to effectively manage radiation toxicities and promote compliance and long-term quality of life during and after radiation therapy. Increased funding from government and industry sponsors is required to support this research.

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

Operational Ontology for Radiation Oncology (OORO): A Professional Society-Based, Multi-Stakeholder Consensus Driven Informatics Standard Supporting Clinical and Research Use of Real-World Data

There is a critical need for large-scale, multi-institutional "real-world" data to evaluate patient, diagnosis and treatment factors affecting oncology patient outcomes. However, lack of data standardization undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), Radiation Oncology Information Systems and other cancer care databases. As next step to promote data standardization beyond the American Association of Physicists in Medicine (AAPM)'s TG-263 guidance for radiotherapy (RT) nomenclature, the AAPM's Big Data Subcommittee (BDSC) has led an international RT professional society collaboration to develop the Operational Ontology for Radiation Oncology (OORO). Initiated July 2019 to explore issues that typically compromise formation of large inter- and intra- institutional databases from EHRs, the AAPM's BDSC membership includes representatives from the AAPM, American Society of Radiation Oncology (ASTRO), Canadian Organization of Medical Physicists (COMP), Canadian Association of Radiation Oncology (CARO), European Society of Therapeutic Radiation Oncology (ESTRO) and clinical trials experts from NRG Oncology. Multiple external stakeholders were engaged, including government agencies, vendors and RT community members through the iterative and consensus-driven approach to OORO development. The OORO includes 42 key elements, 359 attributes, 144 value sets, and 155 relationships, ranked for priority of implementation based on clinical significance, likelihood of availability in EHRs, or ability to modify routine clinical processes to permit aggregation. The initial version of OORO includes many disease-site independent concepts common for all cancer patients and a smaller set specific for prostate cancer. The OORO development methodology is currently being applied/adapted to include additional disease site-specific concepts beginning with head and neck cancers. The first of its kind in radiation oncology, the OORO is a professional society-based, multi-stakeholder, consensus driven informatics standard. The iterative and collaborative approach to ontology development and refinement aims to ensure that OORO serves as a « living » guidance document, facilitating incremental expansion of data elements over time, as disease site-specific standards are set and RT concepts evolve. Supporting construction of comprehensive "real-world" datasets and application of advanced analytic techniques, including artificial intelligence (AI), OORO holds the potential to revolutionize patient management and improve outcomes.

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.

SP-0339 Outcome measures for trials in radiation oncology

SP-0339 Outcome measures for trials in radiation oncology

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.

Disparities in Racial and Ethnic Enrollment and Reporting: An Analysis of Reported NRG Radiation Oncology Trials

<h3>Purpose/Objective(s)</h3> Representation in practice-defining radiation therapy (RT) trials, which is critical to ensuring health equity and generalizability of results, is not well characterized. This study evaluated the frequency of race & ethnic reporting and proportional representation in published RT NRG trials. <h3>Materials/Methods</h3> Reported RT NRG (inclusive of legacy groups) studies were collated using the NRG Oncology Publications Database. Race & ethnicity were tabulated for each study based on available peer-reviewed articles. The proportion of trials reporting racial & ethnic subgroups was calculated among all trials. Among studies that reported this data, using the Surveillance, Epidemiology, and End Results (SEER) database, each study's composition was compared to a representative United States (US) population of patients diagnosed during the study's accrual with the same disease site. Trends in reporting and relative differences in enrollment by year (yr) and disease site were evaluated using 10-yr moving averages. Multivariable analysis (MVA) was performed to identify factors predictive of reporting racial & ethnic factors. To quantify differences in enrollment relative to the US population, enrollment incidence disparity (EID, defined as the percentage difference between the enrolled population and the US population) was used. <h3>Results</h3> A total of 410 studies published between 1975 and 2021 were identified, representing 106,000 total patients. Reporting on race & ethnicity was rare until 1997 (<10% of studies), steadily increasing until 2007 (70%), and stagnating through 2021 (70.5%). On MVA, studies that were more likely to report racial & ethnic data were published in later years (Odds Ratio [OR (95% Confidence Interval)]: 1.13 [1.10-1.16]; p<0.001), phase 3 (OR: 5.13 [2.06-12.80]; p<0.001), randomized (OR: 2.63 [1.10-6.25]; p=0.029), and specific to a single sex (OR: 2.31 [1.34-3.97]; p<0.001). Using EID, Asian and Hispanic patients have persistently been underrepresented in trials, (-3.8% and -4.8% in 1995 and -3.4% and -5.3% in 2015), with changes of 0.07%/yr (p<0.001; r²=0.66) and -0.05%/yr (p=0.001; r²=0.38), respectively. Enrollment of Black patients had exceeded the US population (+0.5% in 1995), but has steadily declined (-0.10%/yr; p<0.001, r²=0.82) to -1.2% in 2015. White patients have been increasingly (0.16%/yr; p<0.001, r²=0.85) overrepresented (+0.9% in 1995 and 4.9% in 2015). EID by disease site is reported in Table 1. <h3>Conclusion</h3> In RT NRG trials, although race & ethnicity reporting has improved, it has plateaued, and associated enrollment disparities have worsened. Further work is required to ensure continued improvement in equitable enrollment and standardization of reporting.

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.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients

ObjectiveFailure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET).Materials and methodsThe 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients’ representatives and patients’ self-help groups addressing the patients’ willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation.Results(i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio.ConclusionThe dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

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.

137: an Exploratory Analysis of Study Outcomes and Foundational Evidence for Five Years of Phase III Trials in Radiation Oncology

137: an Exploratory Analysis of Study Outcomes and Foundational Evidence for Five Years of Phase III Trials in Radiation Oncology

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

European clinical trials in paediatric radiation oncology

Radiotherapy is an important part of multimodality treatment protocols for around a third of children and young people with malignant disease.1 Although ionising radiation has been available in some form for around a century, technology has been continuously refined and developed.2 Together with a better understanding of pathology and molecular biology of cancer through sequential clinical trials, improved radiation technology has led to a transformation of radiotherapy in the past few decades. Paediatric radiation oncology has also evolved and taken advantage of these technical advances.

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.

Screening and Validation of Molecular Targeted Radiosensitizers

The development of molecular targeted drugs with radiation and chemotherapy is critically important for improving the outcomes of patients with hard-to-treat, potentially curable cancers. However, too many preclinical studies have not translated into successful radiation oncology trials. Major contributing factors to this insufficiency include poor reproducibility of preclinical data, inadequate preclinical modeling of intertumoral genomic heterogeneity that influences treatment sensitivity in the clinic, and a reliance on tumor growth delay instead of local control (TCD50) endpoints. There exists an urgent need to overcome these barriers to facilitate successful clinical translation of targeted radiosensitizers. To this end, we have used 3-dimensional (3D) cell culture assays to better model tumor behavior in vivo. Examples of successful prediction of in vivo effects with these 3D assays include radiosensitization of head and neck cancers by inhibiting epidermal growth factor receptor or focal adhesion kinase signaling, and radioresistance associated with oncogenic mutation of KRAS. To address the issue of tumor heterogeneity, we leveraged institutional resources that allow high-throughput 3D screening of radiation combinations with small-molecule inhibitors across genomically characterized cell lines from lung, head and neck, and pancreatic cancers. This high-throughput screen is expected to uncover genomic biomarkers that will inform the successful clinical translation of targeted agents from the National Cancer Institute Cancer Therapy Evaluation Program portfolio and other sources. Screening "hits" need to be subjected to refinement studies that include clonogenic assays, addition of disease-specific chemotherapeutics, target/biomarker validation, and integration of patient-derived tumor models. The chemoradiosensitizing activities of the most promising drugs should be confirmed in TCD50 assays in xenograft models with or without relevant biomarker and using clinically relevant radiation fractionation. We predict that appropriately validated and biomarker-directed targeted therapies will have a higher likelihood than past efforts of being successfully incorporated into the standard management of hard-to-treat tumors.

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades

When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion. This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades. A literature review was performed to determine the publication outcomes of PRO data, including only trials that used PROs in their design and were mature enough to have published results. Fifty-seven (56.4%) of the 101 trials included in this study included PROs in their design. Brain and head and neck trials demonstrated the largest proportional incorporation of PROs (81.8% and 76.9%, respectively), and thoracic and breast trials used the fewest (18.8% and 37.5%, respectively). The EQ-5D family of questionnaires was the most commonly used PROs, used in 22.8% of trials included. The literature review demonstrated a pattern of increased publication of PRO data alongside survival endpoints in manuscripts derived from these trials over time. Though there is room for improvement, the field of radiation oncology has embraced the incorporation of PROs into multicenter, high-impact clinical trials over the past 2 decades and has increased its publication of this data alongside survival data from these trials.

Evaluation of Clinical Trials Addressing Supportive Care Measures for Acute and Chronic Radiation Toxicities

Despite advances in treatment delivery techniques, a variety of acute and late side effects secondary to radiation therapy occur. Significant research efforts have focused on preventing occurrence of toxicity; however, there is continued demand for evidence-based supportive care measures to treat radiation side effects. The purpose of this analysis is to characterize the state of supportive care trials in radiation oncology and to identify areas needing further study. Clinicaltrials.gov was queried using the search term “radiation toxicity” to identify past and current registered trials with a primary endpoint of toxicity management. To evaluate the proportion of supportive care trials, studies were classified as toxicity prevention or as supportive care interventions. Information regarding country of origin, trial era, study phase, disease site, toxicity evaluated, intervention, industry sponsorship, single- vs. multi-institutional status, sample size, and the use of patient-reported outcomes were evaluated for all supportive care trials. A total of 223 trials were identified. After exclusion of terminated trials or trials focused on radiation techniques (e.g., 3D-CRT vs. IMRT, protons), 71 studies met the criteria of either radiation toxicity prevention (n = 50) or supportive care (n = 21). Fourteen of these trials were active (8 prevention, 6 supportive care), with the remainder inactive, unknown, or complete. Within the group of 21 supportive care trials, the design included randomized phase III interventions in 6 studies (29%) with the remainder phase II (n = 4, 19%), phase I/II (n = 1, 5%), phase I (n = 1, 5%), or observational/uncategorized (n = 9, 43%). The most common disease site studied was head and neck (n = 6, 29%), followed by CNS (n = 3, 14%). Xerostomia, mucositis, and neurocognitive function (n = 3, 14% each) were the most commonly evaluated toxicities. The majority of studied interventions (n = 11, 52%) were medications with hyperbaric oxygen and diet as the next most common (n = 3, 14% each). Twelve trials were single institution (57%) and the median sample size was 91 (range: 11 to 320). Twelve studies included patient-reported outcomes (PROs), of which 7 trials (33%) had PROs as a primary endpoint. While numerous studies evaluating toxicity reduction exist, effective management of radiation-related toxicities remains important to promote quality of life during and after radiation therapy. There are few supportive care trials in radiation oncology and only a small portion of these are currently designed to generate level I evidence to evaluate interventions. There is a significant need for well-designed supportive care trials with patient-reported endpoints to guide management of radiation toxicity.

93 Don’t be Fazed by Phase II: The Use of Randomized Phase II Trials in Radiation Oncology

93 Don’t be Fazed by Phase II: The Use of Randomized Phase II Trials in Radiation Oncology