BACKGROUND:Radiotherapy for head and neck cancer (HNC) has significant physical and emotional effects. This study investigated the feasibility of delivering "Prep-4-Radiotherapy (RT)", a multi-modal, risk-stratified approach to prehabilitation for people with HNC. METHODS:HNC patients planned for radiotherapy were screened for psychological distress, malnutrition, sarcopenia, dysphagia, and reduced physical function using self-report measures. Low-risk patients were provided access to self-management resources. High-risk patients were additionally referred to relevant allied health disciplines for specialist prehabilitation and provided access to self-management resources. The feasibility of Prep-4-RT was judged against a priori criteria. Primary feasibility outcomes included patient adoption (uptake: ≥ 70% of eligible patients consent to screening; intention to try: ≥ 60% of patients utilize self-management resources and ≥ 70% of high-risk patient participants verbally accept referrals to specialist prehabilitation) and fidelity (adherence to specialist pathway: ≥ 70% of high-risk patients receive specialist prehabilitation and attend ≥ 70% of scheduled prehabilitation appointments). RESULTS:Point estimates for four of five primary outcomes indicated acceptable feasibility. The point estimate for the fifth primary outcome, adherence as assessed by the percentage of high-risk patients assigned to specialist prehabilitation who received care from required clinicians before radiotherapy, indicated feasibility with further revision. CONCLUSION:Prep-4-RT appears to offer a feasible risk-stratified program to provide prehabilitation to HNC patients prior to radiotherapy, though results for some criteria were characterized by notable missing data. Further evaluation is required to determine its effect on clinical and health service outcomes. REGISTRATION DETAILS:ANZCTA (Australian New Zealand Clinical Trials Registry) ACTRN12623000770662.

Purpose Cutaneous T-cell lymphomas (CTCL) are rare with increasing incidence. Most patients have skin-confined mycosis fungoides: a typically indolent, highly morbid, incurable disease requiring multi-lined treatment. For these patients, radiation therapy (RT) is efficacious, well-tolerated, and cost-effective; total skin electron beam therapy (TSEBT) is a specialized technique with proven quality-of-life benefits. Consensus on optimal treatment sequencing is lacking, creating heterogeneity in care. International data suggest declining RT-utilization. Using a state-wide, population-based, Australian cancer registry with linked data sets, we investigated RT-utilization for CTCL, examining for geographically based disparities. Correlations between dermatologist-availability and linac-density on incidence and RT-utilization rates were also explored. Methods and Materials Retrospective analysis of New South Wales Cancer Registry data set of all patients diagnosed with CTCL from 2009 to 2018, with data linkage to the Outpatient Radiation Oncology Database. Actual RT-utilization rates included all treatment lines, calculated per person. Results A total of 553 patients were diagnosed with CTCL; age-standardized incidence was 7.19/million/year. Geographically, 35% resided in regional/rural local health districts (LHDs); 13% in underaccessible locations; 15% >50 km road distance from the nearest RT center. RT-utilization and TSEBT-utilization rates were 29.0% and 1.8%, respectively. Variation existed between LHDs, with greater RT-utilization in regional/rural over metropolitan LHDs (odds ratio: 1.66; P = .01). Patients residing in major cities had lower RT-utilization than those in inner regional areas (odds ratio: 2.12; P = .001). Shortest road distance to the nearest RT center did not predict for greater RT-utilization. Disparities in access to specialist services existed between LHDs. Dermatologist-availability significantly predicted for diagnosis rates (R2 = 0.34; F(1,11) = 5.58; P = .04). The absence of RT facilities was associated with poor RT-utilization rates. Conclusions Over 10 years, only 29% of patients with CTCL received RT across all treatment lines, with significant geographic-based heterogeneity observed. Contrary to expectation, residence in major cities and proximity to RT facilities were associated with lower RT-utilization rates. Further advocacy is encouraged to overcome diagnostic and treatment disparities for patients with CTCL.

INTRODUCTION:Aboriginal patients face barriers to accessing cancer care. Few studies have evaluated the utilisation of radiotherapy or surgery in Aboriginal people. This study aims at assessing variation in types of cancer, degree of spread (DOS) at presentation, utilisation rates of cancer surgery and radiotherapy between Aboriginal and non-Aboriginal cancer patients. METHODS:Retrospective analysis of de-identified linked datasets. All patients with registered notifiable cancer in the NSW cancer registry 2009-2018 separated by Aboriginality status were included. RESULTS:Totally 389,992 people were diagnosed in NSW during study period; 8970 people (2.3%) identified as Aboriginal. In univariate analysis, Aboriginal people presented at diagnosis with statistically significant younger age, greater comorbidity, advanced (DOS) and greater proportions living in most disadvantaged areas than non-Aboriginal people. Based on univariate analysis, Aboriginal patients received radiotherapy more frequently than non-Aboriginal patients (30.3% versus 26.0%, p < 0.01). Non-Aboriginal patients underwent cancer surgery more frequently than Aboriginal patients (57.0% versus 51.2%, p < 0.01). When stratified by tumour type and adjustment for patient and clinical factors, radiotherapy and surgery utilisation varied by type of cancer. CONCLUSIONS:The degree of cancer spread, and the presence of comorbidities remains a greater issue for Aboriginal people. Access to radiotherapy increased significantly for Aboriginal patients during the past 10 years. However, differences in surgical and radiotherapy utilisation exist. These differences can be partially explained by the greater DOS and presence of comorbidity in Aboriginal patients leading to less surgical intervention and greater requirement for radiotherapy.

PurposeTo (i) determine the actual radiotherapy utilization (RTU) stratified by age, (ii) develop an age- and co-morbidity adjusted optimal RTU model and (iii) examine the tolerance and toxicity of treatment of older patients with head and neck cancer.Materials and MethodsA retrospective cohort study based on New South Wales Cancer Registry records (2010-2014) linked to radiotherapy data (2010-2015) and admitted patient data (2008-2015) for patients diagnosed with head and neck cancer. We calculated the actual RTU, defined as the proportion of patients who received at least one course of radiotherapy within a year of diagnosis, by age group, including patients aged 80+ years. We also calculated the age and comorbidity adjusted optimal RTU. For treatment tolerance, the radiotherapy dose for each age group and the completion rate for a seven week, 70 Gray (Gy) course of curative intent radiotherapy was computed. The number of emergency department (ED) presentations was used as a surrogate measure of acute treatment toxicity for patients receiving 70Gy.ResultsOf the 5966 patients diagnosed with head and neck cancer, 814 (13.6%) were aged 80+ years. For all age groups, the actual RTU was less than the optimal RTU. The age- and comorbidity-adjusted optimal RTU for patients aged 80+ was 52% (95% CI: 51%-53%) and the actual RTU was 40% (95% CI: 37%-44%). Only 4.4% of patients aged 80+ received 70Gy, and the completion rate for a 70Gy course of radiotherapy for these patients was 92%. The ED presentation rate was similar for all age groups.ConclusionThe actual RTU was less in the 80+ years patients and across all age groups. Fewer patients in the 80+ group received curative intent schedules compared to the actual RTU rate for younger age groups despite similar rates of completion of curative intent radiotherapy and acute toxicity.

Report-back of research results (RBRR) is becoming standard practice for environmental health research studies. RBRR is thought to increase environmental health literacy (EHL), although standardized measurements are limited. For this study, we developed a report back document on exposure to air pollutants, Polycyclic Aromatic Hydrocarbons, during pregnancy through community engaged research and evaluated whether the report increased EHL. We used focus groups and surveys to gather feedback on the report document from an initial group of study participants (Group 1, n = 22) and then sent the revised report to a larger number of participants (Group 2, n = 168). We conducted focus groups among participants in Group 1 and discussed their suggested changes to the report and how those changes could be implemented. Participants in focus groups demonstrated multiple levels of EHL. While participant engagement critically informed report development, a survey comparing feedback from Group 1 (initial report) and Group 2 (revised report) did not show a significant difference in the ease of reading the report or knowledge gained about air pollutants. We acknowledge that our approach was limited by a lack of EHL tools that assess knowledge and behavior change, and a reliance on quantitative methodologies. Future approaches that merge qualitative and quantitative methodologies to evaluate RBRR and methodologies for assessing RBRR materials and subsequent changes in knowledge, attitudes, and behavior, may be necessary.

BACKGROUND AND PURPOSE:The optimal utilization rate of radiotherapy (oRUR) serves as a benchmark for assessing service demand and improving access to cancer care. While it is estimated that approximately 50 % of adult cancer patients require external beam radiotherapy during their treatment, there is a scarcity of data regarding the optimal use of radiotherapy in pediatric cancer. In this study, we adopted an established method and developed a model to estimate the oRUR in childhood neuroblastoma. MATERIALS AND METHODS:We developed a decision tree model to calculate the oRUR using indications for radiotherapy and corresponding epidemiological data collected through systematic review and meta-analysis. Sensitivity analyses were performed to evaluate the impact of variations in radiotherapy indications between treatment protocols and variables in the model. We calculated and compared the oRUR for global, high-income, and low- and middle-income settings. RESULTS:The oRUR for pediatric neuroblastoma was 64 % (95 % CI: 58 %-71 %) in the global setting, 50 % in high-income countries, and 68 % in low- and middle-income countries. The impact of variation in radiotherapy indications between major international treatment protocols was negligible. CONCLUSION:The knowledge of oRUR is crucial for evaluating current practices, identifying gaps in access, and planning future radiotherapy services for treating childhood cancer. Based on our results, 64 % of children with neuroblastoma have an indication for radiotherapy. Patients in low- and middle-income countries have more indications for radiotherapy than those in high-income countries, due to a more adverse tumour stage distribution caused by limited access to healthcare resources.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of ‘development’ and ‘validation’ cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion ( r = 0.993) and number of detected lesions ( r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

Background As exposure assessment has shifted towards community-engaged research there has been an increasing trend towards reporting results to participants. Reports aim to increase environmental health literacy, but this can be challenging due to the many unknowns regarding chemical exposure and human health effects. This includes when reports encompass a wide-range of chemicals, limited reference or health standards exist for those chemicals, and/or incompatibility of data generated from exposure assessment tools with published reference values (e.g., comparing a wristband concentration to an oral reference dose). Methods Houston Hurricane Harvey Health (Houston-3H) participants wore silicone wristbands that were analyzed for 1,530 organic compounds at two time-points surrounding Hurricane Harvey. Three focus groups were conducted in separate neighborhoods in the Houston metropolitan area to evaluate response to prototype community and individual level report-backs. Participants ( n = 31) evaluated prototype drafts using Likert scales and discussion prompts. Focus groups were audio-recorded, and transcripts were analyzed using a qualitative data analysis program for common themes, and quantitative data (ranking, Likert scales) were statistically analyzed. Results Four main themes emerged from analysis of the transcripts: (1) views on the report layout; (2) expression of concern over how chemicals might impact their individual or community health; (3) participants emotional response towards the researchers; and (4) participants ability to comprehend and evaluate environmental health information. Evaluation of the report and key concerns differed across the three focus groups. However, there was agreement amongst the focus groups about the desire to obtain personal exposure results despite the uncertainty of what the participant results meant. Conclusions The report-back of research results (RBRR) for community and individual level exposure assessment data should keep the following key principles in mind: materials should be accessible (language level, data visualization options, graph literacy), identify known information vs unknown (e.g., provide context for what exposure assessment data means, acknowledge lack of current health standards or guidelines), recognize and respect community knowledge and history, and set participant expectations for what they can expect from the report.

The OSU/PNNL Superfund Research Program (SRP) represents a longstanding collaboration to quantify Polycyclic Aromatic Hydrocarbons (PAHs) at various superfund sites in the Pacific Northwest and assess their potential impact on human health. To link the chemical measurements to biological activity, we describe the use of the zebrafish as a high-throughput developmental toxicity model that provides quantitative measurements of the exposure to chemicals. Toward this end, we have linked over 150 PAHs found at Superfund sites to the effect of these same chemicals in zebrafish, creating a rich dataset that links environmental exposure to biological response. To quantify this response, we have implemented a dose-response modelling pipeline to calculate benchmark dose parameters which enable potency comparison across over 500 chemicals and 12 of the phenotypes measured in zebrafish. We provide a rich dataset for download and analysis as well as a web portal that provides public access to this dataset via an interactive web site designed to support exploration and re-use of these data by the scientific community at http://srp.pnnl.gov .

INTRODUCTION:Optimal radiotherapy utilisation (RTU) modelling estimates the proportion of people with cancer who would benefit from radiotherapy. Assessment of comorbidities is an important component of the assessment of suitability for radiotherapy in addition to chronological age and life expectancy. Comorbidities have not been considered in previous optimal RTU models. We aimed to develop an age- and comorbidity- adjusted optimal RTU model for patients with lung, rectal, prostate, and cervical cancer, and compare them to actual RTU rates, with a particular focus on those aged 80+ years, METHODS: New South Wales (NSW) Cancer Registry data (2010-2014) linked to radiotherapy data (2010-2015) and hospitalisation data (2008-2015) were used to determine the number of patients diagnosed with lung, rectal, prostate and cervical cancer. The Cancer Specific C3 'all sites' comorbidity index was calculated from hospital diagnosis data for each patient to determine suitability for radiotherapy. The index was then incorporated into a tumour site-specific decision tree model. The actual RTU was also calculated using the linked datasets. RESULTS:14,696 patients were diagnosed with non-small cell lung cancer (NSCLC), 1839 with small cell lung cancer (SCLC), 5551 with rectal cancer, 30,935 with prostate cancer and 1216 with cervical cancer in New South Wales from 2010-2014. The proportion of patients aged 80+ years at cancer diagnosis was 25% (3603 patients), 15% (279 patients), 17% (943 patients), 12% (3745 patients), and 7% (88 patients) respectively. The age- and comorbidity- adjusted optimal RTU rates for patients aged 80+ years using the C3 index were 49% (NSCLC), 49% (SCLC), 43% (rectal), 51% (prostate) and 40% (cervical). The corresponding actual RTU rates for patients aged 80+ years were 25%, 32%, 27%, 16%, and 56%. CONCLUSION:Even after adjusting for age and comorbidities, the actual radiotherapy utilisation rates were lower than optimal radiotherapy utilisation rates in patients aged 80+ years except for patients with cervical cancer. This warrants further assessment and research into reasons and solutions.

INTRODUCTION:There is an increasing incidence of cancer in older people, but limited data on radiotherapy uptake, and in particular, radiotherapy utilisation (RTU) rates. The RTU rate for older adults with cancer may be lower than recommended due to lower tolerance for radiotherapy as well as additional comorbidities, reduced life expectancy and travel for treatment. Radiotherapy use must be aligned with best available, age-specific evidence to ensure older adults with cancer receive optimal benefit without harms.MATERIALS AND METHODS:A systematic review was conducted to synthesise the published data on the actual RTU rate for patients with cancer as a function of age. MEDLINE and EMBASE were systematically searched to identify relevant population-based and hospital-based cohort studies on radiotherapy utilisation for all age groups, published in English, from 1 January 1990 to 1 July 2020. We focused on the following common cancers in older adults for which radiotherapy is recommended: breast, prostate, lung, rectal cancer, glioblastoma multiforme (GBM), and cervical cancer. Age-specific radiotherapy utilisation data were extracted and analysed as a narrative synthesis.RESULTS:From 2606 studies screened, 75 cohort and population-based studies were identified with age-specific radiotherapy utilisation data. The total number of patients in the 75 studies was 4,792,138. The RTU rate decreased with increasing age for all tumour sites analysed, except for patients receiving curative radiotherapy as definitive treatment for prostate or cervical cancer. This reduction with increasing age was demonstrated in both palliative and curative settings.DISCUSSION:There is a global reduction in radiotherapy utilisation with increasing age for most tumour sites. The reduction in delivery of radiotherapy warrants further examination and evidence-based guidelines specific to this population.

Background Resource-stratified guidelines (RSGs) can inform systemic treatment decisions in the face of limited resources. The objective of this study was to develop a customisable modelling tool to predict the demand, cost, and drug procurement needs of delivering National Comprehensive Cancer Network (NCCN) RSG-based systemic treatment for colon cancer. Methods We developed decision trees for first-course systemic therapy for colon cancer based on the NCCN RSGs. Decision trees were merged with data from the Surveillance, Epidemiology, and End Results programme, the International Agency for Research on Cancer's GLOBOCAN 2020 national estimates for colon cancer incidence, country-level income data, and data on drug costs from Redbook (USA), the Pharmaceutical Benefits Scheme (Australia), and the Management Sciences for Health 2015 International Medical Products price guide to estimate global treatment needs and costs, and forecast drug procurement. Simulations and sensitivity analyses were used to explore the effect of scaling up services globally and the effect of alternative stage distributions on treatment demand and cost. We generated a customisable model, in which estimates can be tailored to local incidence, epidemiological, and costing data. Findings First-course systemic therapy is indicated in 608 314 (53 center dot 6%) of 1 135 864 colon cancer diagnoses in 2020. Indications for first-course systemic therapy are projected to rise to 926 653 in 2040; the indications in 2020 might be as high as 826 123 (72 center dot 7%), depending on stage distribution assumptions. Adhering to NCCN RSGs, patients with colon cancer in low-income and middle income countries (LMICs) would constitute 329 098 (54 center dot 1%) of 608 314 global systemic therapy demands, but only 10% of global expenditure on systemic therapies. The total cost of NCCN RSGbased first-course systemic therapy for colon cancer in 2020 would be between about US$4 center dot 2 and about $4 center dot 6 billion, depending on stage distribution. If all patients with colon cancer in 2020 were treated according to maximal resources, global expenditure on systemic therapy for colon cancer would rise to around $8 center dot 3 billion. Interpretation We have developed a customisable model that can be applied at global, national, and subnational levels to estimate systemic treatment needs, forecast drug procurement, and calculate expected drug costs on the basis of local data. This tool can be used to plan resource allocation for colon cancer globally.

Arctic communities are disproportionately exposed to pollutants from sources including global atmospheric transport and formerly used defense sites (FUDS). The effects of climate change and increasing development in the Arctic have the potential to exacerbate this problem. Yupik People of Sivuqaq, or St Lawrence Island, Alaska are one such community with documented exposures to pollutants from FUDS, and their traditional lipid-rich foods such as blubber and rendered oils of marine mammals. Troutman Lake, adjacent to the Yupik community of Gambell, Alaska, was used as a disposal site during the decommission of the adjacent FUDS, leading to community concern about exposure to military pollution and intrusion from historic local dump sites. In collaboration with a local community group, this study utilized passive sampling devices deployed in Troutman Lake. Air, water and sediment deployed samplers were analyzed for unsubstituted and alkylated polycyclic aromatic hydrocarbons (PAHs), brominated and organophosphate flame retardants and polychlorinated biphenyls (PCBs). PAH concentrations were low and comparable to other remote/rural locations. PAHs were generally in deposition from the overlying atmosphere into Troutman Lake. Of the flame retardants, brominated diphenyl ether-47 was detected in all surface water samplers while triphenyl phosphate was detected in all environmental compartments. Both were at concentrations equivalent or lower than other remote locations. Of particular interest, we measured higher atmospheric concentrations of tris(2-chloroethyl) phosphate (TCEP) (0.75-2.8 ng/m3) than previously reported in the literature for remote Arctic sites (<0.017-0.56 ng/m3). TCEP was found to be in deposition to Troutman Lake at magnitudes from 290 to 1300 ng/m2/day. No PCBs were detected in this study. Our findings demonstrate the relevance of both modern and legacy chemicals from local and global sources. These results help us to understand the fate of anthropogenic contaminants in dynamic Arctic systems providing valuable data for communities, policy makers and scientists.

Aims: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer.Materials and methods: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and K-trans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model.Results: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT K-trans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best K-trans cut-off point after CRT for predicting relapse was 28 x 10(-3) mL/g/min (10th quantile), with a higher K-trans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value <= 28 x 10(-3) mL/g/min versus 0.45 for patients with after CRT K(trans )value > 28 x 10(-3) mL/g/min. ADC was not able to predict DFS.Conclusions: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

— Charles Dickens, Great Expectations Ong et al., in this issue of the journal, examine the radiotherapy utilisation rates in Victoria over a 5-year period. The report shows that when compared with older studies radiotherapy utilisation rates have remained static, with only half of the cancer population who have evidence-based indications actually receiving radiotherapy. Of greater concern is that there has been no improvement in the radiotherapy utilisation rate over that time. The results are sobering reading given the investment in radiotherapy over that time. They require action from the radiation oncology profession and cancer consumers.

Abstract. Purpose: Radiomics of magnetic resonance images (MRIs) in rectal cancer can non-invasively characterize tumor heterogeneity with potential to discover new imaging biomarkers. However, for radiomics to be reliable, the imaging features measured must be stable and reproducible. The aim of this study is to quantify the repeatability and reproducibility of MRI-based radiomic features in rectal cancer. Approach: An MRI radiomics phantom was used to measure the longitudinal repeatability of radiomic features and the impact of post-processing changes related to image resolution and noise. Repeatability measurements in rectal cancers were also quantified in a cohort of 10 patients with test–retest imaging among two observers. Results: We found that many radiomic features, particularly from texture classes, were highly sensitive to changes in image resolution and noise. About 49% of features had coefficient of variations ≤10  %   in longitudinal phantom measurements. About 75% of radiomic features in in vivo test–retest measurements had an intraclass correlation coefficient of ≥0.8. We saw excellent interobserver agreement with mean Dice similarity coefficient of 0.95  ±  0.04 for test and retest scans. Conclusions: The results of this study show that even when using a consistent imaging protocol many radiomic features were unstable. Therefore, caution must be taken when selecting features for potential imaging biomarkers.

BACKGROUND:It is unknown how often regional differences in oncology trials are observed. Based on our study findings, we quantified regional variation in registration studies in oncology and developed a question guide to help clinicians evaluate regional differences.METHODS:Using FDA archives, we identified registration studies in solid tumor malignancies from 2010 to 2020. We extracted the baseline study characteristics and participating countries and determined whether the primary publication reported a regional subgroup analysis. For studies presenting outcomes stratified by region, we extracted the stratified hazard ratios (HRs) and extracted or calculated the test for heterogeneity. We performed a random effects meta-analysis and a pairwise comparison to determine whether outcomes differed between high-income versus mixed-income regions.RESULTS:We included 147 studies in our final analysis. Studies supporting FDA drug approval have become increasingly multinational over time (β = 0.5; P=.04). The median proportion of countries from high-income groups was 81.2% (range, 44%-100%), with no participation from low-income countries in our cohort. Regional subgroup analysis was presented for 78 studies (53%). Regional heterogeneity was found in 17.8% (8/45) and 18% (8/44) of studies presenting an overall survival (OS) and progression-free survival endpoint, respectively. After grouping regions by income level, we found no difference in OS outcomes in high-income regions compared with mixed-income regions (n=20; HR, 0.95; 95% CI, 0.84-1.07). To determine whether regional variation is genuine, clinicians should evaluate the data according to the following 5 questions: (1) Are the regional groupings logical? (2) Is the regional difference on an absolute or relative scale? (3) Is the regional difference consistent and plausible? (4) Is the regional difference statistically significant? (5) Is there a clinical explanation?CONCLUSIONS:As registration studies in oncology become increasingly international, regional variations in trial outcomes may be detected. The question guide herein will help clinicians determine whether regional variations are likely to be clinically meaningful or statistical anomalies.