Current and projected gaps in the availability of radiotherapy in the Asia-Pacific region: a country income-group analysis.

BACKGROUND: Cancer incidence and mortality is increasing rapidly worldwide, with a higher cancer burden observed in the Asia-Pacific region than in other regions. To date, evidence-based modelling of radiotherapy demand has been based on stage data from high-income countries (HIC) that do not account for the later stage at presentation seen in many low-income and middle-income countries (LMICs). We aimed to estimate the current and projected demand and supply in megavoltage radiotherapy machines in the Asia-Pacific region, using a national income-group adjusted model. METHODS: Novel LMIC radiotherapy demand and outcome models were created by adjusting previously developed models that used HIC cancer staging data. These models were applied to the cancer case mix (ie, the incidence of each different cancer) in each LMIC in the Asia-Pacific region to estimate the current and projected optimal radiotherapy utilisation rate (ie, the proportion of cancer cases that would require radiotherapy on the basis of guideline recommendations), and to estimate the number of megavoltage machines needed in each country to meet this demand. Information on the number of megavoltage machines available in each country was retrieved from the Directory of Radiotherapy Centres. Gaps were determined by comparing the projected number of megavoltage machines needed with the number of machines available in each region. Megavoltage machine numbers, local control, and overall survival benefits were compared with previous data from 2012 and projected data for 2040. FINDINGS: 57 countries within the Asia-Pacific region were included in the analysis with 9·48 million new cases of cancer in 2020, an increase of 2·66 million from 2012. Local control was 7·42% and overall survival was 3·05%. Across the Asia-Pacific overall, the current optimal radiotherapy utilisation rate is 49·10%, which means that 4·66 million people will need radiotherapy in 2020, an increase of 1·38 million (42%) from 2012. The number of megavoltage machines increased by 1261 (31%) between 2012 and 2020, but the demand for these machines increased by 3584 (42%). The Asia-Pacific region only has 43·9% of the megavoltage machines needed to meet demand, ranging from 9·9-40·5% in LMICs compared with 67·9% in HICs. 12 000 additional megavoltage machines will be needed to meet the projected demand for 2040. INTERPRETATION: The difference between supply and demand with regard to megavoltage machine availability has continued to widen in LMICs over the past decade and is projected to worsen by 2040. The data from this study can be used to provide evidence for the need to incorporate radiotherapy in national cancer control plans and to inform governments and policy makers within the Asia-Pacific region regarding the urgent need for investment in this sector. FUNDING: The Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology for Asia and the Pacific (RCA) Regional Office (RCARP03).

Hypofractionation Adoption in Prostate Cancer Radiotherapy: Results of an International Survey.

PURPOSE: Hypofractionation is noninferior to conventional fractionation in the treatment of localized prostate cancer. Using results from the European Society of Radiation Oncology's (ESTRO) Global Impact of Radiotherapy in Oncology (GIRO) initiative survey on hypofractionation, this study identifies rates of adoption, facilitating factors, and barriers to adoption of hypofractionation in prostate cancer across World Bank income groups. MATERIALS AND METHODS: The ESTRO-GIRO initiative administered an international, anonymous, electronic survey to radiation oncologists from 2018 to 2019. Physician demographics, clinical practice characteristics, and hypofractionation regimen use (if any) for several prostate cancer scenarios were collected. Responders were asked about specific justifications and barriers to adopting hypofractionation, and responses were stratified by World Bank income group. Multivariate logistic regression models were used to analyze variables associated with hypofractionation preference. RESULTS: A total of 1,157 physician responses were included. Most respondents (60%) were from high-income countries (HICs). In the curative setting, hypofractionation was most often preferred in low- and intermediate-risk prostate cancers, with 52% and 47% of respondents reporting hypofractionation use in ≥50% of patients, respectively. These rates drop to 35% and 20% in high-risk prostate cancer and where pelvic irradiation is indicated. Most respondents (89%) preferred hypofractionation in the palliative setting. Overall, respondents from upper-middle-income countries and lower-middle- and low-income countries were significantly less likely to prefer hypofractionation than those from HICs (P < .001). The most frequently cited justification and barrier were availability of published evidence and fear of worse late toxicity, respectively. CONCLUSION: Hypofractionation preference varies by indication and World Bank income group, with greater acceptance among providers in HICs for all indications. These results provide a basis for targeted interventions to increase provider acceptance of this treatment modality.

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Leveling Up the Access to Radiation Therapy in Latin America: Economic Analysis of Investment, Equity, and Inclusion Opportunities Up to 2030.

PURPOSE: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts. METHODS AND MATERIALS: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030. RESULTS: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) $349,650,480 in 2020 would have covered the existing demand. An investment of US $872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only. CONCLUSIONS: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies.

Radiotherapy prioritization in 143 national cancer control plans: Correlation with radiotherapy machine availability, geography and income level.

BACKGROUND: In 2015, the Global Task Force on Radiotherapy for Cancer Control (GTFRCC) called for 80% of National Cancer Control Plans (NCCP) to include radiotherapy by 2020. As part of the ongoing ESTRO Global Impact of Radiotherapy in Oncology (GIRO) project, we assessed whether inclusion of radiotherapy in NCCPs correlates with radiotherapy machine availability, national income, and geographic region. METHODS: A previously validated checklist was used to determine whether radiotherapy was included in each country's NCCP. We applied the CCORE optimal radiotherapy utilisation model to the GLOBOCAN 2020 data to estimate the demand for radiotherapy and compared this to the International Atomic Energy Agency (IAEA) Directory of Radiotherapy Centres (DIRAC) supply data, stratifying by income level and world region. World regions were defined according to the IAEA. FINDINGS: Complete data (including GLOBOCAN 2020, DIRAC and NCCP) was available for 143 countries. Over half (55%, n = 79) included a radiotherapy-specific checklist item within the plan. Countries which included radiotherapy services planning in their NCCP had a higher median number of machines (1.68 vs 0.75 machines/1000 patients needing radiotherapy, p < 0.001). There was significant regional and income-level heterogeneity in the inclusion of radiotherapy-related items in NCCPs. Low-income and Asia-Pacific countries were least likely to include radiation oncology services planning in their NCCP (p = 0.06 and p = 0.003, respectively). Few countries in the Asia-Pacific (18.6%) had a plan to develop or maintain radiation services, compared to 57% of countries in Europe. INTERPRETATION: Only 55% of current NCCPs included any information regarding radiotherapy, below the GTFRCC's target of 80%. Prioritisation of radiotherapy in NCCPs was correlated with radiotherapy machine availability. There was regional and income-level heterogeneity regarding the inclusion of specific radiotherapy checklist items in the NCCPs. Ongoing efforts are needed to promote the inclusion of radiotherapy in future iterations of NCCPs in order to improve global access to radiation treatment. FUNDING: No direct funding was used in this research.

Geographic Accessibility and Availability of Radiotherapy in Ghana.

Importance: Radiotherapy is critical for comprehensive cancer care, but there are large gaps in access. Within Ghana, data on radiotherapy availability and on the relationship between distance and access are unknown. Objectives: To estimate the gaps in radiotherapy machine availability in Ghana and to describe the association between distance and access to care. Design, Setting, and Participants: This is a cross-sectional, population-based study of radiotherapy delivery in Ghana in 2020 and model-based analysis of radiotherapy demand and the radiotherapy utilization rate (RUR) using the Global Task Force on Radiotherapy for Cancer Control investment framework. Exposures: Receipt of radiotherapy and the number of radiotherapy courses delivered. Main Outcomes and Measures: Geocoded location of patients receiving external beam radiotherapy (EBRT); median Euclidean distance from the district centroids to the nearest radiotherapy centers; proportion of population living within geographic buffer zones of 100, 150, and 200 km; additional capacity required for optimal utilization; and geographic accessibility after strategic location of a radiotherapy facility in an underserviced region. Results: A total of 2883 patients underwent EBRT courses in 2020, with an actual RUR of 11%. Based on an optimal RUR of 48%, 11 524 patients had an indication for radiotherapy, indicating that only 23% of patients received treatment. An investment of 23 additional EBRT machines would be required to meet demand. The median Euclidean distance from the district centroids to the nearest radiotherapy facility was 110.6 km (range, 0.62-513.2 km). The proportion of the total population living within a radius of 100, 150 and 200 km of a radiotherapy facility was 47%, 61% and 70%, respectively. A new radiotherapy facility in the northern regional capital would reduce the median of Euclidean distance by 10% to 99.4 km (range, 0.62-267.7 km) and increase proportion of the total population living within a radius of 100, 150 and 200 km to 53%, 69% and 84%, respectively. The greatest benefit was seen in regions in the northern half of Ghana. Conclusions and Relevance: In this cross-sectional study of geographic accessibility and availability of radiotherapy, Ghana had major national deficits of radiotherapy capacity, with significant geographic disparities among regions. Well-planned infrastructure scale-up that accounts for the population distribution could improve radiotherapy accessibility.

Modern Radiotherapy Technology: Obstacles and Opportunities to Access in Low- and Middle-Income Countries.

Low- and middle-income countries (LMICs) have a large burden of cancer with differential population needs and outcomes compared to high-income countries. Access to radiotherapy, especially modern technology, is a major challenge. Modern radiotherapy has been demonstrated with better utility in overall cancer outcomes. We deliberate various challenges and opportunities unique to LMICs' set up for access to modern radiotherapy technology in the light of discussions and deliberations made during the recently concluded annual meeting of Tata Memorial Centre, India. We take examples available from various LMICs in this direction in our manuscript.

Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis.

BACKGROUND & PURPOSE: To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer. MATERIALS & METHODS: We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done. RESULTS: In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I2 = 82%, p < 0.05) relative to volume-based studies (3950 patients) (I2 = 58, p = 0.01). The 3-year DFS for point-A and volume-based studies were 67% (95% CI 60%-73%) and 79% (95% CI 76%-82%) respectively (p = 0.001). Three-year LC for point-A and volume-based studies were 86% (95% CI 81%-90%) and 92% (91%-94%) respectively (p = 0.01). The difference in 3-year OS (72% vs. 79%, p = 0.12) was not statistically significant. The proportion of prospectively enrolled patients was 23% for point-A studies and 33% for volume-based studies. There was no difference in late grade 3 or higher gastrointestinal (3% vs. 4%, p = 0.76) genitourinary toxicities (3% vs. 3% p = 0.45) between the two groups. CONCLUSION: Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning.

Radiotherapy resources in Africa: an International Atomic Energy Agency update and analysis of projected needs.

The number of patients with cancer in Africa has been predicted to increase from 844 279 in 2012 to more than 1·5 million in 2030. However, many countries in Africa still lack access to radiotherapy as a part of comprehensive cancer care. The objective of this analysis is to present an updated overview of radiotherapy resources in Africa and to analyse the gaps and needs of the continent for 2030 in the context of the UN Sustainable Development Goals. Data from 54 African countries on teletherapy megavoltage units and brachytherapy afterloaders were extracted from the Directory for Radiotherapy Centres, an electronic, centralised, and continuously updated database of radiotherapy centres. Cancer incidence and future predictions were taken from the GLOBOCAN 2018 database of the International Agency for Research on Cancer. Radiotherapy need was estimated using a 64% radiotherapy utilisation rate, while assuming a machine throughput of 500 patients per year. As of March, 2020, 28 (52%) of 54 countries had access to external beam radiotherapy, 21 (39%) had brachytherapy capacity, and no country had a capacity that matched the estimated treatment need. Median income was an important predictor of the availability of megavoltage machines: US$1883 (IQR 914-3269) in countries without any machines versus $4485 (3079-12480) in countries with at least one megavoltage machine (p=0·0003). If radiotherapy expansion continues at the rate observed over the past 7 years, it is unlikely that the continent will meet its radiotherapy needs. This access gap might impact the ability to achieve the Sustainable Development Goals, particularly the target to reduce preventable, premature mortality by a third, and meet the target of the cervical cancer elimination strategy of 90% with access to treatment. Urgent, novel initiatives in financing and human capacity building are needed to change the trajectory and provide comprehensive cancer care to patients in Africa in the next decade.

Global Radiotherapy: Current Status and Future Directions-White Paper.

Recognizing the increase in cancer incidence globally and the need for effective cancer control interventions, several organizations, professional bodies, and international institutions have proposed strategies to improve treatment options and reduce mortality along with minimizing overall incidence. Despite these efforts, an estimated 9.6 million deaths in 2018 was attributed to this noncommunicable disease, making it the second leading cause of death worldwide. Left unchecked, this will further increase in scale, with an estimated 29.5 million new cases and 16.3 million deaths occurring worldwide in 2040. Although it is known and generally accepted that cancer services must include radiotherapy, such access is still very limited in many parts of the world, especially in low- and middle-income countries. After thorough review of the current status of radiotherapy including programs worldwide, as well as achievements and challenges at the global level, the International Atomic Energy Agency convened an international group of experts representing various radiation oncology societies to take a closer look into the current status of radiotherapy and provide a road map for future directions in this field. It was concluded that the plethora of global and regional initiatives would benefit further from the existence of a central framework, including an easily accessible repository through which better coordination can be done. Supporting this framework, a practical inventory of competencies needs to be made available on a global level emphasizing the knowledge, skills, and behavior required for a safe, sustainable, and professional practice for various settings. This white paper presents the current status of global radiotherapy and future directions for the community. It forms the basis for an action plan to be developed with professional societies worldwide.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Role of the IAEA in education and training of radiotherapy professionals in Asia Pacific.

In partnership with the Regional Co-operative Agreement for Research, Development and Training Related to Nuclear Science and Technology (RCA), the IAEA has been supporting Member States in the Asia and Pacific region to prepare, initiate and expand radiotherapy services safely and effectively. Education and training are essential components in IAEA-RCA projects and have been delivered through various initiatives both online and offline. In addition to building capacity and enabling technology transfer, these initiatives provided opportunities to foster collaboration at the regional level, leading to the initiation of professional societies and education/training schemes.

Hypofractionated radiotherapy in the real-world setting: An international ESTRO-GIRO survey.

BACKGROUND AND PURPOSE: Multiple large trials have established the non-inferiority of hypofractionated radiotherapy compared to conventional fractionation. This study will determine real-world hypofractionation adoption across different geographic regions for breast, prostate, cervical cancer, and bone metastases, and identify barriers and facilitators to its use. MATERIALS AND METHODS: An anonymous, electronic survey was distributed from January 2018 through January 2019 to radiation oncologists through the ESTRO-GIRO initiative. Predictors of hypofractionation were identified in univariable and multivariable regression analyses. RESULTS: 2316 radiation oncologists responded. Hypofractionation was preferred in node-negative breast cancer following lumpectomy (82·2% vs. 46·7% for node-positive; p < 0.001), and in low- and intermediate-risk prostate cancer (57·5% and 54·5%, respectively, versus 41·2% for high-risk (p < 0.001)). Hypofractionation was used in 32·3% of cervix cases in Africa, but <10% in other regions (p < 0.001). For palliative indications, hypofractionation was preferred by the majority of respondents. Lack of long-term data and concerns about local control and toxicity were the most commonly cited barriers. In adjusted analyses, hypofractionation was least common for curative indications amongst low- and lower-middle-income countries, Asia-Pacific, female respondents, small catchment areas, and in centres without access to intensity modulated radiotherapy. CONCLUSION: Significant variation was observed in hypofractionation across curative indications and between regions, with greater concordance in palliation. Using inadequate fractionation schedules may impede the delivery of affordable and accessible radiotherapy. Greater regionally-targeted and disease-specific education on evidence-based fractionation schedules is needed to improve utilization, along with best-case examples addressing practice barriers and supporting policy reform.

Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review.

A search for effective methods for the assessment of patients' individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4-6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts.

Addressing the burden of cervical cancer through IAEA global brachytherapy initiatives.

PURPOSE: Brachytherapy (BT) is an essential component of definitive therapy for locally advanced cervical cancer. Despite the advantages of the dose distribution with BT in cervical cancer, there is paucity of specific skills required for good-quality BT applications. Furthermore, replacing BT with other modern external beam techniques as a boost can lead to suboptimal results in cervix cancer. METHODS AND MATERIALS: Review of available IAEA resources, research and cooperation programs available from the IAEA was completed. These opportunities can be used to address challenges in Brachytherapy. The International Atomic Energy Agency (IAEA) provides support for BT through various means that includes education and training, both long term, short term and continuing medical education of professionals, providing expert visits to support implementation, development of curricula for professionals, e-learning through the human health campus, contouring workshops, 2D to 3D BT training, and virtual tumor boards. In addition, the IAEA provides support for implementing quality assurance in radiotherapy to its member states and provides guidelines for comprehensive audits in radiation therapy (QUATRO), and produces safety standards and training in radiation safety. In addition, mapping BT resources, making the case for investment and support for setting up BT services and radiotherapy centers are also available. The IAEA Dosimetry Laboratory provides calibration services to Secondary Standards Dosimetry Laboratories for well chambers used to confirm the reference air kerma rate of Co60 and Ir192 high-dose-rate BT sources, as well as for Cs137 low-dose-rate sources. Furthermore, the IAEA supports research and development in radiotherapy (and BT) through coordinated research activities that include controlled randomized clinical trials, Patterns of Care studies among others. Partnerships with professional organizations and funding bodies, as well as through the United Nations Joint Global Programme on Cervical Cancer Prevention and Control support radiotherapy activities, including BT in countries worldwide. CONCLUSION: The IAEA supports brachytherapy implementation, training and research and provides resources to professionals in the area.

The role of the radiation oncologist in quality and patient safety: A proposal of indicators and metrics.

This manuscript represents a collaboration from an international group of quality and safety expert radiation oncologists. It is a position/review paper with the specific aim of defining the role of the radiation oncologist in quality and safety management. This manuscript is unique in that we recommend specific quality assurance/control tasks and correlated quality and indicators and safety measures that are the responsibility of the radiation oncologist. The article addresses the role of the radiation oncologist in quality and safety from a strong perspective of multidisciplinarity and teamwork. Our manuscript is "cross-cutting" and applicable to radiation oncologist in any practice setting (i.e. low middle-income countries).

Organ at risk delineation for radiation therapy clinical trials: Global Harmonization Group consensus guidelines.

BACKGROUND AND PURPOSE: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group (GHG) is a collaborative group of Radiation Therapy Quality Assurance (RTQA) Groups harmonizing and improving RTQA for multi-institutional clinical trials. The objective of the GHG OAR Working Group was to unify OAR contouring guidance across RTQA groups by compiling a single reference list of OARs in line with AAPM TG 263 and ASTRO, together with peer-reviewed, anatomically defined contouring guidance for integration into clinical trial protocols independent of the radiation therapy delivery technique. MATERIALS AND METHODS: The GHG OAR Working Group comprised of 22 multi-professional members from 6 international RTQA Groups and affiliated organizations conducted the work in 3 stages: (1) Clinical trial documentation review and identification of structures of interest (2) Review of existing contouring guidance and survey of proposed OAR contouring guidance (3) Review of survey feedback with recommendations for contouring guidance with standardized OAR nomenclature. RESULTS: 157 clinical trials were examined; 222 OAR structures were identified. Duplicates, non-anatomical, non-specific, structures with more specific alternative nomenclature, and structures identified by one RTQA group were excluded leaving 58 structures of interest. 6 OAR descriptions were accepted with no amendments, 41 required minor amendments, 6 major amendments, 20 developed as a result of feedback, and 5 structures excluded in response to feedback. The final GHG consensus guidance includes 73 OARs with peer-reviewed descriptions (Appendix A). CONCLUSION: We provide OAR descriptions with standardized nomenclature for use in clinical trials. A more uniform dataset supports the delivery of clinically relevant and valid conclusions from clinical trials.

Examining geographic accessibility to radiotherapy in Canada and Greenland for indigenous populations: Measuring inequities to inform solutions.

BACKGROUND: A high cancer burden exists among indigenous populations worldwide. Canada and Greenland have similar geographic features that make health service delivery challenging. We sought to describe geographic access to radiotherapy for indigenous populations in both regions. METHODS: We used geospatial analyses to calculate distance and travel-time from indigenous communities in Canada and Greenland to the nearest radiotherapy center. We calculated the proportion of indigenous communities and populations residing within a 1 and 2-hour drive of a radiotherapy center in Canada, and compared the proportion of indigenous versus non-indigenous populations residing within each drive-time area. We calculated the potential distance and travel-time saved if radiotherapy was available in northern Canada (Yellowknife and Iqaluit), and Greenland (Nuuk). RESULTS: Median one-way travel from indigenous communities to nearest radiotherapy center in Canada was 268 km (3 h when considering any transportation mode), and 4111 km (6 h by plane) in Greenland. In Canada, 84% and 68% of indigenous communities were outside a 1 and 2-hour drive from a radiotherapy center, respectively. Only 2% of the total population in Canada resided outside a 2-hour drive from a radiotherapy center. However, indigenous peoples were 336 times more likely to live more than a 2-hour drive away, compared to non-indigenous peoples. Nearly 3 million km and 4000 h of travel could be saved over a 10-year period for patients with newly diagnosed cancers in Canada, and 7 million km and 10,000 h in Greenland, if radiotherapy was available in Yellowknife, Iqaluit and Nuuk. CONCLUSIONS: Geography is an important barrier to accessing radiotherapy for indigenous populations in Canada and Greenland. A significant disparity exists between indigenous and non-indigenous peoples in Canada. Geospatial analyses can help highlight disparities in access to inform radiotherapy service planning.

Access to radiotherapy and its association with cancer outcomes in a high-income country: Addressing the inequity in Canada.

BACKGROUND AND PURPOSE: Canada is a high-income country with universal healthcare. In international comparisons, its overall level of access to radiotherapy appears sufficient. However, challenges exist due to Canada's large geographic area and small population density. The association between access and cancer outcomes nationally has not yet been described. MATERIALS AND METHODS: We quantified geographic accessibility for 2012 using the linear distance from each Canadian health region centroid to the nearest radiotherapy center. We used geospatial analytic techniques to detect clusters of age-standardized all-cancer mortality-to-incidence ratios (MIRs) across health regions, from 2010-2012. Global ordinary least squares (OLS) and geographically-weighted regression (GWR) were conducted to examine relationships between distance and MIR, adjusting for sociodemographic factors. RESULTS: Median distance from health region centroid to nearest radiotherapy center was 101.73 km (range 1.14-2095.12). One cluster of worse outcomes (MIR range 0.45-0.88) involved most of northern Canada, with a second cluster of better outcomes (MIR range 0.40-0.41) in southern British Columbia. In both regression models, regions with longer distance to radiotherapy center (ß = 0.0001), increased smoking (ß = 0.002), and poorer food security (ß = -0.003) were significantly associated with worse outcomes (OLS R2 = 0.70, GWR R2 = 0.74). Distance remained independently associated with MIR for lung and colorectal cancer subgroups, but not breast and prostate. CONCLUSIONS: A clear north-south discordance in cancer outcomes exists in Canada, with poorer outcomes in the north, while radiotherapy centers are concentrated along the south. Increased distance to radiotherapy, along with other sociodemographic and health-system factors, are associated with poorer cancer outcomes. Our study could be replicated, particularly in other high-income countries, to help identify national patterns and regional disparities in access and outcomes.