Brachytherapy Workflow Practices: Analysis of Different Workflow Scenarios in Patients With Cervical Cancer and Impact on IGBT Implementation-An IAEA Study.

PURPOSE: The workflow of brachytherapy (BT) is an essential aspect of treatment to consider in image-guided brachytherapy (IGBT). It has an overarching effect influencing patient throughput and the number of cancer treatments that can be performed as it occupies equipment, space, and personnel. There is limited research addressing this issue. Under the International Atomic Energy Agency's Coordinated Research Activity titled IGBT for cervix cancer: An implementation study, our study analyzes various scenarios in the clinical workflow of BT delivery for cervical cancer. It aims to determine the extent to which these scenarios allow the routine implementation of IGBT. With this information, current barriers and individualized adaptations to efficient workflows can be identified to enhance the global application of IGBT, leading to better cervical cancer treatment. MATERIALS AND METHODS: A web-based poll of questions regarding practices in BT workflow was presented to 62 participants from low-, lower middle-, upper middle-, and high-income countries (19 countries). RESULTS: This study highlighted diversity in BT practices across countries, income levels, and regions. It identified variations in workflow, patient throughput, and resource availability, which can have implications for the efficiency and quality of BT treatments. Scenario A, utilizing multiple locations for the steps of the BT procedure, was the most commonly used. The availability of resources, such as imaging devices and trained personnel, varied among the participating centers and remained challenging for IGBT implementation and sustainability. CONCLUSION: The design of the BT facility plays a vital role in improving efficiency, with a dedicated BT suite contributing to an efficient workflow but limiting patient throughput, especially for high-volume centers. Although IGBT is effective, its implementation requires consideration of various logistical challenges and should be individualized.

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

PURPOSE: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). METHODS AND MATERIALS: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival. RESULTS: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. CONCLUSIONS: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

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.

Radiotherapy utilization in developing countries: An IAEA study.

BACKGROUND: The planning of national radiotherapy (RT) services requires a thorough knowledge of the country's cancer epidemiology profile, the radiotherapy utilization (RTU) rates and a future projection of these data. Previous studies have established RTU rates in high-income countries. METHODS: Optimal RTU (oRTU) rates were determined for nine middle-income countries, following the epidemiological evidence-based method. The actual RTU (aRTU) rates were calculated dividing the total number of new notifiable cancer patients treated with radiotherapy in 2012 by the total number of cancer patients diagnosed in the same year in each country. An analysis of the characteristics of patients and treatments in a series of 300 consecutive radiotherapy patients shed light on the particular patient and treatments profile in the participating countries. RESULTS: The median oRTU rate for the group of nine countries was 52% (47-56%). The median aRTU rate for the nine countries was 28% (9-46%). These results show that the real proportion of cancer patients receiving RT is lower than the optimal RTU with a rate difference between 10-42.7%. The median percent-unmet need was 47% (18-82.3%). CONCLUSIONS: The optimal RTU rate in middle-income countries did not differ significantly from that previously found in high-income countries. The actual RTU rates were consistently lower than the optimal, in particular in countries with limited resources and a large population.

Quality of radiotherapy services in post-Soviet countries: An IAEA survey.

BACKGROUND: The quality of radiotherapy services in post-Soviet countries has not yet been studied following a formal methodology. The IAEA conducted a survey using two sets of validated radiation oncology quality indicators (ROIs). METHODS: Eleven post-Soviet countries were assessed. A coordinator was designated for each country and acted as the liaison between the country and the IAEA. The methodology was a one-time cross-sectional survey using a 58-question tool in Russian. The questionnaire was based on two validated sets of ROIs: for radiotherapy centres, the indicators proposed by Cionini et al., and for data at the country level, the Australasian ROIs. RESULTS: The overall response ratio was 66.3%, but for the Russian Federation, it was 24%. Data were updated on radiotherapy infrastructure and equipment. 256 radiotherapy centres are operating 275 linear accelerators and 337 Cobalt-60 units. 61% of teletherapy machines are older than ten years. Analysis of ROIs revealed significant differences between these countries and radiotherapy practices in the West. Naming, task profile and education programmes of radiotherapy professionals are different than in the West. CONCLUSIONS: Most countries need modernization of their radiotherapy infrastructure coupled with adequate staffing numbers and updated education programmes focusing on evidence-based medicine, quality, and safety.

Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma.

BACKGROUND AND PURPOSE: Short-course radiotherapy (25 Gy in five fractions) was recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and/or frail patients with glioblastoma multiforme. This study compared the cost-effectiveness of the two regimens. MATERIAL AND METHODS: The direct unit costs of imaging, radiotherapy (RT), and dexamethasone were collected from the five primary contributing countries to the trial, constituting the data of 88% of all patients. Effectiveness was measured by the restricted mean overall survival (RMOS) and progression free survival (RMPFS). The incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were also estimated for comparison. RESULTS: The median OSs for the short-course and commonly used RTs were 8.2 (95% confidence interval [CI] 6.1-10.3) and 7.7 (95% CI 5.5-9.9) months, respectively (log rank p = 0.340). Median PFSs were also not different (p = 0.686). The differences in the RMOS and the ICER, however, were +0.11 life-years and -$3062 United States dollars (USD) per life-year gained, respectively. The differences in the RMPFS and the ICER were +0.02 PFS and -$17,693 USD, respectively. CONCLUSION: The ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen.

Guest short communication: Is education of RTTs really unnecessary?

Radiation TherapisTs (RTTs) are an integral part of the radiation oncology team, however the provision of high quality education for these professionals can be met with difficulties. Over many years, the RTT committee of the European Society for Radiotherapy and oncology (ESTRO), together with the International Atomic Energy Agency (IAEA) have endeavoured to improve the educational standards of RTTs. This article summarises the main difficulties experienced in this field as well as the steps that both the IAEA and ESTRO have taken to improve the education of RTTs and thereby improve the safe treatment of cancer patients internationally.

A review of the Best Practice in Radiation Oncology project from 2008 to 2018.

The European Society of Radiotherapy and Oncology (ESTRO)/International Atomic Energy Agency (IAEA) Best Practice in Radiation Oncology-a project to train RTT trainers has reached its ten year anniversary and will commence its fifth iteration in 2018. This project commenced as a novel way to address the issue of limited RTT education throughout Europe. In many countries the profession of RTT is not officially recognised and there is no formal education programme. RTT education is frequently a very short component of a broader programme such as diagnostic imaging, nursing or a technical discipline. To date, fifty-nine short courses have been delivered, two RTT-specific National societies have been developed, a South East European cooperation with biannual conferences has evolved and significant progress has been made on improving the radiotherapy-specific content of national educational programmes, which will continue with future iterations of this project.

Survival Outcomes With Short-Course Radiation Therapy in Elderly Patients With Glioblastoma: Data From a Randomized Phase 3 Trial.

PURPOSE: To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a randomized phase 3 trial comparing 2 short-course radiation therapy (RT) regimens in elderly and/or frail patients. METHODS AND MATERIALS: The original trial population included elderly and/or frail patients with a diagnosis of glioblastoma. Patients joined the phase 3, randomized, multicenter, prospective, noninferiority trial; were assigned to 1 of 2 groups in a 1:1 ratio, either short-course RT (25 Gy in 5 fractions, arm 1) or commonly used RT (40 Gy in 15 fractions, arm 2); and were stratified by age (<65 years and ≥65 years), Karnofsky Performance Status (KPS), and extent of surgery. For the subset analysis in this study, only patients aged ≥65 years were evaluated (elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70%; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100%); 61 of the 98 initial patients comprised the patient population, with 26 patients randomized to arm 1 and 35 to arm 2. RESULTS: In this unplanned analysis, the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients. The median overall survival time was 6.8 months (95% confidence interval [CI], 4.5-9.1 months) in arm 1 and 6.2 months (95% CI, 4.7-7.7 months) in arm 2 (P=.936). The median progression-free survival time was 4.3 months (95% CI, 2.6-5.9 months) in arm 1 and 3.2 months (95% CI, 0.1-6.3 months) in arm 2 (P=.706). CONCLUSIONS: A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years, mainly those with a poor performance status or contraindication to chemotherapy, which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors.

Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy.

PURPOSE: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT). METHODS AND MATERIALS: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1-(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population. RESULTS: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (<45%, 45%-55%, and >55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001). CONCLUSIONS: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.

Expanding global access to radiotherapy.

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme.

PURPOSE: The optimal radiotherapy regimen for elderly and/or frail patients with newly diagnosed glioblastoma remains to be established. This study compared two radiotherapy regimens on the outcome of these patients. PATIENTS AND METHODS: Between 2010 and 2013, 98 patients (frail = age ≥ 50 years and Karnofsky performance status [KPS] of 50% to 70%; elderly and frail = age ≥ 65 years and KPS of 50% to 70%; elderly = age ≥ 65 years and KPS of 80% to 100%) were prospectively randomly assigned to two arms in a 1:1 ratio, stratified by age (< and ≥ 65 years old), KPS, and extent of surgical resection. Arm 1 received short-course radiotherapy (25 Gy in five daily fractions over 1 week), and arm 2 received commonly used radiotherapy (40 Gy in 15 daily fractions over 3 weeks). RESULTS: The short-course radiotherapy was noninferior to commonly used radiotherapy. The median overall survival time was 7.9 months (95% CI, 6.3 to 9.6 months) in arm 1 and 6.4 months (95% CI, 5.1 to 7.6 months) in arm 2 (P = .988). Median progression-free survival time was 4.2 months (95% CI, 2.5 to 5.9) in arm 1 and 4.2 months (95% CI, 2.6 to 5.7) in arm B (P = .716). With a median follow-up time of 6.3 months, the quality of life between both arms at 4 weeks after treatment and 8 weeks after treatment was not different. CONCLUSION: There were no differences in overall survival time, progression-free survival time, and quality of life between patients receiving the two radiotherapy regimens. In view of the reduced treatment time, the short 1-week radiotherapy regimen may be recommended as a treatment option for elderly and/or frail patients with newly diagnosed glioblastoma.

Quality audits of radiotherapy centres in Latin America: a pilot experience of the International Atomic Energy Agency.

BACKGROUND: In Latin America radiotherapy quality varies significantly among hospitals, where highly equipped academic centers coexist with others not meeting minimal requirements. In 2007, the International Atomic Energy Agency published guidelines for auditing radiotherapy centers, known as the "Quality Assurance Team for Radiation Oncology" (QUATRO) audits. The present report summarizes a pilot experience with QUATRO audits to 12 radiotherapy centres. METHODS: The findings from QUATRO audits conducted in 12 radiotherapy centres in Latin America between 2008 and 2013 were analysed. Events representing weaknesses or gaps in the process of radiotherapy were recorded. Relevant data for estimating human and technological needs of visited centres were processed. The main difficulties and strengths faced by institutions were also documented. RESULTS: All 12 radiotherapy centres were successfully audited following the QUATRO method. IAEA provided a dosimetry kit for quality control. Forty percent of audited institutions were immersed in a health system that did not recognize cancer as a public health priority problem. With few exceptions, local training programs for physicists and technologists were scarce and research was not an activity of interest among physicians. Centres were provided with sufficient staff to meet the local demand, both in the case of radiation oncologists, physicists and radiation therapists. Three centres lacking the minimum infrastructure were identified. Three institutions did not perform gynaecological brachytherapy, and one installation delivered around 900 teletherapy treatments annually without simulation, planning or dosimetry equipment for that purpose. Recommendations to centres were classified as related to personnel, infrastructure, processes and institutional organizational aspects. Many recommendations warned governments about the evident need for allocating more budgetary resources to radiotherapy. Most recommendations pointed out different aspects related to strengthen human resources training and technological support to the audited centres. Scheduled follow-up visits were also stressed. CONCLUSION: The QUATRO audits proved to be a valuable tool for identifying weaknesses in infrastructure, human resources and procedures in radiotherapy centres. Follow-up visits conducted by the IAEA or by regional or local organizations are necessary in order to evaluate outcomes and sustainability of implemented recommendations.

Optimal radiotherapy utilisation rate in developing countries: An IAEA study.

Optimal radiotherapy utilisation rate (RTU) is the proportion of all cancer cases that should receive radiotherapy. Optimal RTU was estimated for 9 Middle Income Countries as part of a larger IAEA project to better understand RTU and stage distribution.

Planning national radiotherapy services.

Countries, states, and island nations often need forward planning of their radiotherapy services driven by different motives. Countries without radiotherapy services sponsor patients to receive radiotherapy abroad. They often engage professionals for a feasibility study in order to establish whether it would be more cost-beneficial to establish a radiotherapy facility. Countries where radiotherapy services have developed without any central planning, find themselves in situations where many of the available centers are private and thus inaccessible for a majority of patients with limited resources. Government may decide to plan ahead when a significant exodus of cancer patients travel to another country for treatment, thus exposing the failure of the country to provide this medical service for its citizens. In developed countries, the trigger has been the existence of highly visible waiting lists for radiotherapy revealing a shortage of radiotherapy equipment. This paper suggests that there should be a systematic and comprehensive process of long-term planning of radiotherapy services at the national level, taking into account the regulatory infrastructure for radiation protection, planning of centers, equipment, staff, education programs, quality assurance, and sustainability aspects. Realistic budgetary and cost considerations must also be part of the project proposal or business plan.