Estimation of the optimal radiotherapy utilization rate for childhood neuroblastoma.

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.

Mapping of Radiation Oncology and Gynecologic Oncology Services Available to Treat the Growing Burden of Cervical Cancer in Africa.

PURPOSE: To meet the demand for cervical cancer care in Africa, access to surgical and radiation therapy services needs to be understood. We thus mapped the availability of gynecologic and radiation therapy equipment and staffing for treating cervical cancer. METHODS AND MATERIALS: We collected data on gynecologic and radiation oncology staffing, equipment, and infrastructure capacities across Africa. Data was obtained from February to July 2021 through collaboration with international partners using Research Electronic Data Capture. Cancer incidence was taken from the International Agency for Research on Cancer's GLOBOCAN 2020 database. Treatment capacity, including the numbers of radiation oncologists, radiation therapists, physicists, gynecologic oncologists, and hospitals performing gynecologic surgeries, was calculated per 1000 cervical cancer cases. Adequate capacity was defined as 2 radiation oncologists and 2 gynecologic oncologists per 1000 cervical cancer cases. RESULTS: Forty-three of 54 African countries (79.6%) responded, and data were not reported for 11 countries (20.4%). Respondents from 31 countries (57.4%) reported access to specialist gynecologic oncology services, but staffing was adequate in only 11 countries (20.4%). Six countries (11%) reported that generalist obstetrician-gynecologists perform radical hysterectomies. Radiation oncologist access was available in 39 countries (72.2%), but staffing was adequate in only 16 countries (29.6%). Six countries (11%) had adequate staffing for both gynecologic and radiation oncology; 7 countries (13%) had no radiation or gynecologic oncologists. Access to external beam radiation therapy was available in 31 countries (57.4%), and access to brachytherapy was available in 25 countries (46.3%). The number of countries with training programs in gynecologic oncology, radiation oncology, medical physics, and radiation therapy were 14 (26%), 16 (30%), 11 (20%), and 17 (31%), respectively. CONCLUSIONS: We identified areas needing comprehensive cervical cancer care infrastructure, human resources, and training programs. There are major gaps in access to radiation oncologists and trained gynecologic oncologists in Africa.

Transitioning India to advanced image based adaptive brachytherapy: a national impact analysis of upgrading National Cancer Grid cervix cancer guidelines.

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility. Methods: Between September 2020 and March 2021, activity mapping was conducted in a high-volume centre that triaged cervical cancer patients for brachytherapy into four workflows; A: two-dimensional (2D) X-Ray point A-based intracavitary brachytherapy, B: CT point A-based intracavitary brachytherapy, C: MRI/CT-volume based intracavitary brachytherapy, D: MRI/CT volume-based intracavitary +/- interstitial brachytherapy. Clinical process time mapping was performed, and case scenarios for transition were modelled at the institutional and national levels based on available incidence and infrastructure levels. Treatment capacity changes were calculated, and potential strategies for workflow reorganisation were proposed. Findings: Eighty-four patients were included in the study. The total time taken for the workflows A, B, C, and D were 176 min (57-208), 224 min (74-260), 267 min (101-302), and 348 min (232-383), respectively. The transition from workflow A to D through sequential steps led to 35%, 49%, and 64% loss of treatment capacity in the index institution. Solutions such as 10-hour or 12-hour overlapping shifts increased treatment capacity by 25% and 50% and performing single implants and delivering multiple fractions increased capacity by 100%. Twenty-three Indian states and Union Territories are predicted to be able to transition to advanced workflows. For four Indian states, it may be detrimental considering the current infrastructure level, and eight Indian states lacked brachytherapy access. Further financial investment is required in the latter 12 states for transition to advanced workflows. Interpretation: Our study demonstrates that unplanned transition to IGBT can lead to treatment capacity loss and increase in waiting lists to access treatment. The proposed solutions of workflow reorganisation, using strategies such as single brachytherapy applicator implant and delivering multiple treatment fractions can improve access to treatment for women with cervix cancer in resource-strained and high patient-volume settings. We recommend state-wise solutions for the upscale from conventional 2D workflows to IGBT, subject to the availability of skilled personnel, infrastructure and training. Financial investments may be needed in some states to achieve this goal. Funding: International Atomic Energy Agency (IAEA) supported the salary of VH through project E33042 that focussed on implementation strategies of image guided brachytherapy.

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.

Value of Geographical Information Systems in Analyzing Geographic Accessibility to Inform Radiotherapy Planning: A Systematic Review.

PURPOSE: Vulnerable populations face geographical barriers in accessing radiotherapy (RT) facilities, resulting in heterogeneity of care received and cancer burden faced. We aimed to explore the current use of Geographical Information Systems (GIS) in access to RT and use these findings to create sustainable solutions against barriers for access in low- and middle-income countries. MATERIALS AND METHODS: A systematic review using the PRISMA search strategy was done for studies using GIS to explore outcomes among patients with cancer. Included studies were reviewed and classified into three umbrella categories of how GIS has been used in studying access to RT. RESULTS: Forty articles were included in the final review. Thirty-eight articles were set in high-income countries and two in upper-middle-income countries. Included studies were published from 2000 to 2020, and were comprised of patients with all-cancers combined, breast, colon, skin, lung, prostate, ovarian, and rectal carcinoma patients. Studies were categorized under three groups on the basis of how they used GIS in their analyses: to describe geographic access to RT, to associate geographic access to RT with outcomes, and for RT planning. Most studies fell under multiple categories. CONCLUSION: Although this field is relative nascent, there is a wide array of functions possible through GIS for RT planning, including identifying high-risk populations, improving access in high-need areas, and providing valuable information for future resource allocation. GIS should be incorporated in future studies, especially set in low- and middle-income countries, which evaluate access to RT.

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.

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.

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.

Assessment of cancer control capacity and readiness: the role of the International Atomic Energy Agency.

During the past six decades, the International Atomic Energy Agency (IAEA) has helped to address the growing cancer burden, by delivering substantial cancer-related assistance to low-income and middle-income member states. IAEA assistance has primarily been facilitated through sustainable radiotherapy and nuclear medicine programmes to establish safe and effective diagnostic imaging, nuclear medicine, and radiotherapy capacity to safely treat patients with cancer. Planning of a National Cancer Control Programme starts with a needs assessment of all aspects of cancer control in the country to ensure evidence-based strategies are adapted to the country's specific needs. The IAEA offers its member states a tool, known as an integrated mission of Programme of Action for Cancer Therapy Review, to assess the status of national capacities for implementation and delivery of cancer control plans and activities and the readiness to develop and implement a long-term radiation medicine infrastructure and plan to improve capacity.

Risk factors and state-of-the-art indications for boost irradiation in invasive breast carcinoma.

PURPOSE: The aim of the study was to give recommendations on patient selection criteria for the administration of boost doses after whole-breast irradiation (WBI) in invasive breast cancer based on available clinical evidence complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the PubMed database was conducted to identify factors associated with increased risk for local failure that can define risk groups, and to provide evidence for an adequate guidance to the use of the boost as a function of the risk of local recurrence in breast-conserving therapy. The authors reviewed the published clinical evidence for the use of boost after WBI, complemented by other relevant studies and, through a series of formal meetings communications, formulated the recommendations presented in this article. RESULTS: The GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for the use of a boost after WBI: (1) a low-risk group for whom boost adds little benefit, including patients aging at least 50 years with unicentric, unifocal, and clear surgical margins of at least 2 mm and no axillary lymph nodes invasion. In this group, a boost of 10-16 Gy EQD2 after WBI (25fr × 2 Gy or 15 fr × 2.67 Gy) is optional and not mandatory, (2) a high-risk group, for whom boost is considered mandatory and where dose escalation above 16 Gy EQD2 should be considered; including patients aging ≤40 years with close margins, extensive intraductal component or triple-negative phenotype, or patients with positive resection margins regardless of patient age, and (3) an intermediate-risk group, for whom the boost (10-16 Gy EQD2) is considered mandatory, includes patients below 40 years without major risk criteria, patients >40 years and <50 years regardless of any risk factors, or patients >50 years with any risk factor (close margins, tumor size >3 cm, extensive intraductal component, lymphovascular invasion, lymph node invasion, multicentric or multifocal tumors, triple-negative phenotype, or after neoadjuvant chemotherapy in case of residual tumor). CONCLUSIONS: These recommendations may provide a clinical guidance regarding the use of boost after WBI in invasive breast cancer and holds for standard and hypofractionated WBI. Furthermore they should promote further clinical research focusing on controversial issues in the treatment of early-stage breast carcinoma.

Improving Quality and Access to Radiation Therapy-An IAEA Perspective.

The International Atomic Energy Agency (IAEA) has been involved in radiation therapy since soon after its creation in 1957. In response to the demands of Member States, the IAEA׳s activities relating to radiation therapy have focused on supporting low- and middle-income countries to set up radiation therapy facilities, expand the scope of treatments, or gradually transition to new technologies. In addition, the IAEA has been very active in providing internationally harmonized guidelines on clinical, dosimetry, medical physics, and safety aspects of radiation therapy. IAEA clinical research has provided evidence for treatment improvement as well as highly effective resource-sparing interventions. In the process, training of researchers occurs through this program. To provide this support, the IAEA works with its Member States and multiple partners worldwide through several mechanisms. In this article, we review the main activities conducted by the IAEA in support to radiation therapy. IAEA support has been crucial for achieving tangible results in many low- and middle-income countries. However, long-term sustainability of projects can present a challenge, especially when considering health budget constraints and the brain drain of skilled professionals. The need for support remains, with more than 90% of patients in low-income countries lacking access to radiotherapy. Thus, the IAEA is expected to continue its support and strengthen quality radiation therapy treatment of patients with cancer.

Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes.

PURPOSE: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). METHODS AND MATERIALS: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). CONCLUSIONS: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

Permanent seed brachytherapy for clinically localized prostate cancer: long-term outcomes in a 700 patient cohort.

PURPOSE: Few large European studies have evaluated long-term outcomes for permanent prostate brachytherapy (PPB) as monotherapy for clinically localized prostate cancer. The objective of the present study was to evaluate long-term survival in this patient profile. METHODS AND MATERIALS: Retrospective study of 700 patients who underwent transperineal ultrasound-guided iodine-125 PPB (145 Gy) between January 2000 and July 2012. Median age was 64.8 years (range, 35-79). Most patients (638 of 700; 91%) had low-risk disease (D'Amico criteria). Eighty-five patients (12%) received hormonal treatment. Overall survival, cause-specific survival, and biochemical relapse-free survival were calculated and estimated using actuarial and Kaplan-Meier methods. Differences between groups were assessed using the log-rank test. RESULTS: Median followup was 63 months (range, 6-164). At 5- and 10-year followup, respectively, overall survival was 94% (95% confidence interval [CI], 92-96) and 84% (95% CI, 78-90); cause-specific survival was 100% and 97% (95% CI, 95-99); and biochemical relapse-free survival was 95% (95% CI, 93-97) and 85% (95% CI, 79-91). CONCLUSIONS: The long-term results presented in this report confirm previous studies and provide additional support for the use of PPB in patients with favorable-risk prostate cancer. Seed brachytherapy provides excellent long-term results in this patient profile.

Anticipated intraoperative electron beam boost, external beam radiation therapy, and limb-sparing surgical resection for patients with pediatric soft-tissue sarcomas of the extremity: a multicentric pooled analysis of long-term outcomes.

PURPOSE: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. METHODS AND MATERIALS: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. RESULTS: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). CONCLUSIONS: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) plus high-dose-rate brachytherapy (HDRB) as a boost in patients (pts) with intermediate or high-risk prostate cancer. METHODS AND MATERIALS: From 2002 to July 2012, 377 pts with a diagnosis of intermediate or high-risk prostate cancer were treated with EBRT plus HDRB. Median patient age was 66 years (range, 41-86). Most patients (347 pts; 92%) were classified as high-risk (stage T2c-T3, or PSA>20 ng/mL, or GS ⩾ 8), with 30 patients (8%) considered intermediate risk. All patients underwent EBRT at a prescribed dose of 60.0 Gy (range, 45-70 Gy) to the prostate and seminal vesicles. A total of 120 pts (31%) received a dose of 46 Gy (45-50 Gy) to the true pelvis. All pts received a single-fraction 9 Gy (9-15 Gy) HDR boost. Most patients (353; 94%) were prescribed complete androgen deprivation therapy (ADT). Overall survival (OS), cause-specific survival (CSS), and biochemical relapse-free survival (BRFS) rates were calculated. In the case of BRFS, patients with <26 months of follow-up (n=106) were excluded to minimize the impact of ADT. RESULTS: The median follow-up for the entire sample was 50 months (range, 12-126), with 5-year actuarial OS and CSS, respectively, of 88% (95% confidence interval [CI]: 84-92) and 98% (95% CI: 97-99). The 5-year BRFS was 91% (95% CI: 87-95) in the 271 pts with ⩾ 26 months (median, 60 months) of follow-up. Late toxicity included grade 2 and 3 gastrointestinal toxicity in 17 (4.6%) and 6 pts (1.6%), respectively, as well as grades 2 and 3 genitourinary toxicity in 46 (12.2%) and 3 pts (0.8%), respectively. CONCLUSION: These long-term outcomes confirm that EBRT plus a single-fraction HDRB boost provides good results in treatment-related toxicity and biochemical control. In addition to the excellent clinical results, this fractionation schedule reduces physician workload, treatment-related expenses, patient discomfort and risks associated with anaesthesia. We believe these findings support the use of single-fractionation boost techniques.

Salvage brachytherapy in prostate local recurrence after radiation therapy: predicting factors for control and toxicity.

PURPOSE: To evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy. METHODS AND MATERIALS: Between 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED(2 Gy)). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0). RESULTS: Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED(2 Gy) level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure. HDR-BT BED(2 Gy) (α/ß 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity. CONCLUSIONS: Prostate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended.

Limb-sparing management with surgical resection, external-beam and intraoperative electron-beam radiation therapy boost for patients with primary soft tissue sarcoma of the extremity: a multicentric pooled analysis of long-term outcomes.

BACKGROUND OR PURPOSE: A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS). METHODS AND MATERIALS: Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study. RESULTS: From 1986-2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316 years), 5-year local control (LC) was 82 %. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p < 0.001). With regard to IOERT in-field control, incomplete resection (HR 4.88, p = 0.001) and higher IOERT dose (≥ 12.5 Gy; HR 0.32, p = 0.02) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that an IOERT dose ≥ 12.5 Gy increases the rate of IOERT in-field control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo- and adjuvant systemic therapy.

Prognostic value of external beam radiation therapy in patients treated with surgical resection and intraoperative electron beam radiation therapy for locally recurrent soft tissue sarcoma: a multicentric long-term outcome analysis.

BACKGROUND: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. METHODS AND MATERIALS: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). RESULTS: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). CONCLUSION: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.