Pan-Canadian Survey of Radiation Oncology Professional Involvement in Global Oncology Initiatives in Low- and Middle-Income Countries.

PURPOSE: Canadian radiation oncology professionals have a strong history of involvement in global oncology initiatives worldwide. This pan-Canadian survey-based study was conducted to determine the current level of engagement of Canadian radiation oncologists (ROs) and medical physicists (MPs) in global oncology initiatives and broaden the development of these activities. MATERIALS AND METHODS: This was a cross-sectional study. The survey was designed to characterize current levels of engagement of Canadian ROs and MPs in global oncology initiatives. The survey was open from March 2019 to April 2020. It was disseminated to all Canadian Association of Radiation Oncology and Canadian Organization of Medical Physicists members with two subsequent email reminders. RESULTS: Survey responses were received from 40 (93%) of the 43 Canadian cancer treatment centers that offer radiotherapy. At least one RO responded at 34 centers (79%) and one MP from 34 centers (79%) with some overlap. A response was received from a total of 93 participants, 47 ROs and 46 MPs. Of all survey participants, 58% reported some experience with global oncology. Nineteen percent of the participants surveyed were currently directly involved in short- or long-term projects, more than half of which have opportunity for additional staff involvement. The projects spanned 26 countries in South America, Africa, and Asia. Quality improvement and capacity building accounted for 27% and 20% of initiatives, respectively. The most common area of engagement was in direct treatment care, accounting for 56% of the projects. CONCLUSION: This study demonstrates the landscape of involvement of Canadian ROs and MPs in global oncology initiatives. The study also highlights areas of opportunity for broadening international participation and collaboration as it relates to global oncology for Canadian radiation oncology professionals.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

BACKGROUND: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. METHODOLOGY:  Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. RESULTS: We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7) or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. CONCLUSIONS: We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on income or distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs. RESULTS: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007). CONCLUSION: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.

Radiation Therapy and Indigenous Peoples in Canada and Australia: Building Paths Toward Reconciliation in Cancer Care Delivery.

Indigenous peoples represent approximately 5% of the world's population and reside in over 90 countries worldwide. They embody a rich diversity of cultures, traditions, languages and relationships with the land that are shared through many generations and that are distinct from those of the settler societies within which they now live. Many Indigenous peoples have a shared experience of discrimination, trauma, and violation of rights, rooted in complex sociopolitical relationships with settler societies that are still ongoing. This results in continuing social injustices and pronounced disparities in health for many Indigenous peoples around the globe. Indigenous peoples exhibit a significantly higher cancer incidence, mortality, and poorer survival compared to non-Indigenous peoples. Cancer services, including radiotherapy, have not been designed to support the specific values and needs of Indigenous populations, resulting in poorer access to cancer services for Indigenous peoples globally across the entire cancer care spectrum. Specific to radiotherapy, available evidence demonstrates disparities in radiotherapy uptake between Indigenous and non-Indigenous patients. Radiotherapy centres are also located disparately further away from Indigenous communities. Studies are limited by a lack of Indigenous-specific data to help inform effective radiotherapy delivery. Recent Indigenous-led partnerships and initiatives have helped to address existing gaps in cancer care, and radiation oncologists play an important role in supporting such efforts. In this article, we present an overview of access to radiotherapy for Indigenous peoples in Canada and Australia, with a focus on strengthening cancer care delivery through education, partnerships, and research.

Equity in adjuvant radiotherapy utilization in locally advanced head and neck cancer: A SEER-data based study.

BACKGROUND: Not all patients with locally advanced head and neck cancer (HNC) who are eligible for adjuvant radiotherapy (RT) following upfront surgery appear to receive it. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients from 2009 to 2018 had locally advanced HNC, underwent upfront surgery, and were eligible for adjuvant RT. Multivariable logistic regression and chi-squared test were used to analyze available patient and tumor characteristics. RESULTS: Of 12 549 patients, 84.5% underwent adjuvant RT, 15.5% did not. Characteristics associated with lowest adjuvant RT utilization included cancers of the larynx (p < 0.0001) and gingivae (p < 0.0001), age 80 and above (p < 0.0001), unpartnered status (p < 0.0001), and residence within a nonmetropolitan area (p < 0.0024). CONCLUSIONS: Tumor subsite, age, partnered status, and rural/urban residence correlate with omission of adjuvant RT in locally advanced HNC.

Ten Years of the International Cancer Control Partnership: Promoting National Cancer Control Plans to Shape the Health System Response for Cancer Control.

Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP has provided key resources for the cancer community by hosting a portal with national cancer control and noncommunicable disease (NCD) plans, strategies, guidelines, and key implementation guides for a growing community of best practices. ICCP partners have responded to the changing needs of country planners, adjusting technical guidance as needs evolve from planning to implementation at the national level with an associated shift to peer-to-peer learning and knowledge exchange. The ICCP offer to assist countries in cancer planning continues to be relevant as countries focus on implementation of global initiatives for breast, cervical, and childhood cancers. These initiatives are important to drive priority actions and a systems approach in the emerging road map on NCDs-a message that will be supported by a second global review of NCCPs in 2023. This is critical for driving national action in all countries on cancer and other NCDs in line with global health commitments made for 2030 and adopted by the United Nations General Assemblies. ICCP sees robust systems and financial planning for implementation, monitoring, and evaluation of NCCPs and protection from cancer-related catastrophic expenditure, as critical to longer-term sustainability and success. ICCP calls for national policymakers to prioritize integration of cancer prevention and control into emerging universal health care approaches, including pandemic preparedness/health system resilience and calls for an equity focus in new NCCPs.

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.

Development of a Curriculum for the Implementation of Stereotactic Radiation Therapy Programs in Middle-Income Countries.

PURPOSE: The aim of this work was to develop a curriculum to be used in the implementation of stereotactic radiation therapy programs in middle-income countries. The curriculum needed to be scalable and flexible to be easily adapted to local situations. METHODS: The curriculum was developed through a partnership between multidisciplinary teams from established clinics in both middle-income and high-income countries. The curriculum development followed a nonlinear progression, allowing greater flexibility throughout the process. A blended learning model was used, combining virtual and in-person interactions. RESULTS: The initial training plan was based on a needs assessment provided by the learners and on the experience of the facilitators with stereotactic radiotherapy. The needs assessment was refined during in-person site visits at each institution which highlighted aspects of the training, such as image guidance workflows and technical specifications, that were not previously emphasized in the curriculum. Both teams found that the in-person visits were important for training purposes, but aspects of the curriculum delivery such as treatment planning and patient selection were well suited to virtual platforms. The training addressed all aspects of the stereotactic program, from patient selection to treatment, and included a review of both technical and clinical workflows. CONCLUSION: The inclusion of contributions from both teams ensured that the curriculum covered the required elements of the stereotactic program implementation, met the needs of the learners, and was relevant to local practices. The nonlinear approach to the curriculum development allowed the flexibility to change the focus as the project progressed. The in-person visits were valuable in conducting a thorough needs assessment.

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.

Breast cancer in Indigenous women living in Canada: a scoping review protocol.

OBJECTIVE: The objective of this review is to describe and synthesize the current state of knowledge pertaining to breast cancer in Indigenous women living in Canada. We will examine the continuum of breast cancer care in this population, including breast cancer screening, diagnosis, treatment, and surveillance. INTRODUCTION: Breast cancer in Indigenous women is an evolving health care concern in Canada, with mounting evidence suggesting that these women present at later stages, and have poorer survival rates compared with the general population. A comprehensive overview of the state of knowledge of breast cancer in this population is required. INCLUSION CRITERIA: The population of interest will include Indigenous women living in Canada aged 18 years or older who have been screened or require screening for breast cancer, or who have been diagnosed with breast cancer. "Indigenous" will include women who identify as First Nations, Métis, or Inuit. Eligible sources must report on breast cancer risk factors, tumor characteristics, health systems access, screening, diagnosis, treatment, surveillance, or breast cancer outcomes. We will include analytic studies, surveys, case series, reviews, meta-analyses, and gray literature. METHODS: We will conduct a search of five health sciences databases for relevant studies published in English or French from database inception onward. We will utilize dual independent screening for titles, abstracts, and full-text articles, and will utilize a similar method for gray literature sources. Data will be synthesized using a narrative approach, and outcomes of interest will be compared with data from the general breast cancer population. REGISTRATION: Open Science Framework https://osf.io/xkde5.

DECOLONIZING CANCER CARE IN CANADA.

Cancer incidence and mortality among Indigenous peoples of Canada (First Nations, Inuit, and Métis) continue to rise in contrast to non-Indigenous Canadians, and Indigenous peoples are at higher risk of cancers associated with known modifiable risk factors. Jurisdictional and administrative challenges have hindered high quality cancer care for Indigenous peoples since the country's inception, and different Indigenous populations face these challenges under similar yet non-identical circumstances. Collaborative initiatives under Indigenous leadership have drawn attention to specific issues such as screening, funding, and culturally appropriate care, and have identified resources necessary to address these problems. The Canadian Partnership Against Cancer and their collaborators have committed significant resources to Indigenous cancer programs with locally and regionally determined leadership and priorities. In the context of broader global movements against systemic racism and inequity, decolonization of cancer care demands critical analysis of the existing cancer systems and restructuring under Indigenous leadership with multidisciplinary collaboration.

Impact of a global radiation oncology scholarship for trainees: An evaluation of early outcomes.

Global Oncology capacity in Radiation Oncology (RO) needs development. We report on early outcomes of a Canadian Global Oncology elective scholarship program for trainees (2014-2019). The number of global oncology electives increased. Academic deliverables and collaborations were observed. There was evidence of personal and professional development.

Breast cancer treatment: A phased approach to implementation.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

The Breast Health Global Initiative 2018 Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation: Methods and overview.

BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

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.

Global palliative radiotherapy: a framework to improve access in resource-constrained settings.

Radiotherapy is an essential component of cancer therapy. Lack of access to radiotherapy in less-developed countries prevents its use for both cure and symptom relief, resulting in a significant disparity in patient suffering. Several recent initiatives have highlighted the need for expanded access to both palliative medicine and radiotherapy globally. Yet, these efforts have remained largely independent, without attention to overlap and integration. This review provides an update on the progress toward global palliative radiotherapy access and proposes a strategic framework to address further scale-up. Synergies between radiotherapy, palliative medicine, and other global health initiatives will be essential in bringing palliative radiotherapy to patients around the globe.

Radiotherapy for Langerhans Cell Histiocytosis of Bilateral Eyelids.

Langerhans cell histiocytosis (LCH) is a rare disorder with numerous clinicopathological variants with differing clinical courses, treatment methods, and prognoses. We report one patient with atypical LCH of the bilateral lower eyelids and subsequent successful treatment with local radiation therapy.

Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency.

BACKGROUND: The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. METHODS: Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR - 11 Gy) or high dose-rate (HDR - 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3-4 adverse events. RESULTS: 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67 patients) (p = 0.343). The grade 3-4 toxicity rate was 21.6% (30/139) and 24.4% (33/135) respectively (p = 0.687). CONCLUSIONS: The addition of a brachytherapy boost to external beam radiotherapy and chemotherapy did not improve outcome in loco-regionally advanced nasopharyngeal carcinoma.