Early radiologic and metabolic tumour response assessment during combined chemo-radiotherapy for locally advanced NSCLC.

Background: The role of early treatment response for patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with concurrent chemo-radiotherapy (cCRT) is unclear. The study aims to investigate the predictive value of response to induction chemotherapy (iCX) and the correlation with pattern of failure (PoF). Materials and methods: Patients with LA-NSCLC treated with cCRT were included for analyses (n = 276). Target delineations were registered from radiotherapy planning PET/CT to diagnostic PET/CT, in between which patients received iCX. Volume, sphericity, and SUVpeak were extracted from each scan. First site of failure was categorised as loco-regional (LR), distant (DM), or simultaneous LR+M (LR+M). Fine and Gray models for PoF were performed: a baseline model (including performance status (PS), stage, and histology), an image model for squamous cell carcinoma (SCC), and an image model for non-SCC. Parameters included PS, volume (VOL) of tumour, VOL of lymph nodes, ΔVOL, sphericity, SUVpeak, ΔSUVpeak, and oligometastatic disease. Results: Median follow-up was 7.6 years. SCC had higher sub-distribution hazard ratio (sHR) for LRF (sHR = 2.771 [1.577:4.87], p < 0.01) and decreased sHR for DM (sHR = 0.247 [0.125:0.485], p  <  0.01). For both image models, high diagnostic SUVpeak increased risk of LRF (sHR = 1.059 [1.05:1.106], p < 0.01 for SCC, sHR = 1.12 [1.03:1.21], p < 0.01 for non-SCC). Patients with SCC and less decrease in VOL had higher sHR for DM (sHR = 1.025[1.001:1.048] pr. % increase, p = 0.038). Conclusion: Poor response in disease volume was correlated with higher sHR of DM for SCC, no other clear correlation of response and PoF was observed. Histology significantly correlated with PoF with SCC prone to LRF and non-SCC prone to DM as first site of failure. High SUVpeak at diagnosis increased the risk of LRF for both histologies.

An experimental setup for proton irradiation of a murine leg model for radiobiological studies.

BACKGROUND: The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. METHODS: The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. RESULTS: The dose-response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose-response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. CONCLUSIONS: We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.

Access to Radiation Therapy: From Local to Global and Equality to Equity.

The discipline of radiation oncology is the most resource-intensive component of comprehensive cancer care because of significant initial investments required for machines, the requirement of dedicated construction, a multifaceted workforce, and recurring maintenance costs. This review focuses on the challenges associated with accessible and affordable radiation therapy (RT) across the globe and the possible solutions to improve the current scenario. Most common cancers globally, including breast, prostate, head and neck, and cervical cancers, have a RT utilization rate of > 50%. The estimated annual incidence of cancer is 19,292,789 for 2020, with > 70% occurring in low-income countries and low-middle-income countries. There are approximately 14,000 teletherapy machines globally. However, the distribution of these machines is distinctly nonuniform, with low-income countries and low-middle-income countries having access to < 10% of the global teletherapy machines. The Directory of Radiotherapy Centres enlists 3,318 brachytherapy facilities. Most countries with a high incidence of cervical cancer have a deficit in brachytherapy facilities, although formal estimates for the same are not available. The deficit in simulators, radiation oncologists, and medical physicists is even more challenging to quantify; however, the inequitable distribution is indisputable. Measures to ensure equitable access to RT include identifying problems specific to region/country, adopting indigenous technology, encouraging public-private partnership, relaxing custom duties on RT equipment, global/cross-country collaboration, and quality human resources training. Innovative research focusing on the most prevalent cancers aiming to make RT utilization more cost-effective while maintaining efficacy will further bridge the gap.

Value-based radiotherapy: A new chapter of the ESTRO-HERO project.

Radiotherapy interventions are rapidly evolving and improving, holding promise for better patient outcomes, yet at the possible detriment of higher societal costs. The ESTRO-HERO value-based radiotherapy project aims to develop a framework defining and assessing the value of radiotherapy innovations, to support clinical implementation and equitable access, within a sustainable healthcare system.

Provision and use of radiotherapy in Europe.

Radiation therapy is one of the core components of multidisciplinary cancer care. Although ~ 50% of all European cancer patients have an indication for radiotherapy at least once in the course of their disease, more than one out of four cancer patients in Europe do not receive the radiotherapy they need. There are multiple reasons for this underutilisation, with limited availability of the necessary resources - in terms of both trained personnel and equipment - being a major underlying cause of suboptimal access to radiotherapy. Moreover, large variations across European countries are observed, not only in available radiotherapy equipment and personnel per inhabitant or per cancer patient requiring radiotherapy, but also in workload. This variation is in part determined by the country's gross national income. Radiation therapy and technology are advancing quickly; hence, recommendations supporting resource planning and investment should reflect this dynamic environment and account for evolving treatment complexity and fractionation schedules. The forecasted increase in cancer incidence, the rapid introduction of innovative cancer treatments and the more active involvement of patients in the healthcare discussion are all factors that should be taken under consideration. In this continuously changing oncology landscape, reliable data on the actual provision and use of radiotherapy, the optimal evidence-based demand and the future needs are crucial to inform cancer care planning and address and overcome the current inequalities in access to radiotherapy in Europe.

How public health services pay for radiotherapy in Europe: an ESTRO-HERO analysis of reimbursement.

Reimbursement is a key factor in defining which resources are made available to ensure quality, efficiency, availability, and access to specific health-care interventions. This Policy Review assesses publicly funded radiotherapy reimbursement systems in Europe. We did a survey of the national societies of radiation oncology in Europe, focusing on the general features and global structure of the reimbursement system, the coverage scope, and level for typical indications. The annual expenditure covering radiotherapy in each country was also collected. Most countries have a predominantly budgetary-based system. Variability was the major finding, both in the components of the treatment considered for reimbursement, and in the fees paid for specific treatment techniques, fractionations, and indications. Annual expenses for radiotherapy, including capital investment, available in 12 countries, represented between 4·3% and 12·3% (average 7·8%) of the cancer care budget. Although an essential pillar in multidisciplinary oncology, radiotherapy is an inexpensive modality with a modest contribution to total cancer care costs. Scientific societies and policy makers across Europe need to discuss new strategies for reimbursement, combining flexibility with incentives to improve productivity and quality, allowing radiation oncology services to follow evolving evidence.

Critical review and quality-assessment of cost analyses in radiotherapy: How reliable are the data?

PURPOSE/OBJECTIVE: Health economic evaluations (HEE) are increasingly having an impact on policymakers, although the results greatly depend on the quality of the methodology used and on transparent reporting. The two main objectives of this study were to evaluate the quality of cost analyses of external beam radiotherapy (EBRT) and to assess the comprehensiveness and relevance of cost criteria defined in three validated quality-assessment instruments. MATERIALS AND METHODS: The selection of articles was based on a previous systematic literature review of EBRT-costing studies retrieved from January 2004 to January 2015 (Period 1) in MEDLINE, Embase, and NHS-EED databases and completed in a second time period from January 2015 to November 2018 (Period 2). Three validated instruments to assess the methodology quality with the CHEC and the QHES, and the methodology with the CHEERS checklists were used. The quality was evaluated by both quantitative and qualitative analyses. The scoring robustness was examined with the Kendall coefficient of concordance and inter-class correlation coefficients. RESULTS: In total, twenty-three articles were selected. The main geographic areas of cost analyses were Canada (n = 5), France (n = 4), and the USA (n = 4). The most commonly studied pathologies and technologies were prostate (n = 7) and head and neck cancer (n = 5) and IMRT (n = 8) and IGRT (n = 2), respectively. The mean instrument scores demonstrated a fair degree of methodological quality, with 69.7% for the CHEC, 73.6% for the QHES, as well as for the reporting quality, with 59.4% for CHEERS for Period 1 (74.4%, 71.5%, and 66.1%, respectively, for Period 2). An additional qualitative analysis per criterion revealed that certain items, essential for understanding the costing methodology and the results (e.g., the time horizon, discount rate, sensitivity analysis) were often only partially completed. Statistical analysis confirmed that the reviewers' scoring was consistent. The instruments identified the same top three articles, albeit with a degree of variation in the ranking. CONCLUSION: Qualitative and quantitative assessment of cost analyses in EBRT exhibits a fair level of study quality in terms of the methodology and reporting transparency. The impact of cost calculations on the final HEE result appears to be underestimated, and increased transparency of the data sources and the methodologies is needed.

National costs and resource requirements of external beam radiotherapy: A time-driven activity-based costing model from the ESTRO-HERO project.

BACKGROUND: The Health Economics in Radiation Oncology (ESTRO-HERO) project aims to provide a knowledge base for health economics in European radiotherapy. A cost-accounting model, providing data on national resource requirements and costs of external beam radiotherapy (EBRT), was developed. MATERIALS AND METHODS: Time-driven activity-based costing (TD-ABC) was applied from the healthcare provider perspective at national level. TD-ABC allocates resource costs to treatment courses through the activities performed, based on time estimates. RESULTS: The model is structured in three layers. The central layer, EBRT-Core, accounts for EBRT care-pathway activities and follows TD-ABC allocation principles. Activities supporting radiation oncology (RO) (RO-Support) and multidisciplinary oncology (Beyond-EBRT) follow standard allocation principles. To demonstrate the model's capabilities, a dataset was constructed for the hypothetical country Europalia, based on published evidence on resources and treatments, whereas time estimates were expert opinions. Applying the TD-ABC model to this example, treatment delivery activities represent 68.4% of the costs; treatment preparation 31.6%. The cost per course shows large variation for different indications, techniques, and fractionation schedules, ranging between €838 and €7193. Resource utilization was estimated to be within the available capacity. Scenario analyses on changes in fractionation and treatment complexity are presented. The ESTRO-HERO TD-ABC tool can model EBRT costs and resource requirements. While the Europalia example illustrates its potential, the results cannot be generalized nor used as a proxy for national evidence. Only real-world data, tailored to the specificities of individual countries, will support National Radiation Oncology Societies with investment planning and access to innovative radiotherapy.

Towards an evidence-informed value scale for surgical and radiation oncology: a multi-stakeholder perspective.

Surgery and radiotherapy, two locoregional cancer treatments, are essential to help improve cancer outcomes, control, and palliation. The continued evolution in treatment processes, techniques, and technologies-often at substantially increased costs-demands for direction on outcomes that are most valued by patients, and the evidence that is required before clinical adoption of these practices. Three recently introduced frameworks-the European Society for Medical Oncology Magnitude of Clinical Benefit Scale, the American Society of Clinical Oncology Value Framework, and the National Comprehensive Cancer Network Blocks-which all help define the value of oncology treatments, were appraised with a focus on their methods and definition of patient benefit. In this Review, we investigate the applicability of these frameworks to surgical and radiotherapy innovations. Findings show that these frameworks are not immediately transferable to locoregional cancer treatments. Moreover, the lack of emphasis on patient perspective and the reliance on traditional, trial-based endpoints such as survival, disease-free survival, and safety, calls for a new framework that includes real-world evidence with focus on the whole spectrum of patient-centred endpoints. Such an evidence-informed value scale would safeguard against the proliferation of low-value innovation while simultaneously increasing access to treatments that show significant improvements in the outcomes of cancer care.

Fear of cancer recurrence and unmet needs among breast cancer survivors in the first five years. A cross-sectional study.

BACKGROUND: It is unclear to which degree the services available after end of treatment are sufficient to meet the needs of women treated for breast cancer. The aim of the present study was to identify patient-reported supportive care needs and the prevalence of fear of cancer recurrence (FCR) following end of treatment in women treated for breast cancer. MATERIAL AND METHODS: Using a cross-sectional design, women treated for breast cancer (n = 155; mean age 63) completed questionnaires concerning supportive care needs and FCR. Inclusion criteria were: ≥18 years of age and treated for primary breast cancer at Aarhus University Hospital, Aarhus, Denmark and between three months and five years after diagnosis. Associations between demographic characteristics, clinical factors, side effects, late effects and the two dependent variables, unmet needs (examined with linear regression model), and FCR (examined with logistic regression model) were analyzed. RESULTS: The response rate was 79.9%. Almost all (82.6%) women reported at least one unmet need (mean number 9.3; range 0-34). More than half (59.3%) of the unmet needs were rated as strong unmet needs. The most frequent unmet needs were concerned with doctors collaborate to coordinate care; the need for having ongoing dialog with healthcare providers to receive available local health care services, understandable and up-to-date information, to manage side effects and feeling reassured that the best medical care are given. Having unmet needs were associated with young age, short time since primary surgery, and having clinical FCR. FCR was reported by 54.8% of the women and was associated with short time since primary surgery, having chemotherapy, having unmet needs, and moderate to severe muscle and joint pain and fatigue. CONCLUSIONS: Breast cancer survivors experience substantial unmet needs years after end of treatment, particularly among younger women and women having clinical FCR. Furthermore, FCR is frequent among women, particularly when closer in time to primary surgery.

Cost evaluations of radiotherapy: What do we know? An ESTRO-HERO analysis.

Although economic evidence is becoming mandatory to support health care decision-making, challenges remain in generating high quality cost data, especially for complex and rapidly evolving treatment modalities, such as radiotherapy. The overall aim of this systematic literature review was to critically analyse the type and quality of radiotherapy cost information available in cost calculation studies, from the health care provider's perspective, published since 1981. A selection process, based on strict and explicit criteria, yielded 52 articles. In spite of meeting our criteria these studies displayed large heterogeneity in scope, costing method, inputs and outputs. The limited use of conventional costing methodologies along with insufficient information on resource inputs hampered comparability across studies. A consistent picture of radiotherapy costs, based on methodologically sound costing studies, has yet to emerge. These results call for developing a well-defined and generally accepted cost methodology for performing economic evaluation studies in radiotherapy.

Cost calculation: a necessary step towards widespread adoption of advanced radiotherapy technology.

Radiotherapy costs are an often underestimated component of the economic assessment of new radiotherapy treatments and technologies. That the radiotherapy budget only consumes a finite part of the total cancer and healthcare budget does not relieve us from our responsibility to balance the extra costs to the additional benefits of new, more advanced, but typically also more expensive treatments we want to deliver. Yet, in contrast to what is the case for oncology drugs, literature evidence remains limited, as well for economic evaluations comparing new radiotherapy interventions as for cost calculation studies. Even more cumbersome, the available costing studies in the field of radiotherapy fail to accurately capture the real costs of our treatments due to the large variation in cost inputs, in scope of the analysis, in costing methodology. And this is not trivial. Accurate resource cost accounting lays the basis for the further steps in health technology assessment leading to radiotherapy investments and reimbursement, at the local, the national and the worldwide level. In the current paper we review some evidence from the existing costing literature and discuss how such data can be used to support reimbursement setting and investment cases for new radiotherapy equipment and infrastructure.

Radiotherapy equipment and departments in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO - the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. METHODS: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 26-29), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.3-1.5) and 1.4 (range 0.4-4.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCT-option). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. CONCLUSIONS: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT).

Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. MATERIALS AND METHODS: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. CONCLUSIONS: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.

Health economics in radiation oncology: introducing the ESTRO HERO project.

New evidence based regimens and novel high precision technology have reinforced the important role of radiotherapy in the management of cancer. Current data estimate that more than 50% of all cancer patients would benefit from radiotherapy during the course of their disease. Within recent years, the radiotherapy community has become more than conscious of the ever-increasing necessity to come up with objective data to endorse the crucial role and position of radiation therapy within the rapidly changing global oncology landscape. In an era of ever expanding health care costs, proven safety and effectiveness is not sufficient anymore to obtain funding, objective data about cost and cost-effectiveness are nowadays additionally requested. It is in this context that ESTRO is launching the HERO-project (Health Economics in Radiation Oncology), with the overall aim to develop a knowledge base and a model for health economic evaluation of radiation treatments at the European level. To accomplish these objectives, the HERO project will address needs, accessibility, cost and cost-effectiveness of radiotherapy. The results will raise the profile of radiotherapy in the European cancer management context and help countries prioritizing radiotherapy as a highly cost-effective treatment strategy. This article describes the different steps and aims within the HERO-project, starting from evidence on the role of radiotherapy within the global oncology landscape and highlighting weaknesses that may undermine this position.