Julieta Corral

MLH1 promoter hypermethylation in the analytical algorithm of Lynch syndrome: a cost-effectiveness study.

The analytical algorithm of Lynch syndrome (LS) is increasingly complex. BRAF V600E mutation and MLH1 promoter hypermethylation have been proposed as a screening tool for the identification of LS. The aim of this study was to assess the clinical usefulness and cost-effectiveness of both somatic alterations to improve the yield of the diagnostic algorithm of LS. A total of 122 colorectal tumors from individuals with family history of colorectal cancer that showed microsatellite instability and/or loss of mismatch repair (MMR) protein expression were studied. MMR germline mutations were detected in 57 cases (40 MLH1, 15 MSH2 and 2 MSH6). BRAF V600E mutation was assessed by single-nucleotide primer extension. MLH1 promoter hypermethylation was assessed by methylation-specific multiplex ligation-dependent probe amplification in a subset of 71 cases with loss of MLH1 protein. A decision model was developed to estimate the incremental costs of alternative case-finding methods for detecting MLH1 mutation carriers. One-way sensitivity analysis was performed to assess robustness of estimations. Sensitivity of the absence of BRAF mutations for depiction of LS patients was 96% (23/24) and specificity was 28% (13/47). Specificity of MLH1 promoter hypermethylation for depiction of sporadic tumors was 66% (31/47) and sensitivity of 96% (23/24). The cost per additional mutation detected when using hypermethylation analysis was lower when compared with BRAF study and germinal MLH1 mutation study. Somatic hypermethylation of MLH1 is an accurate and cost-effective pre-screening method in the selection of patients that are candidates for MLH1 germline analysis when LS is suspected and MLH1 protein expression is absent.

The optimal utilization proportion of external beam radiotherapy in European countries: An ESTRO-HERO analysis.

BACKGROUND AND PURPOSE The absolute number of new cancer patients that will require at least one course of radiotherapy in each country of Europe was estimated. MATERIAL AND METHODS The incidence and relative frequency of cancer types from the year 2012 European Cancer Observatory estimates were used in combination with the population-based stage at diagnosis from five cancer registries. These data were applied to the decision trees of the evidence-based indications to calculate the Optimal Utilization Proportion (OUP) by tumour site. RESULTS In the minimum scenario, the OUP ranged from 47.0% in the Russian Federation to 53.2% in Belgium with no clear geographical pattern of the variability among countries. The impact of stage at diagnosis on the OUP by country was rather limited. Within the 24 countries where data on actual use of radiotherapy were available, a gap between optimal and actual use has been observed in most of the countries. CONCLUSIONS The actual utilization of radiotherapy is significantly lower than the optimal use predicted from the evidence based estimates in the literature. This discrepancy poses a major challenge for policy makers when planning the resources at the national level to improve the provision in European countries.

How many new cancer patients in Europe will require radiotherapy by 2025? An ESTRO-HERO analysis

BACKGROUND The objective of this HERO study was to assess the number of new cancer patients that will require at least one course of radiotherapy by 2025. METHODS European cancer incidence data by tumor site and country for 2012 and 2025 was extracted from the GLOBOCAN database. The projection of the number of new cases took into account demographic factors (age and size of the population). Population based stages at diagnosis were taken from four European countries. Incidence and stage data were introduced in the Australian Collaboration for Cancer Outcomes Research and Evaluation (CCORE) model. RESULTS Among the different tumor sites, the highest expected relative increase by 2025 in treatment courses was prostate cancer (24%) while lymphoma (13%), head and neck (12%) and breast cancer (10%) were below the average. Based on the projected cancer distributions in 2025, a 16% expected increase in the number of radiotherapy treatment courses was estimated. This increase varied across European countries from less than 5% to more than 30%. CONCLUSION With the already existing disparity in radiotherapy resources in mind, the data provided here should act as a leverage point to raise awareness among European health policy makers of the need for investment in radiotherapy.

The impact of cancer incidence and stage on optimal utilization of radiotherapy: Methodology of a population based analysis by the ESTRO-HERO project

BACKGROUND AND PURPOSE The impact of differences in the distribution of major cancer sites and stages at diagnosis among 4 European countries on the optimal utilization proportion (OUP) of patients who should receive external beam radiotherapy was assessed within the framework of the ESTRO-HERO project. MATERIALS AND METHODS Data from Australian Collaboration for Cancer Outcomes Research and Evaluation (CCORE) were used. Population based stages at diagnosis from the cancer registries of Belgium, Slovenia, the Greater Poland region of Poland, and The Netherlands were used to assess the OUP for each country. A sensitivity analysis was carried out. RESULTS The overall OUP by country varied from the lowest of 48.3% in Australia to the highest of 53.4% in Poland; among European countries the variation was limited to 3%. Cancer site specific OUPs showed differences according to the variability in stage at diagnosis across countries. The most important impact on the OUP by country was due to changes in relative frequency of tumours rather than stage at diagnosis. CONCLUSIONS This methodology can be adapted using European data, thus facilitating the planning of resources required to cope with the demand for radiotherapy in Europe, taking into account the national variability in cancer incidence.

Estimation of lung cancer diagnosis and treatment costs based on a patient-level analysis in Catalonia (Spain)

BackgroundAssessing of the costs of treating disease is necessary to demonstrate cost-effectiveness and to estimate the budget impact of new interventions and therapeutic innovations. However, there are few comprehensive studies on resource use and costs associated with lung cancer patients in clinical practice in Spain or internationally. The aim of this paper was to assess the hospital cost associated with lung cancer diagnosis and treatment by histology, type of cost and stage at diagnosis in the Spanish National Health Service.MethodsA retrospective, descriptive analysis on resource use and a direct medical cost analysis were performed. Resource utilisation data were collected by means of patient files from nine teaching hospitals. From a hospital budget impact perspective, the aggregate and mean costs per patient were calculated over the first three years following diagnosis or up to death. Both aggregate and mean costs per patient were analysed by histology, stage at diagnosis and cost type.ResultsA total of 232 cases of lung cancer were analysed, of which 74.1% corresponded to non-small cell lung cancer (NSCLC) and 11.2% to small cell lung cancer (SCLC); 14.7% had no cytohistologic confirmation. The mean cost per patient in NSCLC ranged from 13,218 Euros in Stage III to 16,120 Euros in Stage II. The main cost components were chemotherapy (29.5%) and surgery (22.8%). Advanced disease stages were associated with a decrease in the relative weight of surgical and inpatient care costs but an increase in chemotherapy costs. In SCLC patients, the mean cost per patient was 15,418 Euros for limited disease and 12,482 Euros for extensive disease. The main cost components were chemotherapy (36.1%) and other inpatient costs (28.7%). In both groups, the Kruskall-Wallis test did not show statistically significant differences in mean cost per patient between stages.ConclusionsThis study provides the costs of lung cancer treatment based on patient file reviews, with chemotherapy and surgery accounting for the major components of costs. This cost analysis is a baseline study that will provide a useful source of information for future studies on cost-effectiveness and on the budget impact of different therapeutic innovations in Spain.

Hacia la concentración de la cirugía oncológica digestiva: cambios en la actividad, las técnicas y los resultados

AIM The objective of the present study was to examine changes in the activity, surgical techniques and results from the process of centralization of complex digestive oncologic surgery in 2005-2012 as compared to 1996-2000. MATERIAL AND METHODS A retrospective cohort study employing the minimum basic data set of hospital discharge (MBDSHD 1996-2012) from public centers in Catalonia (Spain) was performed. The population consisted of individuals aged > 18 who underwent digestive oncologic surgery (esophagus, pancreas, liver, stomach or rectum). Medical centers were divided into low, medium, and high-volume centers (≤ 5, 6-10, and > 10 interventions/year, respectively). The tendency Chi-squared test was used to assess the centralization of patients in high-volume centers and hospital mortality evolution during the study period. Logistic regression was performed to assess the relationship between volume and outcome. RESULTS A centralization of complex oncologic digestive surgery between 10% (liver) and 46% (esophagus) was obtained by means of a reduction in the number of hospitals that perform these interventions and a significant rise in the number of patients operated in high-volume centers (all types p ≤ 0.0001, except for esophagus). A significant decrease in mortality was observed, especially in esophagus (from 15% in 1996/2000 to 7% in 2009/12, p = 0.003) and pancreas (from 12% in 1996/2000 to 6% in 2009/12, p trend < 0.0001). CONCLUSIONS A centralization of oncologic digestive surgery in high-volume centers and a reduction of hospital mortality in Catalonia were reported among esophageal and pancreatic cancers. However, no significant changes were found for others cancer types.

Estimating the number of fractions by tumour site for European countries in 2012 and 2025: An ESTRO-HERO analysis

BACKGROUND AND PURPOSE The optimal number of radiotherapy fractions is a relevant input for planning resource needs. An estimation of the total number of fractions by country and tumour site is assessed for 2012 and 2025. METHODS European cancer incidence data by tumour site and country for 2012 and 2025 were extracted from the GLOBOCAN database. Incidence and stage data were introduced in the Australian Collaboration for Cancer Outcomes Research and Evaluation (CCORE) model, producing an evidence-based proportion of incident cases with an indication for radiotherapy and fractions by indication. An indication was defined as a clinical situation in which radiotherapy was the treatment of choice. RESULTS The total number of fractions if radiotherapy was given according to guidelines to all patients with an indication in Europe was estimated to be 30 million for 2012; with a forecasted increase of 16.1% by 2025, yet with differences by country and tumour. The average number of fractions per course was 17.6 with a small range of differences following stage at diagnosis. Among the treatments with radical intent the average was 24 fractions, while it decreased to 2.5 among palliative treatments. DISCUSSION An increase in the total number of fractions is expected in many European countries in the coming years following the trends in cancer incidence. In planning radiotherapy resources, these increases should be balanced to the evolution towards hypofractionation, along with increased complexity and quality assurance.