Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Cost-effectiveness of an exercise and nutritional intervention versus usual nutritional care during adjuvant treatment for localized breast cancer: the PASAPAS randomized controlled trial.

We undertook a cost-effectiveness analysis (CEA) to compare an exercise and nutritional program with the usual nutritional care concomitant to adjuvant chemotherapy in localized breast cancer patients. The CEA was designed as part of the interventional, controlled, randomized, single-center, open-label PASAPAS study. Breast cancer patients receiving first-line adjuvant chemotherapy at a French Comprehensive Cancer Center were randomized 2:1 to a 6-month exercise program of supervised indoor and outdoor group sessions in addition to usual nutritional care (exercise arm) or a usual nutritional care group receiving dietary and physical activity counseling (control arm). Costs were assessed from the French national insurance perspective (in Euros, 2012). Incremental cost-effectiveness ratios (ICERs) were calculated for four criteria: body mass index, waist circumference, body fat percentage, and estimated aerobic capacity. Uncertainty around the ICERs was captured by a probabilistic analysis using a non-parametric bootstrap method. The analysis was based on 60 patients enrolled between 2011 and 2013. Average intervention costs per participant were €412 in the exercise arm (n = 41) and €117 (n = 19) in the control arm. Total mean costs were €17,344 (standard deviation 9,928) and €20,615 (standard deviation 14,904), respectively, did not differ significantly (p = 0.51). The 6-month exercise program was deemed to be cost-effective compared with usual care for the estimated aerobic capacity. Multicenter randomized studies with long-term costs and outcomes should be done to provide additional evidence. Clinical trial: The PASAPAS study is registered under ClinicalTrials.gov. Trial registration ID: NCT01331772.

Inequalities in the control of the occupational exposure in France to carcinogenic, mutagenic and reprotoxic chemicals.

Background: Our study examined the social disparities that exist in the implementation of protection measures for occupational exposure to carcinogenic, mutagenic and reprotoxic agents in France, and its aim was to identify which types of employees/jobs require priority action. Methods: We analyzed data from the 2010 French national cross-sectional survey of occupational hazards. The availability of the various collective and individual protections was explored. The associations of job and company characteristics with protective measures were studied by multilevel regressions. Results: Effective collective protection measures were implemented in 25% of the exposure situations. Managers and intellectual professionals, who accumulated lower CMR exposure prevalences, durations, and intensities than blue-collar workers, benefited the most from effective collective protections. The availability of effective collective protection measures was not influenced by the size of the company. The presence of a Committee for health, safety, and work conditions, as well as intervention of occupational health and safety officers in the past 12 months were associated with a lower exposure intensity, but not with the implementation of more protection measures. Longer exposure durations were associated with more effective collective protection. Conclusion: Substantial discrepancies were observed in exposure levels and protection measures as a function of the characteristics of employees' jobs and the companies that they work for. The main priority in regard to prevention should be a focus on unskilled workers, since their collective protection still appears to be insufficient, while their exposure lengths and intensities were the most substantial.

The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Clinical Outcomes of Several IMRT Techniques for Patients With Head and Neck Cancer: A Propensity Score-Weighted Analysis.

PURPOSE: The Advanced Radiotherapy Oto-Rhino-Laryngologie (ART-ORL) study (NCT02024035) was performed to prospectively evaluate the clinical and economic aspects of helical TomoTherapy and volumetric modulated arc therapy (RapidArc, Varian Medical Systems, Palo Alto, CA) for patients with head and neck cancer. METHODS AND MATERIALS: Fourteen centers participated in this prospective comparative study. Randomization was not possible based on the availability of equipment. Patients with epidermoid or undifferentiated nasopharyngeal carcinoma or epidermoid carcinoma of the oropharynx and oral cavity (T1-T4, M0, N0-N3) were included between February 2010 and February 2012. Only the results of the clinical study are presented in this report, as the results of the economic assessment have been published previously. Inverse probability of treatment weighting using the propensity score analysis was undertaken in an effort to adjust for potential bias due to nonrandomization. Locoregional control, cancer-specific survival, and overall survival assessed 18 months after treatment, as well as long-term toxicity and salivary function, were evaluated. RESULTS: The analysis included 166 patients. The following results are given after inverse probability of treatment weighting adjustment. The locoregional control rate at 18 months was significantly better in the TomoTherapy group: 83.3% (95% confidence interval [CI], 72.5%-90.2%) versus 72.7% (95% CI, 62.1%-80.8%) in the RapidArc group (P=.025). The cancer-specific survival rate was better in the TomoTherapy group: 97.2% (95% CI, 89.3%-99.3%) versus 85.5% (95% CI, 75.8%-91.5%) in the RapidArc group (P=.014). No significant difference was shown in progression-free or overall survival. TomoTherapy induced fewer acute salivary disorders (P=.012). Posttreatment salivary function degradation was worse in the RapidArc group (P=.012). CONCLUSIONS: TomoTherapy provided better locoregional control and cancer-specific survival than RapidArc treatment, with fewer salivary disorders. No significant difference was shown in progression-free and overall survival. These results should be explored in a randomized trial.

Management of Febrile Neutropenias in Adolescents and Young Adults: A Cost-Minimization Analysis Between Adult Versus Pediatric Units.

PURPOSE: Management of adolescents and young adults (AYAs) differs between adult and pediatric units, especially regarding febrile neutropenia (FN). In our previous study, we found that AYAs treated in adult units were significantly less hospitalized for FN than in pediatric units, without difference in morbimortality. The objective of this work was to assess the economic impact of these practices. METHODS: This study retrospectively collected data from the medical records of AYAs treated at the Comprehensive Cancer Center Léon Bérard, Lyon, France, in the Euro-E-W-I-N-G99 protocol between September 1, 2000 and May 31, 2013. We focused on FN occurring after VIDE (vincristine, ifosfamide, doxorubicin, etoposide) courses. Costs were calculated using a micro-costing technique from the hospital's perspective (in 2014-Euro); the time horizon was the induction period. Multivariate analyses were performed on the total cost and cost of FN. Uncertainty was captured by sensitivity analyses. RESULTS: Forty-four AYAs (18 in the adult sector, 26 in the pediatric sector) received 260 courses of VIDE. Mean cost of care was €37,544 in the pediatric sector, including €11,948 (32%) for FN (€11,851 in hospitalization), versus €34,677 in the adult sector, including €6,143 (18%) for FN (€5,789 in hospitalization). Cost for FN was significantly higher in pediatric units (difference in mean cost of €5,830 per patient, 95% bootstrapped confidence interval [1,939.1; 10,028.9]). In multivariate analysis, the only factor significantly influencing this cost difference was the sector of care. The most sensitive parameter was the unit cost of conventional hospitalization. CONCLUSION: These results support the adult sector strategy, in agreement with the results of our first work showing comparable effectiveness.

Trends in occupational disparities for exposure to carcinogenic, mutagenic and reprotoxic chemicals in France 2003-10.

Background: To explore trends in social and occupational inequalities in terms of exposure to carcinogenic, mutagenic and reprotoxic chemicals (CMR) for French employees. Our study assessed data from the French national cross-sectional survey of occupational hazards (SUMER) that was conducted in 2003 and 2010. We included all of the 27 CMR agents that were classified by the International Agency for Research on Cancer or European Union regulations as being known or presumed to have CMR potential in humans. Trends in prevalence and degree of exposure were examined using multilevel logistic regression analysis. The number of employees exposed to CMR agents decreased by 17.5% between 2003 and 2010. The only CMR entities for which exposure rates increased are not considered to be proven CMRs according to the European Union regulations. With the exception of apprentices, there was an overall decrease in exposure prevalence for all employees. This decrease occurred, however, to different extents. The decrease in the risk of exposure to CMR agents was much greater for those on permanent contracts, managers, and in enterprises with more than 500 employees. Nonetheless, in situations where there was potential for exposure, companies with fewer than 10 employees were in fact able to decrease the degree of risk more than the others. Our results confirm the relevance of reinforcing regulatory restrictions for CMR products, while also indicating that monitoring of trends in disparities will allow public health policy makers to better evaluate progress made toward reducing disparities that affect vulnerable populations.

Varied exposure to carcinogenic, mutagenic, and reprotoxic (CMR) chemicals in occupational settings in France.

PURPOSE: To explore varied exposure to carcinogenic, mutagenic, and reprotoxic chemicals (CMR) for French employees. METHODS: Our study assessed data from the French national cross-sectional survey of occupational risks (SUMER) that was conducted in 2010 in a national representative sample of employees. We selected 28 CMR agents that were classified by the International Agency for Research on Cancer or European Union as being known or presumed to have CMR potential in humans. The association of individual and job characteristics with exposure prevalence, duration, and intensity of the CMR agents during a 1-week period was examined using multilevel logistic regression analysis. RESULTS: Overall, 10.4% of employees in 2010 were exposed to one or more CMR agents at their workplace, and 3.4% were subjected to multiple CMR exposures. Blue-collar workers, night-shift workers and workers with short-term employment contracts experienced higher exposure prevalence (p < 0.01) and intensity (p < 0.05). Blue-collar workers and shift workers experienced also longer exposure duration (p < 0.001). Conversely, managers, workers of large companies, and women were less exposed to CMR agents (p < 0.001). The presence of a Committee for Health, Safety, and Working Conditions, and intervention by Occupational Health and Safety officers were significantly associated with reduced exposure intensities (p < 0.001 and p < 0.05). Establishment of European CMR regulations and the existence of an applicable substitution principle reduced the exposure duration (p < 0.001) and intensity (p < 0.05). CONCLUSIONS: Our results point out disparities in CMR exposure and identify high-priority targets for prevention measures to help reducing social health discrepancies.

Cost Analysis of Complex Radiation Therapy for Patients With Head and Neck Cancer.

PURPOSE: This cost analysis aimed to prospectively assess differences in costs between TomoTherapy and volumetric modulated arc therapy (VMAT) in patients with head and neck cancer. METHODS AND MATERIALS: Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the microcosting technique from the hospital's perspective (in 2013 euros), and the time horizon was radiation therapy. Only resources that entered the hospital production process and which were likely to vary between the strategies being compared were considered. Acute adverse events observed within the time horizon were also assessed. RESULTS: The cost analysis was based on a total of 173 patient treatments given between 2010 and 2012 in 14 French cancer centers: 73 patients were treated with TomoTherapy, 92 with VMAT RapidArc, and 8 with VMAT SmartArc. Estimated costs of SmartArc were removed from the comparison due to the small sample size. The mean ± SD cost per patient of the treatment planning phase was €314 (±€214) for TomoTherapy and €511 (±€590) for RapidArc. Mean costs ± SD per patient of irradiation reached €3144 (±€565) for TomoTherapy and €1350 (±€299) for RapidArc. The most sensitive parameter of irradiation was the annual operating time of accelerators. Ninety-five percent confidence intervals for the mean costs of irradiation were €3016 to €3272 for TomoTherapy and €1281 to €1408 for RapidArc. The number of acute adverse events during radiation therapy was not significantly different between strategies. CONCLUSIONS: TomoTherapy appeared to be more expensive than RapidArc mainly due to the higher price of the accelerator, the higher costs of maintenance, and the longer duration of treatment sessions. Because strategies were not significantly different in clinical effect, RapidArc appeared to be the strategy to be recommended at this stage of knowledge.

Cost of prostate image-guided radiation therapy: results of a randomized trial.

PURPOSE: This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). MATERIAL AND METHODS: Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. RESULTS: A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was €679 and €187 for CBCT and EPI-FM, respectively (p<0.0001). CONCLUSIONS: The incremental costs due to different prostate IGRT strategies are relatively moderate, suggesting that daily IGRT combined with intensity-modulated RT (IMRT) could be administered in cases of high-dose radiation delivery to the prostate.

Cancer patients' willingness to pay for blood transfusions at home: results from a contingent valuation study in a French cancer network.

Home blood transfusion may be an interesting alternative to hospital transfusion, especially when given with curative or palliative intent or for terminal care in advanced-stage cancer patients. However, there is limited information about patients' attitude toward this type of care. The purpose of this study was to measure French cancer patients' willingness to pay (WTP) for home blood transfusion and to analyze determinants of their choice. A contingent valuation survey was administered to 139 patients receiving transfusions in the framework of a regional home care network or in the hospital outpatient department. Participation was high (90%). Most patients (65%) had received home care, including 43% blood transfusions. Just under half of the patients gave a zero WTP, among which we identified 8 protest bidders. The median WTP for home blood transfusion was 26.5 per patient. In multivariate analysis, long home-hospital distance, poor quality of life, and previous experience of home care were identified as important factors in determining how much more patients would be willing to pay for transfusion at home. These results demonstrate the benefits of developing domiciliary services to improve patient well-being, notably for the weakest among them. The significant impact of previous home care experience on WTP is probably related to the strong involvement of physicians from the blood center and to their active contribution to a high-level homecare network. Some of our findings could be useful for policy decision-making regarding home care.

Assessing short-term effects and costs at an early stage of innovation: the use of positron emission tomography on radiotherapy treatment decision making.

OBJECTIVES: Positron emission tomography (PET) is an innovative imaging tool. Associated with computed tomography (CT), it allows a better definition for the tumor volume for radiotherapy, compared with CT only. The aim of this study was to assess the effects of PET on resource allocation (costs and savings) and on the choice of the following treatment in radiotherapy. METHODS: In 2004 and 2005, 209 patients were enrolled (97 patients with Hodgkin's disease and 112 with non-small cell lung cancer) in a national study conducted in eight hospitals. Two treatment decisions made on the basis of CT only or CT associated with PET, were compared in a prospective study where each subject was his/her own control. The direct medical cost of using PET was assessed by microcosting, using data collected from specific questionnaires. The costs of new tests and the costs and savings associated with changes in the chosen treatment were calculated on the basis of reimbursement rates. RESULTS: The mean cost of using PET was approximately euro 800 per patient (50 percent for the radionuclide 18F-FDG [2-[18F]fluoro-2-deoxy-D-glucose]). Radiotherapy treatments were modified for 10 percent of patients with Hodgkin's disease versus 40 percent of patients with lung cancer. Overall, the use of PET induced both increases and decreases in the mean cost per patient: the net effect was a euro 425 and euro 931 cost increase in lung cancer and Hodgkin's disease, respectively. CONCLUSIONS: The use of PET for radiotherapy decision making seems more valuable for lung cancer than for Hodgkin's disease, both in terms of costs and changes in radiotherapy treatment. This result might help policy makers for prioritization.

Cost-effectiveness analysis of strategies for HER2 testing of breast cancer patients in France.

OBJECTIVES: A cost-effectiveness analysis was conducted comparing diagnostic strategies for determining the HER2 status of invasive breast carcinomas, as an indication for trastuzumab at metastatic relapse. METHODS: A decision tree compared five strategies distinguished by (i) the use of immunohistochemical (IHC) and/or fluorescent in situ hybridization (FISH) techniques, and (ii) the test schedule (at initial diagnosis or metastatic relapse). Most cost and effectiveness data came from a French multicentric study of 2,045 patients from eight hospitals. We were not able to select final criteria for trastuzumab effectiveness, because published data rely on IHC techniques not used in France (i.e., HercepTest). We, therefore, selected two intermediate criteria for inappropriate treatment at relapse, that is, patients with HER2-amplified tumors not receiving trastuzumab (Criterion 1) and HER2-nonamplified tumors improperly treated with trastuzumab (Criterion 2). Sensitivity analyses were then performed to assess the robustness of the results to (i) discount rate, (ii) cost of FISH, and (iii) tissue fixation technique. RESULTS: The strategy using IHC at diagnosis was dominated by the four other strategies. Among these approaches, the only efficient strategy for both criteria was IHC used alone at metastatic relapse; strategies using FISH, or IHC followed by FISH on IHC2+ cases were efficient for Criterion 1, whereas IHC followed by FISH on IHC2+ and 3+ cases was efficient for Criterion 2. CONCLUSIONS: Determining HER2 status at diagnosis, as an indication for trastuzumab at metastatic relapse, incurs substantial incremental costs, which do not appear to be justified. No other strategy can be excluded at first.

Cost comparison of two surgical strategies in the treatment of breast cancer: sentinel lymph node biopsy versus axillary lymph node dissection.

OBJECTIVES: The feasibility and accuracy of sentinel lymph node biopsy (SLNB) in the treatment of breast cancer is widely acknowledged today. The aim of our study was to compare the hospital-related costs of this strategy with those of conventional axillary lymph node dissection (ALND). METHODS: A retrospective study was carried out to determine the total direct medical costs for each of the two medical strategies. Two patient samples (n = 43 for ALND; n = 48 for SLNB) were selected at random among breast cancer patients at the Centre Leon Bérard, a comprehensive cancer treatment center in Lyon, France. Costs related to ALND carried out after SLNB (either immediately or at a later date) were included in SLNB costs (n = 18 of 48 patients). RESULTS: Total direct medical costs were significantly different in the two groups (median 1965.86 Euro versus 1429.93 Euro, p = 0.0076, Mann-Whitney U-test). The total cost for SLNB decreased even further for patients who underwent SLNB alone (median, 1,301Euro). Despite the high cost of anatomic pathology examinations and nuclear medicine (both favorable to ALND), the difference in direct medical costs for the two strategies was primarily due to the length of hospitalization, which differs significantly depending on the technique used (9-day median for ALND versus 3 days for SLNB, p < 0.0001). CONCLUSIONS: A lower morbidity rate is favorable to the generalization of SLNB, when the patient's clinical state allows for it. From an economic point of view, SLNB also seems to be preferred, particularly because our results confirm those found in two published studies concerning the cost of SLNB.

A qualitative approach to the use of economic data in the selection of medicines for hospital formularies: a French survey.

OBJECTIVE: Qualitative interviews were conducted with pharmacists in hospitals and clinics in the Rhône-Alpes region of France to determine the role of economic data when selecting medicines for formularies, to identify barriers to the use of this information and to study to what degree a healthcare establishment's financing system influences the use of this data. METHOD: A stratified sample of healthcare establishments with over 100 short-stay beds were included: (1) thirteen public and semi-private hospitals financed through annual global budgets and (2) six private clinics financed on a fee-for-service basis. Interviews were carried out between October 1999 and January 2000, and coded independently by two researchers. MAIN OUTCOME MEASURE: A multiple correspondence analysis was performed to compare the two groups of healthcare establishments. RESULTS: The influence of economic data in the decision-making process is limited, for other factors appear to have greater weight: (1) efficacy and safety of medicines (2) relations between decision-makers and the pharmaceutical industry and (3) patient quality of life. Economic data used was mainly related to medication prices and quantities consumed. This data was used in a large number of decisions and seemed to have more importance in hospitals than in clinics. Information related to resources that could be saved by the inclusion of a new medicine on formularies was seldom used and apparently considered less important in hospitals than in clinics. Pharmacoeconomic evaluations were very rarely used. Six barriers to the use of economic data were raised by the pharmacists, including: lack of time, which limits the collection and analysis of such information; insufficient health economics training, an obstacle to decision-makers' analytical capacity; and closed budgets within hospitals. CONCLUSION: Economic data concerning 'medication budgets' appears to have a greater impact in public and semi-private hospitals than in private clinics. Obstacles linked to the decision-making context itself were particularly highlighted, and it can be concluded that in order to increase the use of economic data, it is first necessary to create an environment that is more favourable to its application.