Magali Morelle

Respiratory gating techniques for optimization of lung cancer radiotherapy

Purpose: The primary objective of the STIC 2003 project was to compare the clinical and economic aspects of respiratory-gated conformal radiotherapy (RGRT), an innovative technique proposed to limit the impact of respiratory movements during irradiation, versus conventional conformal radiotherapy, the reference radiation therapy for lung cancer. Methods and Materials: A comparative, nonrandomized, multicenter, and prospective cost toxicity analysis was performed in the context of this project between April 2004 and June 2008 in 20 French centers. Only the results of the clinical study are presented here, as the results of the economic assessment have been published previously. Results: The final results based on 401 evaluable patients confirm the feasibility and good reproducibility of the various RGRT systems. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold (DIBH) techniques (ABC and SDX systems), which markedly increased the total lung volume compared with the inspiration-synchronized system based on tidal volume (Real-time Position Management). These theoretical dosimetric benefits were correlated clinically with a significant reduction of pulmonary acute toxicity, and the pulmonary, cardiac, and esophageal late toxicities, especially with DIBH techniques. Pulmonary function parameters, although more heterogeneous, especially DLCO, showed a tendency to reduction of pulmonary toxicity in the RGRT group. Conclusions: RGRT seems to be essential to reduce toxicities, especially the pulmonary, cardiac, and esophageal late toxicities with the DIBH methods.

Evaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de Soutien aux Thérapeutiques Innovantes et Coûteuses

PURPOSE The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. PATIENTS AND METHODS Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospitals point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. RESULTS The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. CONCLUSION A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.

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.

Deterioration of Physical Activity Level and Metabolic Risk Factors After Early-Stage Breast Cancer Diagnosis

Background: In breast cancer patients, a lack of physical activity (PA) is 1 causative factor of weight gain during adjuvant treatment. It may increase the risk of treatment adverse effects, comorbidities, and deleterious long-term outcomes. Objective: We aimed to describe the evolution of PA level and sedentary behavior in breast cancer patients between diagnosis and adjuvant chemotherapy onset following surgery and identify predictive factors associated with these changes early after breast cancer diagnosis. Methods: Baseline data of 60 patients enrolled in a pilot randomized controlled trial of PA are presented. PA levels were estimated at adjuvant chemotherapy onset after surgery and retrospectively for the period at diagnosis. Height, weight, waist circumference, and bioelectrical impedance were measured at chemotherapy onset. Linear regression analysis evaluated factors associated with relative changes of PA level and sedentary behavior. Results: Moderate PA decreased and sedentary behavior increased between diagnosis and chemotherapy onset. A grade III breast cancer was associated with a greater decrease in PA level. Conversely, keeping a professional occupation and adherence to nutritional guidelines were associated with maintained PA level. The majority (88%) of patients had excessive adiposity at chemotherapy onset. Conclusions: There was a significant deterioration of PA level between diagnosis and chemotherapy onset, and deleterious adiposity was present in most patients. Implications for Practice: This study further emphasizes the need to motivate breast cancer patients toward engaging in a healthy lifestyle early after diagnosis and adhering to PA programs, which should be included in their clinical management.

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 patients 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.

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.

Effects of residential distance to hospitals with neonatal surgery care on prenatal management and outcome of pregnancies with severe fetal malformations

To examine the effect of maternal origin and distance between maternal residence and the nearest maternity ward with a neonatal surgical center in the same hospital, on prenatal diagnosis, elective termination of pregnancy, delivery in an adequate place and neonatal mortality for pregnancies with severe malformations requiring neonatal surgery, and to examine the effect of the place of delivery on neonatal mortality.

Analyzing multiple learning effects in health care using multilevel modeling: Application to radiotherapy at an early stage of innovation

OBJECTIVES Learning effects may have considerable influence on the performance of new health technologies, thereby on cost-effectiveness and ultimately on resource allocation. In the area of radiotherapy, equipment is becoming increasingly costly and the analysis of learning effects is complex given that sequential treatments are necessary, with multiple sessions for each patient. Our study aimed at analyzing learning effects in radiotherapy at an early stage of innovation. METHODS We used multilevel analysis to separate out the different learning effects of the new technique. Statistical analysis of observational data collected in a French National prospective survey was performed using an individual growth model. Intrapatient learning was modeled at level 1, and two types of interpatient learning were considered at level 2, regarding possible influences of professional experience on (i) the duration of each patients first session in a given setting and (ii) the rate of change of session duration over time for a given patient. Conventional radiotherapy was also considered for comparison. RESULTS Our results demonstrate a substantial type-1 interpatient learning effect and an even higher intrapatient learning effect. No type-2 interpatient learning was at work: professional experience did not impact intrapatient learning. Moreover, some intrapatient learning was also reported with conventional radiotherapy and was not significantly modified by innovation. Session duration was in any case strongly influenced by disease. CONCLUSIONS Because professionals highly underestimated the learning phenomenon, assessment of learning cannot be based on professional statements and it requires careful analysis of observational data.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer

PURPOSE Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

Curiethérapie : valorisation et aspects médico-économiques

Economic data in the literature for brachytherapy are still sparse and heterogeneous, with few controlled prospective studies and a perspective most often limited to those of the provider (health insurances). Moreover, these observation and conclusions are difficult to generalize in France. The prospective health economic studies performed in France in the framework of a national program to sustain innovative and costly therapies (STIC program) launched by the French cancer national institute are therefore of most importance. With the exception of prostate brachytherapy with permanent seeds, the valorisation of the brachytherapy activity by the French national health insurance does not take into account the degree of complexity and the real costs supported by health institutions (i.e. no specific valorisation for 3D image-based treatment planning and dose optimization and for the use of pulsed dose rate brachytherapy).