Julia Bonastre

Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin

PURPOSE To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. RESULTS Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). CONCLUSION Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

The burden of age-related macular degeneration: results of a cohort study in two French referral centres.

AbstractObjective: To describe the economic impact of age-related macular degeneration (AMD) and to assess its medical and non-medical costs. Design and settings: An observational study was carried out in 105 patients in two French centres in a sample of 105 French patients. All consecutive patients, consulting during a 3-week period, were included provided they were 60 years of age or older and they presented an exudative form of AMD with a distant visual acuity in the best eye ≤ 20/40. Data collected included clinical items, treatment modalities, medical follow-up, transport costs, impact of AMD on living conditions and welfare payments related to visual impairment. Costs were presented in 2000 values. Perspective: General payer perspective (Social Security, private health insurance and patient). Results: Mean age was 79.3 years and ranged from 62.8–95 years. Average length of disease evolution was 3.5 years. During a 3-month period, patients had a mean of 2.6 visits to the ophthalmologist. Thirty percent of the patients used vascular medications and 72.4% had been previously treated by laser photocoagulation. Only 10% had benefited from visual rehabilitation. Annual AMD cost per patient was 3660.29 euros (EUR) [95% CI: 2881.92–4438.62].Half of these annual costs were medical costs. Other major cost components were home help costs EUR904.91 [95% CI: 478.88–1330.94] and transport costs for care EUR542.73 [95% CI: 146.31–939.14]. Non-medical costs were significantly higher for patients with more severe disease. Conclusions: The economic argument that costs are higher in patients with the lowest visual acuity emphasises the necessity of early detection and treatment of patients with AMD.

Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial

PURPOSE In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. PATIENTS AND METHODS HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed. RESULTS At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by €955 (US

Cost-Effectiveness of Intraperitoneal Chemohyperthermia in the Treatment of Peritoneal Carcinomatosis from Colorectal Cancer

1,018) but with slightly decreased efficacy (-0.007 QALY/patient). CONCLUSION rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.

Implications of learning effects for hospital costs of new health technologies: The case of intensity modulated radiation therapy

OBJECTIVES Our purpose was to assess the cost-effectiveness of intraperitoneal chemohyperthermia (IPCH) compared to palliative chemotherapy (STANDARD) against peritoneal carcinomatosis arising from colorectal cancer. METHODS We performed a retrospective study of 96 patients whose peritoneal carcinomatosis had been diagnosed between January 1998 and December 2003 and treated either with IPCH or with palliative chemotherapy in French comprehensive cancer centers. Patients were followed up over a 3-year period. Effectiveness was measured by restricted mean survival at 3 years. The Bang and Tsiatis method was used to handle cost-censored data. The confidence limits of the mean cost per patient in each group and the mean incremental cost per life-year saved were computed using 1000 bootstrapreplicates. We also computed an acceptability curve for the incremental cost-effectiveness ratio (ICER). RESULTS We found that IPCH improved survival and was more costly than STANDARD treatment. Over a 3-year observation period, IPCH yielded an average survival gain of 8.3 months at the additional cost of euro58,086 (95% confidence interval 35,893-112,839) per life-year saved. CONCLUSION The ICER of IPCH is acceptable given the severity and burden of peritoneal carcinomatosis for which there is no alternative curative treatment.

The economic burden of melanoma in France: assessing healthcare use in a hospital setting.

OBJECTIVES The impact of learning effects on the variability of costs of new health technologies in a prospective payment system (PPS) through the case of intensity modulated radiation therapy (IMRT) was studied. METHODS A series of consecutive patients treated in nine medical centers was enrolled in a prospective study. Direct costs were assessed from the perspective of the healthcare providers. We used a two-level model to explain the variability of costs: patients nested within centers. Learning effects at the center level were considered through a fixed effect (the learning curve slope) and a random effect (the initial cost level). Covariates were introduced to explain the patterns of variation in terms of patient characteristics. RESULTS The mean direct cost of IMRT was 5,962 euro (range, 2,414 euro-24,733 euro). Manpower accounted for 53 percent of this cost. Learning effects explained 42 percent of the variance between centers (which was 88 percent of the total variance) and were associated with a substantial decrease in treatment costs. The mean initial treatment direct cost was 6,332 euro in centers with a previous experience of IMRT, whereas it was 14,192 euro in centers implementing IMRT for the first time. Including logistics costs and overhead, the full cost of IMRT was 10,916 euro. Average reimbursement was 6,987 euro. CONCLUSIONS Learning effects are a strong confounding factor in the analysis of costs of innovative health technologies involving learning effects. In a PPS, innovative health technology involving learning effects necessitates specific reimbursement mechanisms.

Cost of radiofrequency ablation in the treatment of hepatic malignancies.

The objective of this experiment was to describe healthcare use for the treatment of melanoma in a hospital setting and to assess the related annual cost using French hospital records for the year 2004. The 2004 French national database was the main source of data. Hospital stays related to melanoma care were extracted from this database, which exhaustively records hospital stays in the country. We selected stays that included at least one diagnosis of melanoma: International Classification of Diseases (ICD)-10 codes C43 ‘malignant melanoma of skin’ or D03 ‘melanoma in situ’. A second database (the French National Hospital Costs Survey) was used to compute unit costs. For each diagnosis-related group involved in melanoma care, we calculated an average cost per day from this database. Unit costs were then applied to the duration of each hospital stay related to melanoma from the 2004 national database. A total of 42 911 stays related to melanoma were identified for the year 2004. New patients, estimated by the number of surgical stays with a melanoma ICD code as the main diagnosis, amounted to 6897. Annual hospital costs for melanoma care were estimated at 59 million euros. Almost half of these costs (27 million euros) were attributable to stays with a metastasis ICD code. The main cost drivers were surgery (38% of hospital costs), follow-up evaluations (20%) and chemotherapy (17%). It was concluded that the impact of melanoma on hospital expenditures for cancer was modest. Hospital costs for stays related to melanoma represented less than 1% of total annual hospital costs for cancer for the year 2004.

Selection of an early biomarker for vascular normalization using Dynamic Contrast Enhanced Ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

OBJECTIVES Our primary objective was to assess the cost of radio-frequency ablation (RFA) of hepatic malignancies and to compare it to hospital reimbursement paid in the French Prospective Payment System (PPS). PATIENTS AND METHODS A series of 305 patients were enrolled into a prospective study. All resources used during the RFA-related hospital stay were recorded. Costs were assessed from the perspective of the health care providers and computed for four groups of patients: percutaneous RFA in an outpatient setting (group Ia, N=44), percutaneous RFA in an inpatient setting (group Ib, N=94), laparoscopic RFA (group II, N=44) and intraoperative RFA combined with resection (group III, N=120). RESULTS Mean hospital costs were estimated at euro 1581 (group Ia), euro 3824 (group Ib), euro 8194 (group II) and euro 12967 (group III). Costs per stay without intensive care in these groups were respectively euro 1581, euro 3635, euro 6622 and euro 10905 and reimbursement (intensive care excluded) was euro 560, euro 3367, euro 9084 and euro 11780. CONCLUSION In the French PPS, the cost of RFA is covered by lump sums paid to hospitals exclusively for intraoperative and laparoscopic RFA. For percutaneous RFA, which is the most frequent approach, reimbursement is highly insufficient.

Dead space closure with quilting suture versus conventional closure with drainage for the prevention of seroma after mastectomy for breast cancer (QUISERMAS): protocol for a multicentre randomised controlled trial

BACKGROUND Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO 2007-A00399-44.

Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study

Introduction Postoperative wound seroma is common after mastectomy. This complication is associated with significant impact on patient outcomes and healthcare costs. The optimal closure approach for seroma prevention remains unknown but some evidence suggests that quilting suture of the dead space could lower the incidence of seroma. The aim of this trial is to compare seroma formation using quilting suture versus conventional closure with drainage in patients undergoing mastectomy. Methods and analysis This is a multicentre, superiority, randomised controlled trial in women undergoing mastectomy with or without axillary involvement. Exclusion criteria include indication of bilateral mastectomy or immediate reconstruction and any physical or psychiatric condition that could impair patients ability to cooperate with postoperative data collection or that do not allow an informed consent. 320 participants will be randomised in a 1:1 ratio to receive either quilting suture or conventional wound closure with drain. The primary outcome is seroma requiring either aspiration or surgical intervention within 21 days following mastectomy. Secondary outcomes include seroma regardless of whether or not it requires an intervention, surgical site infection, pain score, cosmetic result, patients quality of life, costs and cost-effectiveness. The primary analysis will be an intention-to treat analysis performed with a χ2 test (or Fishers exact test). Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS—Region Centre—Ouest 1, 2014-R20, 16 December 2014). Study findings will be published in peer-reviewed journals and presented at relevant national and international breast cancer conferences. Trial registration number NCT02263651.