Direct medical and non-medical costs of a one-year care pathway for early operable breast cancer: Results of a French multicenter prospective study.

INTRODUCTION: The organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis. METHODS: OPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method. RESULTS: Data from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were €12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were €8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (€3,687/patient/year without chemotherapy versus €10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of €614/patient/year. No drivers of these costs were identified. CONCLUSION: Initial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.

The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the Epidemiological Strategy and Medical Economics (ESME).

PURPOSE: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme. PARTICIPANTS: All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually. FINDING TO DATE: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort. FUTURE PLANS: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings. TRIAL REGISTRATION NUMBER: NCT03275311; Pre-results.

UCBG 2-08: 5-year efficacy results from the UNICANCER-PACS08 randomised phase III trial of adjuvant treatment with FEC100 and then either docetaxel or ixabepilone in patients with early-stage, poor prognosis breast cancer.

PURPOSE: UNICANCER-PACS08 compared adjuvant FEC (5-FU; epirubicin; cyclophosphamide) then docetaxel to FEC then ixabepilone in poor prognosis early breast cancer (BC). We evaluated whether replacing docetaxel with ixabepilone would increase 5-year disease-free survival (DFS). PATIENTS AND METHODS: Triple-negative breast cancer (TNBC) or oestrogen receptor (ER)+/progesterone receptor (PR)-/HER2- BC patients were randomised to receive standard FEC (3 cycles) followed by 3 cycles of either docetaxel (100 mg/m2) or ixabepilone (40 mg/m2). Radiotherapy was mandatory after conservative surgery; ER+ patients received endocrine therapy. RESULTS: Seven hundred sixty-two patients were enrolled between October 2007 and September 2010. Baseline characteristics were balanced between arms. Median follow-up was 66.7 months. Median DFS was not reached; 5-year DFS rate was 76% with docetaxel and 79% with ixabepilone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.58-1.10; p = 0.175). Median overall survival (OS) was not reached; 5-year OS rate was 86% versus 84% (HR = 0.97; 95% CI = 0.66-1.42; p = 0.897). TNBC patients treated with ixabepilone had a 23% lower risk of relapse compared to docetaxel (HR for DFS = 0.77; 95% CI = 0.53-1.11; p = 0.168). DFS was longer with ixabepilone than docetaxel in patients with grade II-III lymphocytic infiltration (HR = 0.55; 95% CI = 0.29-1.05; p = 0.063). All patients experienced ≥1 adverse events (AEs): 75% reported grade III-IV AEs and two (<1%) had grade V AEs (both with neutropenia and infection receiving ixabepilone). CONCLUSION: After adjuvant FEC, ixabepilone was comparable to docetaxel for treating poor prognosis early BC patients. The benefit of ixabepilone in subgroups (patients with TNBC and grade II-III lymphocytic infiltration) requires further evaluation.

Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106).

PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. PATIENTS AND METHODS: Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(-) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. RESULTS: At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P = .12). CONCLUSION: Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY NUMBER: NCT00055679, Agence National de Sécurité du Médicament (ANSM) - France.

[First outpatient satisfaction questionnaire with day-surgery in a French comprehensive cancer center]. / Première enquête de satisfaction dans une unité de chirurgie ambulatoire dédiée à la cancérologie.

INTRODUCTION: To assess the patient's satisfaction in a day-surgery unit in oncology for a surgical diagnosis or therapeutic act. METHODS: Between October 2013 and February 2014, we conducted a satisfaction survey from the validated questionnaire COPS-D. This questionnaire analyse the patient's stages in the care system, from the preoperative consultation to the return home: 9 stages with 23 items rated 1 (bad) to 5 (excellent). It was sent by postmail 3 weeks after their hospitalization. RESULTS: Four hundred and sixty-seven questionnaires were mailed, with a response's rate to 38% (172/467). Participant's characteristics: 88% are women, 45% are full time workers, 54% of senology. Two-third of the assessments were rated 4 or 5. Five percent were rated 1 or 2. The patient's exit is the least preferred step. The operating room's assessment is the most preferred by patients. Sixty-one percent of participants have written a free comment, 31% are positives, 36% are negatives, and 32% are mixed. The wait was the negative recurrent comment (21%). DISCUSSION: Most participants are very satisfied. Improving the wait before the operation and output is already underway. Studies are now needed to assess the care's safety and the economic aspect of day-surgery.

The patient-breast cancer care pathway: how could it be optimized?

BACKGROUND: A care pathway is defined as patient-focused global care that addresses temporal (effective and coordinated management throughout the illness) and spatial issues (treatment is provided near the health territory in or around the patient's home). Heterogeneity of the care pathways in breast cancer (BC) is presumed but not well evaluated. The OPTISOINS01 study aims to assess every aspect of the care pathway for early BC patients using a temporal and spatial scope. METHODS/DESIGN: An observational, prospective, multicenter study in a regional health territory (Ile-de-France, France) in different types of structures: university or local hospitals and comprehensive cancer centers. We will include and follow during 1 year 1,000 patients. The study consists of 3 work-packages: - Cost of pathway The aim of this WP is to calculate the overall costs of the early BC pathway at 1 year from different perspectives (society, health insurance and patient) using a cost-of-illness analysis. Using a bottom-up method, we will assess direct costs, including medical direct costs and nonmedical direct costs (transportation, home modifications, home care services, and social services), and indirect costs (loss of production). - Patient satisfaction and work reintegration Three questionnaires will assess the patients' satisfaction and possible return to work: the occupational questionnaire for employed women; the questionnaire on the need for supportive care, SCNS-SF34 ('breast cancer' module, SCNS-BR8); and the OUTPASSAT-35 questionnaire. - Quality, coordination and access to innovation Quality will be evaluated based on visits and treatment within a set period, whether the setting offers a multidisciplinary consultative framework, the management by nurse coordinators, the use of a personalized care plan, the provision of information via documents about treatments and the provision of supportive care. The coordination between structures and caregivers will be evaluated at several levels. Day surgery, home hospitalization and one-stop breast clinic visits will be recorded to assess the patient's access to innovation. DISCUSSION: The assessment of care pathways encourages the implementation of new payment models. Our approach could help health care professionals and policymakers to establish other cost-of-illness studies and plan the allocation of resources on a patient basis rather than a visit basis.

Choroidal melanoma: does endoresection prevent neovascular glaucoma in patient treated with proton beam irradiation?

PURPOSE: To evaluate the efficacy of endoresection after proton beam radiotherapy to prevent neovascular glaucoma (NVG) in patients treated for choroidal melanoma. METHODS: From a series of 4,867 patients treated for choroidal melanoma were prospectively recorded in the database (Macro Infermed 3.075). One hundred and seventy-one patients presenting a tumor diameter >10 mm and thickness >5 mm treated with proton beam (PB) radiotherapy were selected. One group of 63 patients was treated with PB therapy followed by endoresection (PE) of the scar. This group was compared with 2 historical matched controlled groups: 57 patients treated with PB therapy alone (P) and 51 patients treated with PB therapy followed by transpupillary thermotherapy of the scar (PTTT). Main outcome measures are as follows: age, gender, tumor diameter, tumor thickness, pre- and posttreatment visual acuity, NVG rate, secondary enucleation rate, and 5-year survival. Statistical analysis was performed using R version 2.5.1 software. RESULTS: Correlations between the 3 groups were P = 0.29 for age, P = 4.7×10 for tumor diameter, and P = 6.44×10 for tumor thickness. Comparison between the 3 groups showed that 2-year survival without secondary enucleation was 96.2% for PE, 88.8% for P, and 98% for PTTT (P = 0.203) (95% confidence interval). Two-year survival without NVG (95% confidence interval) was 92.7% (85.1-1.00) for PE, 54.6% for P, and 62.1% for PTTT (P = 0.0001). The difference between the endoresection (PE) group and the PB radiotherapy (P) and PB radiotherapy + TTT (PTTT) groups in terms of reduction of the NVG rate was statistically significant. Relative risk of developing NVG was calculated with the P group as reference, relative risk = 1. The relative risk of the PTTT group was 0.79 (20% reduction of the risk), and the relative risk of the PE group was 0.18 (82% reduction of the risk of developing NVG). CONCLUSION: This study shows that endoresection of the necrotic scar after PB radiotherapy reduces the risk of NVG and secondary enucleation for selected choroidal melanoma patients.

Treatment of uveal melanoma by accelerated proton beam.

Proton beam irradiation of uveal melanoma has great advantages compared to brachytherapy because of the homogenous dose delivered to the tumor and the possibility of sparing normal tissue close to the tumor. We describe the technique of proton beam therapy including the surgical technique of clip positioning, the radiotherapy delivery technique and the dose administered (60 Gy cobalt relative biological effectiveness in 4 fractions). Indications of proton beam are given and the follow-up procedure is described. An inactive residual tumor scar is observed after 2-3 years. Results are given comparing the most recent series of patients treated at the Institut Curie-Orsay proton therapy center with the data published in the literature. The metastasis rate at 10 years varies between 25 and 30%. Local control is excellent. The local recurrence rate at 10 years is usually around 5%. Secondary enucleation is performed in 10-15% of patients either due to complications or local recurrence. Complications such as retinal detachment, maculopathy, papillopathy, cataract, glaucoma, vitreous hemorrhage and dryness are described. The severest complication that usually leads to secondary enucleation is neovascular glaucoma and it is encountered after irradiation of large to extra-large tumors. The toxic tumor syndrome has recently been described. It is hypothesized that the residual tumor scar may produce proinflammatory cytokines and VEGF leading to intraocular inflammation and neovascular glaucoma. Additional treatments after proton beam such as transpupillary thermotherapy, endoresection of the tumor scar or intravitreal injections of anti-VEGF may reduce the rate of these complications.

Screening for psychological distress in two French cancer centers: feasibility and performance of the adapted distress thermometer.

OBJECTIVE: Little is known about the prevalence of psychiatric disorders in French cancer patients. This study aimed to assess the feasibility of a screening procedure using the Psychological Distress Scale (PDS). The PDS is a French adaptation of the National Comprehensive Cancer Network Distress Thermometer. The screening performance of the PDS was assessed by comparison with the established clinical case threshold on the Hospital Anxiety and Depression Scale (HADS). METHODS: Among 598 consecutive cancer outpatients recruited in two cancer centers in Paris, 561 (94%) agreed to complete the PDS, the HADS, the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30), and study-specific psychosocial questions. RESULTS: A receiver operating characteristic (ROC) analysis was performed, using a HADS cutoff score of 15 or greater to identify patients with psychological distress. This yielded a PDS cutoff score of 3, giving 76% sensitivity and 82% specificity. With this cutoff score, the prevalence of psychological distress was 38%. PDS scores were significantly related to scores from the HAD total scale (r=.64), HAD anxiety (r=.61) and HAD depression (r=.39) subscales, and EORTC QLQ-C30 emotional functioning (r=.56) and global health state (r=.44). In multivariate analyses, factors associated with psychological distress were female gender, taking analgesics, receiving professional psychological help, perceived psychosocial difficulties and lack of social support. SIGNIFICANCE OF RESULTS: Using the PDS appeared feasible, acceptable and effective for psychological distress screening in French ambulatory cancer care settings.

Conservative treatments of intraocular retinoblastoma.

OBJECTIVE: To describe the efficacy of conservative management of retinoblastoma by an association of conservative ocular therapies and chemothermotherapy. DESIGN: Phase II prospective nonrandomized trial. PARTICIPANTS: Eighty-three children were included (115 eyes). METHODS: Conservative ocular therapies and chemothermotherapy (intravenous carboplatin followed by transpupillary thermotherapy to the tumor) after chemoreduction by 2 cycles of carboplatin and etoposide. MAIN OUTCOME MEASURES: Use of external beam therapy and ocular tumor control. RESULTS: One hundred fifteen of the 147 affected eyes were eligible for conservative management. Nineteen children had unilateral lesions (22.8%), and 64 (77.1%) had bilateral lesions. Sixty-six children received neoadjuvant chemotherapy before ocular therapy, which consisted of one or a combination of several techniques: chemothermotherapy (65 children [86 eyes]) with a mean of 3 cycles per child, thermotherapy alone (22 children [24 eyes]), cryoapplication (49 children [58 eyes]), and iodine 125 brachytherapy (26 children [29 eyes]). Tumor control was achieved for 97 eyes (84%). At the end of the study, external beam radiotherapy (EBR) was necessary for a total of 9 children (11%) and 13 eyes (12%). Enucleation was necessary for a total of 23 eyes (20%), because of complications in 5 cases. CONCLUSIONS: Neoadjuvant chemotherapy with 2 cycles of carboplatin and etoposide followed by ocular therapy and chemothermotherapy achieves satisfactory tumor control and permits a low need for EBR.

Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial.

PURPOSE: The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. PATIENTS AND METHODS: Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). RESULTS: Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose. CONCLUSION: Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.

Chemothermotherapy in the management of retinoblastoma.

OBJECTIVE: To evaluate the results of chemothermotherapy for the treatment of retinoblastoma. DESIGN: Non-comparative interventional case series. PATIENTS: Fifty-one children (65 eyes and 103 tumors) were treated with chemothermotherapy in a single institution from January 1995 to May 1998. METHODS: Chemothermotherapy consists of a combination of transpupillary thermotherapy delivered shortly after intravenous (IV) injection of carboplatin (560 mg/m(2)). Each tumor is treated separately with a diode laser using a microscope. Laser intensity, spot size, and duration are adapted to the size of each tumor and to the clinical response. After 8 days, thermotherapy alone is repeated. This cycle is performed from one to six times, every 28 days. The treatment data and outcome are analyzed separately. MAIN OUTCOME MEASURES: Assessment of local tumor control. RESULTS: One hundred three tumors were treated in 65 eyes of 51 children. Age at diagnosis was 0 to 60 months (median, 7 months). Median tumor diameter at the time of treatment was 3.5 mm (range, 1.5-12 mm). Laser modalities were as follows: median intensity, 450 mW (range, 150-1000 mW); median spot size, 1.2 mm (range, 0.3-2.0 mm); and median number of cycles required to obtain tumor control, three. Tumor regression was obtained for 99 tumors (96.1%) after a median follow-up of 30 months (17-61 months). Seven tumors relapsed after initial control (6.8%). Salvage treatment (external beam radiation, iodine plaques, or enucleation) was necessary for a total of 11 tumors (10.7%). The only risk factor for relapse was the initial diameter of the lesion greater than 3.5 mm, whereas the other tumor characteristics or treatment variables were not significantly correlated with relapse. Ninety-seven percent of treated eyes were able to be preserved, and 92% of cases were treated without external beam radiation. CONCLUSIONS: Chemothermotherapy is an effective technique to treat small- to medium-sized retinoblastomas in children, avoiding external beam irradiation.

Functional results after treatment of retinoblastoma.

PURPOSE: Because of the long-term complications associated with external beam radiation in retinoblastoma, alternative treatment methods have been investigated. We conducted a retrospective study to evaluate the functional results of new treatment modalities. METHODS: Thirty-seven eyes were treated without external beam irradiation in 31 patients. The median diameter of the largest tumor in each eye was 6 mm. Primary chemotherapy was used in 25 cases, chemothermotherapy was used in 32 cases, cryotherapy was used in 28 cases, iodine 125 Plaques were used in 15 cases, diode laser thermotherapy was used alone in 11 cases, and photocoagulation was performed in 5 cases. The median follow-up after diagnosis of retinoblastoma was 41 months. The visual results were evaluated at a median age of 54 months. RESULTS: The median visual acuity of the treated eyes was 20/33. Twenty-four eyes presented a visual acuity better than 20/40, 4 eyes had a visual acuity between 20/200 and 20/40, and 9 eyes had a visual acuity less than 20/200. Maculopathy was observed in 16 cases, associated with papillopathy in 1 case. A cataract was observed in 1 case and a vitreous hemorrhage was observed in another case. Twenty-one eyes did not develop any complications. No corneal dryness and very few lens changes were observed. CONCLUSION: The functional results after local treatments for retinoblastoma are very good. The most frequent complication is maculopathy, particularly when the tumor involves or is situated close to the macula.