Organizing medical oncology care at a regional level and its subsequent impact on the quality of early breast cancer management: a before-after study.

BACKGROUND: One of the main measures of the French national cancer plan is to encourage physicians to work collectively, and to minimize territorial inequities in access to care by rethinking the geographical distribution of oncologists. For this reason, cancer care services are currently being reorganized at national level. A new infrastructure for multidisciplinary cancer care delivery has been put in place in our region. Patients can receive multidisciplinary health care services nearer their homes, thanks to a mobile team of oncologists. The objective of our study was to assess, using a quality approach, the impact on medical management and on the costs of treating early breast cancer, of the new regional structure for cancer care delivery. METHODS: Before-and-after study performed from 2007 to 2010, including patients treated for early breast cancer in three hospitals in the region of Franche-Comté in Eastern France. The main outcome measures were quality criteria, namely delayed treatment (>12 weeks), dose-intensity and assessment of adjuvant chemotherapy. Other outcomes were 24-month progression-free survival (PFS) and economic evaluation. RESULTS: This study included 667 patients. The rate of chemotherapy tended to decrease, but not significantly (49.3% before versus 42.2% after, p=0.07), while the use of taxanes increased by 38% across all centres (59.6% before versus 98.0% after, p < 0.0001). There was a non-significant reduction in the time between surgery and adjuvant chemotherapy (6.0 ± 3.0 weeks before versus 5.6 ± 3.6 weeks after, p=0.11). Dose-dense chemotherapy improved slightly, albeit non significantly (86.3% versus 91.1% p=0.22) and time to treatment tended to decrease. The new regional infrastructure did not change 24-month PFS, which remained at about 96%. The average cost of treatment was estimated at € 7000, with no difference between the two periods. CONCLUSIONS: Despite a shortage of oncologists, the new organization put in place in our region for the provision of care for early breast cancer makes it possible to maintain local community-based treatment, without negative economic consequences. This new structure for cancer care delivery offers cancer services of similar quality with no modification of 24-month PFS in early breast cancer.

Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis.

BACKGROUND: The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. METHODS: Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization. RESULTS: From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p = 4 × 10(-3)), PR in 29% of cancers (p < 4 × 10(-4)), and HER2 in 4% of lesions (p = .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed. CONCLUSIONS: This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting.

Study design: two long-term observational studies of the biosimilar filgrastim Nivestim™ (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia.

BACKGROUND: Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. METHODS/DESIGN: The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world' clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy.Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. DISCUSSION: The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population. TRIAL REGISTRATION: NEXT NCT01574235, VENICE NCT01627990.

Is extracapsular tumour spread a prognostic factor in patients with early breast cancer?

BACKGROUND: This study searched for extra capsular tumour spread (ECS) as a prognostic factor for recurrence in terms of Disease Free Survival (DFS) and Overall Survival (OS). PATIENTS AND METHODS: For this study, from a retrospective database of the Doubs cancer registry, 823 eligible women with node positive breast cancer treated from February 1984 to November 2000 were identified. The following factors were evaluated: ECS, numbers of involved nodes, histological tumour grade, tumour size, status of estrogen and progesterone receptors, and age of patient. A Cox proportional hazards method was used to search for significant factors related to OS and DFS length. RESULTS: In the multivariate analysis, factors related to DFS length were found to be: tumour grade (aHR 0.76, 95 % CI 0.61-0.96, p = 0.02), ECS status (aHR 0.7, 95 % CI 0.49-0.96, p = 0.03), progesterone (PgR) status (aHR 0.63, 95 % CI 0.44-0.85 p = 0.008), number of nodes involved (aHR 0.75, 95 % CI 0.56-1, p = 0.05). The multivariate analysis for OS found as significant factors: tumour grade (aHR 0.76, 95 % CI 0.61-0.95; p = 0.02) and PgR status (aHR 0.8, 95 % CI 0.56-0.99, p = 0.02). CONCLUSIONS: This study might suggest taking into account ECS status in the adjuvant decision-making process.

Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study.

BACKGROUND: This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer. METHODS: The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter) and every 2 weeks irinotecan (180 mg/m2), FA (400 mg/m2) and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45). RESULTS: Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS. CONCLUSION: The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.

Impact of organised programs on colorectal cancer screening.

PURPOSE: Colorectal cancer (CRC) screening has been shown to decrease CRC mortality. Organised mass screening programs are being implemented in France. Its perception in the general population and by general practitioners is not well known. METHODS: Two nationwide observational telephone surveys were conducted in early 2005. First among a representative sample of subjects living in France and aged between 50 and 74 years that covered both geographical departments with and without implemented screening services. Second among General Practionners (Gps). Descriptive and multiple logistic regression was carried out. RESULTS: Twenty-five percent of the persons(N = 1509) reported having undergone at least one CRC screening, 18% of the 600 interviewed GPs reported recommending a screening test for CRC systematically to their patients aged 50-74 years. The odds ratio (OR) of having undergone a screening test using FOBT was 3.91 (95% CI: 2.49-6.16) for those living in organised departments (referent group living in departments without organised screening), almost twice as high as impact educational level (OR = 2.03; 95% CI: 1.19-3.47). CONCLUSION: CRC screening is improved in geographical departments where it is organised by health authorities. In France, an organised screening programs decrease inequalities for CRC screening.

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy.

INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by six cycles of maintenance temozolomide (150-200 mg/m(2), five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients.

[Prevalence and management of pain in patients with metastatic cancer in Franche-Comté]. / Prévalence et prise en charge de la douleur chez les patients présentant un cancer métastatique en Franche-Comté.

INTRODUCTION: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain. METHODS: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included. RESULTS: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life. CONCLUSION: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate.

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: impact of institutions.

PURPOSE: Trastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given. PATIENTS & METHODS: All patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS). RESULTS: Among 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2-89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64-0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59-0.95; p = 0.02). CONCLUSION: Exposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.

[Economic assessment of the routine use of Oncotype DX® assay for early breast cancer in Franche-Comte region]. / Évaluation économique de l'utilisation en routine du test Oncotype DX® dans la prise en charge des cancers du sein en Franche-Comté.

Oncotype DX® has been validated as quantifying the likelihood of distant recurrence at 10 years and overall chemotherapy benefit in patients with estrogen-receptor-positive and HER-2-negative early breast cancer. In 2012, this genomic signature was routinely available for patients in Franche-Comté, France. Patients eligible for Oncotype DX(®) testing had a ER-positive, HER-2-négative early breast cancer with a nodal involvement limited to 0 or 1 positive-node without extracapsular spread; an adjuvant chemotherapy was indicated based on usual prognostic factors. The aim was to assess the economic impact of Oncotype DX(®) testing in a French region. A cost-minimisation analysis from the French Public Healthcare System perspective was performed. The availability of Oncotype DX(®) in Franche-Comté, France, and its use in clinical routine allowed a decrease of 73 % of adjuvant chemotherapy without increase of the cost of the patients' management and with a potential reduction of the cost for the French Public Healthcare System. This strategy was successful and may allow the reimbursement of this test in France for patients with early breast cancer.

Management of anemia in advanced breast and lung cancer patients in daily practice: results of a French survey.

INTRODUCTION: The purpose of this French survey was to evaluate the adherence to the guidelines (European Organisation for Research and Treatment of Cancer [EORTC]; American Society of Clinical Oncology [ASCO]; French Standards, Options, and Recommendations [SOR]; European Society of Medical Oncology [ESMO]; Food and Drug Administration [FDA]; and National Comprehensive Cancer Network [NCCN]) for the use of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy- induced anemia for patients with advanced breast and lung cancers. METHODS: Two-hundred patients were recruited for each malignancy. The collected items were characteristics of ESA initiation, treatment, adjustment, and discontinuation. Metastatic breast cancer and stage IIIb/IV lung cancer patients who had received chemotherapy were eligible. The endpoint was to compare French daily practices with national and international guidelines. RESULTS: From November 2010 to December 2010, 185 breast cancer and 227 lung cancer files were collected. The main reason of ESA initiation was the correction of anemia (49% and 44%, respectively). The median baseline value of hemoglobin was 9.5 g/dL, and the median target value was 12 g/dL. The mean duration of treatment was 12 and 14 weeks, respectively. The mean gain of hemoglobin was 2.3 g/dL and 1.9 g/dL, respectively. In the breast cancer population, two patients (1%) developed a thromboembolic event, which is lower than what has been described in the literature. An iron supplement was prescribed in 55% of patients with breast cancer and 49% of those with lung cancer, with about one-third administered intravenous iron. The interruption of ESA and chemotherapy was synchronous in about 20% of cases, and was earlier in lung cancer patients than in breast cancer patients. CONCLUSION: The quality and the rigor of the sampling represent one of the key points of this survey. The French and international guidelines for the use of ESA were well respected by the physicians. Overall, the management of chemotherapy-induced anemia was improved compared with what was described in the historical surveys (European Cancer Anaemia Survey [ECAS], French Anaemia Cancer Treatment [F-ACT]).

Cabazitaxel: a novel microtubule inhibitor.

The development of drug resistance is a major obstacle to effective cancer therapy. Several agents are in clinical development with the goal of overcoming resistance. Among them is cabazitaxel, a semisynthetic taxoid that is able to overcome a common mechanism of resistance that limits the efficacy of other chemotherapeutic agents, including the older taxanes. The promise of cabazitaxel as a second-line chemotherapy option for advanced prostate cancer has been confirmed clinically in the phase III TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-Containing Regimen) trial. This trial showed that cabazitaxel is the first chemotherapeutic agent to demonstrate a survival benefit in metastatic castration-resistant prostate cancer (mCRPC) since the approval of docetaxel. On this basis, the US FDA and the European Medicines Agency approved cabazitaxel in June 2010 and January 2011, respectively, for the treatment of patients with mCRPC who have previously been treated with docetaxel. The most prevalent toxicity was neutropenia and the use of primary prophylaxis with granulocyte-colony stimulating factor is recommended in high risk patients. This article presents the preliminary antitumour activity, safety, tolerability and pharmacokinetic data of cabazitaxel, and an overview of the current status of clinical development.

[Follow-up in patients with early breast cancer]. / La surveillance du cancer du sein non métastasé

Breast cancer incidence remains the highest among gynaecologic neoplasms. Once they have achieved their treatments, patients should undergo careful follow-up. It aims at detecting early local recurrence or controlateral breast cancer. Based on large cohorts, clinical and radiological follow-up procedures come from guidelines realised by scientific organisations. We evaluated our regional practices in Franche-Comté and compared them to current guidelines. Patients with early breast cancer positive for hormonal receptors filled a questionnaire concerning their follow-up. It included patients treated from 1999 to 2005. When frequency of consultation is evaluated, only half of the patients undergo what is recommended. Whereas mammography and non-validated complementary exams are more regularly realised. Patients consulting more one practician have a better compliance. Our study underlines significant disparities among patients follow-up. Better interactions between physicians and a greater implication of patients in their follow-up would increase its quality.

Cancer screening in France: subjects' and physicians' attitudes.

OBJECTIVE: Since screening for cancer has been advocated, funded, and promoted in France, it is important to evaluate the attitudes of subjects in the general population and general practitioners (GPs) toward cancer screening strategies. METHODS: EDIFICE is a nationwide opinion poll that was carried out by telephone among a representative sample of 1,504 subjects living in France and aged between 40 and 75 years and among a representative sample of 600 GPs. The questionnaire administered to subjects queried about previous screening for cancer. RESULTS: Ninety-three percent of women stated that they had undergone at least one mammography. Although rated "A" recommendation-strongly recommended-by the US Preventive Services Task Force, screening for colorectal cancer received less attention than prostate cancer screening which is rated "I"-insufficient evidence-(reported screening rates of 25% and 36%, respectively). Six percent of subjects stated that they had undergone lung cancer screening. GPs' attitudes toward cancer screening showed similar inconsistencies. CONCLUSIONS: It thus appears that understanding of cancer screening practices in the French general population does not match scientific evidence. To a lesser extent, this also holds for GPs.

Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity.

AIMS: To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity. METHODS: One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed. RESULTS: The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G>A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity). CONCLUSIONS: The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.