Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral hernia repair.

BACKGROUND: The aim of this study was to compare, in terms of cost and serious complications, the use of biosynthetic resorbable parietal mesh with biologic mesh in patients undergoing contaminated ventral hernia repair (modified Ventral Hernia Working Group grade 3). Poly-4-hydroxy-butyrate (P4HB) biosynthetic mesh has rarely been the subject of comparative studies in the context of contamination. Data are required to confirm the effects of a transition from biological mesh to biosynthetic resorbable mesh. PATIENTS AND METHODS: A cost-effectiveness analysis was conducted. It was based on a decision analysis model built with clinical and economic data issued from a before-after study that included 94 patients hospitalized for ventral hernia repair at the University Hospital of Strasbourg (France) from June 2011 to February 2018. The effectiveness endpoint was the number of patients presenting with a serious specific complication or a general complication at 6 months. Data for surgical hospitalization stays, home hospitalizations and ambulatory care costs were included. RESULTS: We found fewer serious complications with biosynthetic mesh: 21% versus 33% with biologic mesh. A cost savings of US $5146 was determined. Deterministic sensitivity analyses and a probabilistic analysis confirmed our findings and the robustness of the model. CONCLUSION: P4HB biosynthetic resorbable mesh appeared to be the most effective and the least costly option. Additional data will be needed to confirm the superiority of biosynthetic mesh in terms of the recurrence risk reduction over a longer period.

Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients.

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.

Sinusoidal obstruction syndrome/veno-occlusive disease complication in lymphoma patients treated with oxaliplatin-based regimen: A case series report.

AIM: SOS/VOD is a relevant clinical syndrome that usually appears early after hematopoietic stem cell transplantation. The purpose of this article was to report a case series of SOS/VOD in non-susceptible patients and draw physicians' attention to the plausible relationship between liver injury and oxaliplatin-based chemotherapy, preceding autologous transplantation. METHODS: In this study, we report a case series of SOS/VOD in 4 lymphoma patients following autologous transplantation. The data were collected between July 2013 and November 2015 by analyzing patient's characteristics and outcomes. RESULTS: We noticed 4 severe cases of SOS with unusual presentations in patients who did exhibit few classical risk factors. These patients received R-DHAO before transplantation. CONCLUSIONS: Physicians need to be aware that oxaliplatin-based regimen could contribute to SOS/VOD complications in hematological patients.

[News Skin lesions : a case report of fixed drug eruption]. / Apparition soudaine de lésions cutanées : à propos d'un cas d'érythème pigmenté fixe.

Fixed drug eruption is an erythematous eruption of one or more centimetric rounded or oval lesions well demarcated, recurrent at the same place and leaving a residual purple pigmentation. Diagnosis is clinical. Skin biopsy is not essential except in doubtful cases (eg bullous drug eruption can simulate Lyell Syndrome or mucosal reminiscent of erythema multiforme). The etiology is almost always drug-induced; rare cases of toxic or food issue were reported. Histopathology is immuno-allergic; recurrences correspond to re-exposure to allergen. There is no specific treatment except stopping the causing drug.

L'érythème pigmenté fixe est une éruption érythémateuse d'une ou plusieurs lésions arrondies ou ovalaires centimétriques bien délimitées, récidivant au même endroit et laissant une pigmentation violacée résiduelle. Le diagnostic est clinique. La biopsie cutanée n'est pas indispensable sauf dans les cas douteux (exemple : érythème pigmenté bulleux pouvant simuler un Syndrome de Lyell ou une atteinte des muqueuses faisant penser à un érythème polymorphe). L'étiologie est presque toujours d'origine médicamenteuse; des rares cas de cause alimentaire ou toxique ont été rapportés. L'histopathologie est donc immuno-allergique ; les récidives correspondent à la réexposition à l'allergène. Il n'existe pas de traitement spécifique hormis l'arrêt du médicament incriminé.

[Out of addictions: Alcohol, or alcohol to alcohol]. / Sortir des addictions : à l'alcool, par l'alcool ou vers l'alcool.

Pathways from alcoholism to recovery are documented; less often are those from drug addiction to alcoholism. Biographical approaches allow analyzing how people change their uses and talk about their trajectories of recovery. METHODS: Three hundred and forty-one people (34% women) in the Paris area were questioned on their trajectories with a biographical questionnaire. Some open questions were aimed to understand the connection they made between events in their lives, how recovered they felt and what they considered strengths or obstacles. All the participants had stopped at least one product. Their mean age was 43, and 26% were over 50. STUDY OBJECTIVES: How can the differences between one substance addicts and dual abusers be explained? Can we hypothesize a better result for the patients with a single dependence to alcohol in their lives for the following two reasons? (1) They could really be taken in charge for their alcoholism whereas the dual abusers mostly receive cared for their illicit drug problems with an under estimation of their problem with alcohol. In this case, they turn to alcohol after weaning themselves from their drug dependence so as to return to a social consumption, especially when they are given an opiate treatment. (2) Conversely could we suggest that the dual substance abusers had different trajectories from their childhood (more adverse events, more social difficulties, mental health problems), and that this accumulation explains their skipping from one substance or behaviour to another without any real recovery for decades? RESULTS: All respondents were polydrug users. Eighty-two had been dependent mainly on alcohol. One hundred and twenty-one people had been drug addicts (mostly heroin), which they had stopped on average ten years before the survey. The last group included 138 persons who had been heroin or cocaine addicts and alcoholics in their lives, a third of whom had been dependent on alcohol before their drug addiction (35%), a tenth on both at the same time (10%) and more than half of the users (55%) had turned from drug addiction to alcoholism. The group concerning alcohol dependence includes the oldest participants, on average 49.7, and 55% of them were abstinent at the survey. Conversely, the group "with no alcohol dependence" had mainly turned to opiate treatments. Their histories in dependence and in various social statuses also showed a longer duration out of employment, in sickness or invalidity, or in prison, for the drug dependents as opposed to the "mainly" alcoholics. The population with dual substance abuse experienced twice as many adverse childhood events as the others (P<0.005): it was the case for 19.5% in "mainly alcohol" dependence compared to 38.4% in dual abuse. The recovery capital gave a mean score of 7.56±2.35 (median 7). A score below 6 was considered low. The score was significantly different according to the dependence groups: while 7.3% of "mainly alcohol" dependents had a score below 6, this was the case for 30.4% of the dual group (with alcohol and drugs), and 19% for the "mainly drug dependence" group. Controlling ages, sexes and groups of dependence in a logistic regression, the risk of having a recovery capital below six was more than four times higher for the dual dependents as opposed to the "mainly alcohol" dependents. CONCLUSION: Some people stay for decades in drug addiction centers switching from one dependence to another. Their alcohol drinking should be addressed earlier to prevent them from turning to drinking excessively in order to wean themselves from their drug addiction.

[Pregnancy and substance use in France: a literature review]. / Grossesse et usage de substances psychoactives en France. Synthèse de la littérature.

OBJECTIVES: Substance use during pregnancy is an important public health issue. It requires identifying at-risk populations and risk perception among women. MATERIALS AND METHODS: A literature review was conducted. It included French studies conducted since 2000 on substance use during pregnancy (tobacco, alcohol, marijuana, psychotropic drugs) and risk perception. RESULTS: In France, in 2010, 24% of pregnant women smoke--17% in the 3rd trimester. Depending on studies, the prevalence of alcohol use ranged from 12 to 63% and binge drinking ranged from 1 to 7%; daily drinking was below 0.5%. Marijuana use ranged from 1 to 3%, and psychotropic drugs ranged from 2 to 4%. Little research has been dedicated to risk perception. Studies show a lack of awareness about the equivalence of risks between fermented and distilled beverages and about the risks of moderate smoking during pregnancy. CONCLUSION: Data is lacking to characterize at-risk populations and mechanisms underlying risky behaviors.

Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer.

BACKGROUND: Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. PATIENTS AND METHODS: Within the French organised screening programme, 23,231 average-risk individuals, aged 50-74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. RESULTS: The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma. CONCLUSION: The study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.

[Retrospective analysis of neonatal data in a monocentric cohort of 170 newborns of polydrug-using mothers, Île-de-France, 1999-2008]. / Analyse rétrospective des données de 170 nouveau-nés de mères consommatrices de substances psychoactives.

OBJECTIVES: To analyze neonatal morbidity in a single-center retrospective cohort (1999-2008) according to the mothers' polydrug use and to the social and demographic context. MATERIAL AND METHODS: One hundred and seventy newborns were identified whose mothers used two or more substances (such as heroin, cocaine, opioid maintenance treatment, tobacco, alcohol, hashish, amphetamines, benzodiazepines, or other psychotropics) at the beginning of their pregnancies. The database included 168 sociodemographic variables describing mothers' living conditions and their drug-abuse characteristics; perinatal variables such as gestational age, weight, neonatal abstinence syndrome, and modalities of discharge; and correlations with the main neonatal morbidities. RESULTS: The mothers' mean age at delivery was 31.6yrs. It was the first pregnancy for 35.2% of the mothers but the mean number of previous abortions was 1.14 and 16.3% already had previous children in foster care. At delivery only 8.2% used only one product, 52.9% 2 or 3 products, and 37.6% four or more substances. All sociodemographic variables, the deprivation score, the number of previous abortions and miscarriages, and poor prenatal monitoring were significantly different for the mothers using four products or more. The uses changed along the years of study: fewer mothers used heroin but more used hashish, combined with other substances. The medical care also changed: greater participation on the part of mothers in neonatal care, more frequent breastfeeding, less medication for neonatal abstinence syndrome with the same severity score: i.e., 45.5% of infants with a Lipsitz score between 8 and 12 received a morphine treatment in 1999-2000 versus only 5.5% in 2005-2006 and none in 2007-2008. The mean gestational age was 38.1weeks. Preterm births (22.2%) and intrauterine growth restriction (18% with birth weight <10th percentile) were mainly correlated with the number of substances at delivery (17.3% preterm if three substances or less and 31.3% if four substances or more; p<0.001), social deprivation, poor prenatal care, and mothers having gained less than 5kg in weight during pregnancy (57.1% of intrauterine growth restriction versus 14.5%). Birth weight, height, and head circumference were significantly different for mothers having drunken alcohol. Among the newborns, seven showed complete fetal alcohol syndrome. The neonatal abstinence syndrome severity (23% with a Lipsitz score>9, one-quarter of whom were medicated with morphine) was correlated with an in-utero exposure to opiates, mainly in combination with benzodiazepines, and with the use of four or more substances. The mean age of infants at discharge was 18.1days (SD 3.39): 21.1% stayed 30 days or more in the hospital, mainly because of prematurity or intrauterine growth restriction, a high neonatal abstinence syndrome score, maternal polydrug use, psychosocial deprivation, or foster care placement decisions. Decisions for foster care placement (15%) applied to polydrug users, with social deprivation, undermonitored pregnancies, or bonding difficulties. CONCLUSION: The main factors correlated with poor neonatal results were polydrug use, maternal psychiatric pathologies, and social deprivation. Overall, prenatal and postnatal care such as rooming-in improved the results.

[Maternal and obstetrical data in a retrospective cohort of 170 newborns from polydrug using mothers, in the Paris area, 1999-2008]. / Analyse des données maternelles et obstétricales dans une cohorte rétrospective de 170 nouveau-nés de mères polyconsommatrices, Île-de-France, 1999-2008.

OBJECTIVES: Polydrug use in pregnancy is harmful. This survey aimed to explore the issue of the associations of substances during pregnancy and to determine the consumer profiles. PATIENTS AND METHODS: One hundred and seventy newborns whose mothers were psychoactive substances users were identified over the period 1999 to 2008. The data relating to maternal consumption, their reproductive history, and their living environment were collated. RESULTS: At the end of their pregnancy, the mothers reported using on average 3.14 substances. Three profiles were determined: 65 women were heroin users or had consumed it in their lifetime and were currently on substitution treatment, and had a very unfavourable social living environment; 30 women were mainly consumers of alcohol, with or without benzodiazepines or other psychotropic drugs, and had a history of abortions; 75 women were mainly tobacco and cannabis smokers, with or without substitution treatment, had good social living conditions and had wanted the pregnancy. CONCLUSION: Polydrug use increases the risk for the women to avoid prenatal care and is often linked with a history of abortions.

[Interest of immunohistochemic markers (Ki67, HMB45, p53) in risk analysis of congenital naevi of little and middle size]. / Intérêt des marqueurs immunohistochimiques (Ki67, HMB45, p53) dans l'analyse de risque des naevi congénitaux de petite et moyenne taille.

The risk to develop melanoma from small or medium size congenital naevus remain controversial. The main goal of the present study was to determine the interest of three immunohistochemical markers (Ki67, HMB45 and p53) in predicting malignant transformation of these congenital naevi and to see if a specific immunohistochemical profile of such transformed naevi can be identified. The markers (Ki67, HMB45 and p53) have been used retrospectively on sections of small or medium size congenital naevi (group NC, n = 15), of melanoma developed on small or medium size congenital naevi (group MNC, n = 15) and of melanoma developed on acquired naevi (group MNA, n = 15). The labelled cells have been counted in different cutaneous layers: junction, superficial dermal layer and deep dermal layer. No reactivity was observed for the three markers in group NC. The percentage of labelled cells was significantly different for the three markers between the group NC and the groups MNC and MNA. There was no difference between the groups MNC and MNA. In the groups MNC and MNA, a gradient in the percentage of labelled cells was observed between superficial and deep layers. These three markers do not differentiate melanoma developed from congenital naevi of small or medium size and melanoma developed from acquired naevi. Moreover, the results suggest that these three markers are useless in predicting the risk of malignant transformation of small or medium size congenital naevi.

[Obstetrical and pediatric impact of in utero cocaine exposure]. / Conséquences obstétricales et pédiatriques de la consommation de cocaïne pendant la grossesse.

Review of recent publications about perinatal consequences of cocaine use during pregnancy points out that: - dramatic obstetrical, neonatal and developmental abnormalities, reported during 1980-90', are less frequent in recent cohort studies; - pregnant women who use cocaine or crack, also consume other psychoactive drugs (alcohol, tobacco, benzodiazepines, cannabis, opiates, ...) and have a very chaotic life-style; so, it is difficult to distinguish abnormalities caused by cocaine per se, even with numerous cohorts, control groups and multivariate analysis.

[Conducting a cost-effectiveness trial in oncology: justification and method]. / Pertinence et méthodes pour la conduite d'un essai de supériorité médico-économique en cancérologie.

The occurrence of scarce financial resources and the aim of an adequate allocation of available budgets for public community induce to conduct trials where primary endpoint could be a medico-economic criterion. In oncology, the emergent place of "stop and go" strategy and or the diminution of chemotherapy administration induce initially to demonstrate non-inferiority of these strategies for efficacy. Another underlying objective for these trials could be also to demonstrate the medico-economic superiority of these strategies. In this context, medico-economic trials using cost and efficacy composite endpoint as primary endpoint for therapeutical strategies comparison could be an interesting alternative of classical clinical trials using only an efficacy endpoint. Based on a review, the aim of this paper is to focus about design of medico-economic trials: objectives, methods and sample size calculations.

[Pregnancy and psychoactives substances: prevalence study based on the declared consumption]. / Grossesse et substances psychoactives: étude de prévalence de la consommation déclarée.

OBJECTIVES: Evaluate substance use (tobacco, alcohol, psychotropic drugs, illicit drugs) declared before and during pregnancy. PATIENTS AND METHODS: Two hundred and forty-five pregnant women were interviewed through a self-administered and anonymous questionnaire as they were going to a prenatal consultation in a maternity hospital in the Parisian area. RESULTS: Before pregnancy, 16.3% of women reported smoking and 10.2% carried on smoking during pregnancy. Altogether, 40.8% of women reported alcohol consumption before pregnancy; 25.3% of women had contact with alcohol during pregnancy; 4.5% reported tobacco and alcohol consumption during pregnancy. During the month preceding the study, the consumption of psychotropic drugs (hypnotics, antidepressants or sedatives) was reported by 3.7% of women and that of marijuana by 2.4%. Moreover, the marijuana consumers, who tend to drink alcohol more often, combine important social and familial difficulties and represent a high-risk group. CONCLUSION: Tobacco and alcohol use in this study were lower than in any previously conducted French surveys. Methodological specificities and cultural factors might explain those results. However, this is the first study that asses substance use and marijuana use, in particular, by French pregnant women.

Concomitant intensive chemoradiotherapy induction in non-metastatic inflammatory breast cancer: long-term follow-up.

The aim of this study was to evaluate with a long follow-up the efficacy of concomitant chemoradiotherapy in non-metastatic inflammatory breast cancer (IBC) and to evaluate the breast conservation rate. Between 1990 and 2000, 66 non-metastatic patients with IBC were treated with chemotherapy and concomitant irradiation. The induction chemotherapy consisted of epirubicine, cyclophosphamide and vindesine, in association with split-course bi-fractionated irradiation to a total dose of 65 Gy with concomitant cisplatin and 5-fluorouracil. Maintenance chemotherapy consisted of high-dose methotrexate and six cycles of epirubicine, cyclophosphamide and fluorouracil. Hormonal treatment was given if indicated. Mastectomy was not systemic. Among 65 evaluable patients, 57 (87.6%) achieved a complete clinical response and had a breast conservation. Only six loco regional relapses were noted in six patients with a delay of 20 months and with concomitant metastatic dissemination in four cases. Median disease-free survival (DFS) was 28 months. Median overall survival (OS) was 63 months and median follow-up was 55.5 months. Induction chemotherapy and concomitant irradiation is feasible in patients with IBC, permitting a breast conservation with a high rate of local control with an OS comparable to that of the best recent series.

Cost-effectiveness analysis of strategies introducing FDG-PET into the mediastinal staging of non-small-cell lung cancer from the French healthcare system perspective.

AIM: To determine the most cost-effective strategy using PET for mediastinal staging of potentially operable non-small-cell lung cancer (NSCLC). METHODS: Four decision strategies based on French NSCLC work-up practices for the selection of potential surgical candidates were compared, comprising CT only, PET for negative CT, PET for all with anatomical CT, and CT and PET for all cases. The medical literature was surveyed to obtain values for all variables of interest. Costs were assessed with reimbursements from the French healthcare insurance for the year 1999. Expected cost and life expectancy were calculated for all possible outcomes of each strategy. Sensitivity analysis was performed to determine the effects of changing variables on the expected cost and life expectancy. RESULTS: Compared with the CT only strategy, CT and PET for all resulted in a relative reduction of 70% of surgery for persons with mediastinal lymph node metastasis. PET for all with anatomical CT was shown to be a cost-effective alternative to the CT only, with life expectancy increased by 0.10 years and expected cost savings of 61 euros. This strategy was more favourable than PET for negative CT. Overall, sensitivity analyses showed the robustness of the results. CONCLUSION: The introduction of thoracic PET for NSCLC staging is potentially cost-effective in France. Further clinical investigation might help to validate this result.

A simulation model for evaluating the medical and economic outcomes of screening strategies for colorectal cancer.

Mathematical models have been shown to be useful in predicting the cost-effectiveness of cancer screening programmes. We designed a computer macro-simulation model aimed at predicting the cost-effectiveness of alternative colorectal cancer screening strategies. This model was built to determine the cost-effectiveness of a biennial screening programme using the Hemoccult test in Burgundy (France). It was validated with data from the Danish randomized study. Estimates of our model showed an extremely close concordance with observed results in the Danish study. The observed mortality reduction was 18.0% and the estimated mortality reduction was 18.4%. Preliminary data from the Burgundy study predict a 14.6% colorectal cancer mortality reduction after 10 years. Sensitivity analyses were performed with different assumptions regarding the participation rates and the lead-time. This model can serve to assess the cost-effectiveness of a variety of screening modalities.

[A diagnostic strategy for isolated pulmonary nodules less than 2 cm in diameter]. / Gestion diagnostique d'un nodule isolé de plus de 2 cm de diamètre.

The object of this study is to determine the best diagnostic strategy for isolated pulmonary nodules less than 2 cm in diameter starting from decision analysis. The diagnostic pathway included strategies: 1. Observation with a thoracic tomodensitometry (TDM) every 3 months. 2. Percutaneous needle biopsy. 3. Video-assisted thoracoscopic surgery (VATS) resection. 4. Resection by thoracotomy. Observation was the best strategy for non-smokers in their 40's with a cost of 57-69 Francs per year of life gained. Needle biopsy was the best strategy for a 1 cm nodule in patients of 50 years, smokers and non-smokers (life expectancy 29.38 and 24.44 years). The best strategy for a 2 cm nodule was needle biopsy in 40 year old smokers (life expectancy 34.18 years) and in non-smokers aged 50-60 years with a life expectancy from 20.0 to 28.2 years. VATS was the best strategy for a 1 cm nodule in smokers over the age of 60 for a 2 cm nodule over the age of 50. The costs were 1 811, 3 214, 1 873, 1 811 and 6 093 Francs respectively per year of life gained. During the sensitivity analysis VATS remained the best strategy provided the post-operative mortality remained below 2%. When the risk of malignancy is only moderate needle biopsy may be recommended but when the risk of malignancy is high it is preferable to advise VATS as the method of diagnosis.

Bayesian population model of methotrexate to guide dosage adjustments for folate rescue in patients with breast cancer.

BACKGROUND: Methotrexate (MTX) infusions may induce severe side-effects, and alkaline hydration along with folinic acid rescue is a common way to reduce such toxic risks. The purpose of this study was to develop an adaptive rescue strategy based upon the early detection of patients with impaired MTX elimination. METHODS AND RESULTS: In this study, we propose a simple population-based Bayesian approach for predicting MTX plasma concentration from a limited number of samples, so as to adapt both duration and dosage of the rescue agent to be used next. Ten kinetic profiles obtained after 10 courses of MTX (1.5 g/m2) in seven patients with inflammatory breast cancer were used to establish the population pharmacokinetic parameters (Cl, 8.16 L/h; t1/2, 12.7 h). This population was next involved in the Bayesian estimation of MTX individual pharmacokinetic parameters from only two blood samples (T24 and T36 h), thus allowing one to forecast the elimination of this drug by predicting MTX levels at 48 h. According to the MTX concentrations predicted during the elimination phase, folinic acid rescue was then prolonged in patients likely to be overexposed. CONCLUSION: The Bayesian estimation presented in this study was an easy and convenient method to efficiently detect patients with impaired MTX elimination in routine clinical practice. This information enabled the introduction of strategies for minimizing the risk of severe drug toxicity.

Chemotherapy and concomitant irradiation in inflammatory breast cancer.

The purpose of this study was to evaluate the efficacy of concurrent chemotherapy and irradiation in inflammatory breast cancer (IBC). Between January 1990 and December 1998, forty-eight non-metastatic patients with clinical or occult IBC were treated with chemotherapy and irradiation. The induction chemotherapy consisted of epirubicin, cyclophosphamide and vindesin, in association with split-course bi-fractionated irradiation to a total dose of 65 Gy with concomitant cisplatin and fluorouracil. Maintenance chemotherapy consisted of high-dose methotrexate and 6 cycles of epirubicin, cyclophosphamide and fluorouracil Hormonal treatment was given routinely but mastectomies were not routinely performed. A high rate of locoregional control was obtained in 47 evaluable patients of whom 93.6 % achieved a complete clinical response. Three patients had locoregional relapses, always with concomitant metastatic dissemination. In 47 patients, 21 developed metastatic dissemination with a median delay of 23 months. Median disease-free survival (DFS) was 45 months. Median overall survival (OS) has not yet been reached after a median follow-up of 44.5 months. The 3-year DFS rate was 53 % and the 3-year OS rate was 71 %. Toxicity was mainly hematological. During the induction therapy, grade 3 or 4 neutropenia occurred in 54 % of patients, grade 3 or 4 thrombocytopenia in 23 % and grade 3 or 4 anemia in 8 %. The administration of induction chemotherapy and concomitant irradiation is feasible in patients with IBC. The hematological toxicity of this treatment approach is significant but nevertheless, the treatment achieves a high degree of locoregional control and improved survivaL