Reduction of health risk factors through an adapted physical activity program in patients with breast cancer.

PURPOSE: After a breast cancer diagnosis, patients are at high risk of reducing their physical activity and gaining weight. Lack of physical activity and weight gain are known negative but modifiable prognostic factors. An observational study of a 3-month adapted physical activity (APA) program was performed to assess its effectiveness in improving physical activity level and reducing risk factors related to health during or after breast cancer treatments. METHOD: Height, weight, and waist circumference (WC) were measured at the beginning and end of the 26-session program. Body mass index (BMI) and WC to height ratio (WHtR) were calculated. Physical activity profile, aerobic capacity, and usual average daily energy expenditure were estimated. Median values were compared using nonparametric tests. RESULTS: Sixty-one (61) voluntary breast cancer patients attended 80% of the sessions. At baseline, median (minimum-maximum) BMI was 23.3 (16.1-36.8) kg.m(-2) and WC and WHtR showed metabolic risks. After 3 months, anthropometric data remained stable. Moderate physical activity significantly improved (+13 min/day) and sedentary tended to decrease (-18 min/day). CONCLUSION: A 3-month APA program allows patients to limit risk factors related to health such as physical inactivity and metabolic risks. This study reinforces the need to promote physical activity as early as possible in cancer patients' care.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Assessment of long-term exposure to airborne dioxin and cadmium concentrations in the Lyon metropolitan area (France).

Identifying the long-term effects of airborne pollutants requires the computation of the spatial and temporal variability of their concentration in air to estimate the exposure of the population. To estimate exposure levels of individuals in a breast cancer case control study nested in a national prospective cohort, we determine here the differential impact of a variety of cadmium and dioxin sources on urban air over a large urban area and over a period of almost 20years. To that end, we couple an emission model, to estimate dioxin and cadmium atmospheric annual releases, with an urban dispersion model in order to compute pollutant concentration fields at a fine temporal (1h) and spatial (25m) resolution. The reliability of the modelling chain is compared to two types of measurement: i) localized industrial emissions and ii) dioxin and cadmium air monitoring data (from 2007 to 2008), collected at a fixed station, placed in the city centre, as well as at three mobile short-term dioxin monitoring stations, located in the suburbs (the latter providing dioxin data, only). Comparisons between measured and estimated emissions show non-negligible difference, with a correlations for dioxin (rs=0.42) and cadmium (rs=0.41). Despite this, mean values between estimated emissions and emission measurements are close to each other, in particular for cadmium. Weekly average modelled concentrations show an overall good agreement with weekly average measured concentrations in spring and summer but are generally lower than monitored data in winter due to peak concentrations from diffuse sources representing an important proportion of emissions in 2007/2008. The model provides better results for cadmium than for dioxin. Despite the relevant errors in the model predictions, the model meets the validation criteria, defined by Chang and Hanna for an urban dispersion model. Simulation scenarios of air pollutant concentrations, reconstructed over the last 20years, show the effects of the variability of the pollutant sources over time with decreasing levels of dioxin and cadmium concentrations in air. This is primarily due to the reduction in localized industrial releases, which results in a general trend of homogenization of the exposure of the population. The model further allows us to dissociate the contribution of different types of pollutant sources on the population exposure. The impact on local concentrations due to industrial emissions, which were originally responsible for the major impact on air quality, is shown to drop over the years by 99% and 92% for dioxin and cadmium, respectively. Today, the major contributions are due to diffuse miscellaneous sources in the case of dioxin and to traffic-related emissions for cadmium. Average modelled concentrations at the study subjects' residential locations range from 10.2 to 82.1fg-TEQ/m3 for dioxin and 0.10 to 1.6ng/m3 for cadmium and are comparable with data from the literature. The study results will be essential to increase the accuracy of the assessment of long-term airborne dioxin and cadmium exposure and improve the results of epidemiological studies.

[Understanding nephroblastoma. Information dedicated to parents and relatives]. / Comprendre le néphroblastome. Information à l'usage des parents et des proches d'un enfant malade.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiothérapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

International assessment of the quality of clinical practice guidelines in oncology using the Appraisal of Guidelines and Research and Evaluation Instrument.

PURPOSE: To describe the quality of oncology guidelines developed in different countries. METHODS: The Appraisal of Guidelines and Research and Evaluation (AGREE) Instrument was used to assess the quality of 100 guidelines (including 32 oncology guidelines) from 13 countries. The criteria of the instrument are grouped into six quality domains: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. RESULTS: Oncology guidelines had significantly higher scores on rigor of development than nononcology guidelines (42.2% v 29.4%; P =.02). In particular, systematic methods to search for evidence were more often used (P =.01); the methods for formulating the recommendations were more clearly described (P =.02); and health benefits, risks, and side effects were more often considered in formulating the recommendations (P =.03). Although the standardized scores for the other domains were not significantly different, the oncology guidelines had significantly higher scores for items measuring inclusion of all relevant professional groups (P =.05), consideration of patient views (P =.04), and presentation of different options (P =.05). Only three organizations producing oncology guidelines had standardized scores more than 60% for more than three domains. CONCLUSION: The quality of clinical practice guidelines (CPGs) is modest in general, but for certain domains, oncology guidelines seem to be of better quality than others. The experience of the organization may explain higher scores for some items. Research projects and training aimed at improving the quality of guidelines should be developed. The AGREE instrument could provide a basis for defining steps in a shared development approach to produce high-quality CPGs.

Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

Treatment strategies for metastatic Ewing's sarcoma.

Therapy in metastatic Ewing's sarcoma is reviewed using the methodology recommended by the guidelines project of the Federation of French Cancer Centres (FNCLCC) Standards, Options and Recommendation (SOR) Group. Twelve articles relating to conventional dose therapy and seven articles related to high-dose therapy were judged suitable for detailed appraisal. Rates of complete response (CR) at metastatic sites and local control were high using combinations of vincristine, actinomycin, cyclophosphamide and doxorubicin with radiation or surgery. With more recent regimens, including increased doses of alkylating agents and anthracyclines the relapse-free survival has increased from <15 to 20-30%. 'Megatherapy' regimens with haematopoietic stem cell rescue are tolerable in this patient group, but to date there is little evidence of any benefit. It appears that patients with isolated lung metastases do significantly better (approximately 40% EFS) than those presenting with combined sites such as bone, bone marrow and lung. The use of lung irradiation in children with lung metastases is associated with a reduced incidence of subsequent lung recurrence and a consistently better overall relapse-free survival (RFS).

Analysis of the eligibility of published economic evaluations for transfer to a given health care system. Methodological approach and application to the French health care system.

CONTEXT: Economic evaluations are costly and cannot always be carried out locally. Therefore, decision-makers may wish to use studies already performed in other settings. OBJECTIVE: To define a method for assessing the eligibility of published economic evaluations for transfer to a given health care system and apply it to the french health care system in the clinical situation of adjuvant therapy for women with breast cancer. METHODS: (1) Literature search in six databases from 1982 to 1996; (2) critical appraisal of articles based on four inclusion criteria; and (3) assessment of the eligibility of the studies for transfer based on five indicators. RESULTS: We identified 26 published economic evaluations concerning adjuvant therapy in women with breast cancer. Six (23%) met all four criteria used to select studies, but none of these studies were eligible for transfer to the french health care system. The main reason was that cost data was not reported in a transparent way. CONCLUSIONS: To improve the transferability of economic evaluations, we recommend that requirements for data provision in publications be standardized and international collaboration strengthened.

[Standards, Options and Recommendations (SOR): consequences of the SOR guidelines project in terms of liability for French Cancer Centers]. / Standards, Options et Recommandations (SOR): leurs effets juridiques en termes de responsabilité, recommandations et suggestions à l'intention des Centres de lutte contre le cancer.

Context. The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centers (FNCLCC), the 20 French comprehensive Cancer Centers and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives. To identify consequences in terms of liability of the development of SOR guidelines and to formulate recommendations for the FNCLCC and medical doctors using SOR. Methods. Data have been identified by literature search on legal matters by CNEH's Legal Center JuriSanté, then submitted to a group of 8 experts. Results. The main conclusions of the present study are: 1)The SOR attest a high level of quality and methodological rigor; 2) according to legal considerations and in comparison to the available scientific data, the SOR guidelines can be considered as the state of the art in oncology at time of release; 3) the study identified six quality properties of Standards, Options and Recommendations (SOR): information contained in the SOR must be serious, accurate, reliable, complete, up-to-date and secure. The respect of these quality criteria is essential in the matter of liability; 4) when gathered, they can prevent the actors from being implicated on questions of liability. Specialists who use the SOR may avoid problems of liability, nevertheless evidence and the state of the art may evolve with time; 5) clinicians who do not use the SOR, may appear to be responsible for disasters, except if they can justify their medical decision (evolution of scientific knowledge or specific clinical circumstances, etc.); 6) therefore, SOR developers need to keep in mind these essential properties when SOR are prepared; 7) the SOR steering committee (COSOR) analysed the conclusions of the present legal study and defined a series of actions and procedures to guarantee the respect of the above quality criteria.

[Integration of economic criteria in the recommendations for clinical practice in cancerology]. / Intégration des critères économiques dans les recommandations pour la pratique clinique en cancérologie.

Clinical practice guidelines have been defined as "systematically developed statements to assist practitioners and patients in their decisions about appropriate health care for specific clinical circumstances". Their objectives are to improve the quality of health care and to optimise the use of limited health care resources. However reduction of unnecessary costs of delivered health care is proceed most often in an implicit way by identifying inappropriate health care strategies. The increase of health care costs needs to look at this issue in a more explicit way and to consider costs in the guideline development process. The key objective of our study is to analyse the methodological aspects of dealing with cost issues in the guideline development process. The integration of cost issues is in fact limited by two major problems: first, the lack of economic evaluation for many strategies in the scientific literature and second, the lack of generalizability of the published results to temporally and/or geographically different settings. These difficulties are likely to result in the need for local cost evaluation (for a given setting), and though to make the guideline development process much more complex. Further methodological research is important to define the role of economic evaluation in clinical practice guidelines and to enable the integration of cost issues into the guideline development process. They should go closely together with international standardisation of the methodology for designing, conducting and reporting economic evaluation.

[Standards, options and recommendations (SOR) for clinical care of malignant thymoma. Groupe de Travail SOR]. / Standards, options et recommandations pour la prise en charge des patients atteints de tumeurs epithéliales du thymus.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of malignant thymoma in adult. METHODS: Data have been identified by literature search using Medline (december 1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for malignant thymoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and made from a biopsy, except in cases of well-encapsulated tumors which are completely resected. The biopsy, via anterior mediastinostomy, should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical resection must be complete including thymus and perithymic fat and performed by an experienced surgeon; 4) the therapeutic strategy for malignant thymoma is based on the three current staging systems and involves surgery with radiotherapy given if the capsule is invaded or penetrated. Radiotherapy should be given in experienced centres. Inclusion of patients in prospective clinical trials is recommended in order to determine the usefulness of neoadjuvant chemotherapy and multimodality approaches; 5) treatment of metastatic malignant thymoma is based on chemotherapy. Secondary surgery may be performed with the aim of achieving complete resection. Inclusion in clinical trials is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition. Because of late recurrence, follow-up should be long.

[Standards, options and recommendations: concomitant radiochemotherapy for cancer of the cervix: a critical analysis of the literature and update of SOR]. / Radiochimiothérapie concomitante dans les cancers du col de l'utérus: analyse critique des données et mise à jour des standards, options, et recommandations. Groupe de travail SOR.

INTRODUCTION: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy. METHODS: Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRLCC. RESULTS: The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are: 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III et IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement); 2) the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1); 3) these results have been obtained by the combination of chemotherapy based on cisplatin alone, or in combination with 5FU. Although of equal benefit, the toxicity of the cisplatin/5FU/hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed; 4) the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.

[Standards, Options and Recommendations (SOR): clinical practice guidelines for diagnosis, treatment and follow-up of cutaneous melanoma. Fédération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations (SOR) pour la prise en charge des patients atteints de mélanome cutané.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of patients with cutaneous melanoma. METHODS: Data have been identified by literature search using Medline - until December 1998 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the management of cutaneous melanoma (CM) are: 1) The primary prevention of melanoma is based on a reduction in exposure to ultraviolet rays (solar or artificial). 2) The diagnosis of CM requires the surgical removal and histological examination of the lesion (standard). 3) The pathological report must include the diagnosis of primary malignant melanoma, the maximum thickness of the tumour in millimeters (Breslow), the clearance of surgical margins, the level of invasion (Clark), the presence and extension of regression and the presence of any ulceration (standard). 4) The standard treatment of a primary melanoma without lymph node involvement is based on surgery that must ensure adequate margins depending on the thickness of the tumour (standard, level of evidence B). 5) After surgery of a stage I melanoma, there is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B, French Consensus Conference). 6) For a local recurrence without node involvement, in the absence of other metastases, surgical excision is the standard treatment. 7) In the case of metastatic regional lymph nodes, a complete regional lymphadenectomy is required. There is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B). The inclusion of these patients in controlled studies of immunotherapy is recommended. 8) There is no standard therapeutic strategy for metastatic melanoma. Conventional palliative treatment is chemotherapy with dacarbazine (level of evidence B). 9) Follow-up is based on physical examination (standard). Patient information must encourage self-surveillance. Clinical surveillance and self-detection are indicated in all cases throughout life (standard).

[Standards, options and recommendations (SOR) for diagnosis, treatment and follow-up of osteosarcoma. Groupe de travail SOR]. / Standard, Options et recommandations (SOR) pour le diagnostic, le traitement et la surveillance de l'ostéosarcome.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of osteosarcoma in children and adult. METHODS: Data have been identified by literature search using Medline (1985-december 1998) and the expert groups personal reference lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of treatment. Once the guidelines were defined, the document was submitted for review to 27 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular, the 4 which have particular expertise in pediatric cancer management. RESULTS: The main recommendations for osteosarcoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and the biopsy should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical biopsy must be of adequate size and performed by an experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres. Inclusion of high dose methotrexate is recommended for children, and the dose of methotrexate must be adapted for adults. Inclusion of children in SFOP protocols and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases which may be curative. Amputation is rarely appropriate. Inclusion of children in SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

[Concomitant radiochemotherapy for cancer of the cervix: critical analysis based on the Standards, Options and Recommendations methodology]. / Radiochimiothérapie concomitante dans les cancers du col de l'utérus: analyse critique des données et mise à jour des Standards, Options et Recommandations.

INTRODUCTION: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy. METHODS: Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRCC. RESULTS: The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are 1/ the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III and IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement). 2/ the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1). 3/ these results have been obtained by the combination of chemotherapy based oncisplatin alone, or in combination with 5-FU. Although of equal benefit, the toxicity of the cisplatin/5-FU/ hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed. 4/ the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

[Standards, options, and recommendation for external radiotherapy of prostatic cancer: evaluation of the effect of dosage]. / Standards, Options et Recommandations pour la radiothérapie externe des patients atteints de cancer de la prostate: évaluation de l'effet dose.

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.

[Standards, Options, and Recommendations for brachytherapy in patients with prostate cancer: efficacy and toxicity]. / Standards, Options et Recommandations pour la curiethérapie des patients atteints de cancer de la prostate: efficacité et toxicité.

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

[Genetics and cancer of the breast]. / Génétique et cancer du sein.

Breast carcinoma is the commonest cancer in women. Segregation analyses support the existence of a major susceptibility gene with a dominant pattern of inheritance in 4 to 10% of cases. Three genes involved in the genetic predisposition to breast tumors have recently been identified: BRCA-1 associated with early onset familial breast cancer and breast/ovarian carcinoma syndrome, p53 associated with Li-Fraumeni syndrome, and the androgen receptor gene in male breast cancer with Reinfenstein syndrome. A better understanding of inherited contribution may have important implications for screening individuals at high-risk in families.