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.

Occupational exposures in rare cancers: A critical review of the literature.

The contribution of occupational exposures to rare cancers, which represent 22% of all cancers diagnosed annually in Europe, remains insufficiently considered. We conducted a comprehensive review of occupational risk factors in 67 rare cancers (annual incidence <6/100,000). An examination of relevant articles in PubMed (1960-2012) and the International Agency for Research on Cancer (IARC) monographs revealed that 26 cancer sites, such as mesothelioma, nasal, larynx, liver, ovarian cancer, bone sarcoma, and hematopoietic malignancies were consistently linked to occupational factors. Main exposures included asbestos, wood dust, metals/metalloids, formaldehyde, benzene, vinyl chloride, and radiation. There was inconsistent evidence regarding 22 rare malignancies. We did not identify relevant data for 19 rare cancers. Despite limitations of published evidence, our review provides useful information that can facilitate the identification of work-related factors that contribute to rare cancers. International collaborations, development of improved exposure assessment methods, and molecular approaches can improve future studies.

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.

Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study.

INTRODUCTION: After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients' satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. METHODS AND ANALYSIS: The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy. All participants will give written informed consent. The study findings will be disseminated through the scientific public and serve as a foundation for future randomised controlled trials of efficacy.

Guideline adaptation: an approach to enhance efficiency in guideline development and improve utilisation.

BACKGROUND: Developing and updating high-quality guidelines requires substantial time and resources. To reduce duplication of effort and enhance efficiency, we developed a process for guideline adaptation and assessed initial perceptions of its feasibility and usefulness. METHODS: Based on preliminary developments and empirical studies, a series of meetings with guideline experts were organised to define a process for guideline adaptation (ADAPTE) and to develop a manual and a toolkit made available on a website (http://www.adapte.org). Potential users, guideline developers and implementers, were invited to register and to complete a questionnaire evaluating their perception about the proposed process. RESULTS: The ADAPTE process consists of three phases (set-up, adaptation, finalisation), 9 modules and 24 steps. The adaptation phase involves identifying specific clinical questions, searching for, retrieving and assessing available guidelines, and preparing the draft adapted guideline. Among 330 registered individuals (46 countries), 144 completed the questionnaire. A majority found the ADAPTE process clear (78%), comprehensive (69%) and feasible (60%), and the manual useful (79%). However, 21% found the ADAPTE process complex. 44% feared that they will not find appropriate and high-quality source guidelines. DISCUSSION: A comprehensive framework for guideline adaptation has been developed to meet the challenges of timely guideline development and implementation. The ADAPTE process generated important interest among guideline developers and implementers. The majority perceived the ADAPTE process to be feasible, useful and leading to improved methodological rigour and guideline quality. However, some de novo development might be needed if no high quality guideline exists for a given topic.

Clinical practice guidelines.

Transferring results of research into clinical practice and their effective use for decisions in health care have become a major concern and are pivotal to quality improvement. Among the tools that have been developed are clinical practice guidelines (CPG). Developing reliable and valid recommendations requires a rigorous methodological approach that combines a systematic review of the results of clinical research with expert, pondered and explicit judgment. Guaranteeing applicability and implementation of these recommendations implies asking the question of how acceptable the recommendations are for the patient, the availability of the procedure and the expertise necessary in the specific context as well as identification of the organizational impact when put into action. CPG are a source of information not only for physicians but also for policy makers, insurance institutions, continued education programs and production of information for high quality decision making for patients.

[The patient's role in evidence-based medicine]. / La place du patient dans la médecine factuelle.

Medical practice has undergone a significant evolution over the last decade due to two important factors: (1) the theory and practice of Evidence-Based Medicine (EBM) has become widely established; (2) the relationship between health-care professionals and patients or clients has been profoundly modified. In this review, we discuss the heterogeneity and variability of patient preference and the need to develop a doctor-patient relationship, which facilitates shared decision-making in preference to previous models based on patient information without choice and paternalistic attitudes. Thus, this modern concept of care based on EBM shifts the focus of interest from the disease entity itself to that of the patient suffering from a disease. The patient has a right to information concerning his illness; this information helps the patient to participate in medical decisions through the laying out of clinical practice guidelines. These aspects of the patient's role in care management are illustrated by a national program in the field of oncology which empower the patient in the decisions arrived at by a multi-disciplinary oncology team.

[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.

SOR guidelines for concomitant chemoradiotherapy for patients with uterine cervical cancers: evidence update bulletin 2004.

BACKGROUND: In 1993 the French National Federation of Cancer Centres (FNCLCC) initiated the Standards, Options and Recommendations (SOR) project. This is a collaboration between the FNCLCC, the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics, and some specialists learned societies. The main objective is to develop clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. MATERIALS AND METHODS: The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. RESULTS: In 1999, the initial SORs for the management of women with cervical cancer were published. At that time the use of chemoradiotherapy was considered as an option. Since this original publication, five randomised trials comparing chemoradiotherapy with radiotherapy have been published, as well as a systematic review and two other clinical practice guidelines. In the light of this additional evidence, it was decided to update the guidelines on chemoradiotherapy in women with cervical cancer. CONCLUSION: After selection, critical analysis and integration of new evidence, chemoradiotherapy has become a standard for women with cervical cancer.

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.

[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.

A controlled "before-after" study: impact of a clinical guidelines programme and regional cancer network organization on medical practice.

A regional cancer network has been set up in the Rhône-Alpes region in France. The aim of the project is to improve the quality of care and to rationalize prescriptions in the network. In this network, we assessed the impact of the implementation of a clinical practice guidelines project by assessing the conformity of practice with the guidelines and comparing this with the conformity in an external matched control group from another French region without a regional cancer network. Four hospitals (private and public) accepted to assess the impact of the clinical practice guidelines on the management of breast and colon cancer in the experimental group and three hospitals (private and public) in the control group. In 1994 and 1996, women with non-metastatic breast cancer (282 and 346 patients in the experimental group, 194 and 172 patients in the control group, respectively) and all new patients with colon cancer (95 and 94 patients in the experimental group, and 89 and 118 patients in the control group, respectively) were selected. A controlled "before-after" study, using institutional medical records of patients with breast and colon cancer. The medical decisions concerning the patients were analyzed to assess their compliance with the clinical practice guidelines. When medical decisions were judged to be non-compliant, we verified if they were based on scientific evidence in a published article, if they were not, the medical decision was classified as having "no convincing supporting scientific evidence". The compliance rates were significantly higher in 1996 than in 1994 in the experimental group; 36% (126 out of 346) vs 12% (34 out of 282) and 46% (56 out of 123) vs 14% (14 out of 103) (P<0.001) for breast and colon cancer, respectively. Whereas, in the control group the compliance rates were the same for the two periods; 7% (12 out of 173) vs 6% (12 out of 194) (P=0.46) and 39% (49 out of 126) vs 32% (31 out of 96), P=0.19. In the experimental group, in 1994, 101 of the 282 medical decisions (36%) and 27 of the 103 (26%) for breast and colon cancer, respectively, were classified as having "no convincing supporting scientific evidence" compare with 72 out of 346 in 1996 (21%) for breast cancer, and 21 of the 123 (17%) for colon cancer P<0.05. Whereas in the control group these results were 106 out of 194 in 1994 (55%) and 90 out of 172 in 1996 (52%), P=0.65 for breast cancer and 28 out of 96 in 1994 (29%) and 30 out of 126 in 1996 (24%), P=0.36 for colon cancer. The development and implementation strategy of the clinical practice guidelines programme for cancer management results in significant changes in medical practice in our cancer network. These results would suggest that introducing guidelines with specific implementation strategy might also increase the compliance rate with the guideline and "evidence-based medicine".