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The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

In order to help the clinician, mathematical models including several clinical and pathological variables are proposed in the literature with the aim to predict the occurrence of an event of interest. Nomograms allow individual prognosis for each patient. When they are developed, validated and correctly used, nomograms can provide important information for patients' care. But, despite the strong interest in nomograms in oncology, statistical methodologies used remain unknown from the medical community. This paper presents the major steps in the development, the validation and the clinical use of nomograms. Examples are given to illustrate these different points and the limits of this methodology. Finally, guidelines on the use of nomograms are proposed for clinicians., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In the era of personalized medicine, treatment effect can no longer be considered homogeneous for all patients. Subgroups analyses are generally performed in addition to main analysis in order to assess treatment effect in subpopulations. When planned, analyzed, presented and interpreted correctly, results of subgroups analyses can provide important information to guide treatment strategy. Several literature reviews have highlighted a lack of consistency in the analysis and interpretation of results. Indeed, subgroups analyses face different methodological issues (alpha risk inflation, power decrease…). Methodological principles for planification and interpretation of subgroups analyses in a clinical trial are presented in this methodological paper. Recommendations are proposed to assist in the interpretation of results of subgroups analyses., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In clinical research, the reference method to evaluate treatment benefit without bias is the randomized trial. Unfortunately, it is not always possible to realize one, as for example in surgery or for particular observational studies. In these cases, Rosenbaum and Rubin introduced in 1983 a new methodology: the calculation of a propensity score. When several treatments are compared, this calculation enables to take into account confusion bias using a score that synthesizes the influence on treatment choice of clinical parameters evaluated before. This article describes how to build this score, to estimate its validity, and how to use it: as a new variable into a multivariate analysis, as a matching criterion, or as a stratification parameter. Examples are given to illustrate each case and point out the limitations of such a methodology. This approach, although innovative and useful, cannot reach the level of evidence of randomized clinical trials: simulations have demonstrated this fact in several situations. On the other hand, it can be compared to standard multivariate analysis which permits in a non-randomized context, to limit evaluation bias of treatments by adjusting on potential confusion factors. Some guidelines are given in the last chapter to help researchers decide whether to use a propensity score or a standard multivariate analysis., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Tubal lesions detected in specimen of risk reducing salpingo oophorectomy (RRSO) for mutation BRCA1/2 seems to play a role in ovarian carcinogenesis. The main objective of this study is to evaluate the prevalence of occult neoplasia, of Serous Tubal Intraepithelial Carcinoma (STIC), and signature P53 in a cohort of patients who underwent a risk reducing salpingo oophorectomy., Methods: From January 2010 to January 2014 unicentric, retrospective study on a consecutive cases cohort of RRSO for patients with a high risk of ovarian neoplasia (mutation BRCA 1/2 or family history). Pathological specimen should be analysed according to the SEE-FIM protocol., Results: Ninety-three RRSO were recorded. Among them, 44% of the patients had the germ line mutation BRCA1, 30.1% BRAC2 and 18.2% had no identified mutation. In all, 33.3% of the RRSO reveal a signature P53, in the fimbria for 93.9%, 7.9% of them were bilateral. 1,1‰ (n=1) of the patients presented a unilateral STIC. We obtained 4.3% of occult neplasia: 3 ovarian high-grade serous carcinomas and 1 tubal high-grade serous carcinoma. Only the tubal carcinoma coexists with STIC., Conclusion: 5,4% of the patients who underwent RRSO had a diagnostic of occult neoplasia. One percent of the patients had an isolated STIC. These results agree with recent data of the literature. Extensive examination of the Fallopian tube opens up a new way to understand ovarian carcinogenesis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

At the end of the dose escalation step of phase I trials in oncology, it is increasingly frequent to include patients in expansion cohorts. However, the objective of the expansion cohorts, the number of patients included and their justification are insufficiently explained in the protocols. These cohorts are sometimes of considerable size. The aim of this article is to outline the methodology of expansion cohorts in order to provide recommendations for their planning in practice. This work has been undertaken in collaboration with the statisticians of the early phase investigation centers (CLIP(2)), supported by INCA. First, we have outlined the recent articles published on the expansion cohorts in phase I. We then proposed recommendations, in terms of objectives and number of patients to be included, to guide investigators and facilitate the use of these expansion cohorts in practice. Manji et al. have identified 149 phase I clinical trials using expansion cohorts in oncology with a review of the literature between 2006 and 2011 (Manji et al., 2013). Objectives of the expansion cohort were reported in 111 trials (74%). In these trials, safety was the most reported objective (80% of trials), followed by efficacy (45%). According to this review, the number of patients included in these cohorts was insufficiently justified. This result was confirmed by the study of literature that we conducted over the period 2011-2014. We propose to define the number of patients to be included in expansion cohorts in terms of (1) their objectives, (2) the statistical criteria and (3) the clinical context of the trial. The toxicity study remains the primary objective to evaluate in the expansion phase. In some contexts, the activity study is considered as co-primary objective, either for identifying preliminary signs of activity in studies like screening, or for studying the activity when the target population is known. This study is then considered as phase I/II, and experience plans of phase II can be adapted for planning expansion cohorts. Recommendations for the size of expansion cohorts are proposed. Despite the exploratory character of the expansion cohort, a justification of their size based on assumptions statistically defined is recommended in order to provide an interpretable conclusion and to quantify the risk of errors., (Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Evaluate the fiability and feasibility of laparoscopic surgery for the management of uterine cancers [endometrial cancer (EC) and early-stage cervical cancer (ESCC)] with patients who have a BMI ≤ 30 kg/m(2), within the setting of a gynaecological oncology department., Patients and Methods: This retrospective, monocentric and descriptive study was carried out between January 2003 and May 2011 at the Institute Claudius-Regaud, a centre for cancer diagnosis, treatment and research. A policy promoting laparoscopy as a first choice treatment has been established at the institute since 2003., Results: Two hundred and three patients were included. Eighty-five patients were early-stage cervical cancer patients and 118 patients were endometrial cancer patients. The study shows a high fiability rate for laparoscopy in non-obese patients, with a 98.8% rate for EC patients and a 98.8% rate for ESCC patients. The feasibility rates were 80.1% and 96.6%, respectively. The incidence of laparoconversion was reported at 1.2% and 3.1% for ESCC and EC patients, respectively, while the incidence of peroperative complications was 5.9% and 7.4%. The incidence of postoperative complications rank ≥ 3 according to "Memorial secondary events grading system" was 3 (3.5%) for CCUP and 3 (2.5%) for CE., Discussion and Conclusion: The results of this study show high fiability and feasibility levels for the laparoscopic treatment of uterine cancers in non-obese patients. There is no need to implement the more expensive robotic-assisted surgery in this group of patients. Mastering advanced laparoscopic surgery remains a mainstay in gynaecologic oncology., (Copyright © 2014. Published by Elsevier SAS.)

Purpose: To describe long-term outcome after combined-modality treatment including radiation therapy in patients with localized sarcoma within irradiated field., Patients and Methods: Individual clinical data from all consecutive patients diagnosed and treated for a localized sarcoma within irradiated field between January 2000 and October 2011 at the Institut Claudius-Regaud, Toulouse, France, were retrospectively reviewed., Results: Twenty-seven patients were eligible for this study. Ten patients were re-irradiated with a rate of unresectable, gross or microscopically positive margins disease significantly higher than the rest of the cohort (90% vs. 12%; P<0.001). After a median follow-up of 3.8 years, there is a non-significant trend toward longer 4-year relapse free survival in the subgroup of patients who received adjuvant or definitive radiation therapy compared to the rest of the cohort (53% vs. 27%; P=0.09) with an acceptable toxicity profile allowing conservative management., Conclusion: The complete surgical resection sarcoma within irradiated field is often difficult to achieve enhancing the risk of relapse. Radiation therapy should be discussed when faced with an unresectable tumour or after suboptimal surgery as part of intensified local management with a curative intent., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing., Patients and Methods: All consecutive patients treated for a ductal carcinoma in situ with microinvasion at the Institut Claudius-Regaud (Toulouse, France) over a 10-year period were included in this study. We reviewed all available histological materials., Results: Sixty-three patients were eligible for this study. Two patients presented with a lymph node invasion at diagnosis. Each patient benefited from initial surgical management, which consisted either in mastectomy (n=25) or conservative resection (n=37). Axillary exploration was performed in 52 patients (82%). After a median follow-up of 61.3 months [46.9;69], the 5-year overall survival and disease free survival were 98.2 (95% CI=[88.2;99.7]) and 89.5% (95% CI=[76.3;95.6]) respectively. Two delayed invasive relapses occurred leading to one specific death. The pathological review highlighted a trend towards a loss of HR and HER2 expression (9%) in the microinvasive component in comparison with its surrounded in situ carcinoma., Conclusion: The risk of initial lymph node involvement and delayed invasive local relapse deserve an optimal locoregional management including lymph node evaluation. The non-negligible discrepancy's rate between in situ and microinvasive components justifies HR status and HER2 expression assessment on the microinvasive component., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Objectives: Evaluation of mid-term functional results and the quality of life after laparoscopic colorectal resection., Patients and Methods: Twenty-three consecutive patients were included in a retrospective monocentric study. Postoperative functional outcomes and quality of life were analyzed., Results: The median follow-up after colorectal resection was of 24±15.7 months (6-72). Major complications occurred in three cases (12,9%) including one anastomotic stenosis, one digestive and one bladder fistula. A significant improvement in pelvic pain symptoms was observed. De novo constipation and pain on defecation occurred in respectively 23% and 42% of the cases. Transient de novo dysuria occurred in 18% of the cases. The quality of life has been significantly improved., Conclusion: Laparoscopic colorectal resection is associated with unfavourable postoperative digestive and urological outcomes, such as bladder and rectal dysfunction. Radical treatment should be limited to selected patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)