Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study.

BACKGROUND: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. METHODS: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. RESULTS: Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age>14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; P=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P=0.048), and by 9% for each year at age at first birth (P=0.035). ALK alteration frequency was greater in women with high parity (50% in≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; P=0.021). CONCLUSION: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

[Impact of partial nephrectomy in a hybrid operating room on the activity of kidney cancer surgery]. / Évaluation de l'utilisation de la salle hybride sur l'activité de chirurgie en cancérologie rénale.

INTRODUCTION: Partial nephrectomy (NP) after embolization of tumor vessels (NPESH) in a hybrid room combines embolization of tumor vessels and enucleation of the tumor under laparoscopy in the same operative time. The purpose of this study was to assess the impact of the use of NPESH in the management of patients treated with surgery for a localized kidney tumor. MATERIAL AND METHODS: Using the uroCCR database, we included all consecutive patients operated in a university hospital for localized kidney tumor. From 2011 to May 2015, patients were treated by Standard Partial Nephrectomy (NPS) Laparoscopic or Open and from May 2015 to May 2019 by NPESH. We evaluated characteristics of patients, tumors, perioperative data and complications. These data were compared by Student and Khi2 tests. RESULTS: 87 NPS were performed during Period 1 and 137 NPS were performed during period 2. The ASA score of patients undergoing NPESH was higher than NPS (P<0.0001). The tumor complexity and median tumor size were similar in the two groups (P=0.852 and P=0.48). The complication rate for NPS and NPESH was 55.2% and 33.6% (P=0.002). There were less severe complications in the NEPSH group (P=0.012). The median length of stay was 8 and 4 days for the NPS and NPESH groups (P<0.0001). Positive surgical margins were 2 (2.3%) and 6 (4.6%) for the NPS and NPESH group (P=0.713). DISCUSSION: NPESH is an efficient technique compared to NPS. It seems to be an interesting alternative to limit renal ischemia, complication rate and length of stay for the management of localized kidney tumors.

[Management of metastatic renal cell carcinomass]. / Prise en charge des métastases du cancer du rein.

The management of metastatic renal cell carcinoma had changed over the last ten years with the apparition of new treatments and advances in surgery and ablative techniques. The therapies for metastatic patients have also been personalized and different prognostic groups have been established to adapt the treatment to the severity of the disease. Surgical excision, radiotherapy or ablative therapy could be proposed for patients with isolated metastasis and good condition to delay the systemic therapy initiation. Until 2006, in case of metastatic renal cell carcinoma, immunotherapy (IL-2 and TNF-alpha) was proposed. Targeted therapies acting on angiogenesis mechanisms have also been developed. Recently, immunotherapy has revolutionized the therapeutic management and has improved the overall survival of patients with metastatic renal carcinoma. For each patient, a multidisciplinary management is organized with a personal therapeutic project. This global management needs coordination with the medical team and also need a good communication with the patient, his entourage and his doctor.

[Immunotherapy in renal cell carcinoma: A booming clinical research]. / L'immunothérapie dans le cancer du rein : un développement clinique en plein essor.

CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated. OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area. DOCUMENTARY SOURCE: A systematic review of the literature was performed in PubMed/Medline database and Meeting Library Asco by searching for articles in French or English published on immunotherapy in renal cell carcinoma. The research was limited to abstracts and articles published from 2014 to 2017. SELECTION OF TRIALS: We identified 349 publications and abstracts and selected 17 references from prospective studies. RESULTS: Recent data on checkpoint inhibitors, as well as their combination with tyrosine kinase inhibitors or with anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1 in renal cell carcinoma and the latest advances in vaccine therapy have been reported. CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to lead to a paradigm shift in the clinical management of patients. The combination of nivolumab and ipilimumab in the first line will revolutionize the therapeutic management of patients with metastatic renal cell carcinoma.

Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study.

UNLABELLED: Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67 ± 12.7 years, women: 69 %, non smokers: 68 %, PS 0-1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p = 0.4). Overall survival (OS) showed a non-significant trend in favor of continuing TKI therapy (33.0 vs. 21.2 months, p = 0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p < 0.01). Univariate analysis showed a higher risk of death among patients with PS >1 (HR 4.33, 95 %CI: 2.21-8.47, p = 0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p = 0.02), brain metastasis (HR 1.75, 95 %CI: 1.08-2.84, p = 0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p = 0.056 ). In multivariate analysis only PS >1 (HR 6.27, 95 %CI: 2.97-13.25, p = 0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, p = 0.02) at diagnosis remained significant. This study suggests that under certain circumstances, first-line TKI treatment continuation after RECIST progression is an acceptable option in EGFR-mutated NSCLC patients. CLINICAL TRIAL INFORMATION: NCT02293733.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.

Bone metastasis from endometrioid ovarian carcinoma: a case study and literature review.

INTRODUCTION: Bone metastases from epithelial ovarian carcinoma are rare, usually discovered postmortem. The survival of these patients is poor. Furthermore, only two cases of endometrioid ovarian carcinoma with metastasis to the skeletal structures have been described in the literature. CASE REPORT: We present the case of a 58-year-old woman with a lytic metastasis in the left iliac ramus from endometrioid ovarian carcinoma that occurred seven years after the initial diagnosis. DISCUSSION: A review of the literature since 1966 on bone metastasis of ovarian cancer is also presented. In patients suffering from a neoplasm that rarely metastasises to bone, histological proof should be obtained to diagnose uncommon sites of disease relapse.

Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens.

PURPOSE: To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. METHODS: Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m(2) twice daily (1,650 mg/m(2) per day) on days 1-14 and paclitaxel 175 mg/m(2) by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. RESULTS: Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41-84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2-55.7%) with one complete response and 42.3% (95%CI = 17.2-55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4-4.5 months). Median overall survival was 7.5 months (95%CI = 6-10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11-18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). CONCLUSIONS: Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts.