Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

BACKGROUND: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma. METHODS: Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg. RESULTS: The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%). CONCLUSIONS: Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01.

Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study.

BACKGROUND: Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination. PATIENTS AND METHODS: This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively. RESULTS: From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601-0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case-control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672-0.813; 8.1 versus 6.4 months). CONCLUSIONS: In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC.

Prediction of long-term cumulative incidences based on short-term parametric model for competing risks: application in early breast cancer.

Use of parametric statistical models can be a solution to reduce the follow-up period time required to estimate long-term survival. Mould and Boag were the first to use the lognormal model. Competing risks methodology seems more suitable when a particular event type is of interest than classical survival analysis. The objective was to evaluate the ability of the Jeong and Fine model to predict long-term cumulative incidence. Survival data recorded by Institut Curie (Paris) from 4761 breast cancer patients treated and followed between 1981 and 2013 were used. Long-term cumulative incidence rates predicted by the model using short-term follow-up data were compared to non-parametric estimation using complete follow-up data. 20- or 25-year cumulative incidence rates for loco-regional recurrence and distant metastasis predicted by the model using a maximum of 10 years of follow-up data had a maximum difference of around 6 % compared to non-parametric estimation. Prediction rates were underestimated for the third and composite event (contralateral or second cancer or death). Predictive ability of Jeong and Fine model on breast cancer data was generally good considering the short follow-up period time used for the estimation especially when a proportion of patient did not experience loco-regional recurrence or distant metastasis.

BIRC5 (survivin): a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy.

PURPOSE: Neoadjuvant systemic therapy (NAC) is currently used in the treatment of stage II/III breast cancer. Pathological complete response as a surrogate endpoint for clinical outcomes is not completely validated for all subgroups of breast cancers. Therefore, there is a need for reliable predictive tests of the most effective treatment. METHODS: We used a combination of predictive clinical, pathological, and gene expression-based markers of response to NAC in a prospective phase II multicentre randomized clinical trial in breast cancer patients, with a long follow-up (8 years). This study concerned the subpopulation of 188 patients with similar levels of pathological response rates to sequential epirubicin/cyclophosphamide and docetaxel to determine predictive marker of pCR and DFS. We used a set of 45 genes selected from high throughput analysis and a standardized RT-qPCR. We analyzed the predictive markers of pathological complete response (pCR) and DFS in the overall population and DFS the subpopulation of 159 patients with no pCR. RESULTS: In the overall population, combining both clinical and genomic variables, large tumor size, low TFF1, and MYBL2 overexpression were significantly associated with pCR. T4 Stage, lymphovascular invasion, negative PR status, histological type, and high values of CCNB1 were associated with DFS. In the no pCR population, only lymphovascular invasion and high values of BIRC5 were associated with DFS. CONCLUSIONS: We confirm the importance of ER-related and proliferation genes in the prediction of pCR in NAC-treated breast cancer patients. Furthermore, we identified BIRC5 (survivin) as a main pejorative prognostic factor in patients with breast cancers with no pCR. These results also open perspective for predictive markers of new targeted therapies.

Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. METHODS: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. RESULTS: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. CONCLUSION: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of the PIK3CA gene, encoding one of the two PI3K subunits. METHODS: PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n=43), or only after surgery (adjuvant trastuzumab arm, n=37). RESULTS: PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours (P=0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS (P=0.0013) were identified. CONCLUSION: These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours.

[Impact of socioeconomic status on stage at diagnosis of breast cancer]. / Impact du statut socioéconomique sur la gravité du diagnostic initial de cancer du sein.

BACKGROUND: This study aimed to evaluate the potential impact of social inequalities on stage at diagnosis and long-term outcome of breast cancer patients attending the Institut Curie in Paris (France). METHODS: The study population included 14,610 breast cancer patients diagnosed and treated in the Institut Curie between 1981 and 2001. The socioeconomic status was determined from district of residence, median income for town of residence corrected by the consumption unit and body mass index. Logistic regression models adjusted on socioeconomic factors were used to evaluate clinical and pathologic features at diagnosis. Overall survival and distant metastasis were analysed with log-rank tests and Cox proportional hazards regression models. RESULTS: Patients living in lower income districts were more likely to be diagnosed with breast tumors size greater than 20 mm (P=0.01). Residents of high-income urban areas (>15,770 €) exhibited a significant overall survival and distant metastasis advantage (respectively HR=0.93 [0.86-0.99]; P=0.02 and HR=0.91 [0.85-0.98]; P=0.01). Breast cancer screening with mammography was independent of district of residence (P=0.61) or income (P=0.14). After adjusting for age at diagnosis and period, the risk of having breast cancer with unfavorable prognostic factors such as tumor size greater than 20 mm decreased with 1000 € increase in district income (OR=0.986 [0.98-0.99]; P<0.001). Similarly, the risk of cancer death decreased for patients residing in districts with median income greater than 15,770 € (HR=0.92 [0.86-0.98]; P=0.01). CONCLUSION: Despite the limitations of the study (aggregate data used to assess socioeconomic status, non representative cohort of French women), we observed that poorer breast cancer prognosis with advanced disease diagnosis and increased risk of breast cancer mortality was related to low socioeconomic status.

Real-world first-line treatment of patients with BRAFV600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study.

BACKGROUND: BRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients. PATIENTS AND METHODS: CAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety. RESULTS: In total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS. CONCLUSIONS: This study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting.

High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer.

BACKGROUND: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS: Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis. RESULTS: In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%). CONCLUSION: Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.

Prevalence and associated factors of sexual problems after early-stage breast cancer treatment: results of a French exploratory survey.

OBJECTIVE: The objective of this study was to assess the prevalence and associated factors of sexual activity, sexual problems or sexual satisfaction in French early-stage breast cancer survivors (BCS). METHODS: Eight hundred and fifty eligible, post-treatment (6 months-5 years) female patients, aged 18-70 years, randomly selected from a consultation list, were invited to fill in questionnaires exploring quality of life (EORTC QLQ-C30 and QLQ-BR23), body image scale, and sexuality (Sexual Activity Questionnaire-SAQ; Relationship and Sexuality Scale; French Sexual Behaviour Survey-CSF). RESULTS: Fifty-three percent of BCS agreed to participate. Participating women (n=378) were younger, more often premenopausal at diagnosis and with a more recent diagnosis than non-respondents. The prevalence of sexual problems was significantly higher in BCS compared with adjusted data from a French female representative sample (p<0.0001). In logistic regression, no sexual activity (R(2) =0.37) or sexual dissatisfaction (R(2) =0.28) were associated with the feeling of emotional separation in the couple or of partner's fear of sexual intercourse, lower emotional functioning, poorer body image, or co-morbidities. In sexually active women (71% of respondents), lower frequency of sexual activity (R(2) =0.26), lower sexual pleasure (R(2) =0.22), or higher sexual discomfort (R(2) =0.22) were associated with the feeling of emotional separation in the couple or of partner's fear of sexual intercourse, lower emotional functioning, age (>50 years), nausea, or insomnia (all Hosmer-Lemeshow tests: p=NS). CONCLUSIONS: Psychological factors including the perception of the couple relationship appeared prominent in BCS women's experience of sexual problems.

[Five year survival for lung cancer patients managed in general hospitals]. / Survie à cinq ans des cancers bronchiques primitifs dans les centres hospitaliers généraux.

INTRODUCTION: In 2000 the College of Pulmonologists of General Hospitals undertook an epidemiological study (KBP-2000-CPHG) enrolling all new cases of histologically confirmed lung cancer managed in general hospitals. This paper reports the five year survival in these cases. METHODS: Vital status was available for 5447 out of 5667 patients included in the original study. The effect of different prognostic factors on mortality was assessed. RESULTS: At 5 years 567 patients (10.4%) were still alive. Median survival for the 4880 (89.6%) deceased patients was 7 months. Univariate analysis identified age, smoking history, performance status, histological type and disease stage (TMN classification) as determinants of survival. For non-small cell lung cancer (n=4885) multivariate analysis identified five predictive factors for mortality - age, gender histological type, performance status and stage. CONCLUSIONS: Five year survival in lung cancer continues to be poor. As the risk factors for poor outcome at the time of diagnosis are not modifiable and pending the results of screening studies reduction in mortality must rest on primary prevention.

Metastatic NSCLC: Clinical, molecular, and therapeutic factors associated with long-term survival.

BACKGROUND: Patients with metastatic non-small-cell lung cancer (NSCLC) who survive more than 2 years are considered long-term survivors (LTSs). The present study examined factors associated with long-term survival and collected information for future comparison. METHODS: Clinical, molecular, and therapeutic data were collected from patients followed for primary stage IV (7th TNM classification) NSCLC within 2 years from diagnosis in the respiratory medicine departments of 53 French non-teaching hospitals. LTS and non-LTS records were compared. Factors associated with long-term survival were examined by univariate and multivariate analyses using logistic regression models. RESULTS: Vital status at least 2 years after diagnosis was known for 1977 stage IV NSCLC patients; 220 (11.1%) were LTSs. On multivariate analysis, independent positive factors comprised: TTF-1(+) immunochemistry, EGFR-mutation, surgery, rescue radiotherapy, and targeted therapy. Independent negative factors comprised: prediagnosis weight loss>5kg, ECOG performance status>1, and primary radiotherapy. CONCLUSIONS: Molecular biology and targeted therapy were decisive for long-term survival. With their development and their widespread implementation in clinical practice, the percentage of LTSs is expected to grow. Factors determining long-term survival found in this study should be taken into account when considering treatment options for patients with stage IV NSCLC.

[Second- or third-line treatment with erlotinib in EGFR wild-type non-small cell lung cancer: Real-life data]. / Erlotinib en 2e ou 3e ligne pour les cancers bronchiques non à petites cellules sans mutation de l'EGFR : données en vie réelle.

INTRODUCTION: The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. METHODS: The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. RESULTS: Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). CONCLUSION: Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.

[Clinical and dosimetric analysis of 469 prostate cancer patients treated in France in 2005 by permanent implant brachytherapy using the Iodin 125 seeds IsoSeed Bebig: report to the French Economic committee of health products (CEPS)]. / Analyse clinique et dosimétrique de 469 patients traités en France en 2005 par implantation prostatique de grains d'iode 125 IsoSeed Bebig: rapport pour le Comité économique des produits de santé (CEPS).

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.

Risks of second malignancies after breast cancer treatment: Long-term results.

PURPOSE: To estimate the long-term risk of second malignancies after breast cancer treatment in a large homogeneous cohort from a single institution. PATIENTS AND METHODS: All patients in this study were treated for non-metastatic breast cancer at the Curie institute, Paris, between 1981 and 2000. We calculated the cumulative incidence of second malignancies and the risk of developing each type of second malignancies over a period of 10 to 15 years. The observed crude incidence rates in the entire patient population were then compared to the expected incidence in the general population of French women, as provided by age-standardized data. A standardized incidence ratio (SIR) was calculated for all second malignancies. We also calculated second malignancies standardized incidence ratios for patients who underwent adjuvant therapy for breast cancer. RESULTS: The study cohort included a total of 17,745 women. The median follow-up since diagnosis was 13.4 years (range: 2-29 years). The 15-year cumulative incidence of second malignancies was 1.807 per 100,000 (CI 1.729-1.884). A total of 2370 second malignancies were observed during follow-up, 2010 in the radiotherapy arm and 360 in the no radiotherapy arm (relative risk [RR] 1.15 [1.03-1.28], P=0.0134). Crude incidence rates were significantly higher in our cohort than in the general population for contralateral breast cancer (SIR 2.96 [confidence interval (CI) 2.82-3.12], P<0.0001), sarcomas (SIR 8.48 [CI 6.41-11.22], P<0.0001), leukaemia (SIR 2.37 [CI 1.85-3.04], P<0.0001), lung cancer (SIR 1.39 [CI 1.13-1.72], P<0.0022) and gynaecological cancer (SIR 1.31 [CI 1.15-1.50], P=0.0001). Among patients treated for breast cancer, those who received radiotherapy was associated with an excess risk of sarcoma as compared to those have not had (RR 5.59 [CI 1.35-23.17], P<0.001). CONCLUSIONS: Women treated for breast cancer had a significantly increased risk of several kinds of second malignancies compared to the general population.

[First treatment strategies in the 2 years following lung cancer diagnosis. ESCAP-2011-CPHG, a real-life study carried out in French general hospitals]. / Stratégies thérapeutiques les 2 premières années après un diagnostic de cancer du poumon. ESCAP-2011-CPHG, étude en situation réelle réalisée dans les hôpitaux généraux français.

INTRODUCTION: The objective of the ESCAP-2011-CPHG cohort study was to perform a real-life analysis of therapeutic strategies used during the first 2years of follow-up after a diagnosis of primary lung cancer. This paper presents the study and its first results in non-small-cell lung cancer (NSCLC). METHODS: Pulmonologists in the respiratory disease departments of 53 general hospitals consecutively included all patients aged 18years and over with lung cancer newly diagnosed in 2010. RESULTS: Of the 3943 patients included, 3418 (mean age: 65.4 years; male: 76%; never smokers: 12%) had NSCLC (adenocarcinoma: 53%; stages 0-II, IIIA, IIIB and IV: 18, 14, 9 and 59%, respectively). Mean follow-up was 13.2 (SD: 10.1) months; mean number of strategies implemented was 2 (SD: 1.3). Overall, 62% of patients had chemotherapy in the first strategy (74% in the second strategy); the rate of chemotherapy alone increased from 6 to 56% with cancer stage. CONCLUSIONS: ESCAP-2011-CPHG opens the way to many possible analyses of the therapeutic strategies currently implemented in French hospitals, comparing strategies, survival or patient characteristics.