5-year overall survival after early breast cancer diagnosed during pregnancy: A retrospective case-control multicentre French study.

BACKGROUND: Breast cancer diagnosed during pregnancy (BCP) is rare, but the prevalence is expected to rise. Long-term follow-up data regarding this clinically challenging condition are scarce. The main objective of this multicentre case-control French study was to compare the survival between pregnant patients and matched controls. METHODS: Patients from 27 centres diagnosed between 2000 and 2009 with histologically proven invasive breast cancer occurring during pregnancy were retrospectively included. Controls were matched to BCP patients on age, clinical T stage, hormone receptor, HER2, administration of neo-adjuvant chemotherapy and pathological node involvement in the absence of neo-adjuvant chemotherapy. Five-year overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) rates were estimated using the Kaplan-Meier method. RESULTS: One hundred and eleven BCP patients and 253 controls were included. Median age was 33 and 35 years, respectively. Both populations were managed similarly, except for less frequent sentinel node dissection (p = 0.026) and taxane administration (p = 0.03) among BCP patients. Median follow-up was 7.5 years. Survival rates were similar between both BCP and control patients: 5-year OS rates were 83.1% (95% CI: 74.5-89.0) vs 85.5% (95% CI: 80.4-89.4), respectively, p = 0.31; 5-year DFS rates 60.0% (95% CI: 50.1-68.6) vs 68.5% (95% CI: 62.3-73.9), respectively, p = 0.12 and 5-year MFS rates 71.0% (95% CI: 61.3-78.6) and 74.5% (95% CI: 68.6-79.5), respectively, p = 0.21. CONCLUSION: Our study showed that the survival outcomes of patients diagnosed with BCP were not significantly different as compared to those of matched non-pregnant controls. A proper management of women diagnosed with BCP is crucial.

Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: A retrospective analysis.

BACKGROUND: FOLFIRINOX is a polychemotherapy regimen currently used to treat inoperable pancreatic cancer in patients with a good performance status (PS). FOLFIRINOX lengthens overall survival time (OS), but no specific data are available in elderly patients. METHODS: All cases of inoperable pancreatic adenocarcinoma in patients over 70 years old treated with FOLFIRINOX were retrospectively reviewed between 2008 and 2015 in five institutions in France. The primary objective was to evaluate the safety and efficacy of FOLFIRINOX in the elderly. RESULTS: Forty-two patients with a median age of 73 years (range: 70-79) and a median PS of 1 (range: 0-2) were included. 88% of patients treated with FOLFIRINOX were enrolled between 2012 and 2015. 24 patients (57%) needed a primary dose reduction but this did not impact OS (median OS 11.7 months (6.9-16.4) compared to 16.6 months (0.37-32.8) without dose reduction, p = 0.69). Twelve patients (29%) experienced grade 3 toxicity. Sensory neuropathy occurred most often (56%). Primary prophylaxis with granulocyte colony stimulating factor (GCSF) was administered to 14 patients (33%). One treatment-related death occurred (septic shock), although this patient had not had primary prophylaxis with GCSF. Median follow-up was 86 months. Median OS was 11.6 months (95%CI: 8.9-14.3). CONCLUSION: Median OS observed in the elderly was similar to OS previously reported in younger patients in the ACCORD 11 trial. FOLFIRINOX is effective in selected, fit elderly patients but with greater grade 3 neurotoxicity. Primary dose reduction and primary GCSF prophylaxis may control tolerance.

Prediction of early death among patients enrolled in phase I trials: development and validation of a new model based on platelet count and albumin.

BACKGROUND: Selecting patients with 'sufficient life expectancy' for Phase I oncology trials remains challenging. The Royal Marsden Hospital Score (RMS) previously identified high-risk patients as those with ≥ 2 of the following: albumin <35 g l(-1); LDH > upper limit of normal; >2 metastatic sites. This study developed an alternative prognostic model, and compared its performance with that of the RMS. METHODS: The primary end point was the 90-day mortality rate. The new model was developed from the same database as RMS, but it used Chi-squared Automatic Interaction Detection (CHAID). The ROC characteristics of both methods were then validated in an independent database of 324 patients enrolled in European Organization on Research and Treatment of Cancer Phase I trials of cytotoxic agents between 2000 and 2009. RESULTS: The CHAID method identified high-risk patients as those with albumin <33 g l(-1) or ≥ 33 g l(-1), but platelet counts ≥ 400.000 mm(-3). In the validation data set, the rates of correctly classified patients were 0.79 vs 0.67 for the CHAID model and RMS, respectively. The negative predictive values (NPV) were similar for the CHAID model and RMS. CONCLUSION: The CHAID model and RMS provided a similarly high level of NPV, but the CHAID model gave a better accuracy in the validation set. Both CHAID model and RMS may improve the screening process in phase I trials.

Wild brown trout affected by historical mining in the Cévennes National Park, France.

In the protected area of the Cévennes National Park (Southern France), 114 wild brown trout (Salmo trutta fario) were captured at six locations affected to different extents by historical mining and metallurgy dating from the Iron Age to Modern Times. Cadmium and lead in trout livers and muscles reflect high sediment contamination, although an age-related effect was also detected for hepatic metal concentrations. Lead isotope signatures confirm exposure to drainage from mining and metallurgical waste. Developmental instability, assessed by fluctuating asymmetry, is significantly correlated with cadmium and lead concentrations in trout tissues, suggesting that local contamination may have affected fish development. Nowadays, the area is among the least industrialized in France. However, our results show that 60% of the specimens at one site exceed EU maximum allowed cadmium or lead concentration in foodstuffs. The mining heritage should not be neglected when establishing strategies for long-term environmental management.

Dispersion of heavy metals (metalloids) in soils from 800-year-old pollution (Mont-Lozère, France).

Numerous palaeo metallurgical sites (n = 70) characterized by slag presenting a homogeneous typology have been reported on the Mont-Lozère Massif (Southern France). These activities took place in the medieval period. The silicated slag matrix comprises mainly Pb (25%), Sb (0.4%), and several thousand parts per million of As, Cu, and Zn. Soil samples were collected in and around two sites, to understand the dispersion mechanism affecting the slag tailings through use of metal concentrations and lead isotopic compositions. The majority of polluted soil samples show high enrichment factors (EF) for Pb and Sb, slightly lower EFs for Cu, and much lower EFs for As and Zn. We show that this "old" metal pollution was physically dispersed, through erosion of workshop soils and slag tailings, in a restricted area (ca. 200 m down slope form the site). There is no evidence for massive leaching of slag metals by soil waters, except for Zn. Thus, the pollution is mainly due to the metal-making process, i.e., smoke-fallout, pieces of ore, the crackling of smelting ore outside the oven during reduction, and charcoal, etc. The lead isotopic compositions of the soils define a binary mixing trend between local granite or background soil and slag (which represent the workshop soil). Simple mass balance equations using either Pb isotopes or Pb concentrations suggest that between 40 and 100% of the total Pb in soils comes from the Medieval workshop pollution, leaving any later pollution negligible. The large number of sites on the Mont-Lozère means this medieval pollution is significant and poses a real environmental risk.

Record of metal workshops in peat deposits: history and environmental impact on the Mont Lozère Massif, France.

This study aims to document the history of the metallurgical activities on the Mont Lozère massif in the Cévennes Mountains in Southern France. Many medieval sites of metallurgical wastes (slags) have been reported on the massif. These sites are thought to represent ancient lead workshops. The impact of past metallurgical activity on the environment was studied using geochemical and palynological techniques on a core collected in the Narses Mortes peatland near medieval smelting area. Two main periods of smelting activities during the last 2200 years were revealed bythe lead concentration and isotopic composition along the core profile: the first period corresponds to the Gallic period (approximately ca. 300 B.C. to ca. 20 A.D.) and the second one to the Medieval period (approximately ca. 1000-1300 A.D.). Forest disturbances are associated with lead anomalies for the two metallurgical activities described. The impact of the first metallurgy was moderate during the Gallic period, during which beech and birch were the tree species most affected. The second period corresponds to the observed slag present in the field. Along with agropastoral activities, the medieval smelting activities led to the definitive disappearance of all tree species on the summit zones of Mont Lozère. The abundance of ore resources and the earlier presence of wood on the massif justify the presence of workshops at this place. The relationship between mines and ores has been documented for the Medieval period. There is no archaeological proof concerning the Gallic activity. Nevertheless, 2500-2100 years ago, the borders of the Gallic Tribe territory, named the Gabales, were the same as the present-day borders of the Lozère department. Julius Caesar reported the existence of this tribe in 58 B.C. in "De Bello Gallico", and in Strabon (Book IV, 2.2) the "Gabales silver" and a "treasure of Gabales" are mentioned, but to this day, they have not been found.