Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies.

BACKGROUND: Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy. PATIENT AND METHODS: We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy. RESULTS: We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response. CONCLUSION: The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study.

Impact of extensive surgery in multidisciplinary approach of pterygopalatine/infratemporal fossa soft tissue sarcoma.

BACKGROUND: To evaluate a strategy whereby extensive surgery ± external radiotherapy (RT) could improve local control in pterygopalatine/infratemporal fossa (PIF) sarcoma. PROCEDURE: Forty-one patients with a diagnosis of sarcoma involving the PIF and referred to our Institute from 1984 to 2009 were included in the analysis. Patients received multidrug chemotherapy and radiotherapy ± surgery, depending on the period of treatment. RESULTS: The median age at diagnosis was 7.6 years (range: 0.1-22 years). There were 36 RMS, 3 undifferentiated sarcoma and 2 other soft-tissue sarcomas. Sixty-eight percent of patients had meningeal risk factors at diagnosis. Local treatment consisted of RT alone in 19 patients, surgery in combination to RT in 19 patients and surgery alone in 3 patients. The local progression rate (LPR) at 5 years was 45% for the entire population, 59% for the 19 patients treated with RT alone and 34% for the 22 patients who had surgery as part of their treatment. All locoregional failures after extensive surgery occurred at the skull base and/or in leptomeningeal spaces. CONCLUSIONS: Multidisciplinary approach including extensive surgery for PIF sarcoma is feasible and yields good local control with 15/22 patients in local complete remission. Future studies are warranted to confirm these promising results, to evaluate the possibility of avoiding RT or limiting the RT field, and to extend the indication for extensive surgery to other "worse" sites of PM sarcoma such as the paranasal sinuses.

Impact of missing individual patient data on 18 meta-analyses of randomised trials in oncology: Gustave Roussy experience.

OBJECTIVE: To compare the characteristics, quality and treatment effects of randomised clinical trials (RCTs) by individual patient data (IPD) availability, in trials eligible for 18 IPD meta-analyses (MA). DESIGN: Trial characteristics, risk of bias (RoB) and hazard ratio (HR) for overall survival were extracted from IPD-MA publications and/or RCTs publications. Data for the RoB assessment were extracted for a subset of 73 RCTs. Two investigators blinded to whether IPD was available or not evaluated the RoB for these trials. Treatment effects were compared using ratios of global HRs (RHRs) of IPD-unavailable trials and IPD-available trials. RHR were pooled using a fixed-effect model. DATA SOURCES: We examined the IPD availability for each trial eligible for each IPD-MA; when the IPD was not available for a trial, we used information from published sources. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We selected all published IPD-MAs conducted at Gustave Roussy and the RCTs eligible for each. RESULTS: 349 RCTs (73 018 patients) from 18 MAs were eligible: 60 RCTs (5890 patients) had unavailable IPD and 289 RCTs (67 128 patients) had available IPD. The main reason for IPD unavailability was data loss by investigators. IPD-unavailable trials were smaller (p<0.001), more often monocentric (p<0.001) and non-international (p=0.0004) than IPD-available trials. Geographical areas differed (p=0.054) between IPD-unavailable IPD-available trials. RoB was higher in IPD-unavailable RCTs for random sequence generation (p=0.007) and allocation concealment (p=0.006). The HR and 95% confidence interval (CI) for overall survival were extractable from publications in 23/60 IPD-unavailable trials included in 10 different MAs. Treatment effects were significantly greater for IPD-unavailable trials compared with IPD-available trials (RHR=0.86 (95% CI 0.75 to 0.98)). CONCLUSIONS: IPD-unavailable RCTs were significantly different from IPD-available RCTs in terms of trial characteristics and were at greater RoB. IPD-unavailable RCTs had a significantly greater treatment effect.

Systematic reviews of therapeutic interventions frequently consider patient-important outcomes.

OBJECTIVES: To determine whether recently published and ongoing systematic reviews of therapeutic interventions assess patient-important outcomes. STUDY DESIGN AND SETTING: For this methodological review, we searched MEDLINE via PubMed for recently published systematic reviews and online registry of systematic reviews (PROSPERO) for ongoing systematic reviews. We selected systematic reviews with meta-analyses of randomized controlled trials. We extracted all outcomes defined in the methods section and categorized them. Mortality, other clinical events, pain, quality of life, function, and therapeutic decisions were considered patient-important outcomes. RESULTS: We included 420 systematic reviews: 90 Cochrane reviews, 200 other published reviews, and 130 registered ongoing reviews. Primary outcomes were defined in 85 Cochrane reviews (95%), 98 (49%) other published reviews and all ongoing reviews. At least one patient-important outcome was defined as a primary outcome in 81/85 Cochrane reviews (95%), 78/98 other published reviews (80%), and 117/130 ongoing reviews (90%). Considering all outcomes assessed, at least one patient-important outcome was evaluated in 90/90 Cochrane reviews (100%), 189/200 other published reviews (95%), and 121/130 ongoing reviews (93%). CONCLUSION: Most recent systematic reviews aim to assess patient-important outcomes, which contrasts with RCTs. These results suggest some important gaps between primary and secondary research.

Prognostic value of the infarct- and non-infarct like patterns and cardiovascular magnetic resonance parameters on long-term outcome of patients after acute myocarditis.

BACKGROUND: Prognostic value of the infarct- and non-infarct like patterns and cardiac magnetic resonance (CMR) parameters on long-term outcome of patients after acute myocarditis is not well known. METHODS: Between 2006 and 2015, 112 consecutive patients with CMR-based diagnosis of acute myocarditis were identified in our institution. Of them, 88 were available for clinical follow-up and represented our studied population. Patients were divided into infarct-like group (n=48) (association of acute chest pain, elevated Troponin levels and ST-elevation) and non-infarct-like group (n=40) with any other presentation. The composite primary endpoint of major cardiovascular events (MACE) included: all-cause mortality, cardiac mortality, recurrence of myocarditis, heart failure, and sustained ventricular tachycardia. RESULTS: During follow-up, 21 patients (24%) experienced MACE and infarct-like patients were significantly more at risk for MACE than non-infarct-like patients (HR 2.4, 95% CI [1.01-5.80] p=0.04). Infarct-like patients exhibited in particular a higher risk of sustained ventricular tachycardia and recurrence of myocarditis (p=0.03). They had lower CMR-derived left (p=0.03) and right (p=0.001) ventricular ejection fractions, and exhibited larger areas of late gadolinium enhancement (LGE) (p=0.001). In multivariate analysis, both initial NYHA functional class >II and LGE mass were independent predictors for long-term MACE occurrence (HR 5.8 and 1.07 per gram respectively, p=0.007). Moreover, a threshold of LGE mass >17g provided a high discrimination for MACE occurrence (AUC of 0.81). CONCLUSIONS: The infarct-like pattern of acute myocarditis is associated with MACE occurrence. Initial NYHA functional class >II and LGE are independent predictive factors of MACE during long-term follow-up after acute myocarditis.

[Cancer before age 40 in France]. / Les cancers avant 40 ans en France.

Cancer is a rare pathology before the age of 40: a total of 14,000 new cases have been diagnosed in patients under age 40 in 2005, 1,700 under age 15 and 12,500 in the age-group of 15 to 39, this represents 4% of the cancers diagnosed in 2005. The number of deaths is small: in 2008, 2,235 patients died before age 40 in France, 246 under age 15 and 1,989 between age 15 and 39; this corresponds to 1% of the cancer deaths in 2008. The incidence increased between 1980 and 2005, both in the population aged 0 to 14 and in the population aged 15 to 39. Overall, cancer mortality has been decreasing for more than 25 years. The only increase in mortality is observed for brain tumours in children. The overall incidence increase is mostly due to the extension of screening coverage and to improvements in diagnostic procedures. The decrease observed for cervix cancer and lung cancer in men demonstrates the efficacy of screening and of tobacco smoking prevention. The mortality decrease is explained both by improved treatments and by the decreased incidence of some types of cancer. The increasing brain tumours mortality in children is worrying.