Allogenic hematopoietic stem cell transplantation after reduced intensity conditioning regimen for elderly patients (60 years and older) with hematologic malignancies using unrelated donors: a retrospective study for the French society for stem cell transplantation (SFGM-TC)

Peer reviewe

Goftte: A R package for assessing goodness-of-fit in proportional (sub) distributions hazards regression models

International audienceBackground and objectiveIn this paper, we introduce a new R package goftte for goodness-of-fit assessment based on cumulative sums of model residuals useful for checking key assumptions in the Cox regression and Fine and Gray regression models.MethodsMonte-Carlo methods are used to approximate the null distribution of cumulative sums of model residuals. To limit the computational burden, the main routines used to approximate the null distributions are implemented in a parallel C++ programming environment. Numerical studies are carried out to evaluate the empirical type I error rates of the different testing procedures. The package and the documentation are available to users from CRAN R repositories.ResultsResults from simulation studies suggested that all statistical tests implemented in goftte yielded excellent control of the type I error rate even with modest sample sizes with high censoring rates.ConclusionsAs compared to other R packages goftte provides new useful method for testing functionals, such as Anderson-Darling type test statistics for checking assumptions about proportional (sub-) distribution hazards. Approximations for the null distributions of test statistics have been validated through simulation experiments. Future releases will provide similar tools for checking model assumptions in multiplicative intensity models for recurrent data. The package may help to spread the use of recent advocated goodness-of-fit techniques in semiparametric regression for time-to-event data

EUS-guided hepaticogastrostomy in the management of malignant biliary obstruction: Experience and learning curve in a tertiary referral center.

EUS-guided hepaticogastrostomy (EUS-HGS) is a recognized second-line strategy for biliary drainage when endoscopic retrograde cholangiopancreatography fails or is impossible. Substantial technical and procedural progress in performing EUS-HGS has been achieved. The present study wanted to analyze whether growing experience in current practice has changed patient outcomes over time. We retrospectively analyzed data from patients with malignant biliary obstruction treated by EUS-HGS between 2002 and 2018 at a tertiary referral center. A total of 205 patients were included (104 male; mean age 68 years). Clinical success was achieved in 93% of patients with available 30-days follow-up (153), and the rate of procedure-related morbidity and mortality after one month was 18% and 5%, respectively. The cumulative sum (CUSUM) learning curve suggests a slight improvement in the rate of early complications during the second learning phase (23% vs 32%; P = 0.14; including death for any cause and intensive care). However, a significant threshold of early complications could not be determined. Recurrent biliary stent occlusion is the main cause for endoscopic reintervention (47/130; 37%). The rate of procedure-related complications after EUS-HGS has improved over time. However, the overall morbidity rate remains high, emphasizing the importance of dedicated expertise, appropriate patient selection and multidisciplinary discussion

Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era

Background Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC).In a multicenter study we have assessed outcome from mccRCC with or without GMs. Patients and methods Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression. Results In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0–221.3 mo). Median OS was 61.5 months (51.4–81.6 mo) for GM and 37.4 months (31.3–42 mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3–2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0–1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1–1.7, P<0.02; HR = 1.4; 95% CI = 1.1–1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2–2.7, P<0.004). Conclusions This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studie