Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

Summary Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems

Indications et perspectives de l’hormonoradiothérapie des cancers de prostate à haut risque

International audienc

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group

International audienc

Radiotherapy of T4M0 prostate cancer : A multicentric retrospective analysis

International audienc

Radiotherapy of T4M0 prostate cancer : A multicentric retrospective analysis

International audienc

Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial.

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy

Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial

International audienc

Erratum to ‘Clinical progression is associated with poor prognosis whatever the treatment line in metastatic castration-resistant prostate cancer: The CATS international database’ [European Journal of Cancer, Volume 125 (January 2020) Pages 153–163] (European Journal of Cancer (2020) 125 (153–163), (S0959804919308020), (10.1016/j.ejca.2019.10.030))

The publisher regrets that the following corrections were missed during the publication of this article. Figure 2 legend is missing from the published article and should appear as follows: Figure 2: Overall survival from initiation of each life-extending therapy in accordance with the type of progression in 661 patients with mCRPC. (A) OS from first life-extending therapy (LET) initiation (all arms combined), (B) OS from second LET initiation (all arms combined), and (C) OS from third LET initiation (all arms combined). Referring to Table 3, ‘Median OS (all arms combined) in months’, the 1st LET entry for the Clin-p column should appear as 30.7 [27.5; 32.9]. Referring to Figure 2A, median Clin-p should appear as 30.7 [27.5; 32.9]. The correct Figure is included here The publisher would like to apologise for any inconvenience caused. [Figure presented] © 2020 Elsevier Lt