BACKGROUND In a phase 1–2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. METHODS We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. RESULTS A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel–gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel–gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel–gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.)

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Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine

Convolutional Neural Networks (CNNs) have been recently employed to solve problems from both the computer vision and medical image analysis fields. Despite their popularity, most approaches are only able to process 2D images while most medical data used in clinical practice consists of 3D volumes. In this work we propose an approach to 3D image segmentation based on a volumetric, fully convolutional, neural network. Our CNN is trained end-to-end on MRI volumes depicting prostate, and learns to predict segmentation for the whole volume at once. We introduce a novel objective function, that we optimise during training, based on Dice coefficient. In this way we can deal with situations where there is a strong imbalance between the number of foreground and background voxels. To cope with the limited number of annotated volumes available for training, we augment the data applying random non-linear transformations and histogram matching. We show in our experimental evaluation that our approach achieves good performances on challenging test data while requiring only a fraction of the processing time needed by other previous methods.

V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation

BackgroundPatients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. MethodsIn this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. ResultsThe median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to...

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Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

EAU–ESTRO–SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

David Busseuil1, Marianne Zeller 2, Yves Cottin2, Philippe Allouch2, Philippe Maingon3, Isabelle Barillot3, Suzanne Naudy3, Laurent Arnould4, Gabrielle Michalowicz5, Maryvonne Moisant6, Jean-Claude Horiot3, Jean-Eric Wolf2, and Luc Rochette1 1LPPCE, Faculty of Medicine, University of Burgundy; 2Cardiology Department, University, Hospital, Dijon; 3Radiotherapy Department, CGFL, Dijon; 4Pathology Department, CGFL, Dijon; 5Genetics Department, University Hospital, Grenoble, France; Histology Department, Faculty of Medicine, University of Burgundy

Intravascular radiation and stenting: absence of efficacy on intimal proliferation in a rabbit model.

Intensity modulated radiation therapy enables to increase the dose delivered to the target volume while avoiding the irradiation of organs at risk and normal tissues. Indications of such technique are mainly proposed in the treatment of prostatic carcinoma, head and neck cancers and gyneacological pelvic malignancies. The different mandatory steps for implementing these treatments require rigorous quality assurance program in order to validate indications, definitions of target volumes and constraints to be respected for normal tissues. Nowadays its efficiency and results are well-known for high dose irradiation of prostatic cancer and to prevent xerostomia in patients treated for head and neck cancers. The training of the whole team involved in the implementation of these treatments is required. It is a basic requirement to treat an increasing number of patients who will benefit from this technological improvement.

Radiothérapie conformationnelle par modulation d’intensité

6LBA The benefit of regional irradiation in stage I–III breast cancer: 10 years results of the EORTC ROG and BCG phase III trial 22922/10925

Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program.

La radiothérapie de conformation avec et sans modulation d'intensité dans le traitement du cancer localisé de la prostate

Resume Les nouvelles techniques d'irradiation tendent vers des traitements plus sophistiques et plus precis. La radiotherapie conformationnelle avec ou sans modulation d'intensite est devenue le traitement standard des adenocarcinomes localises de prostate et autorise l'escalade de dose. Sa mise en place necessite une grande rigueur dans la definition des volumes, dans la dosimetrie, dans le controle de qualite et dans la reproductibilite du traitement. Ces dernieres annees, se sont developpees de nouvelles techniques de localisation du volume cible en temps reel, telles que l'echographie transabdominale. Cette methode non invasive de repositionnement prostatique permet la maitrise aussi bien des mouvements de prostate que des erreurs de positionnement du patient et contribue a l'essor de la radiotherapie de haute precision.

Philippe Maingon

Papers

Intravascular radiation and stenting: absence of efficacy on intimal proliferation in a rabbit model.

Radiothérapie conformationnelle par modulation d’intensité

6LBA The benefit of regional irradiation in stage I–III breast cancer: 10 years results of the EORTC ROG and BCG phase III trial 22922/10925

La radiothérapie de conformation avec et sans modulation d'intensité dans le traitement du cancer localisé de la prostate

Radiothérapie de haute précision guidée par échographie