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

1Institut Bergonié, service de radiothérapie, 229, Cours-de-l’Argonne, 33076 Bordeaux cedex, France ; 2service de radiothérapie, groupe hospitalier Pitié–Salpêtrière, 47-83, boulevard de l’Hôpital, 756651 Paris cedex 13, France ; 3département de radiothérapie–oncologie, EA 643, centre hospitalier Lyon-Sud, 69310 Lyon-Pierre Bénite, France ; 4centre Georges-François Leclerc, 1, rue du Professeur-Marion, 21079 Dijon cedex, France

Volume tumoral macroscopique (GTV) et volume–cible anatomoclinique (CTV) en radiothérapie

The total mesorectal excision allows the marked increase of the local control rate in rectal cancer. Therefore, the mesorectal space is the usual field for the spread of rectal cancer cells. It could therefore be considered as the clinical target volume in the preoperative plan by the radiation oncologist. We propose to identify the mesorectum on anatomical structures of a treatment-position CT scan.

Volume-cible anatomoclinique dans la radiothérapie préopératoire des cancers du rectum

Improvement of the curative management of rectal cancers by better use of radiotherapy

RTOG and EORTC randomised phase III trials investigated combination of radiation therapy and hormonal treatment in locally advanced prostate cancer T2c-T4 N0-1 M0 (UICC 2002). Complete androgen blockade initiated 2 months prior to starting radiotherapy and stopped at the completion of radiotherapy vs radiation therapy alone, increased overall survival in patients with Gleason score 2-6. Adjuvant androgen suppression started at the end of the radiotherapy and continued indefinitely improved significantly overall survival of patients Gleason score 8 to 10. Complete androgen blockade in two months before and two months during radiation followed by 24 additional months of LHRH analogue alone improved overall survival of patients Gleason score 8-10 with respect to CAB alone. EORTC trial 22861 has shown that androgen suppression with LHRH analogue given during and for 3 years after external irradiation improved overall survival whatever the Gleason score. The role of hormonal treatment is currently assessed in localized prostate cancer (T1-2 N0) with poor prognostic factors: Gleason score 8-10, PSA>20 ng/ml.

Place de l'association de radiothérapie et d'hormonothérapie dans les cancers de la prostate

It is well known that the conservative reference treatment of infiltrative carcinoma of the breast, after en bloc complete excision, should be completed by irradiation of the whole breast delivering 50 Gy in 25 fractions. The discussion related to the validity and the procedures of delivery of the boost of the tumor bed has to be adjusted with our knowledge of specific prognostic factors of local recurrence. Through the two phase III randomized trials published in the literature, the young age of the patient, palpable tumor and negative receptor to progesterone may be recognized as statistically linked to a higher risk of local recurrence. Tumor size and palpable tumor remain unquestionable factors of bad prognosis. The true level of significativeness of age remains controversial as well as peri-tumoral characteristics such as ductal carcinoma in situ. Treatment technique should be rigorous either in terms of prescription of external radiation therapy or for the boost. They have a major impact on the cosmetic result and the fibrosis rate. Improvement of the results is expected through careful analysis of genic and molecularly prognostic factors of the tumor in order to select patients amenable to this type of technique.

Philippe Maingon

Papers

Volume tumoral macroscopique (GTV) et volume–cible anatomoclinique (CTV) en radiothérapie

Volume-cible anatomoclinique dans la radiothérapie préopératoire des cancers du rectum

Improvement of the curative management of rectal cancers by better use of radiotherapy

Place de l'association de radiothérapie et d'hormonothérapie dans les cancers de la prostate

Complément d'irradiation du lit tumoral : l'âge de raison