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.)

/pdf/increased-survival-in-pancreatic-cancer-with-nab-paclitaxel-528ez0fidd.pdf

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...

/pdf/nivolumab-for-recurrent-squamous-cell-carcinoma-of-the-head-63a0kwls87.pdf

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

584 Background: Chemoradiation is the standard treatment for anal cancer. The purpose of this study was to compare outcomes and toxicities in patients treated with either intensity-modulated radiation therapy (IMRT) or 3D conformal radiotherapy (3D-CRT). Methods: Between 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Thirty-nine patients (76.5%) had concomitant chemotherapy: capecitabine alone (1), MMC combined with 5FU or capecitabine (36), MMC and CDDP (4). Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6]. Results: Median duration of the treatment was 56 days [22-103] (59 versus 47 days with 3D-CRT and IMRT respectively, p= 0.0007). A gap was planned in 29 patients (57%), 23 with 3D-CRT and ...

Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

Focal HIFU for prostate cancer

Brachytherapy is proposed for the treatment or prevention of coronary restenosis with encouraging results, especially in intra-stent restenosis. The results of the first clinical studies show benefit, for example those of the American SCRIPPS trial with a 3 year follow-up. However, recent reports in the literature have described secondary effects associated with this technique: 1) stenoses occurring at the limits of the irradiated segments which are attributed to a proliferative effect of low doses on damaged tissue; 2) late occlusions at the irradiated site: their incidence is estimated at 9% at 6 months. The mechanisms of these thromboses are not understood but delayed re-endothelialisation probably plays a role; 3) finally, irradiation is associated with uncovered dissection probably related to delayed healing. Other long-term trials are necessary to provide a more complete assessment of the secondary effects of brachytherapy, especially with regards to their mechanisms, prevention and treatment.

Secondary effects of brachytherapy in the treatment of coronary restenosis

To the Editor: In their article on the use of short-term androgen-deprivation therapy (ADT) before and during radiotherapy in patients with localized prostate cancer, Jones et al. (July 14 issue)1 report an improvement of 5 percentage points in the 10-year rate of overall survival (from 57% to 62%) when ADT was combined with 66.6 Gy of radiotherapy. Should we prescribe shortterm ADT with radiotherapy for patients with intermediate-risk prostate cancer? A positive effect on survival has been observed with higher doses of radiotherapy delivered to the prostate.2 The use of ADT combined with 70 Gy of radiotherapy improved overall survival only for intermediate-risk patients with no coexisting illnesses.3 Another trial using 73.8 Gy or more combined with ADT showed no improvement for intermediate-risk patients,4 which raises questions about the overall value of ADT in such patients. Moreover, in the study by Jones et al., it is unclear how many patients received radiotherapy to the pelvis and how many to the prostate only. Neoadjuvant ADT and pelvic radiotherapy have already shown unexpected local and spatial cooperation in comparison with neoadjuvant ADT and radiotherapy to the prostate only.5 Thus, the question as to whether a further increase in survival would have been observed with pelvic radiotherapy remains to be answered.

Radiotherapy and androgen deprivation for prostate cancer.

The frequent exposure of the heart to radiation during thoracic tumor radiotherapy often results in chronic impairment of myocardial function. The aim of the present investigation was to evaluate the effect of irradiation on coronary vascular tone in rat hearts exposed in vivo to a single dose of 20 Gy gamma rays. The ability of rat hearts to respond to changes in coronary reactivity was analyzed 1, 15, 30 and 60 days following cardiac irradiation, using the Langendorff model, after perfusion of either L-nitro-arginine (LNA), an inhibitor of nitric oxide synthetase or SIN 1, a nitric oxide donor drug. LNA-induced vasoconstriction and SIN 1-induced vasodilation were lost respectively 15 days and 30 days after irradiation, and associated with smooth muscle cell alterations observed in microscopy, but without any changes in myocardial MDA levels. Thus, our results suggest that 1) endothelium may represent an early and specific radiation target, characterized by radiation-induced vascular tone dysfunctions, with no detectable microscopical changes; 2) alterations are progressive, resulting first from endothelial damage, followed by smooth muscle cell injuries. In conclusion, a local cardiac irradiation induced cellular dysfunction, characterized by a loss of coronary reactivity without changes of the lipid peroxidation index in the hearts.

Philippe Maingon

Papers

Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

Focal HIFU for prostate cancer

Secondary effects of brachytherapy in the treatment of coronary restenosis

Radiotherapy and androgen deprivation for prostate cancer.

Effect of in vivo heart irradiation on coronary reactivity in the rat.