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As compared with placebo, extended-release lanreotide (120 mg every 28 days) was associated with delayed disease progression in patients with nonfunctional, slowly progressing neuroendocrine tumors. Progression-free survival at 24 months was 65% with lanreotide and 33% with placebo. Neuroendocrine tumors are rare neoplasms, 1 , 2 with an annual incidence of 5 cases per 100,000 people in the United States. 1 More than 50% of cases involve tumors originating in the gastrointestinal system or pancreas, and patients commonly have distant metastases at diagnosis. 1 Since many of these patients have inoperable disease, medical therapy is often initiated to control disease progression. Treatment may also be required to relieve symptoms arising from the overproduction of amines or peptide hormones in functioning tumors. Few medical treatments for advanced neuroendocrine tumors have been approved on the basis of their antiproliferative effects (i.e., efficacy in inhibiting . . .

Using data from two large data sets of lung-cancer screening by CT, the authors identified factors that increased the likelihood that a nodule was malignant, including older age, female sex, nodule location in the upper lobe, lower nodule count, and certain nodule features. The U.S. National Lung Screening Trial showed that screening with the use of low-dose thoracic computed tomography (CT) reduces mortality from lung cancer by 20%. 1 Major clinical issues in the implementation of low-dose CT screening at the population level include the definition of a positive screening result and the appropriate management of lung nodules detected on a scan. More than 20% of participants in low-dose CT screening programs were found on their first scan to have one or more lung nodules that required further investigation. 1 – 4 The proportion of invasive diagnostic procedures ranged from 1 to 4%. 1 , 3 The risk . . .

In a comparison of tumors from patients with melanoma who benefitted from blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) with tumors from patients who did not benefit, tumor neoantigens were detected that were strongly associated with a response. Immune checkpoint blockade has led to durable antitumor effects in patients with metastatic melanoma, non–small-cell lung cancer, and other tumor types, but the factors determining whether a patient will have a response remain elusive. 1 , 2 The fully human monoclonal antibodies ipilimumab and tremelimumab block cytotoxic T-lymphocyte antigen 4 (CTLA-4), resulting in T-cell activation. Some studies have established correlations between outcomes with ipilimumab and peripheral-blood lymphocyte count, markers of T-cell activation, 3 an “inflammatory” microenvironment, 4 , 5 and maintenance of high-frequency T-cell receptor clonotypes. 6 The relationship among the genomic landscape of the tumor, the mutational load, and the benefit from treatment remains obscure. . . .

The proportion of a physician's screening colonoscopies that detect at least one adenoma (the adenoma detection rate) is a quality measure. In this study involving 136 gastroenterologists, the adenoma detection rate was inversely associated with patients' risk of interval colorectal cancer. Colonoscopy is a commonly used primary or follow-up screening test to detect colorectal cancer, 1 – 3 the second leading cause of death from cancer in the United States. 4 , 5 Colonoscopy can reduce the risk of death from colorectal cancer through detection of tumors at an earlier, more treatable stage and through removal of precancerous adenomas. 3 , 6 Conversely, failure to detect adenomas during colonoscopy may increase the subsequent risk of cancer. The adenoma detection rate, the proportion of screening colonoscopies performed by a physician that detect at least one histologically confirmed colorectal adenoma or adenocarcinoma, has been recommended as a quality benchmark . . .

Abstract Rationale It is now well established that immune responses can take place outside of primary and secondary lymphoid organs. We previously described the presence of tertiary lymphoid structures (TLS) in patients with non–small cell lung cancer (NSCLC) characterized by clusters of mature dendritic cells (DCs) and T cells surrounded by B-cell follicles. We demonstrated that the density of these mature DCs was associated with favorable clinical outcome. Objectives To study the role of follicular B cells in TLS and the potential link with a local humoral immune response in patients with NSCLC. Methods The cellular composition of TLS was investigated by immunohistochemistry. Characterization of B-cell subsets was performed by flow cytometry. A retrospective study was conducted in two independent cohorts of patients. Antibody specificity was analyzed by ELISA. Measurements and Main Results Consistent with TLS organization, all stages of B-cell differentiation were detectable in most tumors. Germinal center somatic hypermutation and class switch recombination machineries were activated, associated with the generation of plasma cells. Approximately half of the patients showed antibody reactivity against up to 7 out of the 33 tumor antigens tested. A high density of follicular B cells correlated with long-term survival, both in patients with early-stage NSCLC and with advanced-stage NSCLC treated with chemotherapy. The combination of follicular B cell and mature DC densities allowed the identification of patients with the best clinical outcome. Conclusions B-cell density represents a new prognostic biomarker for NSCLC patient survival, and makes the link between TLS and a protective B cell–mediated immunity.

Sentinel-node biopsy followed by lymphadenectomy for tumor-positive nodes improved disease-free survival among patients with intermediate-thickness melanomas (1.2 to 3.5 mm) and those with thick melanomas (>3.5 mm). Regional node management in melanoma has remained controversial since Snow 1 recommended elective complete lymphadenectomy for all patients with melanoma, regardless of whether there was clinical evidence of regional nodal metastases. However, routine elective lymphadenectomy exposes all patients to procedure-related complications and cannot benefit the majority, who have no regional nodal metastases. Multiple randomized trials have suggested a benefit of routine lymphadenectomy in at least some groups of patients with melanoma. 2 – 6 Because of dissatisfaction with both elective lymphadenectomy and nodal observation, lymphatic mapping and sentinel-node biopsy were introduced for individualized management of regional lymph nodes. 6 – 9 Sentinel-node biopsy is a . . .

About 1% of non–small-cell lung cancers have ROS1 rearrangements. This oncogene is inhibited by crizotinib. In a cohort of 50 patients with ROS1 -rearranged lung cancer, crizotinib induced responses in 72%; the median duration of response was nearly a year and a half. The ROS1 oncogene encodes an orphan receptor tyrosine kinase related to anaplastic lymphoma kinase (ALK), along with members of the insulin-receptor family. 1 First discovered as the oncogene product of an avian sarcoma RNA tumor virus, 2 – 4 ROS1 (ROS1 proto-oncogene receptor tyrosine kinase) is activated by chromosomal rearrangement in a variety of human cancers, including non–small-cell lung cancer (NSCLC), cholangiocarcinoma, gastric cancer, ovarian cancer, and glioblastoma multiforme. 5 – 9 Rearrangement leads to fusion of a portion of ROS1 that includes the entire tyrosine kinase domain with 1 of 12 different partner proteins. 10 The resulting ROS1 fusion kinases are constitutively activated and drive . . .

Individual participant data meta-analyses of postoperative chemotherapy have shown improved survival for patients with non-small-cell lung cancer (NSCLC). We aimed to do a systematic review and individual participant data meta-analysis to establish the effect of preoperative chemotherapy for patients with resectable NSCLC. We systematically searched for trials that started after January, 1965. Updated individual participant data were centrally collected, checked, and analysed. Results from individual randomised controlled trials (both published and unpublished) were combined using a two-stage fixed-effect model. Our primary outcome, overall survival, was defined as the time from randomisation until death (any cause), with living patients censored on the date of last follow-up. Secondary outcomes were recurrence-free survival, time to locoregional and distant recurrence, cause-specific survival, complete and overall resection rates, and postoperative mortality. Prespecified analyses explored any variation in effect by trial and patient characteristics. All analyses were by intention to treat. Analyses of 15 randomised controlled trials (2385 patients) showed a significant benefit of preoperative chemotherapy on survival (hazard ratio [HR] 0·87, 95% CI 0·78–0·96, p=0·007), a 13% reduction in the relative risk of death (no evidence of a difference between trials; p=0·18, I2=25%). This finding represents an absolute survival improvement of 5% at 5 years, from 40% to 45%. There was no clear evidence of a difference in the effect on survival by chemotherapy regimen or scheduling, number of drugs, platinum agent used, or whether postoperative radiotherapy was given. There was no clear evidence that particular types of patient defined by age, sex, performance status, histology, or clinical stage benefited more or less from preoperative chemotherapy. Recurrence-free survival (HR 0·85, 95% CI 0·76–0·94, p=0·002) and time to distant recurrence (0·69, 0·58–0·82, p<0·0001) results were both significantly in favour of preoperative chemotherapy although most patients included were stage IB–IIIA. Results for time to locoregional recurrence (0·88, 0·73–1·07, p=0·20), although in favour of preoperative chemotherapy, were not statistically significant. Findings, which are based on 92% of all patients who were randomised, and mainly stage IB–IIIA, show preoperative chemotherapy significantly improves overall survival, time to distant recurrence, and recurrence-free survival in resectable NSCLC. The findings suggest this is a valid treatment option for most of these patients. Toxic effects could not be assessed. Medical Research Council UK.

Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors offer potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015.