Surgical Intervention in Gastric Carcinoid is Associated With Improved Survival in Local and Regional Disease.

Introduction: Gastric carcinoid is a rare entity with complex management options. This study aims to determine if surgical intervention in patients with local, regional, and metastatic gastric carcinoid is associated with prolonged survival. Materials and Methods: The California Cancer Registry merged with the California Office of Statewide Health Planning and Development was queried for patients with a diagnosis of gastric carcinoid (2000 to 2011). Clinicopathologic characteristics, management, and outcomes were evaluated. Results: There were 1012 patients with a diagnosis of gastric carcinoid identified. The median age was 63 (range, 18 to 99) and the majority of patients were women (615, 60.7%). Most patients had localized disease (644, 64%), whereas 9.4% (95) had regional and 13.4% (133) had distant metastases at diagnosis. The majority of patients underwent gastric surgery (56.7%, n=574 vs. 43.2%, n=438). Prolonged survival was associated with gastric surgery in patients with both local (median survival not reached; P

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Efficacy of Modified Dose-dense Paclitaxel in Recurrent Cervical Cancer.

Objective: To examine survival outcomes of women with recurrent cervical cancer who received salvage chemotherapy with modified dose-dense paclitaxel (MDDP) monotherapy (paclitaxel 80 mg/m2, administered on day 1, 8, and 15 without day 22). Materials and Methods: A retrospective study was conducted to evaluate cause-specific survival after the first recurrence (SAR) of women with recurrent cervical cancer diagnosed between 2006 and 2014. Pooled analyses were performed to examine SAR in women who received MDDP monotherapy (n=17) for any treatment line, compared with those who received salvage chemotherapy with paclitaxel-doublet (n=18) and nonpaclitaxel regimens (n=52). Results: In the whole cohort, median SAR was 13.7 months including 63 (72.4%) events. MDDP monotherapy regimen was most commonly used in the second-line setting (35.3%) followed by the third/fourth lines (both, 23.5%). Among the women who received MDDP regimen, there were 6 (35.3%) women who received >=6 cycles; there was 1 (5.9%) women who discontinued the regimen due to adverse effects (grade 3 transaminitis); regimen postponement was seen in 2 (1.4%) of 140 total cycles; and the response rate after the sixth cycle of this regimen was 29.4% (1 complete and 4 partial responses). On univariate analysis, MDDP usage had the highest 2-year SAR rate (MDDP 54.1%, paclitaxel-doublet 43.6%, and nonpaclitaxel regimens 28.1%; Ptrend=0.044). On multivariate analysis, MDDP monotherapy remained an independent prognostic factor for improved SAR compared with the nonpaclitaxel regimen (adjusted-hazard ratio, 0.50; 95% confidence interval, 0.26-0.95; P=0.036). Conclusion: Our results suggested that MDDP monotherapy is a tolerable and relatively effective regimen for recurrent cervical cancer. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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A Phase I Clinical Trial of the Phosphatidylserine-targeting Antibody Bavituximab in Combination With Radiation Therapy and Capecitabine in the Preoperative Treatment of Rectal Adenocarcinoma.

Objectives: There is interest in improving the tumoricidal effects of preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers. The safety and toxicity profile of these combination regimens needs rigorous clinical evaluation. The primary objective of this study was to evaluate the toxicity of combining bavituximab, an antibody that targets exposed phosphatidylserine, with capecitabine and radiation therapy. Materials and Methods: Patients with stage II or III rectal adenocarcinoma were enrolled on a phase I study combining radiation therapy, capecitabine, and bavituximab. A standard 3+3 trial designed was used. Results: In general, bavituximab was safe and well tolerated in combination with radiation therapy and capecitabine in the treatment of rectal adenocarcinoma. One patient at the highest dose level experienced a grade III infusion reaction related to the bavituximab. One tumor demonstrated a complete pathologic response to the combination treatment. Conclusions: Bavituximab is safe in combination with capecitabine and radiation therapy at the doses selected for the study. Further clinical investigation would be necessary to better define the efficacy of this combination. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Advanced Age is Not a Contraindication for Treatment With Curative Intent in Esophageal Cancer.

Objectives: The objective of this study is to compare long-term outcomes between younger and older (70 y and above) esophageal cancer patients treated with curative intent. Materials and Methods: Overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free interval were compared between older (70 y and above) and younger (below 70 y) esophageal cancer patients treated between 1998 and 2013. Treatment consisted of neoadjuvant chemoradiotherapy with surgery or definitive chemoradiotherapy: 36 to 50.4 Gy in 18 to 28 fractions combined with 5-fluorouracil/cisplatin or carboplatin/paclitaxel. Results: The study comprised 253 patients, of whom 76 were 70 years and older. Median age was 64 years (range, 41 to 83). Most patients had stage II-IIIA disease (83%). Planned treatment was neoadjuvant chemoradiotherapy with surgery for 169 patients (41 patients aged 70 y and older) and definitive chemoradiotherapy for 84 patients (31 patients aged 70 y and older). The compliance to radiotherapy was 92%, with no difference between older and younger patients. In 33 patients (13 patients aged 70 y and older) planned surgery was not performed. Median follow-up was 4.9 years. Three-year OS was 42%. The multivariable analysis showed no statistical difference in OS or in DFS comparing older and younger patients: OS (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.61-1.28), DFS (HR, 0.87; 95% CI, 0.60-1.25). Elderly showed a longer locoregional recurrence-free interval; HR, 0.53 (95% CI, 0.30-0.92; P=0.02) and a higher pathologic complete response rate (50% vs. 25%; P=0.02). Conclusions: Long-term outcomes of older esophageal cancer patients (70 y and above) selected for treatment with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy were comparable with the outcomes of their younger counterparts. Advanced age alone should not be a contraindication for potentially curative chemoradiotherapy-based treatment in esophageal cancer patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The phytological future of prostate cancer staging: prostate-specific membrane antigen positron emission tomography and the dandelion theory

Future Oncology, Ahead of Print.


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Clinical significance of farnesoid X receptor expression in thyroid neoplasia

Future Oncology, Ahead of Print.


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Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer

Abstract

Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages. Pathways globally dysregulated in cancer relative to normal urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid, and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization for glycolysis and increased sorbitol pathway intermediates, consistent with Warburg effect. Anaplerosis to sustain energy production suggested by increased late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder cancer. Urothelial carcinoma also shows altered membrane lipid membrane metabolism and differential derivation of nucleic acid components pyrimidine and purine. In stage comparison, MIBC appears to preferentially enhance cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism, and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible influence from associated inflammatory cells. We identify numerous metabolomic alterations in NMIBC and MIBC that likely reflect underlying pathway changes. Differential pathway activity may have value in designing stage-specific novel therapeutics in urothelial carcinoma.

Using a highly sensitive metabolomics approach, we identified multiple pathway changes between normal urothelium and high-grade urothelial carcinoma and between high-grade carcinomas of different stages. Several of these differential metabolite profiles suggest the potential for unique targeted therapy in NMIBC and MIBC populations.

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