Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.

AIMS: Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes. METHODS: Unsupervised hierarchical clustering analysis was applied to gene expression data from 177 patients with colorectal cancer to determine a prognostic gene expression signature. Validation of the signature was sought in two independent patient groups. The association between the signature and prognosis of patients was assessed by Kaplan-Meier plots, log-rank tests and the Cox model. RESULTS: The authors identified a gene signature that was associated with overall survival and disease-free survival in 177 patients and validated in two independent cohorts of 213 patients. In multivariate analysis, the signature was an independent risk factor (HR 3.08; 95% CI 1.33 to 7.14; p=0.008 for overall survival). Subset analysis of patients with AJCC (American Joint Committee on Cancer) stage III cancer revealed that the signature can also identify the patients who have better outcome with adjuvant chemotherapy (CTX). Adjuvant chemotherapy significantly affected disease-free survival in patients in subtype B (3-year rate, 71.2% (CTX) vs 41.9% (no CTX); p=0.004). However, such benefit of adjuvant chemotherapy was not significant for patients in subtype A. CONCLUSION: The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.ope

Prognostic factors of second and third line chemotherapy using 5-fu with platinum, irinotecan, and taxane for advanced gastric cancer.

PURPOSE: The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response. MATERIALS AND METHODS: Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study. Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI. RESULTS: The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy. CONCLUSION: It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles. Development of individualized chemotherapy regimens based on gene expression profiles is warranted.ope

Comparison of Prognostic Genomic Predictors in Colorectal Cancer

BACKGROUND: Although several prognostic genomic predictors have been identified from independent studies, it remains unclear whether these predictors are actually concordant with respect to their predictions for individual patients and which predictor performs best. We compared five prognostic genomic predictors, the V7RHS, the ColoGuideEx, the Meta163, the OncoDX, and the MDA114, in terms of predicting disease-free survival in two independent cohorts of patients with colorectal cancer. STUDY DESIGN: Using original classification algorithms, we tested the predictions of five genomic predictors for disease-free survival in two cohorts of patients with colorectal cancer (n = 229 and n = 168) and evaluated concordance of predictors in predicting outcomes for individual patients. RESULTS: We found that only two predictors, OncoDX and MDA114, demonstrated robust performance in identifying patients with poor prognosis in 2 independent cohorts. These two predictors also had modest but significant concordance of predicted outcome (r>0.3, P<0.001 in both cohorts). CONCLUSIONS: Further validation of developed genomic predictors is necessary. Despite the limited number of genes shared by OncoDX and MDA114, individual-patient outcomes predicted by these two predictors were significantly concordant.ope

Treatment of a Patient with Kaposi’s Sarcoma Arising during Hemodialysis with the Multikinase Inhibitor Pazopanib

Kaposi’s sarcoma (KS) is an unusual multifocal neoplastic angioproliferative disorder. We herein report a case of classic KS that occurred in a patient receiving hemodialysis for 7 years. The patient had a history of chronic renal failure due to glomerulonephritis for 20 years. Multiple reddened violaceous patches, plaques, and nodules were found on the right knee. Biopsy revealed positivity for human herpesvirus 8 (KS-associated herpesvirus) consistent with KS. Pazopanib, a multitarget tyrosine kinase inhibitor, is an effective agent for treatment of advanced soft tissue sarcoma. The patient received pazopanib for 6 months investigate its effects on KS. The skin lesions and painful symptoms showed improvement. Further studies are required to determine the mechanism underlying the anticancer action of pazopanib and the pathogenesis of KS.ope

Targeted therapy in gastric cancer: Personalizing cancer treatment based on patient genome

Gastric cancer is the second leading cause of cancer-related deaths worldwide. Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer, with an overall survival of approximately ten months. Recent advances in high-throughput technologies have enabled the implementation of personalized cancer therapy for high-risk patients. The use of such high-throughput technologies, including microarray and next generation sequencing, have promoted the discovery of novel targets that offer new treatment strategies for patients lacking other therapeutic options. Many molecular pathways are currently under investigation as therapeutic targets in gastric cancer, including those related to the epidermal growth factor receptor family, the mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin factors. Advances in molecular diagnostic tools further support the discovery of new molecular targets. Limitations exist, however; not all patients can be tested for biomarkers, and numerous challenges hamper implementation of targeted therapy in clinical settings. Indeed, the scale of tumor genomic profiling is rapidly outpacing our ability to appropriately synthesize all the information in order to optimally refine patient care. Therefore, clinicians must continue to educate themselves regarding new tools and frameworks, and to utilize multidisciplinary team science, comprised of oncologists, geneticists, pathologists, biologists and bioinformaticians, to successfully implement this genomic approach therapeutically.ope

One Case of Thoracic Empyema due to Salmonella choleraesuis

Salmonella are motile, gram-negative, non-spore-forming members of the family Enterobacteriaceae. Among nontyphoid Salmonella serotypes, Salmonella choleraesuis shows a high predilection to cause systemic infections in humans. Thoracic infection is a rare complication of Salmonella infection. So far, most of reported cases of empyema caused by Salmonella spp. have involved immunocompromised patients. Herein, as we had experienced one case of thoracic empyema due to Salmonella choleraesuis related thymoma, we report it with review of literature.ope

Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer

PURPOSE: This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery. EXPERIMENTAL DESIGN: Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort. RESULTS: We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02-2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1-7.9; P = 0.03) and was the only significant independent predictor of recurrence. CONCLUSIONS: The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted. Clin Cancer Res; 22(24); 6228-35. ©2016 AACR.ope

A Case of Adenocarcinomatous Transformation of a Sacrococcygeal Teratoma in an Adult

Sacrococcygeal teratoma (SCT) is an unusual tumor in adults. The incidence of malignant transformation of this tumor increases when its excision is delayed beyond 1 month of age. We report an uncommon case of adenocarcinoma arising within the colonic mucosa of a mature teratoma of the sacrococcyx in a 44-year-old male. The patient received surgical resection for a sacrococcygeal mass in a local hospital and was diagnosed with adenocarcinoma arising from SCT. He was referred to our hospital for further treatment and received chemotherapy as adjuvant treatment. After 4.5 years, the coccygeal mass recurred on follow-up imaging workup, and surgical resection was performed. On pathologic work-up, residual disease at the resection margin was identified microscopically. Pathologic diagnosis was a primary adenocarcinoma arising from the colonic mucosa within a mature teratoma. The patient received adjuvant-chemotherapy and radiotherapy and has been followed up.ope

Gemcitabine Combined with Capecitabine Compared to Gemcitabine with or without Erlotinib as First-Line Chemotherapy in Patients with Advanced Pancreatic Cancer

PURPOSE: The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy-gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)-in patients with advanced pancreatic cancer. MATERIALS AND METHODS: There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and capecitabine 850 mg/m(2) twice daily for 2 weeks followed by 1 week's rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. RESULTS: The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. CONCLUSION: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.ope

Gene expression signature-based prognostic risk score in gastric cancer

PURPOSE: Despite continual efforts to develop a prognostic model of gastric cancer by using clinical and pathologic parameters, a clinical test that can discriminate patients with good outcomes from those with poor outcomes after gastric cancer surgery has not been established. We aim to develop practical biomarker-based risk score that can predict relapse of gastric cancer after surgical treatment. EXPERIMENTAL DESIGN: Microarray technologies were used to generate and analyze gene expression profiling data from 65 gastric cancer patients to identify biomarker genes associated with relapse. The association of expression patterns of identified genes with relapse and overall survival was validated in independent gastric cancer patients. RESULTS: We uncovered two subgroups of gastric cancer that were strongly associated with the prognosis. For the easy translation of our findings into practice, we developed a scoring system based on the expression of six genes that predicted the likelihood of relapse after curative resection. In multivariate analysis, the risk score was an independent predictor of relapse in a cohort of 96 patients. We were able to validate the robustness of the six-gene signature in an additional independent cohort. CONCLUSIONS: The risk score derived from the six-gene set successfully prognosticated the relapse of gastric cancer patients after gastrectomy.ope