bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of circulating tumor cells to predict response to chemotherapy in patients with advanced gastric cancer.
Authors: Matsusaka S. , Chin K. , Mizunuma N. , Ogura M. , Suenaga M. , Ozaka M. , Takagi K. , Oba M. , Mishima Y. , Hatake K. 
Published: February 2017

43 Background: The purpose of this study was to quantify circulating tumor cells (CTCs) in advanced gastric cancer (AGC) patients, and to demonstrate the role of CTCs in cancer therapy. The purpose of this study was to identify CTC threshold proposal for determining response to chemotherapy in AGC. Methods: From November 2007 to June 2009, fifty-two patients with AGC were enrolled into a prospective study. All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital and provided informed consent. The study population consisted of patients of aged 18 years or older with histologically proven AGC. Other inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2; adequate organ function. The subjects were five patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks), twenty-six patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP 60 mg/m2, day 8, repeated every 5 weeks), and twenty-one patients treated with paclitaxel (80 mg/m2, weekly). CTCs of whole blood at baseline, two weeks and four weeks after initiation of chemotherapy, were isolated and enumerated using immunomagnetics. Results: Patients with ≥4 CTCs at two-week points and four-week points had a shorter median PFS (1.4, 1.4 months, respectively), than those with the median PFS of <4 CTCs (4.9, 5.0 months, respectively) (p<0.001, p<0.001, respectively). Patients with ≥4 CTCs at two-week points and four-week points had shorter median OS (3.5, 4.0 months, respectively) than those with the median PFS of <4 CTCs (11.7, 11.4 months, respectively) (p<0.001, p=0.001, respectively). In univariate analysis, PS, treatment regimen, Line of chemotherapy, and CTC levels at 2 weeks and 4 weeks predicted PFS and OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. CTC levels at 2 weeks and 4 weeks were the strongest predictors. Conclusions: A threshold of lower than 4 CTC/7.5 ml at 2 weeks and 4 weeks was a significant predictor of the outcome for AGC patients treated with S-1 based regimen or paclitaxel regimen. No significant financial relationships to disclose.
Analysis of BRAF and KRAS mutations in colorectal cancer and rectal carcinogenesis via fluorescent allele-specific PCR.
Authors: Stover D. G. , Cushman-Vokoun A. M. , Vnencak-Jones C. L. , Berlin J. 
Published: February 2017

436 Background: Molecular analysis has become increasingly relevant in the evaluation of colorectal carcinomas. Mutations in Ras-MAPK pathway proteins KRAS (present in 30-40% of colorectal cancer) and BRAF (10-14% of colorectal cancer) or mismatch repair (MMR) enzymes can impact response to therapy and/or can assist in defining hereditary predisposition. High frequency microsatellite instability (MSI) in colorectal cancer is associated with improved outcomes. Targeted therapies against BRAF and other components of the Ras-MAPK signaling pathway are becoming important aspects of treatment in colorectal and other cancers. Methods: A retrospective study was performed on 111 paraffin-embedded tumor specimens submitted between 1/07 and 3/09 for MSI testing based on family history and/or histologic features. DNA samples were screened for the BRAF V600E mutation and 7 KRAS mutations in codons 12 and 13 using fluorescent allele specific PCR with capillary electrophoresis. Clinical data was collected via chart review. Results: 58 males and 53 females were studied. The incidence of KRAS and BRAF mutations among the 111 samples was 49.5% and 6.3%, respectively. KRAS G12D and G12V were the most common mutations, representing 57% of total KRAS mutations. Dually positive KRAS and MSI tumors exclusively demonstrated G12D and G13D mutations. KRAS and BRAF mutations were mutually exclusive. Rectal cancers did not show evidence of BRAF V600E mutation (p=0.04). KRAS, BRAF, and MSI status did not correlate with survival, however pre-operative and post-operative carcinoembryonic antigen (CEA) levels were significantly associated with survival both in univariate and multivariate analyses. Conclusions: We demonstrate that BRAF V600E mutation is significantly associated with colon cancer and not rectal cancer, suggesting that BRAF mutations are not relevant in rectal carcinogenesis. Correlation between specific KRAS mutation and outcome may require larger populations. No significant financial relationships to disclose.
Simultaneous protection against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR-signaling blockade by oncogenic RAS.
Authors: Schuler M. H. , Breitenbuecher F. , Trarbach T. , Brandau S. , Schmid K. W. , Kasper S. 
Published: February 2017

440 Background: Monoclonal antibodies against the epidermal growth factor receptor (EGFR) have improved treatment options for colorectal cancer (CRC), but tumors harboring RAS mutations are resistant. Full molecular understanding of RAS-mediated protection is key to the development of sensitization strategies. Methods: We have used cell culture and murine CRC transplant models to study whether RAS solely imposes resistance by compensating EGFR signaling blockade, or additionally interferes with antibody-dependent cellular cytotoxicity (ADCC). Results: Both clinically approved anti-EGFR antibodies, cetuximab and panitumumab, were equally cytotoxic in CRC cells in vitro. Interestingly, cetuximab, a chimeric IgG1 antibody capable of triggering ADCC, was more effective than panitumumab (human IgG2) in murine CRC transplant models in vivo. The advantage of cetuximab in vivo was completely abolished by leukocyte depletion following total body irradiation. Moreover, oncogenic RAS neutralized the in vivo therapeutic activity of cetuximab and panitumumab to the same extent. Mechanistically, RAS conferred antibody resistance by upregulation of BCL-XL, which was overcome by cotreatment with a BH3 mimetic. In support, RAS-mutant primary human CRCs exhibited increased BCL-XL expression as detected by immunohistochemistry. Conclusions: RAS-mutant CRCs escape anti-EGFR antibody-mediated receptor blockade as well as ADCC in vivo. Pharmacologic modulation of RAS downstream effectors, such as BCL-XL, can restore sensitivity to antibody effector mechanisms. [Table: see text]
Evaluation of serum CXCL5 as a serum marker for prognosis of colorectal cancer patients.
Authors: Kawamura M. , Toiyama Y. , Tanaka K. , Yasuda H. , Fujikawa H. , Saigusa S. , Inoue Y. , Miki C. , Yamaguchi M. , Kusunoki M. 
Published: February 2017

442 Background: CXCL5 is known as CXC chemokine which promotes angiogenesis related to cancer. However, the function of serum level of CXCL5 (sCXCL5) has not been fully studied in colorectal cancer. The purpose of this study was to evaluate the relationships between preoperative sCXCL5 and clinicopathological features and prognosis in colorectal cancer. Methods: This was a single-institution, retrospective study. Preoperative serum samples of 250 colorectal cancer patients (between 1998 and 2007, median age: 65.3 years, male 159/female 91) were available for the study, and 33 normal serum was examined and used as a control. sCXCL5 level was assayed using a commercially available enzyme-linked immunosorbent assay kit, and analyzed statistically. Results: Mean level of sCXCL5 was significantly higher in colorectal cancer patients than in control group (p=0.013). Patients with liver metastases had significantly higher sCXCL5 level than those without metastases (p=0.0086), and in logistic analysis, sCXCL5 was an independent marker for predicting liver metastasis (p=0.040). Overall survival of patients with elevated sCXCL5 level was significantly worse than those with lower sCXCL5 (p=0.0006). Conclusions: Preoperative sCXCL5 level was increased in colorectal cancer patients compared to in healthy volunteer and elevated sCXCL5 was correlated with liver metastasis and poor prognosis for overall survival in colorectal cancer patients. Elevated sCXCL5 has been proposed as a useful predictive marker for liver metastasis and overall survival in colorectal cancer. No significant financial relationships to disclose.
Relationship of pro-angiogenic factor Cyr61to colorectal cancer development and prognosis.
Authors: Baek M. , Bae S. , Jeong D. 
Published: February 2017

446 Background: Angiogenic factorCysteine-rich 61 (Cyr61) is a member of the CCN protein family that has been implicated in diverse biological processes such as cell adhesion, proliferation, angiogenesis, and tumorigenesis. An altered expression of Cyr61 is found to be associated with several human cancers. However, the correlation of expression of Cyr61 protein and clinical features of colorectal cancer remains unknown. Methods: Cyr61 expression in colorectal cancer and normal tissues was evaluated by Western blot analysis. Immunohistochemical staining was carried out using tissue microassay (TMA) to examine the expression status of Cyr61. Correlations of Cyr61 over-expression with various clinicopathologic factors were also determined. Statistical analysis was performed to explore the links between expression of the Cyr61 and clinicopathological parameters. Results: On Western blot analysis Cyr61 up-regulation was observed in colorectal cancer tissues (17/21, 80.9%). In 234 colorectal cancers, tumor tissue microarray revealed significantly up-regulated Cyr61 protein expression in colorectal cancer tissues versus normal tissues adjacent to tumor. Cyr61 expression was high in 136 of 234 cases of colorectal carcinomas (58.1%). Cyr61 over-expression was significantly associated with TNM stage (p=0.012) and regional lymph node involvement (p=0.018). Kaplan-Meier survival analysis showed that over-expression of Cyr61 was related to poor survival of colorectal cancer patients (p=0.031). But significant associations were not found between CYR61 expression versus tumor grade, age and gender. Conclusions: Our results suggest that Cyr61 is highly expressed in colorectal carcinomas and Cyr61 may play a role in the progression of colorectal cancers. Also, Cyr61 might be a new molecular marker to predict the prognosis and serve as valuable targets for therapeutic intervention of patients with colorectal carcinoma. No significant financial relationships to disclose.
Clinicopathological correlation of beclin-1 expression in human colon cancer.
Authors: Choi S. , Lim S. J. , Kim B. s. , Lee J. J. , Kang W. 
Published: February 2017

464 Background: We investigated the expression of beclin-1 and bcl-2 in human colon cancer tissue by immunohistochemical analysis using a tissue microarray in relation to other prognostic factors. Methods: Tissue samples from 78 cases of invasive colon cancer were used for the present study. A positive control for bcl-2 expression was small lymphocytes in the mantle zone. Immunohistochemical staining for beclin-1 and bcl-2 was evaluated according to intensity and proportion. The intensity score was determined as 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong). The proportion score was determined as 1 (< 30% of tumor cells) and 2 (≥ 30% of tumor cells). The intensity score and proportion score were multiplied together for a total score. Total scores were as follows: 0-1 (negative) and 2-6 (positive). Results: The normal colonic epithelium showed weak to no beclin-1 expression. Positive beclin-1 expression and positive bcl-2 expression of colon cancer cells was observed in 48 cases (61.5%) and 10 cases (12.8%), respectively. beclin-1 expression was significantly correlated with lymph node metastasis (p = 0.035) Bcl-2 expression in colon cancer cells showed no significant correlation with clinocopathologic factors studied. Beclin-1 expression was not correlated with bcl-2 expression in colon cancer cells (p = 0.348). Conclusions: In conclusion, we have characterized the expression of beclin-1 in human colon cancer and the relationship with bcl-2 protein. Our results suggest that it seems reasonable to assume that beclin-1 might play a role in the development of colorectal cancer. No significant financial relationships to disclose.
Clinicopathological analysis of KRAS mutation in an Irish population.
Authors: Teo M. , O'Reilly S. , Moylan E. , Power D. G. 
Published: February 2017

467 Background: Clinical trials have shown that tumor KRAS status predicts response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). We sought to compare distribution of wild-type and mutated KRAS in an Irish population and identify clinicopathologic correlates. Methods: From our prospectively maintained database we retrospectively identified patients with mCRC and documented KRAS status between Jan 2007 to June 2010. Medical notes were examined for patient demographics and disease characteristics. Variables were extracted and compared using unpaired t test and chi2 test. Results: 52 patients were identified, 29 (55.8%) with mutated (mt) and 23 (44.2%) with wild type (wt) KRAS from tumor tissue. Males accounted for 61.5% (n=31). Median age at diagnosis of metastatic disease for the KRASmt group was 66.4 years (range 56.7-82.1) and for the KRAS wt group was 64.2 years (40.1-76.8), p= 0.08. 21 (72.4%) of the KRASmt group and 16 (69.6%) of the KRASwt group had metastatic disease at presentation (p=0.81). For patients who presented initially with localised disease, time to development of metastases was 22.5mo (range 14-37.6) for the KRASmt group and 16.7mo (3.2-123.7) for the KRASwt (p=0.30). 21 (72.4%) of KRASmt and 17 (74.1%) of KRASwt tumors had left-sided primary (p = 0.84) with equal numbers of primary tumor resection in both groups. There was no statistical difference in TN-stage or the presence of liver metastases. Numbers of patients with KRASmt tumors with one, two and three or more different sites of metastases was 22 (75.9%), 5 (17.2%), and 2 (6.9%), and in KRASwt tumors there was no significant difference: 18 (78.3%), 4 (17.4%), and 1 (4.3%), respectively (p = 0.93). Median CEA at diagnosis for both groups were 19.7 μg/l (range 1.2-5958) and 6.1 (1.3-696.9; p = 0.11). Conclusions: We found that the ratio of KRASmt to KRASwt tumours in an Irish population is comparable to that in large international trials. Our analysis revealed no association between KRAS status and clinicopathologic variables. The inclusion of BRAF status, not readily available in our institution, may help define poor prognosis tumors. At present there is no validated molecular biomarker that is superior to standard clinicopathologic variables. No significant financial relationships to disclose.
Quality of life during rehabilitation: Rectal cancer patient and partner experiences with altered bowel function.
Authors: Boucher J. , Piperdi B. , Lundquist D. 
Published: February 2017

468 Background: In 2010, the American Cancer Society has estimated rectal cancer affects over 39,670 adult patients in the United States. Five-year disease-free survival for rectal cancer patients with stage II/III disease ranges from 60-70%. Current gaps exist regarding long-term effects after treatment including altered bowel function and health-related quality of life (HR-QOL) concerns from rectal cancer patient and partners' perspectives both individually and together during rehabilitation and as cancer survivors. The purpose of this study was to: (1) describe the experiences of adult rectal cancer patients and their partners during rehabilitation from cancer treatment, including long- term effects; (2) examine health-related quality of life (HR-QOL) issues for rectal cancer patients and their partners including well-being and coping during their rehabilitation and as survivors. Methods: A qualitative descriptive study for a planned sample of 20 adult rectal cancer patients, stage II/III, and their partners from an academic health science hospital and cancer center has been conducted. Twelve patients and their partners have currently completed face to face semi-structured interviews. Patient participants were at least 6 months to 5 years post treatment. Qualitative descriptive design used purposive sampling to obtain broad information on rectal cancer patients' and partners' perspectives for content analysis. Results: Preliminary findings have revealed unexpected difficulties; chronic bowel function alterations; symptom unpredictability; nutrition intolerances; patient/partner adjustments; social concerns in going places, reactions by friends, work and financial strains; and, acceptance in living with it or chronic life changes as survivors. Partners acknowledged their own needs for information and support to assist their spouse or significant other. Further rich, thick descriptions will be presented in presentation of findings for 20 patient and partner responses. Conclusions: Survivorship follow-up regarding these concerns should be emphasized for rectal cancer patients and their partners to formalize interventions for study to enhance HR-QOL well-being. No significant financial relationships to disclose.
Intratumoral immune reaction: A novel paradigm for cancer.
Authors: Galon J. , Mlecnik B. , Kirilovsky A. , Bindea G. , Tosolini M. , Fridman W. , Pages F. 
Published: February 2017

471 Background: To date the anatomic extent of tumor (TNM classifications) has been by far the most important factors to predict the prognosis of cancer patients. However, the impact of immune responses and tumor escape on patient prognosis in human cancer is poorly understood. Methods: We analyzed large retrospective cohorts of colorectal cancer patients. Results: We showed that tumors from human colorectal cancer with a high density of infiltrating memory and effector memory T-cells (T-EM) are less likely to disseminate to lymphovascular and perineural structures and to regional lymph-nodes (New Engl J Med, 2005). We showed that the combination of immune parameters associating the nature, the density, the functional orientation and the location of immune cells within the tumor was essential to accurately define the impact of the local host immune reaction on patients prognosis (Science, 2006). We proposed to define these immune criteria as “immune contexture.” Analysis of patients with early-stage colorectal cancer confirmed the major role of cyotoxic effector T cells in predicting the prognosis of the patients (J Clin Oncol, 2009). Investigation of the primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response. We described four major immune coordination profiles within primary tumors depending on the balance between tumor escape and immune coordination. Recent advances analyzing mechanisms responsible for lymphocytic infiltration will be discussed. Conclusions: The density and the immune-cell location within the tumor have a prognostic value that is superior of those of the TNM classifications. Tumor invasion is statistically dependent on the host-immune reaction. No significant financial relationships to disclose.
A randomized, multicenter phase III trial of bevacizumab plus capecitabine as maintenance treatment after initial treatment with bevacizumab plus XELOX in previously untreated metastatic colorectal cancer.
Authors: Yalcin S. , Uslu R. , Dane F. , Yilmaz U. , Zengin N. , Buyukunal E. , Buyukberber S. , Camci C. , Sencan O. , Kilickap S. 
Published: February 2017

474 Background: Colorectal cancer is one of the most frequent malignancies, second to breast cancer in women and third to lung cancer and prostate cancer in men. The aim of this study in first-line metastatic colorectal cancer (mCRC) was to achieve a better progression-free survival (PFS) and less risk of toxicity by administrating bevacizumab (BEV) + capecitabine + oxaliplatin (XELOX) for 6 cycles, stop oxaliplatin and go with maintenance therapy (BEV + capecitabine) until progression. Methods: BEV (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1 q3w) were administered until progression (Arm A) or 6 cycles of BEV + XELOX followed by BEV + capecitabine were administered until progression (Arm B). PFS was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. A sample size of 118 patients (pts) was calculated to achieve 80% power to detect an increase of 1.5 months in median PFS between Arm A (9.5 months) and Arm B (11.0 months) with a standard deviation of 3.9 months and significance level of 0.05 using a 10% drop-out rate. Results: A total of 122 pts were randomized. No significant differences were found in demographic characteristics between the two arms. Median treatment period was 6.1 (range 0.7–13.4) and 6.8 (range 0.7–12.4) months in Arms A and B, respectively. Interim analysis showed no statistically significant differences in median PFS and ORR between arms (see table). Tolerability was also acceptable in both arms with grade 3/4 diarrhoea in 7.7% vs. 8.2%, weakness in 15.2% vs. 8.4%, hand-foot syndrome in 6.3% vs. 9.4%, and neuropathy in 2.8% vs. 4.6% of pts in Arms A and B, respectively. Conclusions: BEV + capecitabine as maintenance therapy following induction BEV + XELOX is non-inferior to continuous BEV + XELOX until progression. While this study is ongoing, these interim findings suggest that maintenance therapy with BEV + capecitabine is an appropriate option following induction BEV + XELOX in pts with mCRC. [Table: see text] [Table: see text]
Do cancer centers need to assess quality and outcomes? Introducing a customized ACS-NSQIP for oncology (Onc-NSQIP).
Authors: Bilimoria K. Y. , Wang X. , Cohen M. E. , Hall B. L. , Richards K. , Merkow R. P. , Pisters P. W. , Ko C. Y. 
Published: February 2017

475 Background: To identify quality improvement opportunities, hospitals can use ACS NSQIP to compare their risk-adjusted performance to other hospitals. However, Cancer Centers have few opportunities to compare their outcomes to similar hospitals for oncologic operations. Our objective was to develop an oncology-specific version of ACS NSQIP (Onc-NSQIP) and determine whether it could be useful for Cancer Centers. Methods: From ACS-NSQIP (2006-2009), patients undergoing major colorectal (n=34,858; 221 hospitals) and pancreatic (n=7,667; 65 hospitals) as well as esophageal, gastric, and soft tissue operations for malignancy were identified. Risk-adjusted postoperative outcomes were assessed with regression models adjusting for demographics, comorbidities, and operative procedure. Relative rankings of NCI-designated Comprehensive Cancer Centers in ACS NSQIP among the other ACS NSQIP hospitals were compared. Results: Cancer Center outcomes varied widely for colorectal and pancreas. For overall colorectal morbidity, Cancer Centers were ranked in the top third (n=4), middle third (n=7), and bottom third (n=10). For colorectal 30-day mortality, Cancer Centers were ranked in the top (n=14), middle (n=3), and bottom third (n=4). For overall pancreatic morbidity, Cancer Centers were ranked in the top (n=5), middle (n=7), and bottom third (n=7). For pancreatic 30-day mortality, Cancer Centers were ranked in the top (n=5), middle (n=6), and bottom third (n=8). Similar results were observed for colorectal and pancreas for DVT/PE, SSI, reoperation, and length of stay. Onc-NSQIP models were comparable to standard ACS NSQIP models. At least some Cancer Centers were statistical outliers for most outcomes (P<0.05). Results were similar for other malignancies. Conclusions: Cancer Center outcomes varied as much as other ACS NSQIP hospitals, demonstrating need for quality assessment. Without standardized risk-adjusted outcomes comparisons, Cancer Centers cannot accurately assess their outcomes to identify quality improvement targets. ACS NSQIP's new platform allows customization so hospitals can compare surgical oncology-specific risk-adjusted processes and outcomes. No significant financial relationships to disclose.