bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Immune response-associated gene polymorphisms on tumor response in rectal cancer patients treated with capecitabine +/- oxaliplatine and radiation in the ACCORD-12/PRODIGE-2 phase III trial.
Authors: Boige Valerie , Mollevi Caroline , Chaput Nathalie , Gourgou Sophie , Azria David , Seitz Jean-François , Bigot Ludovic , Juzyna Beata , Miran Isabelle , Gerard Jean-Pierre , Laurent-Puig Pierre 
Published: September 2018

e15151 Background: We examined whether 133 germline polymorphisms (SNPs) in 15 candidate genes (CSF1R, IL8RA, TLR4, IL10, IL10RA, CTLA4, IL2, IL2RA, TGF b1, ICOS, IL13, IL13RA2, IFNgR, IL15 and IL15RA) would predict clinical outcome in the ACCORD-12 phase III trial which randomly compared neoadjuvant radiotherapy (RT) plus capecitabine (CAP45) with dose-intensified RT plus capecitabine and oxaliplatin (CAPOX50) in T3-4 Nx M0 resectable rectal cancer. Methods: A candidate-gene association study was conducted in 316 patients (n = 161 in the CAPOX50 and n = 155 in the CAP45 arm). The primary end-point was tumor response according to the Dworak score in each arm. Logistic regressions were used to assess univariate/multivariate associations. The Storey and Tibshirani method based on the control of false discovery rate was used ( q-value < 0.10 (adjusted p-value) considered as true discovery). Multivariate models adjusted on treatment arm and T stage were performed to determine prognostic and predictive values of SNPs for tumor response. Results: In univariate analysis, two SNPs in IL2RA (rs11256456: OR = 5.1 [2.38; 11] and rs706781: OR = 4.2 [1.98 ; 8.74]) were significantly associated with the Dworak score in the CAP45 arm, and one in IL2RA the CAPOX50 arm (rs2104286: OR = 0.11 [0.01 ; 0.90]. All were confirmed in the multivariate analysis. A significant haplotypic effect was observed in the CAP-45 arm (p = 0.0001). Interaction was significant for IL2RA rs11256456 ( p= 0.03) and rs706781 ( p= 0.002) and no significant for IL2RA rs2104286 ( p= 0.722), suggesting a predictive deleterious effect the first two ones for response to oxaliplatin-based chemoRT, and a prognostic effect of the third one for response to chemoRT (+/- oxaliplatin). None of the three IL2RA SNPs were correlated with survival in the multivariate analysis. Conclusions: This pharmacogenetic analysis shows that SNPs in IL2RA have a significant association with response to chemoRT with capecitabine in patients with locally advanced rectal cancer. Their predictive effect may identify patients in whom oxaliplatin addition to chemoRT is deleterious.
Comparative analysis of survival in colon cancer undergoing sentinel lymph node mapping vs conventional surgery based on number of positive lymph nodes.
Authors: Ramanathan Sabarina , Saha Sukamal , Mukkamala Suresh , Hicks Michael , Knight Patrick , Bajaj Vinay , Mazzaferro Daniel , Siva Thushy , Hutcherson Lori , Livert David , Oza Rajen , Wiese David , Arora Madan L. 
Published: September 2018

e15154 Background: Unlike in breast cancer or melanoma, resection during sentinel lymph node mapping (SLNM) in colon cancer (CCa) includes regional lymphadenectomy including SLNs and non-SLNs. However, SLNM often identifies micrometastases that can be missed by conventional (Conv) surgery and pathologic examination. It is unknown whether this impacts survival or recurrence. Hence, a retrospective analysis was undertaken to study overall (OS) and disease -specific (DSS) survival between patients (pts) undergoing SLNM vs Conv surgery based on the number of +ve LNs. Methods: SLNM was done by subserosal injection with blue dye followed by segmental resection including regional lymphadenectomy. All SLNs were ultrastaged and other nodes were examined by conv. methods with H&E. Results: There were 309 pts in SLNM (GpA) vs 499 pts in Conv surgery (GpB); with average no. of lymph nodes (LNs) and +ve LNs 17.3/1.6 vs 14.4/2.49 respectively. For GpA, success rate was 99.6% and the average no of SLN was 3. Of the pts in GpA vs GpB, 1+ve LN were found in 38% vs 27%, 2+ve LNs in 10% vs 16%, and > 2 LNs in 53% vs 57%, respectively. Comparing 5 years OS between GpA vs GpB, for 1+ve LN was 62.8% vs 52.38%, for 2 +ve LNs 72.7% vs 48.65% and for > 2 +ve LNs 35% vs 33.33%, respectively. Similarly, DSS for 1 +veLN was 54.4% vs 47.6%, 2+ve LNs 40% vs 40.54% and > 2+ve LNs, 30.4% vs 25.76%, respectively (Table). Conclusions: Compared to Conv surgery, SLNM identified higher no. of LNs per pt with high success rate. Five-year OS and DSS also are better in SLNM vs Conv surgery for all +ve LN gps. Hence, SLNM in CCa may have prognostic value. A larger multicenter trial needs to be done to validate such data. [Table: see text]
Response to neoadjuvant chemoradiation in rectal cancer: Experience from the national cancer institute of Peru.
Authors: Muro Johanny F , Veliz Karin , Maldonado Mike M , Flores Claudio J. , Montenegro Paola Catherine 
Published: September 2018

e15157 Background: Preoperative Chemoradiation (CRT) in rectal cancer has benefit in local control. 50 - 60% of cases are down-staged and 20% achieve a pathologic complete response (pCR). Despite the fact that there is no a clear benefit in long-term outcomes, response to preoperative treatment could have a prognostic value. Our objectives were to determine the pCR and down-staging (DS) rates after neoadjuvant CRT, as well as disease free survival (DFS), overall survival (OS) and prognostic factors associated with these outcomes Methods: Patients with rectal cancer treated with preoperativefluoropyrimidine based CRT at the National Cancer Institute of Peru (INEN) from 2007 to 2012 were evaluated. OS and DFS were calculated according to Kaplan-Meyer method. The survival curves were compared using the Log-rank or Breslow test. Multivariate analysis was performed with Cox regression Results: 282 patients were included, median age was 62 years (range 18-93), female: male ratio (1:1). Clinical stages were as follows: I, 13.8%; II, 32.3% and III, 52.9%. Median follow up was 5 years. Patients received capecitabine and 5-FU during radiotherapy in 75.5% and 24.5% of cases respectively. Sphincter preserving surgery was possible in 46% of cases. In patients who underwent surgery, DS and pCR rates were 52% and 10.8%, respectively. Patients who achieved pCR were predominant female and had CEA less of 5 ng/mL. In multivariate analysis, clinical stage, DS, type of fluoropyrimidine (capecitabine) and surgery were associated with OS. 5 year DFS and OS was 54.9% and 60.5% respectively in patient that underwent surgery Conclusions: DS rate achieved at our institution is within the range reported by the literature and is associated with an improvement in OS. Our pCR rate was lower than what has been reported, this might be related to great proportion of patients with advanced clinical stage (EC III) in our study. This patient could have benefit with totally neoadjuvant Chemoradiation.
Can CRM status on MRI predict survival in locally advanced rectal cancers: Experience from the Indian subcontinent.
Authors: Anam Jay Rashmi , Chandarana Mihir , Arya Supreeta , Desouza Ashwin Luis , Ostwal Vikas S. , Engineer Reena , Patil Prachi , Saklani Avanish 
Published: September 2018

e15167 Background: Neoadjuvant chemoradiation has become the standard approach for treatment of locally advanced rectal cancers. Magnetic Resonence Imaging (MRI) is the staging modality of choice in rectal carcinoma. Recent reports have studied the impact of MRI on local recurrence and survival both in treatment naïve and post treatment settings Methods: A retrospective analysis of prospective database was performed over a period of 1 year. All pretreatment patients with carcinoma of rectum were included in the study. The status of CRM on MRI was compared to that on the histopathology and as a predictor of recurrence and survival. For analysis, the MRI scans done for patients at presentation were labeled as MRIT. This included all patients irrespective of further treatment received. Patients who were treated with NACTRT had two MRI scans. The MRI at presentation in this subset of patients was labeled as MRI1 and the reassessment MRI after NACTRT was labeled as MRI2. Thus, MRI1 represented a subset of MRIT with locally advanced tumors treated with NACTRT. All the sets of MRI scans were analyzed separately for prediction of CRM involvement and for their effect on local recurrence and survival rates. Results: 221 patients were included with a median follow-up 30 months. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRIT, MRI1 and MRI2 to predict CRM status were 50%, 62.3%, 96.5%, 5.6% and 61.8%, 50%, 55%, 95%, 6% and 54.7% and 77.8%, 63.7%, 98%, 11%, 64.5% respectively. On multivariate analysis pathological positive margins alone predicted a poor overall survival (OS) whereas involved CRM on pathology and pretreatment MRI predicted poorer disease free survival and OS Conclusions: CRM status on pathology remains the most important prognostic factor to impact overall survival, disease free survival and local recurrence. CRM status on MRI at presentation alone has significant impact on disease free survival and local recurrence. Although MRI done after neoadjuvant treatment may not predict survival, it has a role in helping modify the surgical approach with a goal to achieve a negative CRM on pathology.
Preemptive versus reactive management of EGFR rash among mCRC patients treated with panitumumab: Results of a national survey of treating oncologists in the United States.
Authors: Lowe Kimberly , Hool Kristina , Garawin Tamer , Bergstresser Rachel , Kafatos George , McNamara Michelle , Collins Seth , Bach Bruce A. 
Published: September 2018

e15169 Background: The Skin Toxicity Evaluation Protocol with Panitumumab (STEPP) and the Japan Skin Toxicity Evaluation Protocol with Panitumumab (J-STEPP) were open-label, randomized trials that were designed to evaluate differences in preemptive versus reactive management of dermatologic toxicities associated with panitumumab among patients with mCRC. The objective of this study was to evaluate if there were differences in the knowledge and application of STEPP and J-STEPP among oncologists who self-identified as primarily managing EGFR rash preemptively or reactively. Methods: A total of 250 practicing oncologists who had treated at least three new or continuing mCRC patients with panitumumab in the last year completed an online survey to report their opinions and perceptions regarding the management strategies for mCRC patients who are treated with panitumumab. Preemptive treatment was described in the survey as beginning treatment “prior to the appearance of rash” and reactive treatment was defined as beginning treatment “after signs of rash.” Results: Of the 250 oncologists who participated in this study, n = 58 (23%) reported treating 100% of their patients preemptively and n = 38 (15%) reported treating 100% of their patients reactively. A significantly higher proportion of preemptive treaters than reactive treaters reported following the skin management strategies from STEPP or J-STEPP when managing panitumumab-related skin toxicity (31% vs 13%, p = 0.02). When asked if skin moisturizer, sunscreen, over-the-counter topical steroids, prescription topical steroids, oral antibiotics, topical antibiotics, or UV protective garments were most critical in the preemptive management of panitumumab-related skin toxicity, preemptive treaters more likely to report using oral antibiotics and reactive treaters more like to report using sunscreen (p = 0.05). Conclusions: The results of this survey highlight the wide variability in the management of EGFR-related rash among mCRC patients who are treated with panitumumab and they highlight the need for heighted education among oncologists who treat mCRC patients with panitumumab.
Cost-utility analysis of panitumumab use compared with cetuximab and bevacizumab for the first-line therapy of wild-type RAS metastatic colorectal cancer in the Peruvian health system.
Authors: Milton Valderrama , Apolaya-Segura Moises , Montenegro Paola Catherine 
Published: September 2018

e15171 Background: To estimate the cost-utility of Panitumumab compared to Cetuximab (Erbitux®) and Bevacizumab (Avastin®) for the first-line therapy of metastatic colorectal cancer in the Peruvian health system Methods: A cost-utility analysis was performed using a Markov's model based in epidemiological parameters, metastatic colorectal cancer (mCRC) associated costs, and the efficacy of therapy using specific monoclonal antibodies against wild-type RAS mCRC. The costs of biological agents were estimated from the payers' viewpoint, using a 3.5% discount rate. The model includes the transition between five health states (mCRC, surgery, remission, progression, and death), and each cycle lasts for one month in a 3-year temporal horizon Results: The results of the model indicate that Bevacizumab and Panitumumab were cost–effective compared with Cetuximab. Therapy using Bevacizumab for a three-year period cost PEN 178,950.96 less than Panitumumab, but generated 0.91 less QALYs. The incremental cost-effectiveness ratio (ICER) showed that Cetuximab had extended dominance when compared to Panitumumab and Bevacizumab. This means that Panitumumab is more expensive, but it leads to a greater clinical benefit. Conclusions: Using the best published data available, these results suggest that the clinical effectiveness of Panitumumab and Bevacizumab translates into a favorable cost-utility ratio; and it particularly generates savings. The use of Panitumumab is associated to a longer survival, more QALYs gained and more months in remission.
The prognostic value of systemic inflammatory factors in patient with metastatic gastric cancer.
Authors: Manikhas Georgy M. , Beliak Natalia P. , Kutukova Svetlana I. , Zhukova Natalia V. , Popova Natalia V. , Erdniev Sanal 
Published: September 2018

e15505 Background: Inflammation seems to be significant factor in carcinogenesis and tumor progression of numerous cancers. Blood calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), lactate dehydrogenase (LDH), international normalized ratio (INR) can be evaluated as systemic inflammation markers and prognostic biomarker for many aims: survival outcomes, lymph node metastasis and recurrence, treatment responses in a variety of cancers. The purpose of this study was to investigate baseline associations between blood test parameters (NLR, PLR, LDH, CRP, INR) and their prognostic biomarker role for patient with metastatic gastric cancer, undergoing first-line chemotherapy Methods: Potential baseline inflammatory markers (platelets, neutrophils, lymphocytes, the platelet-lymphocyte ratio, the neutrophil-lymphocyte ratio, the serum C-reactive protein [CRP], the serum LDH, INR) were retrospectively analyzed in 32 patients with metastatic gastric cancer, IV stage (median of age – 60,50). Multivariate analyses were used to identify prognostic factors for overall survival (OS). Baseline values were compared with tumor characteristic and median survival times (MSTs). Results: Multivariate analysis identified due to Cox proportional-hazards regression showed significant longest OS in patients with: localization of primary tumor in antral part of gastric (HR 0,45, 95% CI 0,25-0,80, p = 0,0065); low baseline’s level of WBC (HR 1,17, 95% CI 1.02 - 1,35, p = 0,0219); low baseline’s level of neutrophil (HR 1,18, 95% CI 1.02 - 1,34, p = 0,0251). Level of LDH, CRP, INR didn’t show significant ratio for this cohort of patient. Peritoneum metastatic also didn’t significant affect on OS in patient with metastatic gastric cancer. Patients with low baseline’s platelet to lymphocyte ratio (HR 1,004, 95% CI 1,0009-1,0072, p = 0,0125) and low (from 0 to 3,0) neutrophil to lymphocyte ratio (HR 1,81, 95% CI 1,09-2,99, p = 0,0212) had a significantly longest OS time. Conclusions: Inflammatory markers can predict overall survival in stage IV gastric cancer. Simple and useful.
Advanced signet ring cell type gastroesophageal cancers in Central American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.
Authors: Cannon Timothy Lewis , Ershler William B. , Bijelic Lana , Nizam Amanda , Hosseini Neda 
Published: September 2018

e15515 Background: Gastric Cancer mortality rates in Central and South America are among the highest in the world. Our institution has monitored a cohort of patients who have presented with metastatic gastroesophageal cancer, age 40 or below. Methods: After observing multiple cases of advanced gastric cancer in young immigrants from Latin America, we performed a retrospective cohort study at Inova Fairfax Hospital, a 1000 bed tertiary care center in Northern Virginia. We reviewed our cancer registry from 2013-2016, to identify all patients, age 40 or below, with stage IV gastric adenocarcinoma. We also reviewed the percentage of hispanic patients in our cancer registry for all cancer diagnoses, for comparison. Results: There were thirteen patients with stage IV gastric cancer who were aged 40 or below found in our registry. Ten of the thirteen patients (76.9%) were from Latin America (see Table 1), with the majority of those being from either El Salvador or Honduras. All thirteen cases were notable for signet ring cell differentiation. Hispanic patients make up only 8.3% of the total subjects and 12.9% of gastric cancer subjects in the Inova Fairfax Hospital Cancer registry during that same time period. Conclusions: Stage IV signet ring cell gastric cancers have occurred frequently at our tertiary care center among young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]
A pyrolytic compound of curcumin, a dietary deketene curcumin to inhibit gastric carcinogenesis in a mouse model.
Authors: Yoshida Taichi , Inoue Masahiro , Fukuda Koji , Shimizu Kazuhiro , Taguchi Daiki , Shibata Hiroyuki 
Published: September 2018

e15518 Background: Gastric cancer is the second cause of cancer death in the world, killing more than 700,000 people in 2012. The risk factors are Helicobacter pyloriinfection, obesity, smoking, consumption of red meat or alcohol. However, an effective preventive measure of this disease has bot been established. Curcumin, a dietary pigment, that has been used for more than three thousand years, has an anti-tumor potential. However, bioavailability of curcumin is very poor, and it is not used in clinics. Researchers are trying to overcome this short point. To synthesize a new analog bearing higher anti-tumor potential is our solution, and we have successfully developed a series of new diarylpentanoid analogs. Our diarylpentanoid analogs are structurally different from curcumin, a diarylheptanoid. Recently, a breakthrough finding that a deketene curcumin is formed as a result of pyrolysis of curcumin during cooking of curry, was published. This deketene curcumin is identical to one of our analogs, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one, named GO-Y022. For this reason, we investigate the efficacy and safety issues of GO-Y022 in a mouse gastric cancer model. Methods: We assessed anti-tumor potential of GO-Y022 on gastric cancer cell lines, KATO Ⅲ, H-111-TC, GCIY and SH-10-TC. We also examined the potential to inhibit β-Catenin and pSTAT3 levels. We conducted mouse experiment using transgenic mouse model overexpressing Wnt signaling, COX2 and Prostaglandin E2. This mouse is highly seceptible to gastric carcinogenesis. We orally administrated GO-Y022 mixed with food. We checked the safety issues of the treated mouse, and measured the tissue concentration of GO-Y022 by HPLC method. Results: GO-Y022 can inhibit the growth of gastric cancer cell lines significantly. The average IC50value of GO-Y022 was 5.05 ± 0.93 μm. That is about five times lower than curcumin. This potential was confirmed in mice. Blood concentration and the tissue distribution of GO-Y022 were negligible except gastrointestinal epithelia. GO-Y022 was safe for mouse models. Conclusions: GO-Y022 can inhibit the growth of gastric carcer in vivo. Oral administration of GO-Y022 can suppress gastic cancer topically.
Clinical significance of serum tumor marker for advanced gastric cancer with palliative chemotherapy: A retrospective study.
Authors: Zhu Yahui , Liu Baorui , Wei Jia , Du Juan , Yang Ju , Yang Yan , Wang Kangxin , Yang Yang , Zou Zhengyun 
Published: September 2018

e15524 Background:The predictive value of tumor markers has been previously reported a lot. However, the studies focused on advanced gastric cancer are few. In this study, we tried to investigate the relationship between the tumor markers of advanced gastric cancer and clinical characteristics, therapeutic effect of chemotherapy, and prognosis. Methods:A retrospective study including 146 advanced gastric cancer who had not received any previous anticancer therapy was performed. Blood samples for CEA, AFP, CA125, CA72-4, CA242 and CA19-9 were taken from patients before chemotherapy and monthly during their treatments. Statistical analysis was performed to predict the clinical value of these tumor markers. Results:CEA yielded an ROC value of 0.621 in predicting lymph node metastasis in gastric cancer, which was significantly higher than any of other markers. CA125 had the highest sensitivity, specificity and accuracy in gastric cancer patients with peritoneal metastasis. AFP and CEA were more frequently positive in patients with hepatic metastases. The response rate of Decreasing group, Stable group and Increasing group based on CA19-9, CEA, CA72-4, CA125 and CA242 levels achieved statistical significance. Positive cases of CA125, CA242, CA19-9 and CA72-4 showed poor prognosis, and significant differences in 3 year-survival rates were observed for CA125 and CA242. Conclusions:We found that different tumor markers in gastric cancer indicated different metastasis sits. CEA, CA242, CA19-9, CA125 and CA72-4 are predictive biomarkers in evaluating the effectiveness of chemotherapy. The elevated CA125, CA242, CA19-9 and CA72-4 levels at diagnosed had association with shorter overall survivals, especially CA125 and CA242.