bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of conversion therapy using S1/paclitaxel chemotherapy plus apatinib in unresectable gastric cancer (Ahead-G325 trial).
Authors: Cheng Xiangdong , Xu Zhiyuan , Du Yian , Hu Ping , Yu Guofa , Hu Conggang 
Published: March 2017

53 Background: Occasionally, an initially unresectable gastric cancer (GC) can be converted to a resectable one by chemotherapy. Combination with inhibitors against VEGFR-2 can lead to a clinical improvement. We aimed to investigate the efficacy and safety of S1/paclitaxel chemotherapy plus apatinib, a novel inhibitor of VEGFR-2, in the conversion therapy of unresectable GC. Methods: This was a multicentre, single-arm, open-label, phase II design. Eligible patients (pts) were aged 20-70 years and had histologically proven unresectable, HER-2 negative, advanced GC with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2). The ECOG performance status was 0-2. No prior radiotherapy, chemotherapy, target therapy or immunotherapy was allowed. Patients received 2 cycles of S1/paclitaxel chemotherapy (S1: 60 mg, oral, bid for 2 weeks followed by a drug-free interval of 1 week; paclitaxel: 150 mg/m2, iv, 3h, on day 1) plus apatinib (500 mg, oral, qd) and 1 cycle of S1/paclitaxel chemotherapy prior to radical surgery. Three cycles of adjuvant chemotherapy (S1 and apatinib) were given 4-6 weeks after surgery. Primary endpoint was R0 resection rate. Thirty-three pts were enrolled. Results: Among the 28 pts eligible for preoperative efficacy evaluation, 21 achieved partial response (PR), 5 had stable disease (SD), and 2 had progressive disease (PD), resulting in an overall response rate of 75.0% and a disease control rate of 92.9%. Of the 21 pts with PR, 3 refused consents for surgery and 18 achieved R0 resection. The incidence of adverse events (AEs) was 73.9%. The common hematologic AEs were neutropenia (60.9%), leukopenia (52.2%) and hemoglobin decrease (47.8%), and nonhematologic AEs included hyperbilirubinemia (56.5%), hand-foot syndrome (34.8%), oral mucositis (30.4%), fatigue (30.4%), proteinuria (21.7%) and hypocalcemia (21.7%). There was no severe surgery-related complication. Conclusions: Combination of apatinib with S1/paclitaxel chemotherapy shows clinical benefits in unresectable GC, with acceptable safety profile. Clinical trial information: NCT02529878.
Do patients and doctors have the same conversation about colorectal cancer screening?
Authors: Talcott James Austin , Bezuhly Maureen , Herzstein Jessica , Osborne Michael P. , Cassano Kelly , Chadha Manjeet 
Published: March 2017

532 Background: Participant characteristics affect shared decision making. In a randomized trial of physician (MD) educational interventions to improve cancer screening guideline compliance, we studied patient (PT) and MD recall of discussions and how PT characteristics affected recall. We report the first results for colorectal cancer screening. Methods: In a cluster-randomized trial of educational supports for MDs, we are enrolling an age- (30-89 years) and sex-stratified sample of 216 PTs who underwent a physical examination at two urban hospitals, 18 for each of 12 primary care MDs. Screening guideline formatting (color-coding) and academic detailing were randomly assigned to MDs in a 2x2 design. Immediate post-encounter surveys recorded PT and MD recall of screening discussions and recommendations. Results: We report on the first 174 participants. They were diverse (63% white) and well educated (77% college degree). When MDs reported a colorectal screening discussion, 20% of PTs did not, and MDs had similar disagreement when PTs reported the discussion. Greater disagreement occurred on the MD recommendation: 15% of PTs disagreed when the MD reported screening was recommended, and 33% of MDs disagreed when their patients reported they had recommended it. Agreement between PTs and MDs on whether screening was recommended was fair (kappa = 0.33), and there was no agreement for PTs over 70 years (kappa = -0.15). When PTs under 50 or 75 and older differed from their MDs on screening recommendations, it was for screening not against (8 vs. 2). PTs reported more elements of shared decision making than MDs (data not shown). Conclusions: In a highly educated population of PTs and MDs surveyed immediately after their encounter, reports of whether colorectal screening was discussed, the shared decision making elements and the MD recommendation had important discrepancies, especially for older PTs. Clinical trial information: NCT02430948.
Underuse of microsatellite instability testing and predictors of high microsatellite instability disease among young colorectal cancer patients.
Authors: Shaikh Talha , Handorf Elizabeth , Meyer Joshua E. , Hall Michael J. , Esnaola Nestor F. 
Published: March 2017

534 Background: The purpose was to identify predictors of non-adherence to MSI testing in young CRC patients and identify factors associated with an increased risk of high microsatellite instability (MSI-H) disease. Methods: Patients 18-49 years old diagnosed with invasive colorectal adenocarcinoma between 2010-2012 and known MSI testing status were identified using the National Cancer Data Base. Multivariable logistic regression was used to identify independent predictors of receipt of MSI testing, as well as MSI-H status among those tested. Results: Among 17,218 patients identified, only 7,422 (43%) underwent MSI testing; the proportion of patients tested increased between 2010 (36%) and 2012 (48%; p < 0.001). Higher educational level, early stage disease, and number of regional lymph nodes examined > 12 were independently associated with MSI testing, whereas older age (40-49), Hispanic ethnicity, non-private insurance status, non-academic/research facility, facility location, rectosigmoid/rectal tumor location, non-mucinous histology, unknown grade, non-receipt of definitive surgery were associated with underuse. Among 6,358 tested patients with known MSI status, 531 (8%) patients had MSI-H disease. Lower income, previous cancer history, and stage II disease were independently associated with MSI-H status, whereas older age (40-49), female sex, advanced comorbidity, non-metropolitan facility status, facility location, distal tumor location, non-mucinous histology, unknown/lower tumor grade, and non-receipt of chemotherapy were inversely associated with MSI-H status. Conclusions: Despite national guidelines, significant underuse of routine MSI testing in young patients diagnosed with colorectal cancer persists. Interventions are warranted to improve adherence to guideline-based care in these patients, particularly among those at increased risk of MSI-H disease. [Table: see text]
What about the guys? An assessment of gender differences in hereditary colorectal cancer testing.
Authors: Espenschied Carin , Pepper Jonathan , McFarland Rachel E. 
Published: March 2017

537 Background: Approximately 5-10% of colorectal cancer (CRC) is due to hereditary causes. Identification of an inherited cause may impact surgical and treatment decisions for CRC patients and may identify increased risks for other cancers that warrant increased screening and/or risk reduction measures. Men have testing for hereditary breast and ovarian cancer less often than women, even though these genes may also cause increased risk for cancer in men and men are as likely as women to carry mutations in these genes and pass them onto their children. We aimed to explore whether similar gender differences exist related to testing for hereditary CRC. Methods: We retrospectively reviewed clinical data and test results from consecutive CRC cases, who had a multi-gene panel with 13-49 genes at our laboratory, between March 2012 and June 2016. Statistical comparisons between males and females were conducted using Fisher’s exact test. Results: Of CRC cases (n = 7142), 61.1% were female and 12.8% were positive for mutation or likely pathogenic variant. Average age of CRC onset for men was 47.2, and for women was 49.5. Women with CRC before age 20 had the highest mutation rate (31.8%), but men were more likely to test positive than women overall (14.1% vs 12.0%, p = 1.1e-2). Mutations were most frequent in the same three genes for both men and women, but in different orders: MLH1, CHEK2, and MSH2 for males and CHEK2, MSH2, and MLH1 for females. The only genes with significant differences in mutation rates between men and women were MLH1 (3.2% vs 1.5%, p = 2.0e-6) and MSH6(1.7% vs 0.8%, p = 3.0e-3). Conclusions: Hereditary CRC is expected to affect men and women equally. In our cohort, however, the majority of individuals tested were women, while men were more likely to test positive. Possible explanations include smaller sample size and earlier age of onset in men, perceptions of referring clinicians, and different levels of interest in genetic counseling and testing between male and female patients. These data highlight an important opportunity for educating and identifying more men with hereditary CRC who may benefit from genetic information. Further studies are needed to confirm these results and explore reasons for the differences.
Changes in platelet/lymphocyte ratio after CRT to predict oncologic outcome in patients with rectal cancer.
Authors: Lee In Hee , Hwang Soyoon , Baek Dong Won , Lee Soo Jung , Kang Byung Woog , Chae Yee Soo , Kim Hye Jin , Kim Jong Gwang 
Published: March 2017

539 Background: Previous studies have shown that the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are potential prognostic markers in many different cancers. However, the relationship between the changes of these ratios after concurrent chemoradiotherapy (CRT) and clinical outcome in rectal cancer patients was not reported yet. Accordingly, the aim of this study was to evaluate the prognostic relevance of the changes in NLR and PLR in patients with rectal cancer who treated with CRT followed by surgery. Methods: We enrolled 296 patients with histologically confirmed rectal adenocarcinoma who have received preoperative CRT at Kyungpook National University Medical Center (Daegu, Korea) between January 2006 and December 2015. We analyzed full hematological data both pre CRT (initial visit) and post CRT (before surgery) and oncologic outcomes including pathologic complete response (pCR), relapse-free survival (RFS), and overall survival (OS). An NLR≥5 and PLR ≥235 were considered to cut-off values according to previous studies. The ratio of change in NLR and PLR were calculated by following formula: ratio of change in NLR = (post NLR-pre NLR)/ pre NLR *100, ratio of change in PLR = (post PLR-pre PLR)/pre PLR *100. Significant cut-off value for ratio of change in NLR and PLR were calculated by simulation analysis (SAS Institute Japan, Tokyo, Japan). Results: Of the 296 patients, the majority were male (69.6%), with a median age of 59.1 years (range 25~88). Of these patients, 41 (13.9%) obtained pCR after CRT. Sixty-one patients (20.6%) had high PLR before CRT, which significantly correlated with pCR (p = 0.014) and RFS (p = 0.026), while high NLR was associated with pCR (p = 0.012) only. The optimal cut-off value for the ratio of change in PLR was 200 for RFS. The patients who had relatively higher ratio of change in PLR (ratio of change in PLR ≥ 200) showed better RFS compared to lower ratio of change (ratio of change in PLR < 200) (3-year RFS 90.9% vs. 69.7%, p = 0.05). Changes in NLR did not correlate with oncologic outcomes. Conclusions: Changes in platelet/lymphocyte ratio could also be a potential clinical biomarker in predicting oncologic outcome in rectal cancer patients treated with preoperative CRT.
Topographical incidence and survival analysis of gastrointestinal tract cancer in adolescent and young adults compared with older adults in the United States.
Authors: Levine Oren Hannun , Zbuk Kevin M. , Bleyer Archie 
Published: March 2017

545 Background: Adolescent and young adults (AYAs) who develop gastrointestinal (GI) cancer are rare and have unique needs. There is limited literature defining the epidemiology of malignant disease across the entire GI tract in this age group. The objective of this study was to explore incidence and survival trends in the United States for all types of GI cancers in AYAs compared to older adults. Methods: We analyzed all incident cases of GI tract cancers in AYAs aged 15 to 39 and older adults aged 40 to 64 in the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) program 2000-2013 database. For each age group and sex, we determined incidence rates, temporal changes in incidence, overall prognosis and stage-based prognosis for all primary tumor sites throughout the GI tract. Results: The incidence of colorectal cancer (CRC) distal to the splenic flexure has increased in AYAs whereas all CRC has decreased in older adults. We found that compared to older adults, AYAs have experienced better survival for most cancers arising at or proximal to the cecum regardless of stage. Conversely, more distal tumors were associated with worse prognosis in AYAs for regional or distant-stage disease. For distal CRC, the greatest age-based discrepancy in survival occurred for regional disease. Despite decreasing incidence of anal cancer in AYAs, young females have experienced worse survival with this disease compared to AYA males and older adults. Conclusions: We have identified age and gender-based disparities in survival relating to GI cancers. Rising rates of distal CRC in AYAs highlight the need for further exploration of molecular mechanisms and potential therapeutic targets for these malignancies which are also associated with worse survival in the younger population.
Vitamin D levels and its relationship with successful completion of adjuvant chemotherapy and improved survival in early stage colorectal cancer patients.
Authors: Tariq Khurram Bilal , Gopal Aaron , Nayak-Kapoor Asha 
Published: March 2017

549 Background: Vitamin D deficiency is associated with increased colorectal cancer (CRC) risk and decreased colorectal cancer survival. The purpose of this study was to determine the effect of colorectal cancer adjuvant treatment on the vitamin D status in CRC. Methods: 102 patients at the GCC with Stage I-III CRC were selected between 2009 -2011. A retrospective analyses of baseline vitamin D in these patients was made to determine if vitamin D level predicts survival. Those patients who have received neoadjuvant treatment were excluded. Only patients who had a baseline vitamin D level drawn at baseline were included. Vitamin D sufficiency was defined as serum level of 30ng/ml or greater, insufficiency as 20 to 29ng/ml and deficiency as less than 20ng/ml. Results: Mean age of the patients was 76.4 years. 45 % were Stage I , 35% comprised Stage II and 25% were Stage III. 25OHD Level was insufficient in 85% and deficient in 10% and sufficient in only 5% of the patients. In the patients who received chemotherapy (45% ), those with sufficient vitamin D levels had a statistically longer survival than those with deficient levels (p<0.002). Also the patients with sufficient levels, they were more likely to complete the 6 months of chemotherapy than those with deficient levels (p<0.006). The median Vitamin D level for all 102 patients was 22.8ng/ml. Patients with sufficient vitamin D levels were more likely to have lower body mass index (p<0.01). There was no correlation between race and level of vitamin D. Patients with a sufficient vitamin D Level (25 patients), had a survival which was significantly more than those with deficient levels (p<0.001). Patients with sufficient vitamin D levels were more likely to have stage I and II disease than stage III ( p <0.04). For each stage of CRC, patients with sufficient vitaminD levels had a better overall survival than those with deficient vitamin D level(p<0.01). Conclusions: Patients with sufficient levels of vitamin D are associated with better overall survival in early stage CRC. Whether aggressive vitamin D repletion would improve the outcome in vitamin D deficient CRC patients remains unknown.
Association of PIK3CA H1047R and STK11 F354L mutations with response to neoadjuvant chemoradiotherapy and survival in esophageal cancer.
Authors: Hsu Po Kuei , Chou Teh-Ying ,   Lihpao Life Science Corp.
Published: March 2017

55 Background: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer. However, its efficacy is limited in non-responders and there is no reliable clinical parameter in predicting treatment response. We aim to identify chemoradiation-resistant cancers and avoid unnecessary treatments in non-responders with mutation analysis. Methods: Genomic DNA was extracted from diagnostic biopsy specimens of 20 patients (10 with good and 10 with poor response) with esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and esophagectomy. Using next-generation sequencing, we screened mutation hotspots in 46 cancer-related genes (Ion AmpliSeq Cancer Panel). Potential predictive genetic variations were validated in another cohort of patients. Chemoradiotherapy response was based on pathological evaluation of surgically resected specimens. The prognostic significance of genetic variations was evaluated with Cox regression survival analysis. Results: In the first cohort, we discovered PIK3CA H1047R and STK11 F354L as potential targets to predict chemoradiation resistance. Next, we investigate these genetic variations in another 54 patients. Altogether, 18.9% (14/74) and 6.8% (5/74) of patients had PIK3CA H1047R and STK11 F354L, respectively. In patients with poor response to chemoradiotherapy, 45.8% (11/24) had either PIK3CA H1047R or STK11 F354L; compared to 12.0% (6/50) in patients with good response ( p = 0.001). In other words, 64.7% of patients with either one genetic variation responded poorly to chemoradiotherapy. In survival analysis, the 5-yr survival rates were 7.7% and 43.7% in patients with either one genetic variation and those without, respectively ( p = 0.003). In multivariable analysis, the presence of either one genetic variation was a significant prognostic factor for overall survival (Hazard ratio: 2.43, 95% confidence interval: 1.195-4.944, p= 0.014). Conclusions: PIK3CA H1047R and STK11 F354L mutations are associated with poor response to neoadjuvant chemoradiotherapy and worse prognosis in esophageal cancer. It may potentially be biomarkers to guide treatment decisions.
Cardiotoxicity in Chinese cancer patients treated with 5-fluorouracil or capecitabine: A multicenter prospective observational study.
Authors: Chen Gong , Peng Jianjun , Dong Chao , Qiu Meng , Wang Chang , Li Hua wei , Yu Hao , Zhang Min , Zhao Qun , Zhu Bo , Zhang Jun , Li Wenliang , Wang Fenghua , Wu Qiong , Yuan Ying , Zhou Wen-hao 
Published: March 2017

553 Background: Although the cardiotoxicity associated with 5-Fluorouracil (5-FU) or capecitabine administration has been well addressed in literature, there is still a lack of data from prospective clinical trials in Chinese population. The aim of this study was to evaluate the incidence, manifestations and predisposing factors for the cardiotoxicity in Chinese cancer patients treated 5-FU or capecitabine. Methods: A multicenter prospective observational study was performed in 527 patients with various solid tumors from 12 cancer centers in china . Of these patients, 196 received 5-FU-based and 331 received oral capecitabine-based chemotherapy as either first-line or adjuvant therapy. Outcome measures including electrocardiogram(ECG), myocardial enzymes, cardiac troponin(cTn), BNP and echocardio- graphy(UCG) etc. Univariate analysis and the logistic regression were performed for subgroup analysis and identification of the significant independent variables that are associated with cardiotoxicity of both agents. Results: In total, 161 of 527 patients (30.55%) experienced cardiotoxicity. The incidence of cardiotoxicity was 33.84% (112 out of 331) in the capecitabine-treated population, significantly higher than 25 %( 49 out of 196) in the 5-FU treated population (P = 0.0042). 110 out of 527 patients (20.87%) suffered arrhythmia, 105/527 (19.92%) developed ischemic changes, while 20/527(3.80%) heart failure and 6/527 (1.14%) myocardial infarction only. Among the factors evaluated with univariate analysis and the logistic regression, a history of cardiac disease, chemotherapy agent, duration of treatment and hypertension were significant with cardiotoxicity occurrence. The odds ratio were 15.447(with a history of cardiac history vs without), 2.118 (Capecitabine group vs 5-FU group), 1.079(5-8 vs 1-4 cycles) and 1.698 (with hypertension vs without) respectively. Conclusions: Cardiotoxicity induced by fluoropyrimidines in Chinese population may be underestimated in clinical practice.Possible risk factors are duration of treatment, chemotherapy agents, preexisting cardiac disease and hypertension.
The efficacy of aprepitant for the patients receiving FOLFOXIRI and FOLFIRINOX: A phase II study.
Authors: Hiroki Yukami , Terazawa Tetsuji , Miyamoto Takahiro , Asaishi Ken , Shimamoto Fukutaro , Kuwakado Shin , Nishitani Hitoshi , Kii Takayuki , Goto Masahiro , Higuchi Kazuhide , Sanomura Makoto 
Published: March 2017

560 Background: Aprepitant (APR) showed the efficacy for the prevention of chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic chemotherapy. The combination chemotherapies of moderately emetoegnic agents of oxaliplatin and irinotecan are classified as moderately emetogenic risk according to ASCO guideline, but showed severe vomiting and nausea. Methods: This phase II trial evaluated the efficacy of APR (day1;125mg, day2-3; 80mg) in patients receiving mFOLFOXIRI(oxaliplatin; 85 mg/m2, irinotecan; 150 mg/m2, leucovorin; 200 mg/m2, 5-FU infusional; 2400 mg/m2/46hour, every 2 weeks) and FOLFIRINOX (oxaliplatin; 85 mg/m2, irinotecan; 180 mg/m2, leucovorin;200 mg/m2, 5-FU bolus; 400 mg/m2, 5-FU infusional; 2400 mg/m2/46hour, every 2weeks). The primary objective was the complete vomiting inhibitation rate (CVIR) during first cycle. The null hypothesis and expectation of CVIR were 30% and 60% (one-sided α = 0.05, β = 1.0), so 23 patients were needed. CVIR was assessed according to MAT (MASCC Antiemesis Tool). Results: 25 patients were enrolled. The characteristics were as follows; median age (range), 65 (39-71); male/ female, 16/9; PS0/ 1, 11/ 14; mFOLFOXIRI/ FOLFIRINOX, 20/ 5; BMI < 22/ 22 or more, 14/ 11; history of alcohol yes/ no, 11/ 14. The CVIR was 92% (95%CI: 74-99) and complete response (no vomiting and no rescue medication use) rate was 72% (95%CI: 51-88%). The toxicities (all grade/ grade 3 or 4) were as follows; nausea, 17/ 2; vomiting, 3/ 0; fatigue, 16/ 2; constipation, 6/ 0. Conclusions: APR was effective for CVIR. Further prevention of nausea is expected.