bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence pattern and outcomes in T4 colon cancer: A single institution analysis.
Authors: Macari David , Kawak Samer , Hanna Lilian , Ezekwudo Daniel , Khoury John , Wasvary Harry , Jaiyesimi Ishmael A. 
Published: January 2019

706 Background: Patients with T4 colon adenocarcinoma have an increased risk of peritoneal recurrence due to direct seeding malignant cells. It has been theorized that adjuvant chemotherapy may not sterilize the peritoneal surface due to inadequate intraperitoneal concentration. We seek to further define the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. Methods: We reviewed records of 181 adults [median age 71 (22-97)] with T4 N0-3 colon adenocarcinoma at Beaumont Hospital, Michigan from May 2005 –Nov 2015. Baseline factors and data on follow up, metastasis, and survival were collected and analyzed. Results: Overall recurrence rates for N0, N1, and N2 were 27/85 (32%), 17/50 (34%), and 29/46 (63%) (p = 0.001). Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%) (p = 0.014). Multivariate analysis for distant recurrence was significant only for positive nodes with hazard ratio (HR) 3.3, 95% confidence interval (CI) 1.1-9.9. Multivariate analysis for increased risk of LR was significant for the following variables: perforation (HR 2.7, 95% CI 1.2 – 6.2), lymphovascular invasion (HR 2.7, 95% CI 1.1 – 6.7), positive nodes (HR 2.8, 95% CI 1.2 – 6.9), and positive margins (HR 5.0, 95% CI 2.1 – 12.1). Adjuvant chemotherapy did not decrease risk of LR (HR 0.6, 95% CI 0.3-1.2) or distant recurrence (HR 0.9, 95% CI 0.3-2.8). Multivariate analysis for overall survival revealed the following to be associated with increased risk of mortality: signet ring (HR 2.5, 95% CI 1.2-5.8), positive nodes (HR 2.3, 95% CI 1.2-4.4), positive margin (HR 2.8, 95% CI 1.4-5.8). Adjuvant chemotherapy was not associated with improved survival (HR 0.8, 95% CI 0.4-1.7). Recurrence was strongly associated with colon cancer-specific death with a p < 0.001. Conclusions: Adjuvant chemotherapy is standard of care for most T4 colon cancer patients, however, this data suggests there is no improvement in survival or other significant outcomes. We have identified several risk factors which predict increased risk of LR. This data suggests LR is frequent and not affected by systemic chemotherapy. Prospective trials are needed to reduce the substantial risk of LR in T4 colon cancer.
Effect of time between diagnosis and surgery in colorectal cancer patients on mortality.
Authors: Fangman Benjamin D , Beg Muhammad Shaalan , Sanjeevaiah Aravind , Araghizadeh Farshid , Scielzo Shannon , Kazmi Syed Mohammad Ali 
Published: January 2019

708 Background: Colorectal cancer is the fourth most common cancer diagnosed in the United States and accounts for > 50,000 deaths nationwide annually. With data showing that oncologic treatment at National Cancer Institute (NCI) designated comprehensive cancer centers improves outcomes in a variety of malignancies, understanding the drivers behind this is vital to help bring the world-class care being administered at comprehensive cancer centers to underserved populations across the U.S. One component of colorectal cancer care that has a paucity of data afforded to it is the effect of increased time from diagnosis to surgery on survival. Methods: Patients diagnosed with AJCC stage II or stage III colorectal cancer between 4/2011 and 11/2015 and either underwent surgery or adjuvant chemotherapy within the University of Texas Southwestern system were selected. Several pertinent data points were abstracted via the EMR including date of diagnosis, surgery, adjuvant chemotherapy, progression, and death. A retrospective analysis was performed on the abstracted data to determine if the number of days between diagnosis and surgery was correlated with increased survival. Spearman coefficients were calculated to determine correlations between the data. All tests were two-sided. Results: Out of 203 patients identified, 113 patients had complete data available and were included in the study. The average age at diagnosis was 62.6 and average follow-up time was 41.4 months. Median time to surgery was 21 days (25th percentile-75th percentile: 4 – 53 days). There was a significant negative correlation between days from diagnosis to surgery and mortality (Spearman’s r = -.392, p < .001). Survivors had a mean of 42.7 days from diagnosis to surgery (SD = 56.4) and nonsurvivors had a mean of 61.7 days (SD = 46.9). Conclusions: There was a significant negative correlation seen in days between diagnosis and surgery and survival during the study period, which indicates that early surgical intervention may be an underappreciated indicator of quality colorectal cancer care. Further research should be conducted to better understand the relationship between early surgical intervention and prognosis in limited-stage colorectal cancer.
Mortality and glycemic control among patients with gastric and esophageal cancer and diabetes mellitus.
Authors: Karlin Nina J. , Buras Matthew , Kosiorek Heidi E. , Verona Patricia M. , Cook Curtiss B. 
Published: January 2019

73 Background: This study evaluated the impact of diabetes mellitus (DM) on survival in gastric and esophageal cancer patients, and examined the impact of these cancers on glycemic control in DM. Methods: Patients with newly diagnosed gastric and esophageal cancers with DM (n = 92) were identified from the Institutional Cancer Registry and matched to 92 gastric and esophageal cancer patients without DM according to age, gender and year of cancer diagnosis (2006 to 2016). The electronic medical record provided information on DM and cancer therapies and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis using stratification for matched pairs. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose during the year following cancer diagnosis. Results: Mean age of the entire cohort was 68 years, 91% were white, 78% were men, and 53% had stage III/IV disease. Adenocarcinoma (79%) was the most common histologic type. BMI was significantly different between DM and non-DM patients (p = 0.006). Alcohol use at time of cancer diagnosis was more prevalent in non-DM patients vs. DM (p = 0.018). Among those with DM, mean HbA1c during the year following cancer diagnosis was 6.8%. Mean glucose was significantly different between DM and non-DM patients (149 mg/dL vs. 116 mg/dL, p < 0.001). For glucose, there was a significant interaction effect (p = 0.005) as DM patients demonstrated a decrease in glucose values over time compared to non-DM patients. Median follow-up time was 35 months. Three year OS was estimated at 46% (95% CI: 36-58%) for DM patients versus 52.0% (95% CI: 41-64%) in non-DM (p = 0.25). Hazard ratio (stratification for matched pairs) was 1.95 (95% CI: 1.14 – 3.43; p = 0.02). Three year PFS was estimated at 40% (95% CI: 31-53%) for DM patients versus 50% (95% CI: 40-63%) for non-DM patients (p = 0.12). Hazard ratio (stratification for matched pairs) was 1.74 (95% CI: 1.04-2.90; p = 0.03). Conclusions: Gastric and esophageal cancer and its treatment did not affect glycemic control. Risks of death and progression are greater in DM patients as compared to non-DM.
Evaluation of efficacy of nivolumab by baseline factors from ATTRACTION-2.
Authors: Kang Yoon-Koo , Satoh Taroh , Chao Yee , Kato Ken , Chung Hyun Cheol , Chen Jen-Shi , Muro Kei , Kang Won Ki , Yoshikawa Takaki , Oh Sang Cheul , Tamura Takao , Lee Keun-Wook , Morita Satoshi , Chen Li-Tzong , Boku Narikazu 
Published: January 2019

8 Background: Nivolumab (Nivo) has shown superior efficacy with manageable safety for G/GEJ cancer refractory to, or intolerant of, standard chemotherapy in phase 3 study (ATTRACTION-2). Subgroup analysis of OS according to baseline demographics and disease characteristics favored Nivo over placebo in all subgroups. However, about half of patients had early disease progression even after administration of Nivo. Here, we explored factors of patients who had early progression after administration of Nivo. Methods: A statistical random forest method, a type of machine learning method, was used to explore clinical factors that could contribute to early progression after Nivo. In this analysis, the outcome variable was 56-day PD rate and covariates were patients’ clinical background factors. Factors were explored by comparing Nivo and placebo arms in all subgroups, constructed with 1) every single factor; 2) every pair of factors coming from the covariates. Results: In a single factor extraction, hyponatremia was identified as the most highly contributing factor to early progression. Of 330 patients in the Nivo arm, 59 patients showed hyponatremia at the baseline. Importantly, in a pair factor extraction, the patient population with hyponatremia and any of high NLR (N = 31, 9.4%, cut off; second tertile), high neutrophil (N = 28, 8.5%, cut off; second tertile), PS1 (N = 50, 15.2%) or no prior use of ramucirumab (N = 55, 16.7%), were found as risk factors of early progression in Nivo. PFS-KM curves were almost overlapped between Nivo and placebo arms in these patients with any pair of these risk factors. Conclusions: Our exploratory analysis suggested that a patient population with both ‘poor general condition’ represented by hyponatremia and PS 1, and ‘inflammatory conditions’ represented by high NLR and/or high neutrophil count, would be potential risk factors associated with early progression. This needs further validation with other potential biomarkers in tumor tissue and additional studies. Additional analysis with biomarkers such as PD-L1 will be presented at the meeting. Clinical trial information: NCT02267343.
Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel in gastric cancer with severe peritoneal metastasis (JCOG1108/WJOG7312G).
Authors: Yamaguchi Kensei , Nakajima Takako Eguchi , Boku Narikazu , Hyodo Ichinosuke , Mizusawa Junki , Hara Hiroki , Nishina Tomohiro , Sakamoto Takeshi , Shitara Kohei , Shinozaki Katsunori , Katayama Hiroshi , Nakamura Shinichiro 
Published: January 2019

80 Background: Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients (pts) with severe peritoneal metastasis (PM) often cannot tolerate it. 5-fluorouracil (F), l-leucovorin (L) and paclitaxel (P) therapy (FLTAX) showed a promising activity in a feasibility study for such pts. We conducted a phase II/III (P-II/III) study comparing FLTAX vs FL. Methods: Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20–75 years; performance status (PS) 0–2; PM+; massive ascites and/or inadequate oral intake; no prior chemotherapy. Pts were randomly assigned to receive FL (F 600 mg/m2, L 250 mg/m2 on day1, 8, 15, 22, 29 and 36 q8w), or FLTAX (F 500 mg/m2, L 250 mg/m2, P 60 mg/m2 on day1, 8 and 15 q4w). In the P-II, decision to proceed to the P-III was made based on the median survival time (MST) in both arms and treatment success rate at week 8 with the threshold of 30% in the FLTAX. Primary endpoint of the P-III was overall survival. Results: A total of 101 pts (51 in FL and 50 in FLTAX) were enrolled to the P-II. Because of poor accrual, the protocol was amended for termination and the final analysis for the P-III was conducted. Treatment success rate at week 8 in FLTAX was 66.7% (95% confidence interval [CI] 51.6-79.6). MST was 6.1 M and 7.3 M for FL and FLTAX, respectively (HR 0.79; 80% CI 0.60-1.05; p = 0.14). MST was 2.5 M for FL and 5.1 M for FLTAX (HR 0.59; 95% CI 0.27-1.28) in pts with PS2 (n = 27); 6.5 M and 8.6 M, respectively (HR 1.02; 95% CI 0.62-1.68) in pts with PS0/1 (n = 74). Median progression-free survival was 1.9 M for FL and 5.4 M for FLTAX (HR 0.64; 95% CI, 0.43-0.96; p = 0.029). Common adverse events of grade ≥ 3 were neutropenia (FL 30.0%, FLTAX 20.8%), and anorexia (FL 47.1%, FLTAX 31.3%). Conclusions: Although this study could not show a survival benefit of FLTAX over FL for pts with severe PM, FLTAX would be an option with longer PFS and feasible toxicity, especially for pts with PS2. Clinical trial information: UMIN000010949.
Prognostic Nutritional Index as a predictive factor of survival in patients with gastric cancer in a Mexican population.
Authors: Herrera Marytere , Miranda Arturo , Villalobos Peña Fernando Javier , LYRA-GONZALEZ IVAN , Caderillo-Ruiz German , Diaz Dr. Consuelo , Ruiz Garcia Erika 
Published: January 2019

85 Background: Gastric cancer is a health problem that is gaining great relevance because despite the multidisciplinary treatment the clinical outcomes are not encouraging; with a diversified prognosis, considering that the results are not only influenced by tumor properties, but also by the patient's condition in an integral way, especially by the nutritional and immunological state. In this study we studied the prognostic nutritionalindex (PNI) as predictive value of survival in patients with gastric cancer. Methods: This is a observational study, 251 patients with diagnosis of gastric adenocarcinoma with locally advanced disease (confirmed by computed tomography (CT)) were analyzed from January 2010 to June 2016. Patients with locally advanced disease confirmed by laparoscopy were taken to radical surgery. Those patients who were taken to laparoscopy and who have been documented metastatic disease, were treated only in a palliative form (chemotherapy, radiotherapy, palliative care). Results: In the analysis of survival through the curves of Kaplan-Meier, and the test log-rank, it was found that patients with a larger tumor size pathological (PT) (3/4/unclassifiable vs 1/2) had an average survival of 25.5 versus 55.5 months (P = < 0.0001). With advanced pathological stages (EP) (III/IV/non-classifiable vs. complete pathological response/I/II) reaching a survival average of 20.4 versus 59.1 months (P = < 0.0001). In the multivariate analysis, it was found that the EP (Hazard radio [HR]: 1.54, confidence interval 95% [CI]: 1.323-1.810, p = < 0.0001) and having received adjuvant chemotherapy (HR: 0332, CI 95%: 0.217-0.508, p = < 0.0001), were independently associated with the overall survival. Conclusions: This study demonstrates that low levels of PNI are associated with advanced diseases and, therefore, worse prognosis, with a tendency towards a decrease in overall survival.
Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy.
Authors: Jo Ik Hyun , Kim Yeon Ji , Chung Woo Chul 
Published: January 2019

9 Background: The relationship between polymorphisms in vascular endothelial growth factor (VEGF) and gastric cancer is still inconclusive. We investigated whether there is an association between VEGF genetic polymorphisms and risk of gastric cancer, and evaluated the recurrence of advanced gastric cancer after curative resection with adjuvant chemotherapy according to VEGF genetic polymorphisms. Methods: The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene (+936C > T, -634G > C, -2578C > A, +1612G > A) were evaluated. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A total of 151 patients with gastric cancer were enrolled, and the control group consisted of 413 individuals with esophago-gastroduodenoscopy who were randomly selected through health screening. All of the enrolled patients had curative resections with completion of adjuvant capecitabine and oxaliplatin combination chemotherapy and the initial metastatic cases were excluded. During the regular follow-up protocol, the episodes of the recurrence were documented and the specific genotype and allelic frequencies were evaluated. Results: As for the cancer risk, there were no significant differences in specific genotypes and allelic frequencies. The mean follow-up period was 28.82 ± 30.92 (12 ~ 72) months and the recurrence rate was 28.3%. In the patients carrying the 936-C allele, the recurrence rate of gastric cancer was high ( P = 0.02). Disease-free interval was significantly different between the patients carrying the 936-CC and 936-CT/TT genotype ( P = 0.02). Conclusions: VEGF +936 C > T genetic polymorphism is associated with poor prognosis, but not risk of gastric cancer. In the patients carrying the 936-C allele, more potent adjuvant treatment would be considered.
Downstaging and survival after neoadjuvant approaches to gastroesophageal junction adenocarcinoma.
Authors: Xiang Michael H. , Chang Daniel Tandel , Heestand Gregory M. , Pollom Erqi L. 
Published: January 2019

92 Background: Outcomes after neoadjuvant chemoradiation (NACRT) versus chemotherapy alone (NAC) in gastroesophageal junction (GEJ) adenocarcinoma are unclear, as such tumors can be treated with equipoise using either approach. Methods: We included patients in the National Cancer Database with non-metastatic T2-4 or N1-3 GEJ adenocarcinoma who underwent definitive surgery within 6 months of diagnosis and NAC or NACRT. Overall survival (OS) was compared using the Kaplan-Meier method and logrank test. Multivariable logistic and Cox regressions were used to obtain odds and hazard ratios (OR, HR) adjusted for age, comorbidity, and other patient and tumor characteristics. Results: We identified 2,362 patients treated with NACRT and 658 patients treated with NAC. Median follow-up was 3.9 years. OS modestly favored NAC compared to NACRT (54% vs 51% at 3 years, P = 0.05; adjusted HR 0.86, P = 0.01). Further analysis stratified by the extent of pathological downstaging revealed large separations in the survival curves for both NAC and NACRT according to pathological response (complete, partial/mixed, or none; see table). Patients with no response did equally poorly after either preoperative regimen. NAC was significantly less likely to produce any response than NACRT (adjusted OR 0.62, P < 0.0001). Since NACRT had increased downstaging but not survival, we analyzed use of adjuvant chemotherapy (AC). AC was used significantly less after NACRT than after NAC ( P < 0.0001) (see table). In patients with residual disease in both tumor and lymph nodes, AC was associated with increased OS (47% vs 39% at 3 years, P = 0.05; adjusted HR 0.81, P = 0.07) after NACRT, but not after NAC. Conclusions: NACRT had superior pathological downstaging compared to NAC, but was not associated with increased OS. Adjuvant chemotherapy is relatively underused after NACRT and warrants further study as a risk-adapted means to improve survival, especially in patients with larger burden of residual disease. [Table: see text]
Anlotinib in chemotherapy-refractory metastatic esophageal squamous cell carcinoma (ESCC): A randomized, double-blind, multicenter phase II trial.
Authors: Huang Jing , Xiao Juxiang , Fang Wentao , Lu Ping , Fan Qingxia , Shu Yongqian , Feng Ji Feng , Zhang Shu , Ba Yi , Liu Ying , Bai Chunmei , Bai Yu-Xian , Tang Yong , Song Yan , He Jie 
Published: January 2019

95 Background: The treatment option for ESCC patients (pts) progressing after chemotherapy is still uncertain. Anlotinib is a multi-target tyrosine kinase inhibitor involved in tumor angiogenesis and growth, such as vascular endothelia growth factor receptor (VEGFR) 2/3, etc. Methods: Eligible pts were advanced ESCC who had progressed after platinum or taxane containing chemotherapy. Between January 6, 2016 and May 22, 2018, a total of 165 pts from 13 centers in China were randomly assigned (in a 2:1 ratio) to anlotinib arm (n=110), and placebo arm (n=55). Pts were given anlotinib (12 mg/day) or placebo orally from day 1 to day 14 in a 21-day cycle until disease progression or had unacceptable toxic effects. The primary end point was progression-free survival (PFS). Results: Median PFS was 3.0 months with anlotinib and 1.4 months with placebo (HR 0.5, 95% CI, 0.3-0.7; P<0.0001). Complete response occured in 2 pts with anlotinib and 0 pt with placebo. The objective response rates were 7% in the anlotinib group and 4% in the placebo group (P=0.498), and the disease control rates (DCR) were 64% and 18%, respectively (P<0.0001). In anlotinib arm, median duration of response was 5.8 months (range, 3.1-19.7+). Grade 3/4 treatment-related adverse events (TRAE) were reported in 36.7% and 11.0% of the two group pts, and grade 5 TRAE were 2.8% and 0%, respectively. The most common grade 3/4 TRAE (>5%) in anlotinib arm were hypertension (15.6%) and loss of appetite (5.5%). Median overall survival were similar between the groups (6.1 months vs 7.2 months; HR 1.2, 95%CI 0.8-1.8, P=0.4261). The ratio of pts received post study treatments was 41.2% (40/97) in anlotinib arm and 72.7% (40/55) in placebo arm (P=0.0002), including chemotherapy (23.7% vs 54.6%), PD-1 inhibitors (4.1% vs 11.0%), and Apatinib, a VEGFR inhibitor, (10.3% vs 20.0%), etc. Conclusions: In pretreated advanced ESCC pts, anlotinib significantly improved PFS and DCR compared with placebo, with a manageable safety profile. Clinical trial information: NCT02649361.
A phase Ib/II open label study of IMU-131 HER2/Neu peptide vaccine plus cisplatin and either 5-fluorouracil or capecitabine chemotherapy in patients with HER2/Neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction.
Authors: Wiedermann Ursula , Good Anthony J , Garner-Spitzer Erika , Chao Yee , Bulat Iurie , Dechaphunkul Arunee , Arpornwirat Wichit , Charoentum Chaiyut , Yen Chia-Jui , Yau Thomas Cheung , Maglakelidze Marina , Tanasanvimon Suebpong , Maneechavakajorn Jedzada , Sookprasert Aumkhae , Bai Li-Yuan , Chou Wen-Chi , Ungtrakul Teerapat , Chong Leslie , Ede Nick 
Published: January 2019

TPS176 Background: Gastric cancer is the 5th most frequently diagnosed cancer and the 3rd leading cause of cancer deaths. HER2/neu is overexpressed in 15% to 25% of patients with gastric cancer and associated with a poor prognosis. Monoclonal antibodies against HER2/neu have been shown to be effective but alternative treatments are needed due to cost and global availability issues. IMU-131 is a B-cell peptide vaccine composed of 3 B cell epitopes derived from the extracellular domain of HER2/neu. Polyclonal antibodies against IMU-131 peptides binding 3 separate regions (DIII, IV) of HER2/neu have been shown to elicit antitumor activity in vitro and a phase I study demonstrated safety and immunogenicity in Her-2 +/++ metastatic breast cancer patients. Fusion of the single peptides into a hybrid peptide conjugated to CRM197 in conjunction with the adjuvant Montanide (P467-CRM-Montanide) improved formulation and stability of the vaccine. With the present Phase 1b/2 trial performed in patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma, we hypothesized that administration of IMU-131 in addition to chemotherapy is safe and immunogenic, and will prolong survival and may delay tumor progression and/or reduce tumor burden. Methods: This study is an international open-label multicenter study performed in 16 Asian and Eastern European sites with a maximum of 18 patients enrolled in Phase 1b. This dose escalation study is designed to assess safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. Each patient is administered three injections of IMU-131, at a single dose level on Days 0, 14, and 35, accompanied by chemotherapy cycles of cisplatin and 5-fluorouracil or capecitabine every 21 days. The RP2D will be evaluated in the dose expansion Phase 2 study with 68 patients being enrolled. Results: The study is ongoing with the completion of the phase 1b portion in 4Q18. Conclusions: No conclusions can be drawn at this time. Clinical trial information: NCT02795988.