bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant nivolumab plus concurrent chemoradiation in stage II/III esophageal/gastroesophageal junction cancer.
Authors: Kelly Ronan Joseph , Smith Kellie Nicole , Anagnostou Valsamo , Thompson Elizabeth , Hales Russell K. , Battafarano Richard J. James , Voong K Ranh , Yang Stephen C. , Feliciano Josephine Louella , Shin Eun Ji , Hu Chen , El Asmar Margueritta , Chan Hok Yee , Velculescu Victor E. , Sears Cynthia , Pardoll Drew M. , Amjad Ali Imran , Guerrieri Patrizia , Jobe Blair Anderson , Zaidi Ali Hussainy 
Published: January 2019

142 Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (E/GEJ) cancer results in a complete pathologic response rate (pCR) of 20-30%. The appearance of favorable microenvironment features (enhanced tumor infiltrating lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest early stage tumors may respond favorably to immune based therapy and in particular to PD-1 blockade when combined with cRT. Methods: In this pilot study, we administered 2 cycles of induction nivolumab (N) q2 weekly prior to standard of care carboplatin/paclitaxel/radiation plus 3 additional cycles of N on week 1, 3 and 5 of cRT. An Ivor-Lewis esophagectomy (E/MIE) was performed 6-10 weeks after the last IO dose. The primary endpoints of the study were safety and feasibility. We also evaluated the pCR, survival and temporal dynamics of T cell receptor clonotypes. Results: Between August 2017 and July 2018, 16 patients were enrolled on study. Induction N and neoadjuvant N combined with cRT in stage II/III E/GEJ cancers has an acceptable toxicity profile and was not associated with delays in surgery. Toxicities of note include steroid responsive grade 3 dermatitis (1/16), grade 3 hepatitis (1/16) and no cases of pneumonitis. To date, 10 patients with E adenocarcinoma have had an E/MIE and the pCR is 4/10 (40%). T cell receptor sequencing of the tumor bed and serial peripheral blood T cells revealed high peripheral representation of tumor-associated T cells. In one notable case, the highest-frequency intratumoral clone decreased in frequency in the peripheral blood upon treatment and rapidly increased after surgical resection, potentially signifying trafficking to the tumor site. Conclusions: Induction N and N combined with cRT has limited side-effects, did not result in surgical delay or enhanced surgical morbidity/mortality and induced a pCR of 40% in stage II/III E/GEJ cancers. Additional efficacy data on the full cohort and more in depth correlative studies will be presented to validate systemic activation of anti-tumor T cell responses. Clinical trial information: NCT03044613.
Impact of antibiotic use on response to treatment with immune checkpoint inhibitors.
Authors: Khan Uqba , Peña Cristian , Brouwer Julianna , Hoffman Katherine , Choudhury Arindam Roy , Zhang Chao , Thakkar Prashant , Betel Doron , Sarkar Sandipto , Sonnenberg Gregory , Saxena Ashish , Shah Manish A. 
Published: January 2019

143 Background: There is an emerging evidence that the gut microbiome may influence anti-tumor immune response during treatment with checkpoint inhibitors (CPIs). A number of factors can cause gut microbiome dysbiosis including the use of antibiotics (ABX). We hypothesized that the use of ABX during immunotherapy can adversely affect the efficacy of CPIs. We explored the prevalence of ABX use amongst patients (pts) using CPIs, and whether the use of ABX influences the response to CPIs. Methods: We performed an institutional retrospective review of all the pts treated with CPIs from 2/2015-3/2018. A patient was considered to have used ABX if he or she was prescribed ABX within 6 months before or after, initiating CPIs. Statistical analysis was done using logistic regression with overall response rate (ORR) (CR, PR and SD) as the outcome. 9 separate analyses were done: one for each temporality (30 days, 60 days, 6 months) and use-order (before, after, neither) combination. Odds ratios for ORR as univariate analysis, and adjusted for age and sex; and adjusted for age, sex, and tumor type were calculated. Results: Out of 242 pts, 111 were lung, 36 bladder, 35 renal, 16 gastrointestinal and 44 other cancers. 50% (121) pts received nivolumab, 28% (68) pembrolizumab and 21% (52) atezolizumab. 75%, 46% and 32% of the pts received ABX within 6 months, 60 days and 30 days of starting CPIs. Only ABX use in the first 30- or 60-days following CPI initiation was associated with inferior ORR (OR 0.42 [95% CI:0.23,0.76] p = 0.005 for 60-days). ABX use prior to initiation of CPI at any time point, or ABX use in the first 6 months of CPI use did not impact CPI efficacy, Table 1. Conclusions: ABX use within the first 60 days of starting CPI therapy is prevalent (32%). This study suggests that the use of ABX within 60 days following initiation of CPIs significantly negatively impacts the ORR. Unnecessary usage of ABX should be avoided, especially during the early phase of starting CPIs. [Table: see text]
Timing after neoadjuvant therapy predicts mortality in patients undergoing esophagectomy.
Authors: Maramara Taylor , Huston Jamie , Shridhar Ravi , Meredith Kenneth L 
Published: January 2019

157 Background: Neoadjuvant therapy (NT) prior to esophagectomy has dramatically improved survival in patients with esophageal cancer. Currently, most surgeons will allow 6-12 weeks after NT prior to recommending esophagectomy. Given that complete pathologic response (pCR) correlates to an improvement in survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded NT-surgery timing is not currently well understood. Methods: Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent NT followed by esophagectomy. Patients were divided into 4 time intervals: < 6 wks, 6-12 wks, 3-6 mo, and > 6 mo. Mann-Whitney U, Kruskal Wallis, and Pearson’s Chi-square test were used as appropriate. Survival analyses were performed using the Kaplan-Meier method and p < 0.05 was considered significant. Results: We identified 9,256 patients who received NT followed by esophagectomy. There were 8,053 (87%) adenocarcinomas and N = 1203 (13%) squamous cell carcinomas. 7,858 (84.9%) were male and 1,398 (15.1%) female with a median age was 62 (24-88). R0 resections decreased as the NT-Surgery interval increased: < 6 wks, 6-12 wks, 2-6 mos, and > 6 mos at 93%, 94.1%, 94.1%, and 86.2% respectfully p = 0.004. Additionally, the median lymph nodes harvested decreased as timing increased: 12, 12, 10, and 9 p < 0.001 and the median nodes positive decreased as timing increased 1.5, 1.3, 1.1, and 2.4 p = 0.01. The complete response rates increased as timing increased 15.5%, 20.1%, 22.7%, and 25.8% p < 0.001. However, this improvement in pCR did not translate into an increase in median survival: < 6 wks 40.9 mos, 6-12 weeks 38.5 mos, 3-6 mos 34.8 mos, and > 6 mos 39.8 mos of survival, p = 0.94 90-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, 9.4%, and 16.0%, respectively p = 0.001. Conclusions: Our data demonstrates that patients who have a prolonged NT- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a NT-surgery timing of 6-12 weeks should remain.
Which is the best procedure for the treatment of gastric cancer in the upper stomach?
Authors: Sato Reo , Tokunaga Masanori , Watanabe Masahiro , Sugita Shizuki , Tonouchi Akiko , Tanaka Yuri , Akimoto Eigo , Ono Takeshi , Kameyama Akira , Kaito Akio , Kinoshita Takahiro 
Published: January 2019

159 Background: The incidence of upper-third early gastric cancer (EGC) has been increasing in East Asia. Although total gastrectomy (TG) has been a standard treatment for upper-third EGC, proximal gastrectomy (PG) or distal gastrectomy (DG) can be indicated for some selected patients. Theoretically, the more we preserve stomach volume, the better postoperative quality of life will be. However, this issue is not fully investigated. The aim of this study was to clarify the most suitable procedure for upper-third EGC. Methods: This study included 187 patients who underwent TG (n = 20), PG (n = 138), or DG (n = 29) for cT1N0 upper-third gastric cancer between 2009 and August 2017. Surgical outcomes, including bodyweight change one year after the surgery, were retrospectively compared among surgical procedures. DG was generally selected if the distance between the esophagogastric junction (EGJ) and proximal margin of the tumor was more than 20 mm. PG was chosen if at least the distal half of the stomach could be preserved. Otherwise, TG was performed. Results: Background characteristics and proportion of laparoscopic approach were not different among the groups. The duration of surgery was not significantly different, but intraoperative blood losswas significantly less in DG than PG (19 vs. 39 g, p = 0.02). The incidence of Clavien-Dindo classification grade IIIa or more anastomosis-related complications was less frequent in DG (3.4%) than in PG (15.9%, p = 0.13) or TG (10%, p = 0.56), although the differences were not statistically significant. Albumin and hemoglobin levels one year after surgery were not significantly different among the groups. Bodyweight loss one year after surgery was less in DG (11.1%) than in PG (14.6%, p = 0.03) or TG (16.6%, p < 0.01). Conclusions: DG was a safe procedure with less bodyweight loss, and thus preservation of the EGJ should be considered for all patients with tumors at least 2 cm apart from the EGJ. If the distance between EGJ and tumor is less than 2 cm, PG or TG will be indicated. However, surgical outcomes between PG and TG in this study were not different, and therefore, further investigations including long term quality of life are necessary.
Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastroesophageal cancer.
Authors: Ma Lucy Xiaolu , Espin-Garcia Osvaldo , Lim Charles Henry , Sun Peiran , Jiang Di Maria , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Suzuki Chihiro , Chen Eric Xueyu , Liu Geoffrey , Swallow Carol Jane , Darling Gail Elizabeth , Wong Rebecca , Hafezi-Bakhtiari Sara , Conner James , Elimova Elena , Jang Raymond Woo-Jun 
Published: January 2019

164 Background: A microscopically positive (R1) resection margin following resection for gastroesophageal (GE) cancer has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. Methods: A retrospective analysis was performed for patients (pts) with GE cancer treated at the Princess Margaret Cancer Centre from 2006-2016. Electronic medical records of all pts with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. Results: We identified 78 GE cancer pts with an R1 resection. 11% had neoadjuvant chemotherapy, 14% chemoradiation (CRT), 75% surgery alone. 28% had involvement of the proximal margin, 13% distal, 56% radial, 3% had multiple positive margins. By the American Joint Committee on Cancer 7th edition classification, 88% had a pT3-4 tumour, 66% pN2-3 nodal involvement, 64% grade 3, 68% with lymphovascular invasion. 3% were pathological stage I, 21% stage II and 74% stage III. Adjuvant therapy was given in 46% of R1 pts (24% CRT, 18% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS for all pts was 12.6 months (95% CI 10.3-17.2). Site of first recurrence was 71% distant, 16% locoregional, 13% mixed. Median OS was 29.3 months (95% CI 22.9-50) for all pts. The 5 year survival rate was 23% (95% CI 12%-43%). There was no significant difference in RFS (log-rank test p= 0.63, adjusted p= 0.14) or OS (log-rank test p= 0.68, adjusted p= 0.65) regardless of adjuvant therapy. Conclusions: Most pts with positive margins after resection for GE cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one pt had reresection. The main failure pattern was distant recurrence, suggesting that pts being considered for adjuvant RT should be carefully selected. Further studies are required to determine factors to select pts with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.
The association of 5FU-based chemotherapy with pathological response or survival compared to carbo/taxol with locally advanced resectable esophageal cancer.
Authors: Al-Jumayli Mohammed , Abbasi Saqib , Kasi Anup , Saeed Anwaar 
Published: January 2019

165 Background: Neoadjuvant chemoradiation followed by esophagectomy is the standard of care in advanced EC. While 5FU based chemoradiation has been a common regimen in the past, its utilization has declined in recent years as the CROSS trial study regimen of carboplatin/paclitaxel has become widely adopted. A prospective evaluation of the CROSS regimen compared to the 5FU based regimen was never performed. The aim of this study is to report our institutional experience with these two chemotherapy regimens. To the best of our knowledge, this is the largest retrospective study comparing the two types of chemotherapy regimens. Methods: We performed an IRB-approved retrospective review of a prospectively maintained institutional cancer registry. EC patients who completed trimodality therapy with either carboplatin/paclitaxel or 5FU/platinum were identified and divided into groups based on their chemotherapy regimens. Multivariable logistic regression was used to analyze pathologic complete response (pCR) rates, while the Kaplan–Meier and Cox proportional hazards models were utilized to evaluate DFS and OS. Analytical models were adjusted for age, stage, radiation dose, histology sub-type, and time interval from completion of neoadjuvant therapy to surgery. Results: 224 patients treated between January of 2007 and July of 2017 were identified . Of this group, 139(62%) had received Carbo/Taxol, while 85 (37%) had received 5FU/platinum. There was no increase in the odds of pCR with 5FU based chemo compared to CROSS regimen (OR = 2.68, P = 0.671). Furthermore, the OS and DFS of 159 patients(80 5FU/platinum, 77 carbo/taxol) with median follow up of ~ 5 yrs were not statistically different with HR 1.08 (0.6-1.7) and P value 0.71. Conclusions: Neoadjuvant chemoradiation with 5FU/platinum in resectable EC is not associated with higher rates of pCR, DFS and OS compared to the CROSS regimen of carbo/taxol. Those findings will need to be validated in a larger cohort.
Impact of preoperative treatment with chemoradiotherapy or chemotherapy in patients with locally advanced or irresecable gastric cancer (LAGC).
Authors: Diaz Romero C , Calderillo Ruiz G , Herrera Marytere , Ruiz Garcia E , Lopez Basave H , Leon Takahashi A 
Published: January 2019

167 Background: The only curative treatment for gastric cancer remains surgery neoadjuvant chemoradiotherapy (NACRT) has shown decrease of staging and improve survival. La NACRT has been studied in esophagus cancer and Gastroesophagic Junction cancer but this trials did not include advanced gastric disease. The aim of our study was to investigate the role of Chemoradiotherapy (CTR) and chemotherapy (CT) in the treatment of LAGC. Methods: We retrospectively reviewed the medical records of 108 patients who were treated between December 2010 and January 2015, with preoperatory CRT or chemotherapy preoperatory (CT). Evaluating parameters of resectability, pathological response complete, prognostic with a 3-year follow-up. Results: 108 patients were analyzed, 61 man and 47 women, with median age 55 years, 83 (76.8%) with diffuse, 25 (23.2%) intestinal histology, however 83 patients (76.8%) had component of signet ring cells. Of the 108 patients, 41 (38%) received chemotherapy and 67 (62%) received CRT preoperative. R0 radical surgery was possible in 41 patients of which 24.3% (10/41) were in the group of CT and 46% (31/67) CRT group. Radiological progression was documented in 8 (19.5%) patients with CT and 11 (16.4%) with CRT. 7 patients were considered inoperable and 17 unresectable at the end of the preoperative treatment. The carcinomatosis was documented during the surgery in 11 and 12 patients in the CT or CRT group respectively. 10 patients developed complications gastrointestinal and hematologic to the treatment with CT and 23 patients with CRT, which 4 patients in CRT needed reoperation post-surgery. Any patient in the chemotherapy group reached complete pathologic response while of the CRT group achieved 5 complete pathological responses. Medium-3 years follow-up survival rate was 11% in the group treated with CT and 23% with CRT. Conclusions: Our revision showed a high rate of pathologic response and survival in patients with LAGC that received CRT preoperative followed by gastrectomy. On the other hand R0 resection has been reported to be a predictive factor for survival in this study were found more patients with resectable tumor after CRT preoperative.
Feasibility study of diet counseling (DC) with oral nutritional supplements (ONS) for advanced esophageal and gastric cancer during chemotherapy (CT) or chemoradiotherapy (CRT): First report of ONS compliance from a prospective randomized controlled clinical study (DiCON study).
Authors: Izawa Yukiko , Ichimura Takashi , Chin Keisho , Shinozaki Eiji , Takahari Daisuke , Suenaga Mitsukuni , Ogura Mariko , Wakatsuki Takeru , Osumi Hiroki , Nakayama Izuma , Mine Shinji , Hiki Naoki , Ishizuka Naoki , Yamaguchi Kensei 
Published: January 2019

17 Background: Most advanced esophageal and gastric cancer patients(pts) experience fatigue, anorexia, and may arise malnutrition and sarcopenia, for which effective treatment has not been established. Nutritional support especially protein supplementations may prevent loss of body mass related with malnutrition and sarcopenia. We therefore, conducted a prospective randomized study to explore compliance and the best available ONS intake for pts undergoing CT or CRT. Methods: Eligibility criteria included: chemo-naïve advanced gastric cancer or esophageal cancer; performance status (PS) of 0–1; pts who can eat more than as 50% as usual; age over 20 years. Pts were randomly allocated into four groups within each strata, i.e. esophageal or gastric cancer, Group A: Diet counseling (DC) only, Group B-1: DC and ONS 1 pack/day, Group B-2: DC and ONS 2 packs/day, and Group B-3: DC and ONS 3 packs/day. We use jelly type ONS which is easy to intake and include rich branched-chain amino acid. We assessed ONS compliance, the change of nutritional index (body weight, albumin, pre-albumin, and muscle mass), diet record (daily), and toxicity before CT or CRT and 14 days after administration of CT. Results: Among forty pts (11 in A, 11 in B-1,8 in B-2,10 in B-3) were enrolled from August 2017 to August 2018, median age was 64 years (range 46-81), median BMI was 20.6 (range 15-29), and 28 gastric cancer, 12 esophageal cancer. Median intake was 12 packs/2w (range 0-14), 15 packs/2w (3-28), 12 packs/2w (2-28), in B-1, B-2, and B-3 respectively. Mean compliance of ONS was 72.7%, 50.0% and 33.1%, in B-1, B-2, and B-3 respectively. There was a significant linear trend across the 3 groups (P = 0.0104). B-1 was significantly better than B-3 (P = 0.0270). There were no pts in group B-3 who could intake ONS for 14 consecutive days. Over 80% of pts in B-1 group were able to intake for 14 consecutive days. Conclusions: We found ONS 3 packs/day was clearly denied because of compliance. Choice of 1 or 2 packs/day should be determined by taking into account the total calories of foods. Clinical trial information: 000026705.
Impact of clostridium difficile infection on gastrointestinal malignancies.
Authors: Perimbeti Stuthi , Shrivastav Rishi , Pati Prateeth , Ward Kristine Marie , Styler Michael , Jain Maneesh Rajiv , Nandi Neilanjan 
Published: January 2019

170 Background: According to the Centers for Disease Control and Prevention, there were half a million documented cases with 83,000 re-infections and 29,000 deaths due to Clostridium Difficile Infection(CDI) in the year 2011. The influence of CDI on outcomes in gastrointestinal(GI) malignancies is not well described, although the incidence is known to be higher in this subgroup of patients. Methods: National Inpatient Sample 1999-2014 was analyzed to identify adult admissions (>18 years of age) using ICD-9-CM codes with a primary diagnosis of esophageal(EC), Gastric(GC), Colorectal(CRC), Small intestinal(SIC), Hepatobiliary(HCC) and Pancreatic(PC) cancers. ICD-9 code 00845 was used to stratify these for the presence of CDI. We performed Chi-Square test to determine the in-hospital mortality percentage, and Cox Proportional Hazard model to control for confounders and determine the Hazard Ratio(HR) of death within 30 days of admission during hospitalization in patients with and without CDI. Results: See table. Conclusions: Despite controlling for potential confounders, patients with GI cancers and CDI are at an increased risk of death compared to those without CDI. Taking the more detrimental effects of CDI in this subgroup of patients into consideration, healthcare professionals should strive to avoid the inordinate use of antibiotics and strictly maintain current guidelines designed to prevent spread. It may be prudent to treat these patients as severe CDI, even if current criteria are not met. More scientific research is warranted in analyzing the specific outcomes of CDI in GI cancer patients and if more aggressive therapy for CDI is warranted, considering the limitations of this study. [Table: see text]