bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of metabolic syndrome and fatty liver in gastric cancer survivors: A propensity score-matched analysis.
Authors: Park Hyojin 
Published: January 2022

266 Background: With the recent development in cancer treatments, the number of cancer survivors is rapidly increasing. The aim of this study was to investigate the prevalence and risk of metabolic syndrome and fatty liver in GC survivors compared with that in non-cancer (NC) subjects. We also analysed the risk for metabolic dysfunction-associated fatty liver disease (MAFLD)8 in GC survivors compared with that in NC subjects. Methods: In this cross-sectional study, participants who visited Gangnam Severance Hospital from 2014 to 2019 for health check-ups were enrolled. After age- and sex-matched 1:4 propensity score matching, 119 GC survivors and 476 NC subjects were included. GC survivors were divided into operated gastric cancer survivors (OpGC) (n = 95) and non-operated survivors (non-OpGC) (n = 24). MetS was diagnosed by metabolic components and FL was assessed by ultrasonography. Results: MetS was observed in 21.0% of GC survivors and 30.5% of NC subjects, and in 13.7% of OpGC survivors and 50.0% of non-OpGC survivors. FL was observed in 25.2% of GC survivors and 37.6% of NC subjects, and in 21.1% of OpGC survivors and 41.7% of non-OpGC survivors. After adjusting for age, sex, MetS risk was significantly lower in OpGC survivors (odds ratio [OR] = 0.377, 95% confidence interval [CI]: 0.200-0.711, P = 0.003). FL risk was significantly lower in OpGC survivors (OR = 0.467, 95% CI: 0.267–0.816, P = 0.007), but not in non-OpGC survivors, compared with NC subjects. Risk of metabolic dysfunction-associated fatty liver disease was significantly lower in OpGC survivors (OR = 0.412, 95% CI: 0.233–0.729, P = 0.002) compared with NC subjects. Conclusions: OpGC survivors showed a lower risk of MetS and FL compared with NC subjects. These associations can be explored to ensure timely medical intervention in GC survivors.
Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC, RATIONALE 302): Impact on health-related quality of life (HRQoL).
Authors: Van Cutsem Eric , Kato Ken , Ajani Jaffer A. , Shen Lin , Xia Tianyu , Ding Ningning , Zhan Lin , Barnes Gisoo , Kim Sung-Bae 
Published: January 2022

268 Background: RATIONALE 302 was a global phase 3 study (NCT03430843) that investigated tislelizumab (TIS) compared with investigator-chosen chemotherapy (ICC) as second-line treatment for patients (pts) with advanced or metastatic ESCC, in which TIS demonstrated a significant and clinically meaningful improvement in overall survival hazard ratio (HR = 0.70 [95% CI 0.57–0.85], P=0.0001), and a favorable safety profile compared with ICC. Here we assess the HRQoL of pts receiving TIS vs ICC in a pt population that usually experiences HRQoL deterioration. Methods: Adults with advanced or metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1:1 to either TIS 200 mg IV every 3 weeks or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the global health status/quality of life (GHS/QoL), physical functioning, and fatigue scores from EORTC QLQ-C30 and the dysphagia, reflux, eating, and pain scores from the EORTC QLQ-OES18 from screening through Cycle 6 or until treatment discontinuation (whichever occurs first) Least-squares mean score change from baseline to Cycles 4 and 6 in HRQoL scores was assessed using a mixed model for repeated measurements. Time to deterioration (TTD) for the GHS/QoL score and the symptom scales of the QLQ-OES18 was examined using the Kaplan-Meier method. Results: Overall, 512 pts (median age 62) were randomized to TIS (n=256) or ICC (n=256). Compared with ICC, TIS-treated pts had stable GHS/QoL and fatigue scores as well as less decline in physical functioning at Cycles 4 and 6 (table). Except for pain, the TIS arm experienced less OES18 symptoms relative to baseline than the ICC arm. TTD analysis showed pts in TIS arm were at lower risk of worsening dysphagia (HR = 0.76 [95% CI 0.53, 1.07], P=0.0562) compared with ICC. Conclusions: The analysis showed that ESCC pts treated with TIS in the second line had a longer maintenance of HRQoL compared to pts treated with ICC. These results, along with improved survival and favorable safety profile, suggest TIS represents a potential new second-line treatment option for pts with advanced or metastatic ESCC. Clinical trial information: NCT03430843.[Table: see text]
Correlation of surgical volume and outcomes with gastrectomy.
Authors: Schuster Cassandra , Glasser Jamie , Huston Jamie , Shridhar Ravi , Meredith Kenneth Lee 
Published: January 2022

272 Background: Gastric cancer(GC) is associated with significant mortality worldwide. Radical gastrectomy with lymphadenectomy is considered the only curative option for GC. Traditionally, these operations are associated with significant morbidity. However, a significant proportion of gastric resections are performed at low volume centers. We sought to compare oncologic outcomes of gastrectomy by surgical volume. Methods: Utilizing the National Cancer Database we identified patients with gastric cancer who underwent gastrectomy. We then stratified based upon volume of institution. Low volume(LV) < 10 gastric resections per year, and high volume(HV) > 10 gastric resections per year. Mann-Whitney U and Kruskal were used to compare continuous variables and Pearson’s Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed to identify predictors of survival. All statistical tests were two-sided and p < 0.05 was considered significant. Results: We identified 29,216 patients who underwent gastrectomy with a median age of 66.5 (18-90) years. There were 21,166 (72%) gastric resections performed at LV centers and 8,050 at HV centers, p < 0.001. Neoadjuvant therapy was most often utilized in the HV centers at 41.7% vs 24.1% in the LV centers, p < 0.001. The median number of lymph nodes removed were 19 (13-28) in the HV and 14 (8-21) in the LV groups respectively, p < 0.001. The R0 resection rates were 91.1% in high volume centers and 84.6% in the low volume centers p < 0.001. The length of hospitalization did not differ between groups (median 8 (6-12) days), p = 0.33. The 30-day readmission rates however, were higher in the low volume centers at 6.5% compared to 5.8% in the high volume centers. The 30 and 90-day mortality was 1.7% and 4.1% in the HV and 4.9% and 9.2% in the LV groups, p < 0.001 and p < 0.001 respectively. The median and overall 5-year survival was 83.8mo and 56% in the HV and 49.4mo and 46% in the LV cohorts, p = 0.001. Multivariate analysis revealed that age, sex, Charlson/Deyo score, tumor location, histology, grade, stage, facility volume, and neoadjuvant therapy were all predictors of survival. Conclusions: While the majority of gastric resections are performed at LV centers, oncologic outcomes, survival and mortality rates are worse compared to patients who undergo gastric resection at high volume centers. Gastric resections should be regionalized to high volume centers to ensure the best surgical and oncologic outcomes.
A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of patients in CheckMate 649: Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC).
Authors: Sugarman Ryan , Botteman Marc , Rusibamayila Nifasha , Nguyen Hiep , Lin Daniel 
Published: January 2022

273 Background: In CheckMate 649 (CM 649), a randomized phase 3 trial of first-line treatment of advanced GC/GEJC/EAC, patients receiving nivolumab combined with chemotherapy (NIVO plus chemo) experienced superior overall survival (OS), progression-free survival (PFS), and maintained their HRQOL for longer duration versus chemo alone. In this analysis, we combined efficacy and HRQOL data from CM-649 into a single metric, quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST), to compare the net benefits of NIVO plus chemo versus chemo alone. Methods: In this analysis, OS was partitioned into three health states: time with grade 3/4 toxicity after randomization and before progression (TOX), time without symptoms of disease progression or toxicity (TWiST), and time from relapse or progression until death (ie, relapse, REL). Mean Q-TWiST was determined by multiplying each state’s duration with its utility (U) (U[TWiST], 1.0; U[TOX], 0.5; U[REL], 0.5). Relative Q-TWiST gains (calculated as Q-TWiST difference divided by chemo only OS) of ≥ 10% and ≥ 15% were defined as clinically important and clearly clinically important, respectively, based on established thresholds for clinical importance in prior Q-TWiST literature. Q-TWiST differences between treatments were calculated separately for patients whose tumors expressed PD-L1 CPS ≥ 5 and for all randomized. A threshold utility analysis assessed Q-TWiST differences by varying the TOX and REL utility between 0 and 1. Results: Compared with chemo alone, treatment with NIVO plus chemo was associated with Q-TWiST improvement of 2.8 months (95% CI 1.0-3.7; relative gain 20.6% [clearly clinically important]) in patients with PD-L1 CPS ≥ 5, and 1.8 months (95% CI 0.9-2.7; relative gain 12.7% [clinically important]) in all randomized patients, respectively. Threshold analyses showed that compared with chemo alone, treatment with NIVO plus chemo was associated with statistically significant Q-TWiST improvements exceeding minimum clinically important differences across the full range of TOX and REL utility values. Conclusions: Among previously untreated patients with GC/GEJC/EAC in CM-649, NIVO plus chemo significantly improved quality-adjusted survival compared with chemo alone. Q-TWiST gains with NIVO plus chemo were driven mostly by longer time patients experienced without symptoms of disease progression or toxicity (TWiST), and were associated with statistically significant and clinically meaningful gains. These Q-TWiST results provide further understanding of both a survival and quality of life benefit of NIVO plus chemo versus chemo alone, and may aid clinicians and patients in management decisions for this patient population.
Surgical, pathological and clinical features of advanced collorectal cancers with metastasectomy. "Onco-Colon Turkey Registry" real-life data.
Authors: Karadurmus Nuri , Yildirim Emre , Yalcin Suayib , Gumus Mahmut , Bilir Cemil , Cubukcu Erdem , Simsek Eda Tanrikulu , Arslan Cagatay , Dane Faysal , Celik Sinemis , Bilici Ahmet , Sendur Mehmet Ali Nahit , Oven Basak Bala , Isikdogan Abdurrahman , Turk Haci Mehmet , Karaca Mustafa , Karabulut Bulent , Ozcelik Melike , Cevik Duygu , Kefeli Umut ,   Onco-Colon Registry Group
Published: January 2022

299 Background: The contribution of metastasectomy to progression-free survival (PFS) and overall survival (OS) in patients (pts) with advanced stage colorectal cancer has been demonstrated in clinical trials. However, clinical trials may not represent the efficacy of treatment given to the whole population in daily practice, therefore evaluation of real-life data is needed. Methods: The demographic, pathological and clinical characteristics of 1064 RAS wild type pts were recorded in 28 centers in Turkey between January 2016 and March 2019 as part of the Onco-Colon Registry Program ( NCT04757311 ). Metastasectomy was performed in 169 patients (15.9%). In this study, pts with and without metastasectomy were compared in terms of demographic, histopathological and clinical features and treatment results. Results: Median follow-up time was 24 months(mos) (1-74), median age was 59 years (30-81). 32.5% of the pts were women. The proportion of pts with primary right colon was determined to be 16.8%. Synchronous metastasis was detected in 76.3% of those who underwent metastasectomy. Isolated liver metastasectomy was performed in 85.8% of the pts. It has been shown that 21.1% of the pts have MSI-H and 23.3% have a mucinous component. Metastasectomy was performed after conversion therapy in 54.8% of pts. In the patient group who underwent metastasectomy after medical treatment, the median time between the beginning of treatment and metastasectomy was found to be 7 mos (2-34). When the patient characteristics were compared, no significant difference was found between the groups with and without metastasectomy (p > 0.05). The median PFS (mPFS) was 13.5 mos in the group that underwent metastasectomy and 9.9 mos in the group that was not performed (p < 0.0001; HR: 0.63 (95% CI: 0.51-0.77). The median OS (mOS) was 47.3 mos in the group that underwent metastasectomy and 24.3 mos in the group without metastasectomy (p < 0.0001; HR: 0.36 (95% CI: 0.27-0.48). Conclusions: The significant contribution of metastasectomy on mPFS and mOS was shown in this reallife data based trial, where no difference was found in terms of general participation characteristics. In daily practice, prolonged mPFS and mOS emerges as pts who are followed-up radiologically at regular intervals from the beginning and who are appropriate for surgery have the chance of metastasectomy.
A phase II study of TAS-102 (FTD/TPI) in combination with ramucirumab (RAM) in advanced, refractory gastric (GC) or gastroesophageal junction (GEJ) adenocarcinomas (GEAs).
Authors: Mehta Rutika , Kim Richard D. , Martinez Jimenez Maria E , Blue Kirsten , Avriett Trenton , Kelbert Emily , Miller Kara , Ray Christopher , Valone Tiffany , Lee Woojoo , Kim Youngchul , Kim Dae Won 
Published: January 2022

302 Background: The RAINBOW trial established the standard of care for treatment of metastatic GEAs with ramucirumab and paclitaxel after failure of fluoropyrimidine and platinum-based chemotherapy. While the combination achieved an objective response rate (ORR) of 28%, the incidence of any grade neuropathy was 46%. Therefore, there is an unmet need for novel treatment combinations that minimize the long-term toxicity of neuropathy. In a recently published Asian study, the combination of RAM+TAS-102 showed good disease control and acceptable toxicity profile. Methods: This was a single arm, single institution phase II trial using the combination of TAS-102 plus RAM in refractory GEAs. Patients (pts) received RAM 8mg/kg intravenously on day 1 and 15, and TAS-102 35mg/m2 orally twice daily on days 1-5 and days 8-12 every 28-day cycle. The primary endpoint was 6-months overall survival (OS) rate and secondary endpoints were progression free survival (PFS), ORR and safety profile. The trial was registered at www.clinicaltrials.gov (NCT03686488). Results: At data cut-off of August 15, 2021, 23 pts were enrolled. Baseline demographics are as follows: median age of 62 years (range: 23-74), median lines of prior therapy of 1 (1: 14 pts vs ≥2: 9 pts) and location of primary tumor (GEJ:19 vs GC: 4). 6-month OS rate was 56.2%. Median OS was 6.2 month (95% CI: 5.4-7.0) and median PFS was 4.9 months with median observation of 2.3 months. Of 17 evaluable pts defined as more than one baseline imaging, 1 (6%) had partial response (PR) and 15 (88%) had stable disease (RECIST v1.1). Eleven pts came off the study due to progression of disease, 8 for toxicities and 4 for consent withdrawal. Most common treatment-emergent adverse events (TEAEs) were diarrhea (39%), fatigue (39%) and hypertension (39%). Total 11 pts (48%) experienced grade 3 and 4 TEAEs, and most common Gr3 and 4 TEAEs were neutropenia (17%) and anemia (13%). Conclusions: The combination of RAM and TAS-102 showed very similar disease control rate as the study in Asia. The combination has now shown modest activity in advanced GEAs and should be investigated further now in the context of patients receiving immunotherapy-based treatment as first-line treatment. A randomized phase II study is currently enrolling patients with ramucirumab and TAS-102 or paclitaxel. Clinical trial information: NCT03686488.
Clinical outcomes and appropriate treatment strategies of locally advanced resectable cervical esophageal cancer.
Authors: Miyakoshi Jun , Honma Yoshitaka , Yokoyama Kazuki , Yamamoto Shun , Ishiyama Koshiro , Oguma Junya , Kashihara Tairo , Inaba Koji , Murakami Naoya , Igaki Hiroshi , Kato Ken , Daiko Hiroyuki 
Published: January 2022

313 Background: Due to its rare nature, no standard treatment based on the randomized controlled trials for locally-advanced resectable cervical esophageal cancer (rCEC) has been established. Prognostic factors of locally-advanced rCEC are not also well evaluated. When considering the treatment for rCEC, larynx preservation (LP) is an important issue, as well as the prolongation of survival. This study aimed to clarify the clinical outcomes and prognostic factors on locally-advanced rCEC, and the appropriate treatment strategies focused on both LP and long-term survival. Methods: We retrospectively reviewed the medical records of rCEC patients treated with surgery or definitive chemoradiotherapy (CRT) at our institute from 2010 to 2020. This retrospective study was approved by the institutional review board of NCCH (2017-229). Results: A total of 123 cases were extracted as subjects, treated with surgery in 53 and CRT in 70. 1/3/5-year PFS and OS in all subjects were 52/40/36% and 84/60/56%, respectively. Univariate analysis indicated that clinical tumor depth might be a prognostic factor (T1 vs. T≥2, hazard ratio [HR]: 2.30, p=0027. in PFS; HR: 2.86, p=0.046 in OS). In the subjects with ≥T3 lesion (N=95) who usually require laryngectomy, both PFS (31.0 vs. 7.0 months, HR: 0.50, p=0.013) and OS (not reached vs. 25.0 months, HR: 0.28, p=0.005) were better in subjects treated with surgical approach than with CRT. Focused on the cases with ≥T3 lesion and initially treated with induction chemotherapy (N=33), the surgical approach also showed better clinical outcomes than the CRT approach (median PFS: 19.0 vs. 8.0 months, HR: 0.37, p=0.007; median OS: not reached vs. 18.0 months, HR: 0.18, p=0.007). Especially, subjects treated with induction chemotherapy followed by larynx-preserving surgery achieved better outcomes. Conclusions: This study indicated that clinical depth might be a significant prognostic factor in rCEC. A chemo-selection approach using induction chemotherapy might be a good strategy to achieve LP and improve survival outcomes in locally-advanced rCEC.
A novel circulating diagnostic and prognostic metagenomic signature in esophageal adenocarcinoma: Implications for precision oncology.
Authors: Pratama Muhammad Yogi , Omstead Ashten , Gillece John D , Gorbunova Anastasia , Kreft Rachael , Highlander Sarah K , Jobe Blair Anderson , Wang David H. , Kelly Ronan Joseph , Zaidi Ali Hussainy , Goel Ajay 
Published: January 2022

336 Background: The high incidence of esophageal adenocarcinoma (EAC) remains a major clinical challenge as majority of these cases are diagnosed at advanced stages, with poor survival outcomes. Emerging evidence indicate intriguing associations between unique microbial profiles and cancer pathogenesis. More recent data also indicates the potential clinical significance of specific microbial signatures as diagnostic and prognostic biomarkers. However, to date, no studies have systematically interrogated circulating metagenome profiling in EAC patients, particularly as non-invasive, early detection, surveillance and prognostic classifiers that may improve the current management paradigms. Methods: Metagenome sequencing was performed on 81 serum specimens collected from 51 EAC, 10 high grade dysplasia (HGD), 10 Barretts’s esophagus (BE), and 10 gastro-esophageal reflux disease (GERD) patients, respectively. Sequencing reads were classified using Bracken and MetaPhlAn3 to determine relative abundance between various classes. The Linear Discriminant Analysis effect size (LEfSe) method was performed to identify potential conserved and discrete microbial profiles between groups. Logistic regression and Kaplan-Meier analyses were used to build a model according to clinical and metagenomic classifiers to examine the diagnostic and prognostic potential of the identified metagenomic signature. Results: A significant loss of alpha and beta diversity was identified in serum specimens from EAC patients. We observed a shift in microbial taxa between each group – at the phylum, genus, and species level – with Lactobacillus sakei as the most prominent species in GERD vs. other patient groups. Interestingly, LEfSe analysis identified a complete loss of Lactobacillus ( L.Sakei and L. Curvatus), Collinsella stercoris and Bacteroides stercoris, but conversely a significant increase in Escherichia coli in patients with EAC. Finally, we developed a metagenome panel that discriminated EAC from GERD patients with an AUC value of 0.89 (95% CI, 0.78 – 0.95), and this panel in conjunction with the TNM stage was a robust predictor of overall survival (≥24 months; AUC = 0.84 [95% CI 0.66 – 0.92]) and an accompanying hazard ratio (HR) of 6.23 (95% CI, 2.65 – 14.46, P<0.001). Conclusions: This study describes unique blood-based microbial profiles in patients with GERD, BE, HGD, and EAC, that are further utilized to establish a novel circulating diagnostic and prognostic metagenomic signature in EAC.
Assessment of methylated BCAT1 and IKZF1 circulating tumor DNA as a potential diagnostic and prognostic biomarker in esophagogastic cancers.
Authors: Chan Mei Mei , Winter Jean M. , Pedersen Susanne Kartin , Roy Amitesh Chandra , Watson David I. , Hussey Damian , Young Graeme P. , Symonds Erin L. 
Published: January 2022

348 Background: Esophagogastric cancers (EG cancers) are associated with high mortality and poor treatment outcomes due to advanced disease at diagnosis. Reliable non-invasive biomarkers are lacking for detection and prognostication. The aim of this study was to assess the clinical utility of methylated BCAT1 and IKZF1 circulating tumour DNA (ctDNA) for detection and prognosis of EG cancers. Methods: Blood samples were collected from patients diagnosed with either esophageal or gastric adenocarcinoma prior to commencing any treatment. DNA was extracted from plasma and analysed for methylation of BCAT1 and IKZF1, and ACTB as the reference gene, by multiplex qPCR. ctDNA positivity rates were assessed against cancer clinicopathological features using chi-squared tests and age-adjusted logistic regression with odds ratios (OR). Secondary outcome was overall survival after 12 months using cox-proportional hazard ratio (HR). Results: Ninety-seven patients (77/97 (79%) male; 70 (72%) with esophageal cancer and 27 (28%) with gastric cancer) were enrolled with median age 72 years (IQR = 61-79). Fifty-three (55%) were ctDNA positive. There was no difference between the ctDNA positivity rate of esophageal and gastric cancers (p > 0.05). Positivity was significantly associated with node positive tumours (N0 = 6/23 (20.7%), N1 = 5/10 (50%), N2 = 11/17 (64.7%), N3 = 3/4 (75%); p = 0.01) and depth of invasion (T1 = 0/9 (0%), T2 = 5/12 (41.7%), T3 = 17/36 (47.2%), T4 = 5/6 (83.3%), p = 0.049). ctDNA positivity was independent of history of GORD or Barrett’s disease (p > 0.05). There was a significant association between ctDNA and advanced stage disease (Stage I = 1/13 (7.7%), Stage II = 2/12 (16.7%), Stage III = 25/40 (62.5%), Stage IV = 25/32 (78.1%)), with stage IV cases having a 43-fold increased odds for a positive ctDNA result compared to stage I (OR = 43.1, 95%CI 4.7-392.0; p = 0.001). Patients testing positive for ctDNA had poorer overall survival outcomes compared to those testing negative (HR 4.23, 95% CI 1.84-9.68, p < 0.001). Conclusions: Our study demonstrates a potential role for methylated BCAT1 and IKZF1 ctDNA as a biomarker for the detection of EG cancers. The detection of ctDNA is significantly associated with poorer survival outcomes, with further studies warranted to determine whether ctDNA can be an independent predictor of survival. The integration of this ctDNA assay into clinical practice could further improve risk stratification, which may guide treatment strategies.