bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multiplex DNA methylation assay for noninvasive early detection of gastric cancer.
Authors: Ruan Weimei , Lei Xiaotian , Sha Weihong , Li Bin , Wang Hong , Xia Yuying , Shen Junran , Kong Lingchen , Ma Juan , Chen Zhiwei , Bibikova Marina , Cui Chunhui , Fan Jian-Bing 
Published: January 2023

300 Background: Gastric cancer (GC) is the fifth leading cancer that ranked fourth in cancer mortality worldwide. Early screening and detection can significantly improve patients’ prognosis and survival. Although in standard GC diagnosis, gastroscopy provides sufficient diagnostic power for identifying GC in early stages, the invasive and costly procedure is not suitable for screening and has low compliance in countries with high GC incidence and large populations. Furthermore, the serum-based GC related biomarkers and non-invasive tests (serum pepsinogen I and II, gastrin-17, and anti-Helicobacter pylori IgG antibody tests) showed insufficient evidence as cost-effective GC screening approaches. A non-invasive DNA methylation assay with high sensitivity was aimed to develop and validate as a potential alternative for GC early detection. Methods: A multiplex quantitative PCR (qPCR) assay for detecting GC-specific DNA methylation markers in plasma was developed, in which the markers were further optimized from a reported seven-marker panel based on a pilot case-control study with 63 GC and 130 non-GC samples. The GC detection model of the assay was developed and locked down in the first cohort consisting of 54 GC and 79 non-GC samples. The second validation cohort with 117 GC and 309 non-GC samples was used to evaluate the assay performance. All plasma samples used in the two cohorts were prospectively collected from patients diagnosed with GC or other gastrointestinal diseases or from healthy donors. Results: The multiplex DNA methylation assay showed an overall sensitivity and specificity of 80% (95% CI: 77–83%) and 65% (95% CI: 63–66%) in the model development cohort, respectively, with a sensitivity of 80% (95% CI: 65–95%, n=10) in the detection of stage I GC. The assay revealed similar performance characteristics in the validation cohort, with an overall sensitivity of 82% (95% CI: 80–83%), a specificity of 69% (95% CI: 68–69%), and a sensitivity of 78% (95% CI: 74–82%, n=41) for the stage I GC detection. The DNA methylation assay outperformed the reported serum-based GC related biomarkers and non-invasive tests (sensitivity of 69.6-70.7% and specificity of 66.8-67.8%) with higher sensitivity, particularly in the stage I GC with a comparable specificity. Conclusions: The multiplex DNA methylation assay provides a potential cost-effective tool that features high sensitivity for GC early detection.
Short-term safety of adjuvant nivolumab therapy after neoadjuvant docetaxel plus cisplatin and 5-FU therapy for locally advanced esophageal squamous cell carcinoma.
Authors: Hirose Toshiharu , Yamamoto Shun , Kadono Toru , Ikeda Go , Ohara Akihiro , Itoyama Mai , Yokoyama Kazuki , Honma Yoshitaka , Ishiyama Koshiro , Oguma Junya , Daiko Hiroyuki , Kato Ken 
Published: January 2023

312 Background: CheckMate 577 trial demonstrated efficacy of adjuvant nivolumab (Ad-Nivo) therapy in locally advanced esophageal cancer patients (pts) who underwent surgery after neoadjuvant chemoradiotherapy and did not achieve pathologic complete response. In Japan, neoadjuvant docetaxel plus cisplatin, 5-FU (NeoDCF) therapy is the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. The efficacy and safety of Ad-Nivo therapy after NeoDCF therapy were unknown, so guidelines recommendations have not been determined. Methods: The subjects of this retrospective study were pts with histologically confirmed resectable locally advanced ESCC who received Ad-Nivo (480mg/body, every 4 weeks for 12 times) after NeoDCF in our hospital from Jan 2022 to Sep 2022. We evaluated safety as adverse events during treatments and clinical outcomes. Results: Twenty pts were selected in this study. Characteristics were median age (range) 65 (51–75) years, male/female 70/30%, PS 0/1 85/15%, Ce/Ut/Mt/Lt 5/15/50/30%, clinical stage II/III/IVA/IVB (supraclavicular lymph node) 10/70/0/20%, pathological stage IIB/IIIA/IIIB/IVA/IVB 30/5/40/10/15%. The pathological response according to Japanese Classification of Esophageal Cancer was Grade 0/1a/1b/2/3 5/20/20/40/15%. Median time (range) from surgery to Ad-Nivo was 9 weeks (4-20 weeks). The adverse events included fatigue (30%), increase AST (30%), increase ALT (15%), pruritus (15%), hyperthyroidism (15%), diarrhea (10%), decreased appetite (10%), and pneumonitis (10%). Grade >3 adverse events were not observed. Recurrence was observed in three pts (15%), which site was regional lymph node (2 pts of pathological stage III and IVB) and anastomosis (1pt of pathological stage IVA). Three pts with recurrence received definitive chemoradiotherapy, and still continue the treatment. Conclusions: The short-term toxicity of Ad-Nivo after NeoDCF was well-tolerated and acceptable.
Lower risk of depression after smoking cessation and alcohol abstinence in patients with gastric cancer who underwent gastrectomy: A population-based nationwide cohort study.
Authors: Kim Bokyung , Han Kyungdo , Chung Hyunsoo , Kim Sang Gyun , Cho Soo-Jeong 
Published: January 2023

314 Background: Although depression is associated with poor treatment outcomes and lower quality of life in cancer patients, little is known about whether lifestyle modifications could help prevent depression in these patients. This study aimed to identify the effect of lifestyle modifications such as smoking cessation, alcohol abstinence, and starting exercise on depression development in gastric cancer patients who underwent gastrectomy. Methods: Using the Korean National Health Insurance Service database, we identified gastric cancer patients who underwent gastrectomy between 2010 and 2017. Self-reported lifestyle behaviors within two years before and after gastrectomy were analyzed using health examination database. We classified the patients according to changes in lifestyle behaviors and compared their risk of developing depression. Results: Among 18,902 patients who underwent gastrectomy, 2,302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (Hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.66-0.91) and alcohol abstinence (HR = 0.79, 95% CI: 0.69-0.90) were associated with reduced risk of depression development compared to persistent smoking and persistent drinking, respectively. Starting exercise was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (one point each for not smoking, not drinking, and being physically active), the risk of depression showed a decreasing tendency as lifestyle scores increased from 0 (reference) to 1 (HR = 0.69, 95% CI: 0.55-0.83), 2 (HR = 0.60, 95% CI: 0.50-0.76), and 3 (HR = 0.55, 95% CI: 0.45-0.68) points. Conclusions: Smoking cessation and alcohol abstinence can reduce the risk of depression in gastric cancer patients who undergo gastrectomy. [Table: see text]
Impact of chemotherapy on COVID-19 vaccination in patients with gastrointestinal cancer.
Authors: Suenaga Mitsukuni , Yamauchi Shinichi , Sato Yuya , Noji Rika , Morikawa Ryo , Kano Yoshihito , Tokunaga Masanori , Kinugasa Yusuke 
Published: January 2023

32 Background: Multiple doses of vaccine against COVID-19 provide cancer patients with the opportunity to continue their cancer treatment. We previously reported the results that COVID-19 vaccination are tolerable, and treatment schedule changes could be minimized in gastrointestinal (GI) cancer patients receiving chemotherapy. In the present study, we investigated the differences in the occurrence of vaccine-related adverse events (AEs) in patients receiving chemotherapy and those not receiving chemotherapy. Methods: 141 patients with GI cancer who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and April 2022 with sufficient data on vaccination were included in this retrospective observational study at the Tokyo Medical and Dental University hospital. This study combined two different cohorts: an evaluation cohort of 89 patients (median age 70 years, male 57.8%) receiving chemotherapy; and a control cohort of 52 patients under follow-up after radical surgery (median age 68.5 years, male 69.2%). All patients had no history of COVID-19 infection. Treatment- and vaccine-related AEs were recorded by outpatient interviews and self-reports. Results: Patient characteristics of the two cohorts were similar except for the location of primary tumor: colorectal (80.9% vs 7.7%) and gastric (15.7% vs 88.5%). There were no significant differences in comorbidities between the cohorts (67.4% vs 55.8%). In the evaluation cohorts, 65 patients (73.0%) had vaccine-related AEs: injection site pain (68.5%), fever (9.0%), fatigue (6.7%), headache (3.4%), gastrointestinal symptoms (2.2%), redness (1.1%) and sleepiness (1.1%) after the first dose; and 66 patients (74.2%) had vaccine-related AEs with increased rate of fever (32.6%) and fatigue (19.1%) after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) after the first dose and 37 (71.2%) patients after the second doses, and similarly, fever and fatigue increased after the second dose. There were no significant differences in the number of vaccine-related AEs and their changes between cohorts. There was no treatment- and vaccine-related deaths. Conclusions: The results of this study suggest that systemic chemotherapy in patients with GI cancer does not have a marked negative effect on COVID-19 vaccination.
Integrating patient-reported-outcomes into prognostication in gastroesophageal cancer: Results of a population-based retrospective cohort analysis.
Authors: Megid Thais Baccili Cury , Sharma Divya , Ma Lucy Xiaolu , Wang Xin , Barron Carly C. , Jang Raymond Woo-Jun , Swallow Carol Jane , Mesci Aruz , Yeung Jonathan , Wong Rebecca KS , Chen Eric Xueyu , Brar Savtaj Singh , Veit-Haibach Patrick , Kim John , Bach Yvonne , Aoyama Hiroko , Elimova Elena 
Published: January 2023

320 Background: Patient reported outcomes (PRO) measures are accurate self-reflections of an individual’s physical functioning and emotional well-being. The prognostic value is unknown in gastroesophageal (GE) cancer patients (pts). The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated 10-item PRO tool which uses a 0 to 10 rating of ten common symptoms (total rating 0-100). In this study, we examined the association between the ESAS score and overall survival (OS) in pts with localized and metastatic GE adenocarcinoma (GEA). Methods: This study is based on the retrospective cohort database of pts with localized (stage I-III) and metastatic GEA. We included pts who were diagnosed with GEA between 2011 and 2021 and completed at least 1 baseline ESAS prior to the treatment. Pts were grouped into 3 cohorts based as follows: High symptom burden (SB) ESAS score ≥ 26, Moderate SB (11-25) or low SB (0-10). OS was defined as time from the first visit date to death. OS was assessed using the Kaplan-Meier method and significance was set at 2-sided P < 0.05. Univariate statistical analyses were used to examine the relationships between OS and multiple variables in the presentation. Results: 233 pts met the inclusion criteria: median age was 60.8y [51.4, 69.4]; 58% of pts were ECOG PS 1; 81% were non-Asian and 18.9% Asian; 67.4% of pts were male and 32.6% female. In terms of tumor location, gastric represented 47.2% of pts, GEJ 40.8% and esophageal 12.0% primaries; 43.7% pts were stage I-III, while 56.3% were de-novo metastatic pts. Median OS in Low, Mod, High SB pts cohorts were 22.7m, 17.6mm, & 14.6m, respectively (p < 0.036). Although worse OS and worse ESAS levels were not statistically significant in the localized pts (p, 505) and metastatic subgroup (p 0,092), there was a numerical tendency, especially in the metastatic pts. In the univariate analysis, there was a significant association between OS and high-symptom burden (Hazard ratio [HR] = 1.64 (95% CI, 1.12-2.38; p = 0.0104), ECOG ≥2 (HR= 2.79 (95% CI, 1.62-4.79; p = 0.0002) and metastatic pts (HR= 3.50 (95% CI, 2.51-4.86, p<0.0001). Conclusions: Higher SB based on ESAS was associated with poorer OS among GEA pts. ESAS is a reliable tool that carries a prognostic significance that could be used in practice.[Table: see text]
Real-world effectiveness of drugs newly approved in Japan on survival in patients with advanced gastric cancer.
Authors: Kadono Toru , Iwasa Satoru , Hirano Hidekazu , Shoji Hirokazu , Okita Natsuko Okita , Takashima Atsuo , Kato Ken 
Published: January 2023

322 Background: Ramucirumab (RAM), nivolumab (NIVO), and trifluridine/tipiracil (FTD/TPI) were approved for advanced gastric cancer (AGC) between 2010 and 2020 in Japan. However, the impact of these newly approved drugs on survival in the real-world clinical setting is not clear. Methods: This retrospective study investigated the effectiveness of RAM, NIVO, and FTD/TPI in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy including platinum agents in first-line (1L) for advanced gastric adenocarcinoma at our hospital between 2010 and 2020. Patients were divided into two groups before or after 2017 to compare the effectiveness. Results: From a total of 825 patients, 533 were assigned to the pre-2017 group and 292 to the post-2017 group. Baseline characteristics of the pre- and post-2017 groups were, respectively, as follows: median age, 64 (range, 20-83) and 65 (25-85) years; PS 0, 206 (39%) and 89 (31%), and PS 1-2, 327 (61%) and 202 (69%); peritoneal metastasis, 334 (63%) and 189 (65%); liver metastasis, 157 (30%) and 68 (23%); and HER2 positive, 82 (15%) and 57 (20%). There was no difference in the proportion of fluoropyrimidine and platinum agents between the two groups. For the pre- and post-2017 groups, 1L chemotherapy comprised fluoropyrimidine plus platinum agents (FP) for 71% and 68% of patients, FP plus taxanes for 15% and 1%, FP plus trastuzumab for 11% and 15%, and FP plus immune checkpoint inhibitors (ICIs) for 1% and 10%, respectively. Taxanes and irinotecan were used significantly more often in any treatment line in the pre-2017 group (taxanes, 74% vs. 64%, p<0.01; irinotecan, 32% vs. 7%, p<0.01), whereas RAM, ICIs, and FTD/TPI were used significantly more often in any line in the post-2017 group (RAM, 50% vs. 17%, p<0.01; ICIs, 48% vs. 9%, p<0.01; FTD/TPI, 6% vs. 0%, p<0.01). Overall survival was significantly longer in the post-2017 group than in the pre-2017 group (median, 16.9 months vs. 13.8 months, HR 0.74, p<0.01). Progression-free survival did not differ between the pre- and post-2017 groups in relation to 1L (median, 6.0 vs. 5.9 months, p=0.74); second-line treatment (median, 3.0 months [95%CI, 2.6-3.3] vs. 3.1 months [95%CI, 2.3-3.6]; HR 0.96 [95%CI, 0.82-1.14], p=0.57); third-line treatment (median, 2.1 months [95%CI, 1.8-2.5] vs. 1.8 months [95%CI, 1.4-2.1]; HR 1.03 [95%CI, 0.82-1.29], p=0.80); or fourth-line treatment (median, 1.9 months [95%CI, 1.7-2.5] vs. 1.8 months [95%CI, 1.5-2.8]; HR 0.85 [95%CI, 0.57-1.25], p=0.39). Rates of second-, third-, and fourth-line treatment in the pre- and post-2017 groups were 83% and 79% (p=0.23), 45% and 56% (p<0.01), 16% and 22% (p=0.07), respectively. Conclusions: Newly approved drugs in salvage-line treatment of AGC may have contributed to prolonged survival.
Multifocal early gastric neoplasms of three or more lesions versus single lesion without recurrence: A comparative study.
Authors: Pih Gyu Young , Yoon Ji Hoon 
Published: January 2023

329 Background: As indication for endoscopic resection for gastric neoplasms have been expanded, patients receiving multiple times of endoscopic resection for metachronous or synchronous lesions have been increasing. We aimed to compare clinicopathologic characteristics of patient with gastric neoplasm in a single location and multifocal lesions of three or more. Methods: From January 2006 to December 2021, 255 patients underwent endoscopic resection for three or more of multifocal lesions at tertiary medical institution were reviewed retrospectively and 8667 patient showed no recurrence after endoscopic resection for single lesion. The clinicopathologic characteristics of index gastric lesions were compared. Results: The male ratio was higher in multifocal lesions group than single lesion group (83.9% vs. 68.4%, P < 0.001). Diabetes mellitus was significantly more in multifocal lesions group than single lesion group (20.4% vs. 18.4%, P = 0.046), however hypertension, cardiovascular disease, kidney disease, and hepatitis showed no significant difference between the two groups. Smoking rate was significantly higher in the multifocal lesions group (current smoker 31.0% vs. 25.4%, and ex-smoker 24.7% vs. 24.8%, P = 0.028). In rapid urease test for Helicobacter pylori infection, the multifocal group showed significantly higher positives (54.9% vs. 40.8%, P < 0.001). Tumor depth, lymphovascular invasion, and perineural invasion showed no significant differences. Conclusions: Patients with multifocal early gastric neoplasms showed higher male ratio, higher rate of diabetes mellitus, and smoking rate compared with single lesion group. In addition, Helicobacter pylori infection was also significantly higher in patients with multifocal gastric neoplasm.
Short-term outcomes of robotic gastrectomy vs laparoscopic gastrectomy for patients with gastric cancer: A randomized clinical trial.
Authors: Ojima Toshiyasu , Hayata Keiji , Kitadani Junya , Goda Taro , Tominaga Shinta , Ohi Masaki , Yamaue Hiroki , Kawai Manabu 
Published: January 2023

344 Background: Robotic gastrectomy (RG) procedure for gastric cancer (GC) patients may be associated with decreased incidence of intra-abdominal infectious complications. Prospective randomized controlled trials (RCTs) comparing laparoscopic gastrectomy (LG) and RG are required, however. We completed an RCT to compare short-term surgical outcomes of LG and RG for GC patients. Methods: This was a randomized, two-center clinical trial. All included patients are adults with primary carcinoma of the stomach, in whom the tumor is considered surgically resectable (cStage I-III). Included in this trial were 240 patients with GC. The primary endpoint was to assess the incidence of postoperative intra-abdominal infectious complications including pancreatic fistula, intra-abdominal abscess, and anastomotic leakage. Secondary endpoints included incidence of postoperative complications, surgical results, postoperative course, and oncological outcomes. Lymphadenectomy without touching the pancreas was basically performed during robotic gastrectomy using assisting articulating forceps. Results: A total of 241 patients were randomly assigned to the LG group (n = 122) or the RG group (n = 119), and 236 patients (LG119 RG117) were analyzed for ITT population. Overall incidence of intra-opereative infectious complications higher than Clavien-Dindo grade II were not significantly different (LG 8.4%, RG 6%). However, overall incidence of any complications higher than grade II were significantly lower in the RG group (19.3 vs 8.5% P = .019). In RG group, postoperative pancreatic fistula was not found. Amylase levels in drainage fluid on POD 1 were significantly lower in the RG group (893IU/L) than in the LG group (438 IU/L) ( P = 0.039). Conclusions: Regarding short-term surgical outcomes, RG is feasible, safe and ideal treatment procedure for GC. Our RG procedure without touching the pancreas may be associated with decreased incidence of postoperative pancreatic fistula. Clinical trial information: UMIN000031536 .
Phase 2 study of cabozantinib (cabo) and pembrolizumab (pembro) in metastatic gastric/gastroesophageal adenocarcinoma (mGEA) refractory to immune checkpoint inhibitors (ICIs).
Authors: Dayyani Farshid , Ghio Kristian , Lee Fa-Chyi , Cho May Thet , Chao Joseph , Taylor Thomas H , Neumann Kristen 
Published: January 2023

345 Background: Most mGEA patients (pt) progress on therapy including ICI, with about 5% progression-free at 6mo (PFS-6) with single agent ICI in later lines of therapy. Alternative therapeutic approaches are needed. Cabo is a multi-tyrosine kinase inhibitor which might modulate immunosuppression in the tumor microenvironment. This study reports on safety and efficacy of the combination of Cabo+Pembro in mGEA refractory to ICI. Methods: Investigator-initiated, single‐arm, two-stage, single institution, phase 2 study in pts with mGEA after ≥1L of fluoropyrimidine and platinum-containing regimens. Additionally, pts with a PD-L1 CPS score ≥10% had also progressed on ICI. Cabo dose was 40mg p.o. daily on days 1 through 21 of a 21‐day cycle, with Pembro 200 mg i.v. on day 1. The primary endpoint was PFS-6, with H0=5%, Ha≥20%. Stage one results (n=19) exceeded the futility threshold. The complete design requires 27 evaluable pts and n≥4 pts with PFS-6 to reject H0 in favor of Ha. Results: 25 pts are currently enrolled. Because stage one did not signal futility, enrollment continues. Median age 58 years (24-75), female (n=13), ECOG 0/1= 13/12, GC/GEJ= 14/11, Caucasian/Hispanic/Asian/other = 7/7/8/3. After a median follow-up of 5.1mo (1.2-24.6), the median PFS and OS are 2.9mo (95% CI 2.1-4.6) and 9.5mo (95% CI 3.1-14.6), respectively. 11/25 had disease progression on or before the first imaging timepoint at 8 weeks, i.e. the clinical benefit rate is 56% (14/25). 13/20 pts had measurable disease by RECISTv1.1: PR 1(7.7%), SD 7(41.2%), PD 5(38.5%). The most common any grade (G) treatment related adverse events (TRAE) were diarrhea (28%), fatigue (20%), and hypertension (16%). G3-4 TRAE were seen in n=3 pts (Hypertension, Thromboembolic event, esophageal perforation; each n=1). No G5 were reported. Conclusions: In this interim analysis of this ongoing study, the combination of Cabo+Pembro shows promising clinical benefit with an estimated OS of 9.5mo in mGEA pts resistant to prior ICI. Follow-up of the primary endpoint is ongoing. The regimen appears tolerable with no new safety signals. More mature data including the primary endpoint and correlative studies will be presented at the meeting. Clinical trial information: NCT04164979 .