bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptom burden and functioning status in patients with advanced upper gastrointestinal cancers.
Authors: Wang Xin Shelley , Hess Lisa M. , Shen Shu-En , Gonzalez Elizabeth , Jomaa Mona K , Liepa Astra M. 
Published: January 2023

311 Background: Providing accurate symptom profiles is essential to facilitate integration of patient-reported outcome measures (PROs) into routine oncologic care. This study described the symptom trajectories and functioning status in patients with advanced esophageal, gastroesophageal junction (GEJ), or gastric cancers. Methods: The study included adult patients with advanced upper gastrointestinal (UGI) cancers who were initiating a new line of therapy at time of enrollment. Multiple symptoms were assessed weekly for 12 weeks, then every two weeks until Week 36 using the electronically administered M.D. Anderson Symptom Inventory GI module (MDASI-GI). Patients also completed the EORTC QLQ-C30 every six weeks. Longitudinal PRO data were analyzed using mixed-effect models. Time to deterioration was estimated using Kaplan-Meier method. Multivariable regression models evaluated the association of PROs with tumor response. Patients were classified in a high symptom burden group if their MDASI-GI symptoms were scored > 4 (scale of 0-10) for trajectory analysis. Results: Of the 111 enrolled patients, primary tumor site was available for 108 patients: esophageal (33%), GEJ (26%), gastric (41%). The mean age was 60.2 years; 70% were male. Nineteen patients who dropped within one week after baseline reported more severe vomiting and inability to eat than those who provided more post-baseline data (n=92). For the 92 patients, the top 6 most severe items at baseline were fatigue, lack of appetite, disturbed sleep, pain, drowsiness, and inability to eat. At baseline, patients who were treatment-naïve (n=43) reported more severe symptom burden and financial difficulty than patients who had received prior therapy (n=49). Those who were treatment-naïve reported faster general activity deterioration during the first 12 weeks than those who had received prior treatment (hazard ratio=2.183, 95% CI: 1.018, 4.673). More severe shortness of breath at baseline was significantly associated with better tumor response by Week 12 (odds ratio=1.35, 95% CI: 1.05, 1.74) for all patients with tumor response data. Trajectory analysis showed high symptom burden for pain (35% of patients), fatigue (60%), disturbed sleep (32%), lack of appetite (60%), drowsiness (54%), difficulty swallowing (37%), and inability to eat (50%) during the initial 12 weeks. High symptom burden continued for pain (41% of patients), fatigue (55%), lack of appetite (59%), drowsiness (48%), and numbness (29%) for Weeks 12-36. Conclusions: This longitudinal study documented high prevalence of disease- and treatment-related symptom burden and functioning deterioration among patients with advanced UGI cancers. These data support the implementation of PRO assessment in the routine patient care of this cohort of patients with significant physical and psychosocial challenges.
Tumor mutational burden as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer.
Authors: Jang Jae Yeon , Jeong Sun Young , Kim Seung Tae 
Published: January 2023

324 Background: Tumor mutational burden (TMB) is known as an independent predictive factor in predicting treatment response of immunotherapy. We aimed to evaluate the efficacy of immunotherapy in advanced gastric cancer (AGC) according to TMB and other markers. Methods: The patients with AGC, aged ≥ 18, who received pembrolizumab or nivolumab from October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, were analyzed retrospectively. TMB was measured by next-generation sequencing-based assays, and PD-L1 is tested using immunohistochemical assay 22C3 pharmDx. Referring to the results of previous studies, TMB-high was defined as 14.31 mutations/megabase (mt/Mb) or above. Results: A total of 54 AGC patients who were treated with immunotherapy, pembrolizumab or nivolumab, were analyzed. Seven patients were TMB-high, and 47 patients were TMB-low. Compared to TMB-low group, TMB-high group showed higher overall response rate (ORR) (42.9% vs 6.4%, p=0.023), and disease control rate (66.7% vs. 22.9%; p=0.033). The median OS was longer in the TMB-high group with 22.4 months (95% CI, 19.738-25.115), while the TMB-low group with 3.6 months (95% CI, 2.109-5.104; p=0.020). In addition to TMB, microsatellite status was statistically significantly associated with the efficacy of immunotherapy in AGC. Microsatellite instability group had better ORR (n=3/4, 75%) compared to microsatellite stable group (n=4/50, 8.0%; p=0.005). Other than that, the ORR of the patients whose PD-L1 CPS was 1 or above did not differ from the patients whose PD-L1 CPS was lower than 1. Although there was no statistical significance, among TMB-low patients, PD-L1 CPS ≥1 group numerically exhibited a higher overall response rate (13.0% vs 4.0%; p=0.338). Conclusions: In our analysis, the cut-off value of TMB was set to 14.31mb/Mt, and TMB-high was associated with the better ORR and OS of immunotherapy in AGC. TMB could be a potential predicting marker for a therapeutic response of immunotherapy in AGC.[Table: see text]
Exploring real-world outcomes with nivolumab plus chemotherapy in patients with advanced gastroesophageal adenocarcinoma.
Authors: Chen Clara , Zhang Ying , You Min , Theodorou Eleni , Bertwistle David 
Published: January 2023

325 Background: In the pivotal CheckMate-649 trial, nivolumab in combination with chemotherapy (nivo + chemo), compared with chemotherapy alone (chemo), demonstrated superior efficacy in patients with previously untreated, advanced gastric, gastro-esophageal junction, or esophageal adenocarcinoma (collectively: gastroesophageal adenocarcinoma). This study aimed to describe the real-world patterns of use and effectiveness of nivo + chemo for first-line (1L) treatment of advanced gastroesophageal adenocarcinoma. Methods: Patients aged ≥18 years, newly diagnosed with unresectable, advanced or metastatic, HER2-negative gastroesophageal adenocarcinoma, who received nivo + chemo or chemo only between 4/1/2021 and 5/31/2022 were identified from the Flatiron Health database. Chemo regimens included FOLFOX or CAPEOX. Patients were followed from index date (start of 1L therapy) until death, loss of data availability, or end of data abstraction (05/31/2022), whichever occurred first. Results: 352 patients with advanced or metastatic gastroesophageal adenocarcinoma were eligible for the analysis (N=158 in the nivo + chemo group and N=194 in the chemo group). Baseline demographic and clinical characteristics were balanced between groups. Median follow-up was 3.6 (interquartile range [IRQ]: 1.5–8.1) months for nivo + chemo and 4.4 (IQR: 1.9–7.6) months for chemo. 44.3% of patients in the nivo + chemo group and 36.1% in the chemo group had <3 months of follow-up available. Median overall survival (OS) from index date was not reached (95% confidence interval [CI]: 9.0 months, –) in the nivo + chemo group and was 10.0 (95% CI: 8.5, 11.6) months in the chemo group. 43 patients (27.2%) in the nivo + chemo group died during the study period compared with 64 patients (33.0%) in the chemo group. Median progression-free survival (PFS) from index date in patients who received nivo + chemo was 6.9 (95% CI: 5.6, 8.2) months compared to 5.5 (95% CI: 4.8, 7.4) months in patients who received chemo. Similar trends were observed in the subgroup of patients with a PD L1 combined positive score (CPS) ≥1, while data on the CPS ≥5 subgroup were not mature enough for meaningful analyses. Conclusions: The addition of nivolumab to chemotherapy for 1L treatment of advanced or metastatic gastroesophageal adenocarcinoma showed a trend towards survival benefit in the real-world setting. The study is ongoing. Subsequent analyses will capture a larger patient sample and longer follow-up, and describe PD L1 CPS-based subgroups. [Table: see text]
Impact of obesity on postoperative outcomes in patients undergoing esophagectomy for resectable esophageal cancer.
Authors: Patel Nikhil , Patel Pranav , Doyle Joseph , Geropoulos Georgios , Bhogal Ricky Harminder , Allum William H. , Chaudry M. Asif , Kumar Sacheen 
Published: January 2023

327 Background: The prevalence of obesity (Body Mass Index>30kg/m^2) is rising in the western world and is a risk factor for gastrointestinal malignancy. It is considered a risk factor for poor surgical outcomes including impaired wound healing and venous thromboembolism. Dysphagia is a late sign of esophageal cancer and is associated with pre-operative malnutrition and weight loss. However, the true impact of obesity on outcomes after esophagectomy is controversial. This analysis investigates the impact of pre-operative obesity on outcomes following esophagectomy for esophageal cancer. Methods: All patients with recorded pre-treatment BMI, who underwent surgery from January 2005 to June 2022 at a single tertiary, specialist cancer centre in the United Kingdom (UK), were included in this study. Demographic details including BMI and tumour staging (TNM classification) were collected, as well as total length of inpatient and critical care admission (LOS), 30- and 90- day mortality. Statistical analyses were performed on the R platform. Results: A total of 401 patients (348 male, 53 female) underwent resectional surgery for esophageal cancer; 132 (32.9%) were of normal BMI (18.5-24.9kg/m^2), 162 (40.1%) were overweight (BMI of 25-29.9kg/m^2), and 108 (26.9%) were obese (BMI>30kg/m^2). The mean BMI for obese patients was 33.6kg/m^2 and mean age was 62.5 years in this cohort. Laparoscopic Ivor-Lewis esophagectomy was the commonest procedure performed on obese patients (57/108, 52.3%). When all patients were categorised into healthy BMI, overweight or obese cohorts, there was no statistically significant difference in post-operative complications at Clavien-Dindo grade II or lower, (p=0.500) or grade IIIa or higher (p=0.201). Furthermore, there was no statistically significant difference in total inpatient LOS (p=0.503), length of critical care admission (p=0.358), 30-day (p=0.836) or 90-day mortality (p=0.691). Conclusions: Obesity is not significantly associated with increased risk of postoperative complications, LOS, 30- or 90-day mortality in patients undergoing esophagectomy for cancer. The increasing uptake of minimally invasive surgery for esophageal cancer resections may also be associated with favourable surgical outcomes being achieved in patients with BMI>30kg/m^2.
Prediction of risk factors associated with readmission after robotic esophagectomy.
Authors: Meredith Kenneth Lee , LeBlanc Gabrielle , Takahashi Caitlin , Huston Jamie , Shridhar Ravi 
Published: January 2023

328 Background: Approximately, 20,640 new esophageal cancers (EC) will be diagnosed in 2022 and this will result in 16,410 deaths. Surgical resection remains the only potentially curative option, however significant morbidity and mortality ensues. Robotic approaches to esophageal resection have decreased overall length of hospitalizations. However, readmissions rates continue to be a significant concern. We sought to evaluate factors predicting readmission after robotic assisted trans-thoracic esophagectomy (RATE). Methods: Utilizing a prospectively maintained esophageal database, we identified patients with EC who underwent RATE between 2009-2022. We then stratified by readmissions, length of hospitalization and post-operative complications. Pre-operative, peri-operative and post-operative risk factors were identified as predictors of readmissions. Baseline univariate comparisons were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests. Pearson’s Chi-square test was used to compare categorical variables. Multivariate analysis was performed identifying predictors of readmission. Results: We identified 312 patients, who underwent RATE with a median age of 68 (38-91). There were 29 (9.3%) patients who underwent readmission. There were no differences in age (p=0.10), gender (p=0.39) BMI (p=0.22), or histology (p=0.35) between patients that were readmitted and those that were not. ASA scores were higher in those that were readmitted p=0.01 compared to those who were not. The median length of hospitalization (LOH) was 8 (7-11) and did not differ between those that were re-admitted and those that were not p=0.79. The most common reasons for re-admissions were pulmonary 16 (5.1%), anastomotic leak 6 (1.9%), soft tissue infection 2 (0.6%), nutrition 3 (1%) and gastrointestinal 2 (0.6%). Pre-operative risk factors predictive of readmissions included cardiac disease p=0.002 and diabetes p=0.04. Operative risk factors: estimated blood loss p=0.9 and operative time p=0.24 did not predict readmission. Post-operative complications occurred in 93 (29.8%) of patients. Any post-operative complication p=0.32 did not predict re-admission with the exception of anastomotic leak p=0.04. Additionally, length of ICU did not differ between those re-admitted and those who were not, p=0.96. Ninety-day mortality was significantly higher in those that were re-admitted, 13.8% vs 4% in those that were not re-admitted, p=0.001. Multivariate analysis revealed that cardiac disease, diabetes, ASA score, and anastomotic leak were all predictors of readmission. Conclusions: Readmission after RATE remains low despite decreased LOH. Patients that are readmitted will have a significantly higher risk of mortality at 90-days. Pre-operative, peri-operative and post-operative factors can be used to accurately predict risk for readmission after robotic esophagectomy.
Randomized, global, phase 3 study of tislelizumab (TIS) + chemotherapy (chemo) versus placebo (PBO) + chemo as first-line (1L) treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Non-Asia subgroup.
Authors: Raymond Eric , Hubner Richard , Gotovkin Evgeny , Wyrwicz Lucjan , Van Cutsem Eric , Jimenez-Fonseca Paula , Pazo-Cid Roberto , Xu Jianming , Kato Ken , Tao Aiyang , Wang Lei , Peng Yanyan , Li Liyun , Yoon Harry H. 
Published: January 2023

340 Background: TIS, an anti-programmed cell death protein 1 (PD-1) antibody, + chemo as 1L therapy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) vs PBO + chemo in patients with advanced or metastatic ESCC (hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.54, 0.80]; P< 0.0001), with a manageable safety profile, at interim analysis of the phase 3, double-blind RATIONALE-306 study (NCT03783442). Here, we report data from the non-Asia subgroup (Europe, Northern America, and Oceania). Methods: Adults with advanced or metastatic ESCC, with no prior systemic treatment for advanced disease were randomized 1:1, (stratified by region, prior definitive therapy, and investigator [INV]-chosen chemo) to receive TIS 200 mg intravenously (IV) once every 3 weeks (Q3W) (Arm A) or PBO IV Q3W (Arm B), with platinum + fluoropyrimidine, or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) by INV per RECIST v1.1; OS in the programmed death-ligand 1 score ≥10%; and safety. Results: Of 649 randomized patients, 163 (25.1%) were from the non-Asia subgroup (Arm A, n = 83; Arm B, n = 80). At data cutoff (Feb 28, 2022), the median study follow-up time in the non-Asia subgroup was 16.0 months (mo) in Arm A vs 8.4 mo in Arm B. OS (median 16.3 vs 9.0 mo; unstratified HR 0.66 [95% CI 0.45, 0.96]) and PFS (median 7.7 vs 5.5 mo; unstratified HR 0.59 [95% CI 0.41, 0.83]) were improved in Arm A vs Arm B, respectively. Arm A had higher ORR (61.4% vs 41.3%, odds ratio 2.27 [95% CI 1.21, 4.25]) and longer median DoR (7.1 mo [95% CI 5.6, 9.6] vs 5.7 mo [95% CI 3.8, 8.3]) than Arm B. More patients in Arm A vs Arm B experienced ≥1 treatment-related adverse event (TRAE; 94.0% vs 88.5%), serious TRAEs (25.3% vs 17.9%), and discontinuation due to treatment-emergent AEs (42.2% vs 35.9%, respectively). Similar proportions of patients in Arm A vs Arm B had ≥grade 3 TRAEs (56.6% vs 52.6%), and TRAEs leading to death (1.2% vs 1.3%), respectively. Conclusions: In the non-Asia subgroup, 1L TIS + chemo showed a clinically meaningful improvement in OS vs PBO + chemo in patients with advanced or metastatic ESCC, with a manageable safety profile, consistent with published results in the overall population. Clinical trial information: NCT03783442 .
Two cycles versus four cycles of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC): A prospective, multicenter and randomized study.
Authors: Zhang Qin , Cao Guochun , Fan Zhaohui 
Published: January 2023

350 Background: Increasing evidences support the effects of neoadjuvant immune checkpoint inhibitors plus chemotherapy in locally advanced ESCC. However, the period of neoadjuvant is yet to be completely elucidated. This study was designed to compared the efficacy and safety of two cycles with four cycles of neoadjuvant camrelizumab plus chemotherapy in ESCC. Methods: Patients (pts) aged 18 to 75, with pathological confirmed and resectable ESCC were eligible. Enrolled pts were randomly assigned to two or four cycles of neoadjuvant with intravenous camrelizumab (200 mg, day 1) plus albumin-bound paclitaxel (175mg/m2, day 1) and carboplatin (area under curve 5, day 2) of 21-day cycle. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints included the R0 resection rate, objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). ChiCTR2100051154. Results: From 1/2022 to 8/2022, 41 pts were enrolled randomized (21 in the two-cycle and 20 in the four-cycle group). There were 15 (71.4%, 15/21) and 6 (30.0%, 6/20) pts underwent surgery. Compared with (46.7%, 7/15) in two-cycle group, we observed a higher pCR rate (50.0%, 3/6) in four-cycle group. The ORR achieved 60% (two-cycle group) and 66.7% (four-cycle group) respectively. DCR and R0 resection rate achieved 100% in both groups. Pts were well-tolerated in both groups, and 4.8% (1/21) and 5.0% (1/20) pts experienced grade 3/4 AEs. Conclusions: It is the first study to compare the periods of immuno-chemotherapy in the neoadjuvant setting for ESCC. Four cycles neoadjuvant achieved a numerically higher pCR rate and ORR compared with two cycles. Moreover, pts in 4-cycle group did not experienced more frequent or serious AEs. Clinical trial information: ChiCTR2100051154 .
Effect of robot-assisted gastric ESD in difficult ESD locations.
Authors: Kim Sang Hyun , Keum Bora , Choi Hyuk Soon , Jeen Yoon Tae , Chun Hoon Jai 
Published: January 2023

355 Background: Since its introduction, endoscopic submucosal dissection (ESD) has become a standard treatment for early malignant lesions of stomach. However, ESD is technically demanding and it bears a high risk of complication for beginners. The difficulty of the ESD technique tends to depend on the location of the lesion. We compared and analyzed the efficacy of the ESD assistive robot that we developed in the location where stomach ESD is considered difficult. Methods: We have developed an automated simulator that can implement gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator to implement a virtual gastric location where ESD is difficult. "Difficult ESD locations" were selected in consideration of the location where a lot of muscle damage and frequent blind dissections occurred when conventional ESD was performed. An experienced endoscopist performed ten robot-assisted ESDs or conventional ESDs in 3 difficult and 3 easy positions, respectively. Results: While there was no significant difference in dissection speed of robot ESD and conventional ESD in easy positions, the submucosal dissection speed was remarkably faster in robotic ESD than in conventional ESD in difficult positions (P < 0.05). In difficult positions, there was significantly more muscle damage in conventional ESD than in robotic ESD. (P < 0.05). Conclusions: Dissection speed was greatly improved when assistive robots aided gastric ESD procedures in difficult locations. Our robotic device can thus provide simple, effective, and safe multidirectional traction during gastric ESD in difficult location.
A phase-Ib study of TRK-950 combined with anticancer treatment regimens in patients with gastric and gastro-esophageal junction (GEJ) cancer.
Authors: Cassier Philippe Alexandre , Matrana Marc Ryan , Hanna Diana L. , George Ben , Sharma Sunil , Kelly Ronan Joseph , Okano Fumiyoshi , Von Hoff Daniel D. , Blay Jean-Yves 
Published: January 2023

361 Background: TRK-950 is a first-in-class humanized antibody raised against CAPRIN-1 which we have identified as a novel and universal target for cancer therapies. TRK-950 strongly and specifically binds to various cancer cells and shows anti-tumor effects via engagement of immune cells. A series of pre-clinical studies demonstrates its potency and safety. In the phase I study of TRK-950 monotherapy (NCT02990481), it appears safe and well tolerated. No DLT was observed and MTD was not reached at doses of 3-30mg/kg IV weekly. Here, we report on select cohort of the ongoing, multicenter phase Ib study of TRK-950 combined with standard of care (SOC) regimens in patients (pts) with gastric cancer including GEJ cancer (NCT03872947). Methods: Patients with gastric or gastro-esophageal junction (GEJ) cancer and measurable disease were enrolled in phase Ib study, and received paclitaxel on D1, 8, 15 and ramucirumab on D1, 15 of 28-day cycles. In addition TRK-950 was given 10 mg/kg IV weekly. DLT was evaluated during the first cycle. Response was assessed every 2 cycles up to Cycle 6 and every 3 cycles thereafter. Primary endpoint was safety and tolerability. Secondary endpoints included overall response rate (ORR), disease control rate (DCR) per REClST v1.1. Tumor CAPRIN-1 expression was retrospectively assessed by IHC. Results: Nine patients were enrolled, median age 58 yrs; Karnofsky performance status 80 (11%), 90 (67%), 100 (22%); 89% male, 11% female; median number of prior treatments 2 [1, 4]. TRK-950 in combination with ramucirumab and paclitaxel was well tolerated with no DLTs. Most common all-grade treatment-related AEs (TRAEs) were fatigue (67%), vomiting (33%), anemia (22%), nausea (22%), diarrhea (22%), neutrophil count decreased (22%) and decreased appetite (22%). Most common grade ≥ 3 TRAE in ≥ 20% of pts were anemia (22%) and neutrophil count decreased (22%). In 9 response-evaluable pts, ORR was 55.6% and DCR was 100%. Four patients had a screening CAPRIN-1 score of 3+, and all achieved partial response. Conclusions: TRK-950 binds to a newly described target, CAPRIN-1, and has an acceptable safety and tolerability profile when combined with ramucirumab and paclitaxel in gastric cancer including GEJ cancer. Preliminary clinical activity is demonstrated in pre-treated patients with encouraging response rates, particularly enriched by the expression of CAPRIN-1. Further antitumor activity is being confirmed by limiting patients to only 1 prior treatment regimen with an eye towards a randomized trial. Clinical trial information: NCT03872947 .