bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptom burden in patients with early-onset colorectal cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial.
Authors: Storandt Michael H. , Kour Oudom , Ruddy Kathryn Jean , Cheville Andrea L. , Pachman Deirdre R. , Rahman Parvez , Wilder Smith Ashley , Mitchell Sandra A. , Shi Qian , Jin Zhaohui 
Published: January 2024

31 Background: Incidence of early-onset colorectal cancer (eoCRC, <50 years of age at diagnosis) is increasing globally. However, little is known regarding symptom burden in this sub-population. We compared symptoms in patients with eoCRC to those of patients with average-onset CRC (aoCRC, diagnosed at age ≥ 50). Methods: E2C2 is a stepped-wedge, cluster-randomized pragmatic trial evaluating a collaborative care model for the assessment and management of six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, emotional Distress, and Energy deficit (SPPADE)]. Patients were asked to complete assessments rating each of these symptoms on an 11-point numerical rating scale. Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of patients with CRC, comparing SPPADE symptoms on an initial survey, regardless of timing in treatment course, between patients with eoCRC and aoCRC. Results: Patients with CRC (n=4281) completed a survey between March 2019 and December 2022. Patient demographics and SPPADE symptoms are reported in the table. Patients with eoCRC were more likely to report severe sleep disturbance ( p<0.0001), pain ( p=0.03485), anxiety ( p<0.0001), emotional distress ( p<0.0001), and fatigue ( p=0.01083). In patients with eoCRC, women were more likely to report severe pain (12.6% vs 6.9%, p=0.0069), anxiety (16.1% vs 10.0%, p=0.012), emotional distress (12.1% vs 5.4%, p=0.00066), fatigue (18.9% vs 13.4%, p=0.038), and physical function impairment (10.1% vs 5.8%, p=0.026) compared to men. Conclusions: Patients with eoCRC reported higher symptom severity than patients with aoCRC. This suggests unique needs for symptom management in patients with eoCRC. Additional research is needed to evaluate how time since diagnosis, disease characteristics, cancer-directed treatment patterns, and co-occurring symptoms are associated with specific symptoms in this population. [Table: see text]
Clinical outcomes of early gastric cancer resected by endoscopic submucosal dissection at young age.
Authors: Park Jong-Jae , Joo Moon Kyung , Kim Jun Hee , Kwon Chan Mi , Kang Ji Min , Kang Min Hyung , Lee Si Eun , Kim Sunsuk , Kim Won Shik , Kim Seung Han , Lee Beom Jae , Chun Hoon Jai 
Published: January 2024

314 Background: A small portion of patients are diagnosed as early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at young age, however, their clinical outcomes are rarely known. We investigated clinical characteristics and outcomes of patients who underwent ESD for treatment of EGC at age under 50. Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. We divided them either for young age (YA) group if age ≤ 50 years and other age (OA) group if > 50 years. Results: We enrolled 1,349 patients (YA group: 105 patients [7.8%], OA group: 1244 [92.2%]). Compared with OA group, YA group contained more female patients (36.2 vs. 26.5%, P= 0.033), their tumor was located at middle third (41.0 vs. 29.6%, P= 0.006) and was depressed (40.0 vs. 28.8%, P= 0.001), and had more undifferentiated (30.5 vs. 12.1%, P< 0.001) and diffuse type (22.9 vs. 7.3%, P< 0.001) histology. However, synchronous tumor was less frequent in YA group (2.9 vs. 12.4%, P= 0.001). When we sorted 884 patients who achieved curative resection and were followed-up longer than 12 months, Kaplan-Meier analysis showed that metachronous neoplasm (dysplasia or cancer) and metachronous cancer were significantly less in YA group than OA group ( P= 0.003 and 0.013, respectively), however, local recurrence was not significantly different between two groups. Conclusions: ESD is a favorable and effective therapeutic modality for EGC patients who are aged under 50, once curative resection is achieved.
Phase 2 study of cabozantinib (Cabo) and pembrolizumab (Pembro) in metastatic gastric/gastroesophageal adenocarcinoma (mGEA) resistant or refractory to immune checkpoint inhibitors (ICI).
Authors: Dayyani Farshid , Chao Joseph , Lee Fa-Chyi , Taylor Thomas H. , Neumann Kristen , Cho May T 
Published: January 2024

315 Background: Most mGEA patients (pt) progress on therapy including ICI, with about 5% progression-free at 6 mo (PFS-6) with single agent ICI in later lines of therapy. Alternative therapeutic approaches are needed. Cabo is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study reports on safety and efficacy of the combination of Cabo+Pembro in mGEA resistant or refractory to ICI. Methods: Investigator-initiated, single‐arm, single institution, phase 2 study in pts with mGEA after ≥1L of fluoropyrimidine and platinum-containing regimens. 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%, requiring n=27 evaluable pts and n≥4 pts with PFS-6 to reject H0 in favor of Ha. Results: 27 pts were enrolled. Median age 58 years (24-87), female (n=14), ECOG 0/1= 13/14, GC/GEJ= 16/11, Non-Hispanic White/Hispanic/Asian= 12/8/7. The primary endpoint was met with n=6 pts having PFS>6mo. After a median follow-up of 31.4mo (range 3.3-42.5), PFS-6 is 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3mo (95% CI 1.7-4.1) and 5.5mo (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). In exploratory analyses, 5/7 (71.4%) pts in the top quartile for PFS had alterations in the cMET-PI3K-AKT pathway. The most common any grade (G) treatment related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension and muscle cramps (14.8% each). G3-4 TRAE were seen in n=3 pts (Hypertension, Thromboembolic event, esophageal perforation; each n=1). No G5 were observed. Conclusions: The addition of Cabo to Pembro shows clinical benefit in ICI resistant or refractory mGEA with an observed PFS-6 of 22.2%. The regimen appears tolerable with no new safety signals. An exploratory association of alterations in the cMET-PI3K-AKT pathway with prolonged PFS needs to be confirmed in a larger cohort. Clinical trial information: NCT04164979 .
Network meta-analysis of global trials of 1L therapies in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma.
Authors: Shah Manish A. , Shitara Kohei , Lonardi Sara , Chao Yee , Yamaguchi Kensei , Kukielka-Budny Bozena , Ryu Min-Hee , Ungureanu Andrei , Oh Mok , Chang Lawrence , Yang Hongbo , Chai Xinglei , Bhattacharya Pranob P. , Matsangou Maria , Ranganath Radhika , Ajani Jaffer A. , Xu Rui-Hua 
Published: January 2024

325 Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies reported statistically significant improvement in PFS and OS with 1L zolbetuximab (anti-claudin-18 isoform 2 [CLDN18.2]) + mFOLFOX6 or CAPOX in pts with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. This network meta-analysis (NMA) indirectly compared the relative efficacy of 1L therapies. Methods: A systematic literature review of phase 2, 3, or unknown phase randomized, global trials of 1L therapies (capecitabine + cisplatin [CX]; capecitabine + oxaliplatin [CAPOX]; fluorouracil + cisplatin [CF]; oxaliplatin + folinic acid + fluorouracil [FOLFOX]; S-1 + cisplatin [SC]; nivolumab + CAPOX/FOLFOX; pembrolizumab + CF/CAPOX or CX; and zolbetuximab + CAPOX/FOLFOX) in adults with LA unresectable or mG/GEJ adenocarcinoma. To form a connected main network, FOLFOX and CAPOX were assumed equally efficacious and combined. In the latest publicly available data, hazard ratios (HRs) of PFS and OS for intent-to-treat (ITT) populations were extracted or reconstructed from Kaplan-Meier curves when not reported as inputs for Bayesian fixed-effects NMAs. Comparative effectiveness was reported using median HR and 95% credible intervals (CrIs). Results: Trials reporting ITT populations were included, resulting in 9 trials (6663 pts) for PFS analysis and 10 trials (6735 pts) for OS analysis representing 8 regimens. Pts were randomly assigned to an experimental arm vs FOLFOX/CAPOX. Pts on 1L zolbetuximab, nivolumab, or pembrolizumab in combination with CF/CAPOX or FOLFOX/CAPOX had significantly reduced risk of disease progression or death vs FOLFOX/CAPOX (Table). Zolbetuximab + FOLFOX/CAPOX had the highest probability of being ranked first in treatment efficacy for both PFS (probability =0.54) and OS (0.36); followed by pembrolizumab + CX (0.27) and pembrolizumab + CF/CAPOX (0.13) for PFS; and by pembrolizumab + CF/CAPOX (0.3) and nivolumab + FOLFOX/CAPOX (0.24) for OS. Conclusions: This NMA examined the relative benefit of different targeted therapies when combined with chemotherapy. Zolbetuximab + FOLFOX/CAPOX for CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma confers a significant PFS and OS benefit, similar to that achieved with PD-1/PD-L1 inhibitors + CF/CAPOX or FOLFOX/CAPOX. [Table: see text]
Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial.
Authors: Ma Xiaoting , Ou Kai , Liu Xiu , Wang Qi , Gao Lizhen , Sun Yongkun , Yang Lin 
Published: January 2024

327 Background: Immune checkpoint inhibitors (ICIs) expanded choices of early-line therapies in advanced gastric (G)/gastro-esophageal junction (GEJ) cancer. In addition, it’s observed that early-line ICI therapy, compared to chemotherapy, could enhance the efficacy of VEGFR inhibitors with chemotherapy in late lines. This single-center prospective clinical trial was aimed to explore the efficacy and safety of fruquintinib with nab-paclitaxel as second-line in patients (pts) with G/GEJ cancer exposed to ICIs in early lines. Methods: This is a single-center, prospective, open-label clinical trial. Pts with advanced G/GEJ cancer who had been exposed to ICIs before the second line were eligible. 42 pts would receive 100g/m2 nab-paclitaxel on day 1 and day 8 every 3 weeks, and 4mg fruquintinib from day 1 to day 14 every 3 weeks. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method would be used to evaluate time-to-event outcomes. Results: Up to Aug 10, 2023, 25 pts had been enrolled, 23 of whom were evaluable. 14 (60.9%) pts in evaluable set were male. All these pts was with stage Ⅳ of TNM staging. The median age was 58 (range: 33-74), and 6 (26.1%) pts were elder than 65 yr. 12 (63.2%) pts were with PD-L1 CPS greater than 1, 9 (47.4%) pts greater than 5, and 4 (17.4%) pts greater than 10. PD-L1 CPS of 4 pts was unknown. The pts had received a median of 5 (range: 1-20) cycles in early-line ICI therapy. 17 (73.9%) pts suffered metastasis in retroperitoneal lymph node and 7 (30.4%) pts in liver. With a median follow up time of 5.6 (range: 2.1-16.6) mo, the PFS achieved 4.8 (95% CI: 4.6-NA) mo. Despite the immatureness of overall survival (OS), the 1-year OS rate was 56.25% (95% CI: 17.27%-95.23%). The ORR was 47.8% (n=11), and DCR was 100% (n=23). As to safety, the most common (≥20%) AEs of all grades were white blood cell decrease, peripheral sensory neuropathy, and neutrophil count decrease, while that of grade≥3 was white blood cell decrease. Conclusions: Fruquintinib with nab-paclitaxel as second-line therapy demonstrated good efficacy and safety in advanced G/GEJ cancer after exposure to ICIs. ICIs might increase benefit from this therapy, which warrants further investigations in a large cohort. Clinical trial information: ChiCTR2200059976 .
Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia.
Authors: Wang Hoyoung , Choi Kee Don , Noh Jin Hee , Na Hee Kyong , Jung Kee Wook , Ahn Ji Yong , Lee Jeong Hoon , Kim Do Hoon , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong 
Published: January 2024

336 Background: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. Results: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01–1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm ( p <0.004). Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring. [Table: see text]
Phase I trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology.
Authors: Badgwell Brian D. , Blum-Murphy Mariela A. , Ikoma Naruhiko , Estrella Jeannelyn , Li Jenny Jing , Kawedia Jitesh D. , Mansfield Paul F. , Ajani Jaffer A. 
Published: January 2024

360 Background: The purpose of this Phase I trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel for patients with gastric cancer metastatic to the peritoneum. Methods: In patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology, a Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel administered as 3 weekly treatments followed by a 1-week break and then 3 additional weekly treatments. The primary objective was to define the maximum tolerated dose (MTD). Secondary objectives included determining the safety and tolerability of escalating doses of intraperitoneal paclitaxel and making a preliminary assessment of the anti-tumor activity based on the peritoneal carcinomatosis index (PCI) and overall survival (OS). Results: A total of 25 patients were treated between January 2020 and April 2023. The MTD for intraperitoneal paclitaxel was 100 mg/m2. Five patients (20%) had dose-limiting toxic effects at 100 mg/m2. Treatment-related grade 3-4 toxic effects included leukopenia in 8 patients (32%) and neutropenia in 8 (32%). Seven patients (28%) required a schedule change to every-other-week treatment. The PCI after intraperitoneal paclitaxel demonstrated progression in 5 patients (20%), stable disease in 5 (20%), and improvement in 10 (40%); 5 patients (20%) were not evaluable for PCI. Eight patients (32%) had resolution of their peritoneal disease, and 7 (28%) underwent attempted resection. The median OS from the time of diagnosis of metastatic disease was 17.9 months (95% CI 14.5-29.5) and from the date of treatment initiation was 10.3 months (95% CI 6.5-18.8). One-, 2-, and 3-year OS rates from the time of diagnosis of metastatic disease were 84%, 36%, and 22%, respectively. Pharmacokinetic analysis showed there was systemic absorption of paclitaxel and plasma AUC0-∞ and Cmax was (13955 ± 6683 h.ng/ml) and (390 ± 191 ng/ml) respectively, while intraperitoneal concentration at the end of infusion was 232 ± 65 µg/ml. Conclusions: Paclitaxel may be safely administered at an intraperitoneal dose of 100 mg/m2. Neutropenia was common with weekly treatments, and we would recommend every-other-week treatment for future studies. Rates of resolution of peritoneal disease with multimodality therapy were promising, supporting future trials of this strategy and molecular profiling to identify factors associated with treatment response. Clinical trial information: NCT04220827 .
Safety and efficacy of zolbetuximab for CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials.
Authors: Celso Davi Said Gonçalves , Reis Pedro Cotta Abrahão , Escalante-Romero Lorena , Dacoregio Maria Inez , Gomy Israel , Marin Comini Ana Carolina , Camandaroba Marcos Pedro Guedes 
Published: January 2024

370 Background: Monoclonal antibody (Nivolumab, Trastuzumab, Bemarituzumab) with chemotherapy has shown benefit for patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Zolbetuximab, a new monoclonal antibody against Claudin (CDLN) 18.2 has demonstrated interesting results in clinical trials, however, there is still a need to find a safe and effective first-line treatment, especially for epidermal growth factor receptor (HER) 2-negative patients. Therefore, we aimed to perform a meta-analysis exploring the use of combined immunotherapy (Zolbetuximab) and standard chemotherapy versus chemotherapy alone. Methods: We searched PubMed, Embase and Cochrane Central for randomized controlled trials (RCTs) comparing Zolbetuximab to chemotherapy alone in patients with CLDN18.2-positive gastric or GEJ adenocarcinoma. The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS), Objective Response Rate (ORR) and Treatment-Emergent Adverse Events (TEAE). We pooled hazard ratio (HR) for PFS and OS endpoints and risk ratio (RR) for ORR and TEAE, with 95% confidence intervals (CI). Statistical analyses were performed using R software version 4.3.1 with a random-effects model. I² analysis was used to assess heterogeneity. Adverse Events (AE) were graded according to the National Cancer Institute Common Terminology Criteria for AE. Results: From sixty-six studies, three were included, with a total of 1349 patients. 671 (49.7%) were part of the intervention group, 769 (57.0%) were male, 360 (26.7%) underwent prior gastrectomy and 1304 (96.7%) had a more than 70% CLDN18.2 cellular staining rate. Age range was 21-83 years. Treatment with Zolbetuximab was associated with significantly higher PFS (HR 0.64; CI 0.49-0.84; p = 0.0011; I² = 59.6%) and OS (HR 0.70; CI 0.59-0.84; p<0.0001; I² = 40.0%). TEAEs grade ≥ 3 (RR 1.09; CI 1.03-1.16; p = 0.0051; I² =0.0%) were greater for the intervention group. ORR and serious TEAE had no difference when compared with the control group. Most frequent AEs were nausea (34.6%), vomiting (30.2%) and decreased appetite (18.6%). Conclusions: In summary, the use of Zolbetuximab alongside standard chemotherapy reduces mortality and disease progression, although it might increase the risk for grade ≥ 3 treatment-emergent AEs.
Camrelizumab combined with concurrent chemoradiotherapy for locally recurrent esophageal cancer: A single-arm, open-label study.
Authors: Jia Ruinuo , Zhang Junqian , Zhang Yaowen , Li Shuoguo , Sheng Manxi , Ma Jianguang , Zheng Anping , Tian Chuntao , Wang Jianli , Li Liuyan , Gao Shegan 
Published: January 2024

371 Background: Local recurrence is the main failure pattern after radical treatment of esophageal cancer. There is no uniform treatment specification for such patients(pts) so far. The combination of immune checkpoint inhibitors and concurrent chemoradiotherapy (CCRT) has emerged as a novel strategy to treat esophageal cancer. This research was to evaluate the efficacy and safety of camrelizumab (ICI targeting PD-1) combined with CCRT in the treatment of locally recurrent esophageal cancer. Methods: This open clinical study planned to enroll 62 pts with locally recurrent esophageal cancer following radical treatment who aged 18-75 years with ECOG performance status of 0-1. Pts received the following treatments: camrelizumab (200 mg q2w, continuous medication until disease progression, intolerable toxicity, or withdrawal); simultaneous radiotherapy (the total radiation dose was 50-50.4 Gy, which was given by 25-28 fractions, 5 fractions per week, with 1.8-2 Gy for each fraction); chemotherapy (capecitabine, 625mg/m2, bid, oral, d1-5, qw, total 5 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Feb 2022 and Jul 2023, 14 pts with a median age of 71 years old had been enrolled. Among the evaluable pts, the ORR was 69.2% (9/13), the DCR was 100.0% (13/13). With a median follow-up of 16.0 months (95% CI 13.5-18.5), the median PFS was 7.6 months (95% CI 4.2–11.0), the median OS was 18.6 months (95% CI NE–37.6) in the full analysis set. The incidence of any grade adverse events (AEs) was 100.0% and that of grade ≥3 AEs was 57.1% of 14 pts. The most common AEs included lymphocyte count decreased (11/14, 78.6%), neutrophil count decreased (5/14, 35.7%), white blood cell count decreased (5/14, 35.7%) and anemia (5/14, 35.7%). The most grade ≥3 AE was lymphocyte count decreased (6/14, 42.9%). No new safety signals or treatment-related deaths were observed. Conclusions: Current results suggested the promising efficacy and acceptable safety of camrelizumab combined with CCRT in pts with locally recurrent esophageal cancer. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT04390945 .