bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study.
Authors: Shah Manish A. , Sun Jong-Mu , Shen Lin , Kato Ken , Enzinger Peter C. , Adenis Antoine , Doi Toshihiko , Kojima Takashi , Li Zhigang , Kim Sung-Bae , Cho Byoung Chul , Mansoor Wasat , Li Shau-Hsuan , Sunpaweravong Patrapim , Alsina Maqueda Maria , Buchschacher Gary L , Wu Jimin , Shah Sukrut , Bhagia Pooja , Metges Jean-Philippe 
Published: January 2024

250 Background: First-line (1L) pembro + chemo significantly improved survival versus placebo (pbo) + chemo in patients (pts) with advanced esophageal cancer after a median follow-up of 22.6 mo in the randomized phase 3 KEYNOTE-590 study (NCT03189719). We report 5-yr follow-up data. Methods: Eligible pts had locally advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus (ESCC), or Siewert type I gastroesophageal junction adenocarcinoma; measurable disease per RECIST v1.1; and ECOG PS 0 or 1. Pts were randomized 1:1 to receive pembro 200 mg or pbo IV every 3 weeks for ≤35 cycles both with chemo (5-fluorouracil [≤35 cycles] and cisplatin [≤6 cycles]). Primary end points were OS in pts with ESCC and PD-L1 CPS ≥10 and OS and PFS per RECIST v1.1 by investigator in all pts, pts with ESCC regardless of PD-L1, and pts in the ITT population with CPS ≥10. Secondary end points included ORR and DOR per RECIST v1.1 by investigator and safety. Pt-reported outcomes will also be presented. Data cutoff was July 10, 2023. Results: Overall, 749 pts were randomized to receive pembro + chemo (n = 373) or pbo + chemo (n = 376). Median time from randomization to data cutoff was 58.8 mo (range, 49.2-70.6). A total of 701/740 pts (94.7%) discontinued treatment; most commonly due to progressive disease (n = 449; 60.7%). ORR and DOR by pt population are provided (Table). In the ITT population, median OS was 12.3 mo for pembro + chemo and 9.8 mo for pbo + chemo (HR 0.72 [95% CI 0.62-0.84]); 5-yr OS rates were 10.6% and 3.0%, respectively. Median PFS was 6.3 mo for pembro + chemo and 5.8 mo for pbo + chemo (HR 0.64 [95% CI 0.54-0.75]); 5-yr PFS rates were 5.5% and 0%, respectively. Grade 3-5 treatment-related AEs occurred in 266 (71.9%) pts in the pembro + chemo arm and 250 (67.6%) pts in the pbo + chemo arm. Treatment-related AEs led to death in 9 (2.4%) and 5 (1.4%) pts in the pembro + chemo and pbo + chemo arms, respectively. Conclusions: After 5 yrs, use of pembro + chemo showed durable efficacy versus pbo + chemo, with no new safety concerns in pts with untreated advanced esophageal cancer. Long-term results continue to support 1L pembro + chemo for advanced esophageal cancer. Clinical trial information: NCT03189719 . [Table: see text]
Unveiling survival strategies: The impact of treatment modalities on patients with esophageal cancer and the role of racial disparities.
Authors: Castillo Dani Ran , Jeon Won Jin , Chong Esther G , Kim Jae Y. , Wu S.Peter 
Published: January 2024

257 Background: Managing esophageal cancer (EC) involves neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy as the standard of care. However, some patients may remain unsuitable for esophagectomy. This study explores real-world outcomes in EC patients across different treatments, considers prognostic factors, and examines potential racial disparities. Methods: Data from 44,181 patients diagnosed with locally advanced EC between 2004-2017 were extracted from the National Cancer Database. The cohort was stratified into three groups: nCRT followed by esophagectomy, definitive RT (dCRT), single-modality RT. The dataset included 24,676 patients who received nCRT with esophagectomy or dCRT (N=17,534) and 1,971 patients who received single-modality RT. Endpoints included overall survival (OS). Cox Proportional Hazards Model was employed for multivariate survival analysis. Chi-square test was applied to the covariate demographic data. Results: nCRT followed by esophagectomy significantly improved OS compared to dCRT (mOS 43.5 vs. 20.1 months, p < 0.001). Single-modality RT had an mOS of 14.4 months. In the RT group, 73% were over 65 years old compared to 59% in the dCRT group (p < 0.001). Over 60% of patients had node-positive disease in both RT and dCRT groups (69% vs. 61.4%). More privately insured patients received multimodal treatment compared to publicly insured patients (27.3% vs. 16.8%, p < 0.001). Over 70% of patients were willing to travel within 20 miles for treatment, 60% underwent treatment in community programs. Racial disparities were observed, with Black patients experiencing worse outcomes compared to all other groups, while Asian and Hispanic patients had better outcomes (table1). In the squamous cell histology subset treated with dCRT, mOS was 22 (20.6 – 23.6 months) for Black patients, 27 (26 – 28) months for White patients, 36 (30-46) months for Hispanic patients, and 37 (30-44) months for Asian/Pacific Islander patients (p < 0.001). Conclusions: This real-world data analysis underscores the effectiveness of nCRT followed by esophagectomy in providing the best survival benefit for EC patients compared to dCRT or RT alone. Racial disparities emerged as significant factors influencing cancer survival outcomes. These identified factors including race and age can assist clinicians in making better-informed decisions regarding treatment pathways for specific patient populations. [Table: see text]
INTERCEPT Program of circulating tumor DNA (ctDNA) testing for minimal residual disease (MRD) in colorectal cancer (CRC): Results from a prospective clinical cohort.
Authors: Maddalena Giulia , Pellatt Andrew Jared , Eluri Madhulika , Parseghian Christine Megerdichian , Aziz Kathryn , Alfaro Kristin , Kell Robert J. , Bent Alisha Heather , Huey Ryan W , Uppal Abhineet , Konishi Tsuyoshi , Overman Michael J. , Morelli Maria Pia , Willis Jason , Shen John Paul Y.C. , Raghav Kanwal Pratap Singh , Newhook Timothy E. , Morris Van K. , Dasari Arvind , Kopetz Scott 
Published: January 2024

27 Background: Minimal residual disease, defined by ctDNA+ in the absence of macroscopic of disease, represents a new and clinically poorly defined subset of patients (pts). While observational cohorts have been reported on the prognosis of MRD, there is little information on the impact of returning and acting on ctDNA results on the subsequent ability to detect radiographic disease. Here we provide real-world evidence form a large prospective cohort where ctDNA testing was routinely performed and returned to pts and providers, providing opportunities to understand the prognostic performance of ctDNA in practice, including the rate of false negatives defined as radiographic recurrence without detectable ctDNA. Methods: The INTERCEPT program enrolled pts undergoing curative intent surgery for stages II-IV CRC at MD Anderson Cancer Center. A tumor-informed MRD assay (Signatera) was drawn post-operatively and every 3 months as per established reimbursement guidelines. Pts enrolled between Jan-Dec 2022 were included with follow up through Aug, 2023. Post-op timepoint was defined as any test within 6.5 months of surgery to include adjuvant therapy. A false negative result was defined as a negative test but with radiographic detection of recurrence within the subsequent 4 months. Results: A total of 1,140 pts were included, with 44.7% female and 39% with advanced disease. At least one ctDNA+ result was obtained in 338 patients (29.6%). When limited to pts with a post-operative/post-adjuvant timepoint (n= 520) and a median follow up of 10.4m, the 12m DFS was 94.2% for ctDNA-, and 54.3% for pts with at least 1 ctDNA+ test (median DFS of 14.9m); HR 17.67 (95% CI: 10.08 – 30.99), p<0.0001. When segregated by stage, ctDNA remained the most important predictor of outcomes [Table], such that pts with stage IV ctDNA- had better prognosis than pts with stage II ctDNA+ (38.9% vs 87.7% 12mDFS, p=.002). For 15 pts, we detected a false negative ctDNA, representing a rate of 1.3% (15/1140) corresponding to a negative predictive value (NPV) of 98.1%. Conclusions: In this first prospective real-world ctDNA program, MRD testing had a high NPV (98.1%) with very few false negative cases. The prognostic importance of ctDNA was confirmed and exceeded the risk prediction of stage alone, underlying and supporting the importance of introducing the test in practice and the need to investigate interventional studies, as are ongoing in the INTERCEPT program (crcmrd.org). [Table: see text]
Clinical risk factors for splenic hilar nodal metastasis in remnant gastric cancer after distal gastrectomy.
Authors: Sakon Ryota , Yoshikawa Takaki , Ogawa Rei , Nishino Masahi , Ishizu Kenichi , Watanabe Masahiro , Kinoshita Takahiro , Wada Takeyuki , Hayashi Tsutomu , Yamagata Yukinori 
Published: January 2024

270 Background: Splenectomy is usually considered to be required for complete dissection of splenic hilar lymph node (#10 LN) in gastric cancer (GC). Although spleen-preserving D2 was established for the advanced GC not invading the grater coverture based on the JCOG0110 clinical trial, D2 gastrectomy with splenectomy remains the standard procedure for the advanced GC involving grater coverture in Japan. However, the applicability of this treatment for remnant gastric cancer (RGC) is unclear because the lymphatic flow and lymphatic metastatic pattern may have been changed after initial gastrectomy. There are no guidelines for splenic hilar nodal dissection for RGC. In this study we evaluated risk factors for #10 nodal metastasis in RGC. Methods: This study retrospectively examined RGC patients who received gastrectomy with #10 nodal dissection after distal gastrectomy at two high-volume cancer centers in Japan between 1998 and 2015. Results: 99 patients were entered in this study. The #10 nodal metastatic rate was 12.1% (12/99). Initial gastrectomy was performed for benign in 42 patients and for malignant in 52 patients. The median duration from the initial gastrectomy was 20 (1-55) years. Main tumor location was lesser curvature in 46 patients, anterior wall in 11, greater curvature in 19, posterior wall in 11, and the whole in 12. Large type 3(≥8cm) and type 4 were found in 18 cases. The median tumor size was 50 (10-232) mm. The depth of invasion was cT1 in 31 patients, cT2 in 19, cT3 in 11, cT4a in 28, and cT4b in 10. Histology was differentiated type in 46 patients and undifferentiated type in 56. Completion gastrectomy was performed in 98 patients and partial gastrectomy in 1. 89 patients underwent splenectomy. The univariate analysis showed that tumor location (lesser curvature vs others, p=0.027) and depth of invasion (cT1-3 vs cT4, p=0.032) were significant risk factors for #10 nodal metastasis. By multivariate analysis, these two factors remained significant. Metastasis to #10 nodal metastasis was 0% (0/28) in patients without both risk factors, 11-12% in those with at least one risk factor, and 30% (6/20) in those with both risk factors. Conclusions: The tumors not confined to the lesser curvature and cT4 were significant risk factors for #10 nodal metastasis of RGC after distal gastrectomy. Splenectomy should be considered for complete splenic hilar nodal dissection when these risk factors are positive.
Retrospective cohort study to evaluate the efficacy and safety of T-DXd in HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction cancer: EN-DEAVOR study.
Authors: Nakanishi Koki , Kodera Yasuhiro , Kawakami Hisato , Makiyama Akitaka , Konishi Hirotaka , Morita Satoshi , Narita Yukiya , Sugimoto Naotoshi , Minashi Keiko , Imano Motohiro , Inamoto Rin , Kume Hiroki , Yamaguchi Keita , Hashimoto Wataru , Muro Kei 
Published: January 2024

274 Background: Relatively limited clinical data exists for patients who receive T-DXd treatment in the 3L+ setting for HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer. Insufficient data exists on real world patient populations that are likely to be excluded from clinical trials (e.g., elderly patients, those with significant co-morbidities). Therefore, this study was designed to evaluate the real-world clinical effectiveness and safety of T-DXd in patients with HER2-positive gastric cancer. Methods: This study (UMIN000049032) was a real-world, multicenter, non-interventional, retrospective cohort study conducted in Japan. Patients with HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer treated with T-DXd were enrolled. The patients were first administered T-DXd between Sep 2020, when T-DXd became available for clinical use in Japan, and Sep 2021. We followed up on these patients' records until Sep 2022. The endpoints were overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response (ORR), adverse events (AEs) of Grade ≥3, and adverse events leading to dose reduction, interruption, or discontinuation. Results: A total of 318 patients were enrolled, and 312 patients were analyzed, excluding 6 patients due to double enrollment or miss-enrollment (median age 70 years, performance status 0 or 1/≥2 [87%/12%], 43% patients with ascites). Median OS, rwPFS, and TTF were 8.90 months, 4.57 months, and 3.94 months, respectively. Overall ORR was 32.7%; it was 43.8% in the 226 patients with a target lesion. Regarding safety, the incidence of Grade ≥ 3 AEs was 48.4%. A total of 190/312 (60.9%) patients treated with T-DXd experienced dose reduction, interruption, or discontinuation of T-DXd treatment due to AEs. The most common reasons for dose reduction or interruption were neutrophil count decreased, anorexia, and malaise, while the most common reasons for discontinuation were interstitial pneumonia, anorexia, malaise, and nausea. Conclusions: This study demonstrates the effectiveness and safety of T-DXd in the 3L+ setting in real-world patients with HER2-positive gastric or gastroesophageal cancer. No new safety signals were identified on the basis of this study.
Diagnostic performance of endoscopy and MRI in identifying true response among patients with rectal cancer treated with total neoadjuvant therapy and selective watch and wait or TME.
Authors: Omer Dana Mohamed Rashid , Williams Hannah , Lin Sabrina T. , Thompson Hannah M , Verheij Floris S. , Yuval Jonathan B. , Buckley James T. , Qin Li-Xuan , Gollub Marc J. , Garcia-Aguilar Julio ,   OPRA Consortium
Published: January 2024

28 Background: The success of a watch-and-wait (WW) strategy for rectal cancer relies on restaging endoscopy and MRI to correctly identify a true response (TR) to neoadjuvant treatment. This secondary analysis of the OPRA trial is the first study to evaluate the restaging assessment’s diagnostic performance in a large cohort of WW patients. Methods: In the OPRA trial, patients with stage II/III rectal cancer were treated with total neoadjuvant therapy (TNT) and restaged with endoscopy and MRI 8±4 weeks post-treatment. Patients with a clinical complete (cCR) or near complete (nCR) response were offered WW; patients with an incomplete clinical response were recommended for total mesorectal excision. Diagnostic parameters, including accuracy, sensitivity, specificity, positive and negative predictive values, were calculated using TR as the reference standard. TR was defined as pathologic complete response for patients treated with TME or sustained cCR for ≥2 years for patients on WW. Contingency tables were prepared for two approaches: one considering either cCR or nCR positive for a TR, and one considering cCR as the only response grade positive for a TR. Results: Of the 304 patients restaged after completing TNT, 265 (87.2%) with ≥2 years of follow-up data available were included. Restaging endoscopy outperformed MRI across all parameters. Accuracy improved minimally to 66% when both modalities agreed on a cCR or nCR (Table). Restricting a positive result to cCR resulted in higher specificity, lower sensitivity, and higher accuracy (75%) (Table 1B). The positive posttest probability that a patient with a cCR had a TR was 81%, while the negative posttest probability that a patient with a non-cCR had a TR was 30%. Conclusions: Restaging endoscopy outperforms MRI in predicting TR, but the assessment’s overall accuracy even when both tests are combined remains suboptimal. Our results highlight the challenge of recognizing TR using subjective restaging exams. Opportunities to improve diagnostic accuracy include machine learning and radiomics, which have the potential to aid clinicians in identifying true responders. [Table: see text]
First-line FOLFOX therapy for advanced esophageal squamous cell carcinoma: Multicenter prospective study in Japan.
Authors: Fushiki Kunihiro , Tsushima Takahiro , Tsubosa Yasuhiro , Notsu Akifumi , Yamamoto Shun , Nakayama Izuma , Imazeki Hiroshi , Hamai Yoichi , Motoori Masaaki , Nomura Motoo , Nakachi Kohei , Fumita Soichi , Otsu Satoshi , Tanaka Yoshihiro , Murakami Kentaro , Furuta Mitsuhiro , TAKEUCHI HIROYA , Kato Ken 
Published: January 2024

280 Background: Cisplatin (CDDP) plus fluoropyrimidine was the standard first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). FOLFOX is promising option especially in patients with ESCC intolerant to CDDP but there were limited data on efficacy and safety of FOLFOX. We conducted a multicenter prospective observational study of FOLFOX for Japanese patients with ESCC intolerant to CDDP. Methods: Eligible participants had clinical stage IVB ESCC, with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, intolerant to CDDP, but tolerant to FOLFOX. FOLFOX (oxaliplatin 85 mg/m², leucovorin 200 mg/m², bolus fluorouracil 400 mg/m², and infusional fluorouracil 2400 mg/m²) was administered every 14 days. The primary endpoint was the response rate (RR) by RECIST v1.1 and the null hypothesis of RR was 10%. Based on the assumption of performing a one-sided test with an α of 0.10, 29 patients were needed to ensure the statistical power of 90% assuming RR of 30%. Results: In this study, 31 patients were enrolled from 14 hospitals between Apr. 2021, and Jul. 2022 and 30 patients received FOLFOX. The patient characteristics were: median age, 77 (range 66–89); male/female, 30/1; ECOG PS 0/1/2, 16/12/3; median creatinine clearance, 49.9 ml/min (33.4–80.2); median G8 score, 12 (range 7–17); and median CARG score, 8 (range 6–13). As the data cutoff of Jul 2023, all 30 patients discontinued FOLFOX. The reason for treatment discontinuation was disease progression, 86.7%; adverse events, 13.3%. Median follow-up time (interquartile range: IQR) was 20.2 (IQR 13.7–23.1) months. Median number of cycles administered were 5 (range 1–24). The RR was 22.6% (80%CI 0.13–0.35; p = 0.031) and disease control rate was 42.0%. Median progression-free survival was 3.9 months (95% CI 2.3–6.1). Median overall survival was 13.3 months (95% CI 9.5–not reached). The incidence of grade 3 or higher adverse events was 40% (neutropenia 26.7%, anemia 3.3%, nausea 6.7%, anorexia 6.7%, infection 6.7%, peripheral sensory neuropathy 3.3%). There was no treatment related death. Twenty-three patients (76.7%) received subsequent therapies, such as nivolumab (70%). Conclusions: First-line FOLFOX showed an acceptable safety profile and the prespecified statistical efficacy target was achieved. FOLFOX might be a treatment option for advanced ESCC patients who are intolerant to CDDP. Clinical trial information: UMIN000044485 .
A phase Ib/II study of ASKB589 (anti-Claudin 18.2 [CLDN18.2] monoclonal antibody) combined with CAPOX and PD-1 inhibitor as first-line treatment for locally advanced, relapsed and metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma.
Authors: Peng Zhi , Shen Lin , He Ying , Chen Jing , Hickingbottom Barbara , Lu Jianfeng 
Published: January 2024

317 Background: ASKB589 is a humanized IgG1 monoclonal antibody against Claudin 18.2 (CLDN18.2) with high affinity and enhanced antibody-dependent cytotoxicity. We report preliminary safety and efficacy data from an ongoing Phase Ib/II, dose-escalation and expansion study of ASKB589 combined with capecitabine, oxaliplatin(CAPOX) and Sintilimab as first-line treatment of G/GEJ adenocarcinoma (NCT05632939). Methods: The study enrolled G/GEJ adenocarcinoma patients(pts) with CLDN18.2 positive expression. The dose-escalation phase used a 3 + 3 design to determine the maximum tolerated dose (MTD). In expansion, the dose of ASKB589 selected for expansion was based on the safety, tolerability, pharmacokinetics and antitumor activity during escalation phase. Responses were assessed by RECIST 1.1 every 2 cycles (6 weeks). Adverse events (AEs) were graded using CTCAE v5.0. In escalation, pts received ASKB589 intravenously (IV) at doses of 6 mg/kg (n = 3) and 10 mg/kg (n = 6) every 3 weeks (Q3W) combined with CAPOX and Sintilimab. In expansion, all pts received ASKB589 IV at a dose of 6 mg/kg. Results: As of July 20, 2023, 9 pts were enrolled in escalation. No DLT was observed and thus the MTD was not identified. 9(100%)pts had treatment-related adverse events (TRAEs), the most common being nausea (77.8%), hypoproteinemia (66.7%), and hyponatremia (55.6%). While the majority of TRAEs were grade 1 or 2, 1 pt (11.1%) had a grade 3 TRAE (decreased neutrophils [10mg/kg]). In expansion, 26 pts with CLDN18.2 moderate-to-high expression (≥2+ membrane staining intensity in ≥40% of tumor cells) were included in the safety set. 24(92.3%) pts had TRAEs, the most common being nausea (65.4%), vomiting (53.8%), hypoproteinemia (53.8%), anemia (50.0%), fatigue (26.9%) and decreased neutrophils (23.1%). 3 pts (11.5%) had TRAEs of grade ≥3 including hypocalcemia, hypokalemia, decreased neutrophils, fatigue and bone marrow suppression. For the 15 evaluable pts who had at least one post-baseline tumor assessment, 12 pts (80.0%) achieved PR for an unconfirmed objective response rate (ORR) of 80.0%. 3 pts (20.0%) had SD for a disease control rate (DCR) of 100.0%. The PK of ASKB589 at doses of 6mg/kg and 10mg/kg combined with CAPOX and anti-PD1 therapy was consistent with that of monotherapy. Conclusions: ASKB589 combined with CAPOX and PD-1 inhibitor has manageable safety and promising antitumor activity. 6mg/kg is chosen as the recommended dose in subsequent studies. Clinical trial information: NCT05632939 .