bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucin 5 AC (MUC5AC) to predict pathologic treatment response (TR) to neoadjuvant chemotherapy (NAT) in resected-pancreatic ductal adenocarcinoma (R-PDA).
Authors: Manne Ashish , Sheel Ankur , Sara Amir , Noonan Anne M. , Yu Lianbo , Yang Wancai , Hays John L. , Mittra Arjun , Malalur Pannaga G. , Rahman Shafia , Roychowdhury Sameek , Elkatib Rifat , Jin Ning , Cloyd Jordan M. , Dillhoff Mary , Ejaz Aslam , Esnakula Ashwini K. 
Published: January 2024

690 Background: MUC5AC is a gel-forming glycoprotein that exists in two major glycoforms in PDA. We studied the differential expression and predictive value of heavily glycosylated mature MUC5AC (MM) detected in the apical (Ap) and/or extracellular region (EC) and less-glycosylated immature MUC5AC (IM) detected only in the cytoplasm (Cy) in R-PDA. Methods: R-PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores were calculated. Analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis. Results: Tissue samples from 100 R-PDA (43 received NAT and 57 had upfront surgery (UpS)) were available for testing. The median age of diagnosis was 65 years, and 50% were females. MM and IM were positive in 96% R-PDA (MM-95% Ap and 72% EC).In the NAT group, 89% (n=38) had 5-fluorouracil (5FU) based (36 FOLFIRINOX and 2 FOLFOX), and the rest received gemcitabine (Gem)-based therapy; patients received a median of 6 cycles of NAT; 37% (16) had preoperative chemoradiation (CRT) after NAT; 63% (27) had adjuvant systemic therapy (AST); pathologic objective response (OR = near complete or partial) and no response (NR) to NAT was reported in 63% (27) and 37% (16), respectively. In UpS group, 92% and 4% had AST (48 Gem-based, 4 5FU-based) and adjuvant CRT, respectively. The median time to recurrence (mTTR) and overall survival of the group was 15 and 33 months (m), respectively. NAT group had significantly (p<0.05) lower EC-positive MM (mean H-score 108 vs. 151), IM (mean H-score 122 vs. 162), and mTTR (11 vs 15 m) than UpS group. IM levels were directly proportional to the response (near complete (mean H-score 98) < partial (105) < NR (152) < UpS (162), p=0.04). Other TR results are discussed in the table. Conclusions: MUC5AC (IM > MM) is a potential predictive marker for TR among PDA patients, specifically among those receiving FOLFIRINOX. These associations must be validated in further prospective studies.[Table: see text]
Is lymph node metastasis an event indicating an advanced gastrointestinal stromal tumor?
Authors: Zhang Peng , Yang Weili , Fu Yingfeng , Zhang Jun , Feng Fan , Zhai Gang , Fu Yang , Wu Xin , Zhang Xinhua , Wu Xiao-Jun , Gao Zhidong , Liang Han , Zhou Yanbing , Liu Heli , Tao Kaixiong 
Published: January 2024

754 Background: The clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) with lymph node metastasis remain controversial owing to their low incidence. A multicenter retrospective cohort study was conducted to compare the clinicopathological features and oncologic outcomes of GIST with and without lymph node metastases. Methods: The medical records of patients with GISTs in 16 large medical centers in China from January 2014 to December 2020 were reviewed. Patients were divided into three groups: no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis. Propensity score matching (PSM) was performed to reduce confounding factors. Results: A total of 1109 cases of primary GIST were included in this study, comprising 607 males (54.7%) and 502 females (45.3%), with a mean age of 56.6±11.9 years. There were 1024 patients (92.3%) with no lymph node metastasis after surgery, and 85 patients (7.7%) had lymph node metastasis. Compared to that in GIST without lymph node metastasis, the proportion of non-gastric GIST was higher in GIST with lymph node metastasis (52.9% vs. 40.7%) with a larger tumor diameter (>10 cm: 36.5% vs. 18.1%) and more patients with distant metastasis (11.8% vs. 3.5%). Tumor location not in the stomach, the largest tumor diameter, and distant metastasis were independent risk factors for GIST with lymph node metastasis (all P < 0.05). After PSM, 96, 48, 24 patients comprised no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis, respectively. The relapse-free survival (RFS) of the lymph node metastasis group was comparable to that of the distant metastasis group without lymph node metastasis ( P = 0.368) and significantly inferior to that of no metastases ( P = 0.042). Conclusions: The prognosis of patients with GIST with lymph node metastasis was comparable to that of patients with distant metastasis and significantly worse than that of patients without metastasis. Lymph node metastasis may be an advanced event in GIST.
Clinical validation of Northstar Response, a novel methylated ctDNA therapy response monitoring assay in patients with advanced GI cancer undergoing active treatment.
Authors: Sahin Ilyas , Kahramangil Doga , Rogers Sherise C. , Ramnaraign Brian Hemendra , Manda Pravalika , Varga Matthew Gordon , Palmer Gary A. , Ye Patrick Peiyong , George Thomas J. 
Published: January 2024

756 Background: ctDNA is a non-invasive way to holistically assess the tumor. Several assays developed for therapy response monitoring rely on variant allele frequencies to detect scarce somatic variants in the blood. In contrast, methylated ctDNA measurement has shown promise as a treatment monitoring biomarker without requiring a tumor biopsy, yet accuracy is limited in ability to precisely quantify the amount of methylation present in the ctDNA. The CLIA-approved Northstar Response assay (BillionToOne, Inc.) quantifies on average 90 methylated loci, a 10-fold increase in signal over the average tissue-informed assays. Methods: This prospective, observational study assesses the clinical validity of Northstar Response, a quantitative methylated ctDNA therapeutic response monitoring assay that does not require prior tumor tissue. A cohort of 100 advanced cancer patients with a variety of GI malignancies submit serial ctDNA measurements in a blinded fashion. Eligibility includes advanced GI cancer patients starting a new line of systemic therapy (IO, targeted, chemo or combination) who are not pregnant or s/p organ or bone marrow transplantation. Blood samples are collected at baseline, at the time of imaging, and at least two intermediate time points (~30 days and 60 days post tx initiation). The primary endpoint is to measure the concordance and temporal relationship between disease progression measured by ctDNA compared to RECISTv1.1, clinical confirmation, or death. A Cox proportional hazards model will be used to quantify the association between the change in tumor methylation score (TMS; total methylated tumor molecules per 1000 assayed genomic equivalents) and clinical progression. The cohort will be split equally between a training and validation set. Results: Enrollment began in June 2023 and continues. To date, 28 patients with a variety of advanced GI cancers (table) have been enrolled with 37 samples processed. All samples have passed established QC metrics with average turn-around-time from receipt of sample to final report of 9.1 days (95% were <15 days). TMS ranged from <120 to >160,000 across individual samples, indicating that the assay can detect a broad range of tumor load in blood. We detected a median of 69 methylated loci per sample (range 4-451). Out of 21 pts, 17 had at least one sample with TMS measured above the noise floor of 120. Conclusions: The Northstar Response assay can consistently detect ctDNA across a variety of advanced GI cancers. Enrollment continues with formal comparison to clinical progression planned. Additional data on the complete training set will be available at the meeting.[Table: see text]
Single cell transcriptomic profiling of appendiceal adenocarcinoma to identify rare tumor cells and a myeloid-enriched tumor microenvironment (TME).
Authors: Gunes Betul Beyza , Hornstein Nicholas James , Wang Mingshuang , Chowdhury Saikat , Yousef Mahmoud M.G. , Yousef Abdelrahman M.G. , Zeineddine Mohammad A. A. , White Michael , Shen John Paul Y.C. 
Published: January 2024

760 Background: Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct clinical and molecular characteristics compared to colorectal cancer (CRC). Currently there is little knowledge regarding how tumor cells from AA interact with the tumor microenvironment (TME). In this study, we performed single cell RNA sequencing (scRNAseq) on metastatic AA tumors taken from three patients undergoing curative intent surgical resection. Methods: After obtaining informed consent, tumor tissue from three patients with AA and one patient with CRC undergoing cytoreductive surgery at the MD Anderson Cancer Center (MDACC) was harvested and dissociated into single cell suspension for scRNAseq; libraries were prepared with ‘5 sequencing (10X Genomics). Bulk RNA sequencing from 19 additional patients with AA was available as a validation cohort. Results: scRNAseq analysis of a cohort of 3 patients with AA, 1 with CRC, and 12 healthy control samples identified 39,451 evaluable single cells after filtering and doublet removal. Separating cells into immune, stromal, and epithelial compartments identified that epithelial cells are rare in AA tumors. On average, AA constituted 62% stroma, 36% immune and only 2% epithelial cells, in contrast to healthy appendix (46% immune, 29% epithelial, 25% stroma). Sub-classification of immune cells revealed enrichment of myeloid cells in AA tumors (67% myeloid, 27% T, 5% B and 1% plasma B cells). This is in contrast to healthy appendix tissue (44% T, 26% plasma B, 22% B, 6% myeloid and 2% mast cells). In CRC, the majority of immune cells from the CRC sample were T cells (69%). These single cell data were used to improve deconvolution of bulk RNAseq, allowing for evaluation of TME contribution to transcription using bulk RNAseq data. Analysis of tumors from 19 patients with AA confirmed myeloid predominance in AA tumors. We performed pseudobulk differential expression analysis between compartments comparing CRC and AA which identified significant differences between compartments. Gene set enrichment analysis enabled identification of organized compartment specific changes. Conclusions: Findings from this study provide new insights into AA's biological distinctions from CRC and represent a crucial step toward better understanding this rare malignancy. Myeloid cells need further investigation in AA to develop specialized management approaches and improve patient outcomes.
The impact of multidisciplinary care for locally advanced rectal cancer referrals: A systems perspective.
Authors: Lo Victor , Mallick Ranjeeta , Goodwin Rachel Anne , Gotfrit Joanna 
Published: January 2024

85 Background: Locally advanced rectal cancer patients require multidisciplinary care for treatment planning. We sought to determine whether the order of surgical and radiation oncology consultation in relation to medical oncology consultation affects the time from cancer diagnosis to treatment initiation and the requirement for additional pre-treatment visits with medical oncology. Methods: We conducted a retrospective chart review of adult patients referred to The Ottawa Hospital with locally advanced rectal adenocarcinoma, seen in consultation by a surgical, radiation, and medical oncologist between January 2018 and December 2022. Results: Of 195 patients, the median time from diagnosis to treatment was 55 days (IQR: 45-68). Both surgical and radiation oncology consultation preceded medical oncology consultation in a minority of patients (72; 37%), and 48 (25%) patients required multidisciplinary cancer conference (MCC) discussion. However, the time from cancer diagnosis to treatment initiation was not significantly different between patients who were and were not seen by the surgeon and radiation oncologist prior to the medical oncologist (56 vs. 55 days respectively), nor if MCC discussions were or were not required (55 vs. 55 days). However, almost half of all patients (93; 48%) required an additional pre-treatment visit with their medical oncologist, and patients who saw both surgical and radiation oncology prior were significantly less likely to require additional pre-treatment visits with medical oncology (25% vs. 61%; p<0.0001). Conclusions: The time from cancer diagnosis to treatment initiation was not significantly impacted by the order of specialist consultations with the multidisciplinary team, nor if patients required MCC discussion or additional pre-treatment visits with medical oncology. However additional pre-treatment visits with medical oncology were significantly more likely to occur when patients were seen by medical oncology prior to surgical and/or radiation oncology, representing a logistical and financial inefficiency in the system, and a potential area for process improvement. [Table: see text]
NRG-GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA).
Authors: Lieu Christopher Hanyoung , Yu Guan , Kopetz Scott , Puhalla Shannon L. , Lucas Peter C. , Sahin Ibrahim Halil , Deming Dustin A. , Philip Philip A. , Hong Theodore S. , Rojas-Khalil Yesenia , Loree Jonathan M. , Wolmark Norman , Yothers Greg , George Thomas J. , Dasari Arvind 
Published: January 2024

TPS243 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (SignateraÔ, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines vs. serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs. delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .
A randomized, multicenter, open-label, phase 2 study of TRK-950 in combination with ramucirumab and paclitaxel as second-line therapy in patients with CAPRIN-1 positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Kelly Ronan Joseph , Rha Sun Young , Lee Jeeyun , Okano Fumiyoshi , Shitara Kohei 
Published: January 2024

TPS420 Background: CAPRIN-1 is strongly expressed on the cell membrane of many cancer types including G/GEJ and on cancer stem cells. High expression is associated with enhanced in vitro colony-forming activity and in vivo tumorigenicity. TRK-950 is a first in class humanized antibody targeting CAPRIN-1.1 In the phase I study (NCT02990481), TRK-950 was well tolerated as monotherapy with no DLTs and MTD not reached at doses of 3-30mg/kg IV weekly. Subsequently the Phase 1b demonstrated that TRK-950 was well tolerated with a high potential for synergistic anti-tumor activity when used in combination with standard of care treatment(s) in selected advanced solid tumors (NCT03872947). Specifically, Regimen D which evaluated TRK-950 in combination with Ramucirumab and Paclitaxel in G/GEJ showed a DCR of 100% in all nine patients receiving 10 mg/kg and partial responses were seen in 5/9 (55%) patients. CAPRIN-1 strong expression was observed in 4/9 patients and an ORR of 100% was seen in those patients.2 A Phase II clinical trial in gastric/GEJ cancer patients with strong CAPRIN-1 is now enrolling patients. Methods: The phase II study is a multi-national, open-label, randomized, multicenter study evaluating the efficacy of TRK-950 in combination with ramucirumab (Ram) + paclitaxel (PTX) as compared with Ram + PTX treatment alone in patients with previously treated metastatic G/GEJ adenocarcinoma (NCT06038578). Patients enrolled across 10 sites in Japan, South Korea and the United States are randomized 1:1:1 by the permuted block method to (arm A) TRK-950 5mg/kg plus Ram + PTX, (arm B) TRK-950 10mg/kg plus Ram + PTX or (arm C) Ram + PTX alone. Inclusion criteria include patients with CAPRIN-1 positive (cutoff; 30% at ≥ 2+ staining) advanced/metastatic G/GEJ adenocarcinoma who have received first line therapy. Key exclusion criteria include HER2 positive disease. The primary endpoint is progression free survival (PFS) based on Independent Central Review (ICR) assessment per RECIST v1.1. Key secondary and exploratory endpoints include overall survival (OS), ORR, DoR, and biomarker evaluation. An interim analysis will be performed after 105 patients are randomized in stage 1 to determine the optimal dose of TRK-950 (5mg/kg or 10mg/kg) that will be evaluated in stage 2. In total 146 patients will be enrolled (40 patients in one arm and 53 patients in the other two arms). This study opened in September 2023. 1. Okano F, et al. Cancer Res Commun. 2023 Apr 18;3(4):640-658. 2. Cassier P, et al. J Clin Oncol. 2023 Vol. 41, No. 4, suppl. Clinical trial information: NCT06038578 .
A phase II trial of CapeOX plus nivolumab for early relapsed HER2-negative gastric cancer (JACCRO GC-11: FirSTAR trial).
Authors: Arai Hiroyuki , Inoue Eisuke , Terashima Masanori , Baba Eishi , Matsuhashi Nobuhisa , Muro Kei , Yamaguchi Toshifumi , Yuki Satoshi , Ichikawa Wataru , Fujii Masashi , Sunakawa Yu 
Published: January 2024

TPS423 Background: Fluoropyrimidine-based post-operative chemotherapy is one of the standard adjuvant therapies for curatively resected gastric cancer (GC).1,2 The current standard first-line chemotherapy consists of fluoropyrimidine and oxaliplatin combined with nivolumab in advanced HER2-negative GC patients including cases with a recurrence > 6 months after completion of post-operative chemotherapy, based on the CheckMate 649 and ATTRACTION-4 trials. However, in GC patients with early recurrence during or ≤ 6 months after completion of post-operative 5-FU based chemotherapy, optimal treatments remain to be established. A previous phase II study showed that capecitabine plus cisplatin is an active regimen for early relapsed GC after post-operative S-1 monotherapy.3 This trial aims to investigate the efficacy of capecitabine plus oxaliplatin (CapeOX) plus nivolumab for patients with early relapsed HER2-negative GC. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria include: histologically confirmed HER2-negative adenocarcinoma of stomach or esophagogastric junction; radiologically diagnosed recurrence during or ≤ 6 months after post-operative chemotherapy with S-1 or S-1 plus docetaxel conducted for stage II/III GC after curative resection; age ≥ 18 years; ECOG performance status 0-1; having measurable lesions according to RECIST ver. 1.1; and adequate oral intake and organ functions. Enrolled patients will receive 21-day cycles of nivolumab with CapeOX at the following dose until disease progression or unacceptable toxicities: capecitabine, 1000 mg/m2 twice per day on day 1-14; oxaliplatin, 130 mg/m2 on day 1; and nivolumab, 360 mg on day 1. The primary endpoint is objective response rate (ORR), and the secondary endpoints include overall survival, progression-free survival, disease control rate, duration of response, and safety. PD-L1 combined positive score will be tested for the association with efficacy. We assume null ORR of 20% and alternative ORR of 32%. With two-sided alpha level of 10% and 80% power, sample size would be calculated as 85. Thus, a total of 92 patients are planned for enrollment within a 2.5-year accrual period. Enrollment opened in March 2023. Clinical trial information: jRCTs031220572. 1. N Engl J Med. 2007;357:1810-20. 2. J Clin Oncol. 2019;37:1296-1304. 3. Gastric Cancer. 2018;21:811-8. Clinical trial information: jRCTs031220572 .
A randomized phase II/III study to evaluate the safety and efficacy of disitamab vedotin (DV) plus toripalimab and chemotherapy/trastuzumab as first-line treatment for HER2-expressed, locally advanced, or metastatic gastric cancer.
Authors: Shen Lin , Ding Guoliang , Feng Dan , Fang Jianmin 
Published: January 2024

TPS427 Background: For HER2-positive (IHC 2+/FISH-, IHC 3+) advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ), trastuzumab in combination with chemotherapy is the standard first-line treatment. Adding pembrolizumab to trastuzumab and chemotherapy significantly improves objective response rate. However, the overall survival results did not meet statistical significance. DV, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE) via a cleavable linker. We aimed to evaluate DV combined with toripalimab and chemotherapy/ trastuzumab as first-line treatment for HER2-expressed (IHC 1+, 2+ or 3+) locally advanced or metastatic GC/GEJ. Methods: This is a randomized, seamless phase II/III trial. Key eligibility criteria include participants confirmed GC/GEJ and systemic treatment naïve. In phase II period, participants will be divided into two cohorts. Ninety participants with HER2-positive (IHC2+ FISH+ or IHC3+) will be randomly (1:1:1) assigned to receive DV every 2 weeks (Q2W) plus toripalimab Q2W and oxaliplatin and capecitabine (CAPOX) every 3 weeks (Q3W), or DV plus toripalimab and trastuzumab Q3W, versus toripalimab plus trastuzumab and CAPOX. Forty participants with HER2-low (IHC1+ or IHC2+/FISH-) will be randomly (1:1) assigned to receive DV plus toripalimab and CAPOX, versus toripalimab and CAPOX. In phase III period, HER2-positive participants will be randomly (1:1) assigned to receive DV plus toripalimab and CAPOX or trastuzumab versus CAPOX plus trastuzumab±anti-PD-1 antibody, based on results from phase II, and evolution of treatment landscape. HER2-low participants will be randomly (1:1) assigned to receive DV plus toripalimab and CAPOX versus CAPOX±anti-PD-1 antibody based on evolution of stand of care. The primary endpoint is PFS by IRC in PD-L1 CPS ≥5 population. To the best of our knowledge, this is the first Phase III clinical trial exploring the combination of anti-HER2 ADC with trastuzumab and chemotherapy in first-line GC/GEJ. This trial began in August 2023 and has enrolled 4 patients at the time of submission. Clinical trial information: NCT05980481 .