bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atezolizumab and trastuzumab plus chemotherapy in patients with HER2+ locally advanced resectable gastric cancer or adenocarcinoma of the gastroesophageal junction: A multicenter, randomized, open-label phase II study.
Authors: Peng Zhi , Zhang Xiaotian , Liang Han , Zheng Zhichao , Wang Zhenning , Liu Hao , Hu Jiankun , Sun Yihong , Zhang Yanqiao , Yan Han , Tong Lin , Xu Jiahui , Xie Jessica , Ji Jiafu , Shen Lin 
Published: January 2024

312 Background: Currently, there are no standard perioperative regimens for human epidermal growth factor receptor 2 positive (HER2+) gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. Furthermore, despite advances in neoadjuvant or perioperative chemotherapy, the efficacy of treatment for locally resectable advanced GC or GEJ cancer remains unsatisfactory. To address this need, we evaluated the effectiveness of adding atezolizumab (programmed death ligand-1 inhibitor) to treatment with trastuzumab (a HER2 antibody) + capecitabine and oxaliplatin (XELOX) compared with trastuzumab + XELOX in patients eligible for surgery with HER2+ locally advanced GC or adenocarcinoma of the GEJ. Methods: Patients aged 18–75 years were randomized 1:1 to atezolizumab + trastuzumab + XELOX (Arm A) or trastuzumab + XELOX (Arm B) and received the regimen for three neoadjuvant cycles (3 weeks per cycle) and five adjuvant cycles. Treatment administration was atezolizumab 1200 mg, trastuzumab 6 mg/kg, oxaliplatin 130 mg/m2 intravenously on Day 1, and capecitabine 1000 mg/m2 orally twice daily on Days 1–14 of each 3-week cycle. The primary endpoint was the pathological complete regression (pCR) rate. Secondary endpoints were the objective response rate (ORR) during neoadjuvant systemic therapy (NAST) and the R0 resection rate. Time-to-event endpoints are not reported because of immaturity. Efficacy endpoints were analyzed in the intention-to-treat population. The clinical cutoff date for the primary analysis was 12 March 2023. Results: Forty-two Asian patients who provided informed consent were screened and randomized to Arm A (n = 21) or Arm B (n = 21); all patients completed NAST. Most patients were male (92.9%), and the median (range) age was 61 (33–72) years in Arm A and 65 (49–72) years in Arm B. The pCR rate was 38.1% (8/21) in Arm A and 14.3% (3/21) in Arm B (treatment difference: 23.8% [90% confidence interval (CI), 1.3%–44.7%]). The pCR rate was significantly better in Arm A than in Arm B (P = 0.079 <0.1; lower limit of the 90% CI >0). Subgroup analysis showed that age <65 years, male sex, and intestinal Lauren classification were associated with a better pCR rate for the atezolizumab inclusive treatment arm (Arm A); however, these results require further confirmation in future studies. No significant difference was detected between the two arms in ORR during NAST or the R0 resection rate. Conclusions: The addition of atezolizumab to trastuzumab + XELOX therapy was effective in patients with HER2+ locally advanced resectable GC or adenocarcinoma of the GEJ. Clinical trial information: NCT04661150 .
Infusional fluorouracil and weekly docetaxel as first-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation: A multi-center, phase II trial (Zhen Long).
Authors: Xiao Jian , Zhai Xiaohui , Li Shanshan , Zhang Haibo , Li Yong , Peng Jin , Huang Yisheng , Shi Lishuo , Liu Hailing , Zhang Rongqin , Hu Meiyu , Pang Xiaolin , Lin Xiaoru 
Published: January 2024

337 Background: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) constitute a highly aggressive GC (HAGC) sub-type with distinctive features. The prognosis is poor and most HAGC patients die in weeks without effective treatment. Undue concerns about the myelosuppression mitigate against the application of cytotoxics in HAGC which is characterized by thrombocytopenia. Retrospective analysis showed low dose chemotherapy might relieve the DIC and bring with survival benefit but the standard of care (SOC) has not yet been established without a prospective study available. We completed a multi-center phase II trial evaluating the safety and efficacy of infusional fluorouracil and weekly docetaxel as first-line (1L) treatment for HAGC. Methods: This was a single-arm trial. A Simon's two-stage optimal design was applied. Eligible cases were: 18-75 years old, histologically confirmed GC, established BMM, overt DIC, platelet ≤ 50*109/L and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3. Fluorouracil 200mg/m2/d continuous infusion on days 1-21 and docetaxel 25mg/m2/d on days 1, 8, 15 were given every four weeks. Hematological response (HeR) was defined as the platelet restored to normal range. The primary end point was HeR rate. Secondary end points were time to HeR (TTHeR), one month mortality (OMM), overall survival (OS), adverse events (AEs) and quality of life (QoL). Results: From Jan 2021 to Sep 2022, 24 HAGC cases from three Chinese centers were enrolled (details shown in table below). 20 HeRs were achieved and the HeR rate was 83.3%. Median TTHeR was 13 days and OMM was 12.5%. Till the data cut-off date (Jul 31, 2023), 3 patients were still alive with a median follow-up of 403 days. The median OS was 242 days. Totally, twelve Grade 3 AEs were recorded in 7 (29.2%) patients, among which stomatitis (4, 16.7%) and aminotransferase elevation (3, 12.5%) were the most frequent. No drug-related grade 4 or 5 AEs were observed. QoL outcomes were significantly improved both during and after the treatment. Conclusions: Anti-cancer treatment is the key point to control DIC of HAGC. The Zhen Long regimen was well tolerated and showed promising efficacy in the 1L setting. It should be considered as the SOC in current practice, but further randomized trials are still needed. Clinical trial information: NCT04547153 . [Table: see text]
Real-world analysis of patient characteristics and outcomes among patients with metastatic colorectal cancer receiving trifluridine/tipiracil (FTD/TPI) plus bevacizumab versus FTD/TPI monotherapy.
Authors: Hubbard Joleen M. , Lee Lulu K. , Grisolano Jay L. , Perkowski Kacper , Salimi Tehseen , Kazerooni Reza , Epstein Robert S. 
Published: January 2024

34 Background: Trifluridine/tipiracil (FTD/TPI) is a standard of care therapy for patients with refractory metastatic colorectal cancer (mCRC). Recently, FTD/TPI in combination with bevacizumab (BEV) was also approved in this setting based on outcomes from the phase 3 SUNLIGHT trial, including statistically significant improvements in overall survival (OS) compared with FTD/TPI. This study examined demographic/clinical characteristics, treatment duration, OS, and healthcare resource use (HCRU), including outpatient/emergency room (ER) visits and hospitalizations, among patients with mCRC receiving FTD/TPI+BEV versus FTD/TPI in a real-world setting. Methods: This was a retrospective study of adults with CRC, who initiated FTD/TPI as monotherapy or in combination with BEV, identified from the Cerner Enviza electronic health records (EHR) database (12/2020–06/2023). A manual chart review of patients’ medical records was conducted where last follow-up was defined as death or last encounter in the EHR. Descriptive statistics were reported for all study variables; Kaplan Meier curves were used to estimate OS. Results: Of 197 patients abstracted, 122 (62%) received FTD/TPI+BEV combination therapy and 75 (38%) FTD/TPI monotherapy. Mean age was similar between the FTD/TPI+BEV and FTD/TPI groups (60.2 y vs 61.8 y) and 66% vs 63%, respectively, were male. Mean Charlson Comorbidity Index was 8.9 for the FTD/TPI+BEV group vs 8.5 for the FTD/TPI group and body mass index was 26.9 kg/m2 vs 27.3 kg/m2, respectively. Most patients received treatment in the third or fourth line (65% FTD/TPI+BEV; 75% FTD/TPI). Median follow-up was 5.3 and 4.6 mo, respectively. Mean duration of treatment was 3.7 vs 2.7 mo for FTD/TPI+BEV vs FTD/TPI monotherapy (Table). Median OS (from FTD/TPI initiation to death) was 11.5 and 9.6 mo for FTD/TPI+BEV and FTD/TPI groups (number of deaths: 38 and 22), respectively. Patients receiving FTD/TPI+BEV had numerically more outpatient visits (20.5 vs 13.9), but similar ER visits (0.5 each) and slightly fewer hospitalizations (1.1 vs 1.2) compared with FTD/TPI, during follow-up. Overall HCRU costs were similar between groups (27,175 vs 27,891). Conclusions: This real-world study supports the value of FTD/TPI+BEV combination therapy vs FTD/TPI monotherapy as seen in the SUNLIGHT trial. Patients with FTDTPI+BEV were treated for longer duration with improved OS and no difference in trends for HCRU and associated costs. [Table: see text]
A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).
Authors: Imai Toru , Hirano Hidekazu , Shoji Hirokazu , Hirose Toshiharu , Okita Natsuko Tsuda , Takashima Atsuo , Kato Ken 
Published: January 2024

342 Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.
Phase 1b/II study of durvalumab (D) and tremelimumab (T) plus PET-adjudicated chemoradiation (CRT) in patients (Pts) with esophageal adenocarcinoma.
Authors: Ku Geoffrey Yuyat , Wu Abraham Jing-Ching , Trivedi Nikhil , Maron Steven Brad , Joshi Smita Suhas , Ilson David H. , Janjigian Yelena Y. , Shcherba Marina , Li Jia , Tang Laura H. , Yeh Randy , Sihag Smita , Park Bernard J. , Jones David Randolph , Molena Daniela 
Published: January 2024

355 Background: We previously evaluated adding D, an anti-PD-L1 antibody, to PET-directed CRT and found the combination to be safe and promising in terms of pathologic response and survival outcomes.1 Here, we add T to the combination. Methods: Pts with locally advanced esophageal/GEJ adenocarcinoma were enrolled. Pts received 2 cycles of mFOLFOX6 prior to repeat PET/CT. PET responders (≥35% reduction in SUV (PETr)) received 5-FU/capecitabine and oxaliplatin with RT, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received T 300 mg ×1 and D 1,500 mg q4W ×2 starting 2 weeks prior to CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts with R0 resections received adjuvant T 300 mg ×1 and D 1,500mg q4W ×6. The primary endpoint was the pathologic complete response (pCR) rate. Initially, 6 Pts were enrolled to evaluate for toxicity; they received RT to 50.4 Gy. Subsequently, RT was lowered to 41.4 Gy to decrease the length of preop treatment (tx). Results: 16 pts have been enrolled. All Pts had clinical ≥T3 and/or N+ disease. PD-L1 CPS was ≥1 in 9 (60%) of 15 tested. 1 Pt (6%) had a microsatellite unstable (MSI) tumor. 9 (56%) Pts were PETr; 3 Pts (19%) were PETnr but had improved clinical symptoms and other PET parameters (MTV/TLG) and also continued with 5-FU/capecitabine and oxaliplatin during RT. Significant tx-related adverse events (AEs) are shown in the Table. Immune-related AEs (irAEs) were: gd 3 enterocolitis (1 Pt), gd 3/4 colitis (2 Pts, 12%), gd 1 diarrhea (1 Pt), gd 2 pruritis (1 Pt), gd 1 and gd 3 dermatitis (1 Pt each) and gd 2 arthralgias in 1 Pt. 1 Pt died of aspiration pneumonia while being treated for gd 4 colitis during CRT; 1 Pt developed gd 3 enterocolitis and cholecystitis during CRT, achieved a clinical CR and did not undergo surgery. He developed local recurrence and had surgery off-study 16 months after start of tx; 1 Pt developed a bone metastasis after CRT. 4 Pts are awaiting restaging post-CRT. Of 9 Pts who had surgery, 4 achieved a pCR (44%, including the MSI Pt) and 3 (33%) had ypN0 tumors and ³90% tx response. All 9 Pts have initiated/completed adjuvant D+T. Conclusions: The addition of D+T to induction FOLFOX and PET-directed CRT prior to surgery is feasible, although irAEs seem numerically higher than in our prior study of D and CRT. Pathologic response data are promising. Accrual is ongoing and updated data will be presented. 1. Ann Surg 2023;278:e511. Clinical trial information: NCT02962063 . [Table: see text]
Short-term outcomes of pedicled jejunum reconstruction after esophagectomy for esophageal cancer.
Authors: Matano Mamoru , Kanetaka Kengo , Kobayashi Shinichiro , Kobayashi Kazuma , Inoue Yusuke , Soyama Akihiko , Adachi Tomohiko , Eguchi Susumu 
Published: January 2024

369 Background: The number of patients with esophageal cancer after gastrectomy and patients accompanied with simultaneous gastric cancer has gradually increased because of the prevalence of gastric in Japan. Pedicled jejunum is one of the choices for esophageal reconstruction when the stomach is not available. However, surgical outcomes of jejunal reconstruction and the effect of the timing of gastrectomy remain to be elucidated. Methods: This study was a retrospective, cohort study that included 24 patients who underwent supercharged pedicled jejunal conduit for esophageal reconstruction in our institution between May 2007 and July 2023. The patients were divided into two groups: gastrectomy was performed before esophagectomy (A group) and gastrectomy was performed simultaneously for accompanied gastric cancer (S group). Surgical outcomes and postoperative complications were compared between the two groups. As a nutritional assessment, perioperative change in body composition such as visceral fat area (VFA) with computed tomography was analyzed. Results: In 24 patients, the median operative time was 769 minutes and the median blood loss was 543 g. Severe postoperative complications developed in 6 cases (25%). The A group included 15 cases and the S group did 9 cases. There was no statistical difference in postoperative complication between the two groups, however, postoperative hospital stay was statistically longer in the S group than in that of the A group (37 days vs. 21 days, p=0.02). Although weight loss at 1 year after operation was almost identical in the two groups, the loss of VFA was more severe in the S group than in the A group (23 % of preoperative VFA vs. 77% of preoperative VFA, p=0.03). Conclusions: The use of a pedicled jejunal conduit after esophagectomy could be performed safely. Postoperative nutritional support is needed for patients especially those who underwent simultaneous gastrectomy.
Phase II trial of cabozantinib (cabo) plus durvalumab (durva) in chemotherapy refractory microsatellite stable (MSS) patients with advanced gastric and esophageal (G/E) adenocarcinoma: CAMILLA G/E cohort results.
Authors: Saeed Anwaar , Park Robin , Dai Junqiang , Kasi Anup , Barbosa Lori , Mulvaney Kelly , Rarden Jordan , Phadnis Milind A. , Saeed Azhar , Sahin Ibrahim Halil , Baranda Joaquina Celebre , Williamson Stephen K. , Sun Weijing , Al-Rajabi Raed Moh'd Taiseer 
Published: January 2024

373 Background: Cabo is a multi-tyrosine kinase inhibitor harboring anti-VEGFR2, MET, AXL, MER and TYRO3 activity. Immunomodulatory and synergistic anti-tumor activity of cabo in combination with PD-1/L1 inhibitors have been demonstrated preclinically and in prior studies in various solid tumors. The phase Ib gastrointestinal (GI) basket CAMILLA trial evaluating cabo + durva confirmed manageable toxicity and anti-tumor activity, leading to the expansion into a multi-cohort phase 2 study. Herein, we report the results of the phase II G/E adenocarcinoma cohort. Methods: Patients (Pts) enrolled in the phase II G/E adenocarcinoma cohort were administered cabo + durva at the RP2D of 40mg QD and 1500mg IV Q4W respectively. Enrolled pts must have progressed on >1 line(s) of systemic therapy. Prior exposure to PD-1/L1 inhibitors was allowed. Those with HER2 positive disease must have progressed on anti-HER2 therapies. The primary outcome was objective response rate (ORR). Secondary outcomes were treatment-related adverse events (TRAEs), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Exploratory subgroup analyses were conducted in PD-L1 CPS >5. Results: 31 patients were enrolled, with 29 patients evaluable for efficacy. The median age was 61 years (range 32-79). 86% had an ECOG performance status of one. 48% had ≥ 2 prior lines of systemic therapies (range 1-4). Of the 29 pts evaluable for efficacy, 6 pts had confirmed objective responses (5 PR + 1 CR = ORR 20.69%). The most common TRAEs were fatigue (65%), anorexia (58%), elevated liver enzymes (39%), and diarrhea (35%). Grade >3 TRAEs occurred in 19% of pts. Grade >3 immune-related adverse events (irAE) rate was 6%. DCR was 86.2% (25/29). Median PFS and OS were 4.4 (95% confidence interval (CI) 2.2-5.4) and 5.6 months (95% CI 3.6-8.3) respectively. In patients with PD-L1 CPS >5 (12/29), ORR was 25%, and median PFS and OS were 5.5 months (95% CI 1.8-12.4) and 19.3 months (95% CI 2.3-28.2) respectively. Conclusions: Cabo + durva showed anti-tumor activity and manageable toxicity in advanced chemotherapy refractory G/E adenocarcinoma. Further evaluation in patients with high PD-L1 CPS ≥ 5 is warranted in a future randomized trial. Clinical trial information: NCT03539822 .
Genomic analysis of oesophageal carcinoma (EC) to identify recurrent mutations in histone methyltransferases as a distinctive subset.
Authors: Wang Jingyuan , Xiu Joanne , Oberley Matthew James , Battaglin Francesca , Arai Hiroyuki , Soni Shivani , Zhang Wu , Goldberg Richard M. , Shields Anthony F. , Grothey Axel , Hwang Jimmy J. , Marshall John , Astsaturov Igor A. , Weinberg Benjamin Adam , Lou Emil , Hall Michael J. , Shroff Rachna T. , Khushman Moh'd M. , Sohal Davendra , Lenz Heinz-Josef 
Published: January 2024

379 Background: Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility, which is associated with tumorigenesis and immune tolerance, indicating its possible correlation with the efficacy of immunotherapy. Recurrent mutations of KMT2 have been identified in EC, but data addressing the molecular features of KMT2 mutated (MT) EC are lacking. We aimed to understand the molecular profile of KMT2 -MT EC. Methods: A total of 787 oesophageal carcinoma [adenocarcinoma (EAC), N=604; squamous cell carcinoma (ESCC), N=183] were analyzed using next-generation sequencing (NGS) and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous mutations, and mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) status was evaluated by a combination of IHC, Fragment analysis and NGS. Results: The mutation spectrum of KMT2A/C/D was significantly different between ESCC and EAC ( KMT2A, 2.7% vs. 1.2%; KMT2C, 3.8% vs. 1.2%; KMT2D, 14.2% vs. 2.0%, P <0.05). KMT2-MT EAC tumors showed significantly higher mutation rates in CIC (13% vs 1.1%), NF1 (12.5% vs 2.2%), FBXW7 (12% vs 3.4%), ATM (11.5% vs 2.6%) and BRCA1 (11.5% vs 1%, all q<0.05), compared to KMT2-WT tumors. However, in ESCC there were no significant differences in gene mutations between the KMT2-MT and WT groups. Significantly higher rates of dMMR/MSI-H (19.2% vs 1.0% in EAC, 5.4% vs. 0% in ESCC, both p<0.01) were seen in both KMT2-MT ESCC and EAC, compared to KMT2-WT cohorts, respectively. TMB was significantly higher in both KMT2-MT ESCC (median: 10 vs 8.6 mut/Mb, P=0.042) and EAC (23.9 vs 8.0 mut/Mb, P<0.0001), compared to KMT2-WT cohorts, respectively. A numerically longer immune-related overall survival was observed in KMT2 -MT EC patients, compared to KMT2 -WT EC patients (9.05 vs 6.98 months, HR=0.744, 95%CI: 0.52-1.07, P =0.11). Conclusions: This is the largest study to investigate the distinct genomic landscapes between KMT2 -MT and WT EC to date. Our data showed the KMT2 -MT EC has a distinctive genetic profile, indicated by higher TMB, and higher frequency of dMMR/MSI-H and gene mutations involved in DDR and epigenetic regulation. Understanding these molecular characteristics may be informative in the development of effective treatment strategies in KMT2 -MT EC.