bluuebunny/crossref_metadata_2025_split huggingface dataset:
PERSIST: A multicenter, randomized phase II trial of perioperative oxaliplatin and S-1 (SOX) with or without sintilimab in resectable locally advanced gastric/gastroesophageal junction cancer (GC/GEJC).
Authors: Ding Xuewei , Wang Xuejun , Li Bin , Wang Longgang , Guo Honghai , Shang Liang , Huang Wenbai , Wu Liangliang , Ke Bin , Liu Yong , Liu Ning , Wang Baogui , Cai Mingzhi , Deng Jingyu , Zhang Rupeng , Zhang Jiancheng , Chai Jie , Zhao Qun , Li Leping , Liang Han 
Published: January 2023

364 Background: RESOLVE study shows clinically meaningful improvement in perioperative SOX in patients with locally advanced GC/GEJC undergoing D2 gastrectomy. Addition of PD-1 inhibitor to chemotherapy shows significant clinical benefit in first-line treatment of advanced GC/GEJC. This trial was designed to compare the perioperative sintilimab combined with SOX versus perioperative SOX in patients with resectable locally advanced GC/GEJC. Methods: PERSIST is a multicenter, prospective, open-label, randomized-controlled phase II study. Patients with histologically or cytologically confirmed GC/GEJC, clinical stage II-III, no previous systemic treatment, ECOG performance status (PS) of 0 or 1 were eligible for inclusion. Patients will be randomized (1:1) to received either perioperative sintilimab (200 mg d1 Q3W, three cycles preoperatively and up to 1 year postoperatively) in combined with SOX (oxaliplatin 130 mg/m² d1, oral S-1 40–60 mg BID d1-14 Q3W, three cycles preoperatively and five cycles postoperatively) in experimental group or perioperative SOX alone in control group. The primary endpoint was the pCR rate. The secondary endpoints were the MPR rate, down-staging rate, 3-years DFS rate, 5-years OS rate, safety. The study is registered with Clinicaltrials.gov: NCT04982939. Results: As of September 2022, 101 patients were enrolled, with median age 61 years (range 31-75 years), males 85 (84.2%), cT2/3/4/X 2(2.0%)/5(5.0%)/93(92.1%)/1(1.0%), cN0/1/2/3/X 10(10.0%)/42(41.6%)/27(26.7%)/9(8.9%)/13(12.9%), and GC/GEJC 92(91.1%)/9(8.9%). Forty-seven patients (experimental group:26, control group:21) underwent radical resection and all achieved R0 resection. The pCR rates in the experimental group and control group were 26.9% (95%CI 11.6%-47.8%) and 4.8% (95%CI 0.1%-23.8%), respectively. The MPR rates in the experimental group and control group were 69.2% (95%CI 48.2%-85.7%) and 28.6% (95%CI 11.3%-52.2%), respectively. 76.9% (20/26) and 52.4% (11/21) patients achieved down-staging in the experimental group and control group. Three patients developed grade 3–4 surgical complications. Grade 3–4 TRAEs included thrombocytopenia (4.0%), anemia (3.0%), neutropenia (2.0%), allergic reaction (2.0%), pneumonia (1.0%), myocardial infarction (1.0%). The median postoperative hospital stay in the experimental and control group were 10 days (range 7-38 days) and 11 days (range 7-66 days). Conclusions: Compared to SOX chemotherapy alone, sintilimab combined with SOX resulted in an encouraging pCR rate, MPR rate and downstaging rate as perioperative treatment for resectable locally advanced GC/GEJC, and safety was manageable. Clinical trial information: NCT04982939 .
Anlotinib combined with nab-paclitaxel and cisplatin as neoadjuvant treatment (NAT) for esophageal squamous cell carcinoma (ESCC): Update results of a single-arm, phase II clinical trial.
Authors: Zhang Yan-Feng , Li Xiao-Bing , Hong Yong-Gui , Li Xiao-Ming , Liang Wei-Min , Zheng Zhi-Xin , Yang Guang-Yi , Wen Yan-Yan , Cao Heng , Wu Wei-Long , Su Wen-Zhong 
Published: January 2023

366 Background: Neoadjuvant chemoradiation is associated with improved OS, DFS and pCR in patients (pts) with locoregional ESCC. Nevertheless, it is still needed to explore more tolerable preoperative regimen in ESCC. Anlotinib is a multi-targeted angiogenesis inhibitor and has been demonstrated effective and safe as second-line monotherapy in ESCC patients in China (NCT02649361). The combination therapy might be a possible strategy. The preliminary results of nab-paclitaxel and cisplatin combined with anlotinib as NAT for ESCC had been reported in 2022 ASCO (e16015) and 2022 ESMO (1252P). Here, we updated the results. Methods: ESCC pts with clinical stage II-III and radical resectable potential were recruited. The calculated sample size was 62 and eligible pts received anlotinib (12mg, po, d1~14, q3w), nab-paclitaxel (175mg/m2, iv, q3w) and cisplatin (20mg/m2, iv, d1~3, q3w) for 2 cycles as NAT before surgery. Four weeks later, pts underwent radical surgery after exclusion of contraindications. The primary endpoint was ORR assessed by investigator per RECIST 1.1, secondary endpoints included R0 resection rate, DFS, OS, DCR and safety. Results: From Apr 2021 to Sep 2022, 40 eligible pts were enrolled. Among them, 29 pts underwent surgery after 2 cycles of NAT, 6 pts chose other treatment options, and 5 pts are still receiving NAT. Pts who had received surgery (n=29) were included in this analysis. In best overall response assessment, ORR was 86.2% (95%CI: 68.3-96.1%) and DCR was 100.0% (95%CI: 88.1-100.0%). R0 resection was achieved in all 29 pts who underwent subsequent esophagectomy. Among them, 4 pts (13.8%) were confirmed to be pCR. At the data cut-off date (September 15, 2022), the median DFS was not yet available. Among the 40 enrolled cases, the safety profile revealed that the most common treatment-emergent adverse events (TEAEs) were gastrointestinal reactions (80.0%), liver damage (15.0%), nausea (12.5%), hypokalemia (10.0%) and myelosuppression (10.0%). Grade 3 TEAEs occurred in 2 pts (5.0%) included neutropenia (2.5%) and gastrointestinal reactions (2.5%). Conclusions: Anlotinib in combination with nab-paclitaxel and cisplatin is safe and feasible as neoadjuvant therapy in patients with ESCC.
Cytoreductive surgery and HIPEC in colorectal cancer peritoneal metastases (CRPM): Real-world outcomes in systemic anticancer treatment–naïve patients.
Authors: Tinsley Nadina , Nagaraju Raghavendar , O'Dwyer Sarah , Braun Michael , Mullamitha Saifee , Kamposioras Konstantinos , Aziz Omer , Barriuso Jorge 
Published: January 2023

39 Background: The role of heated intraperitoneal chemotherapy (HIPEC) in colorectal cancer peritoneal metastases (CRPM) is confounded by cytoreductive surgery (CRS) or receipt of peri-operative systemic anticancer therapy (SACT). Following Prodige-7, the role of Oxaliplatin HIPEC in addition to CRS has been debated. We evaluated a patient series undergoing CRS with Oxaliplatin (368mg/m2 for 30 mins) or Mitomycin C (MMC) (35mg/m2 for 90 mins) HIPEC stratified by extent of CRS and SACT. Methods: Data collected retrospectively from a prospective database of CRPM patients undergoing CRS +/- HIPEC at a single UK Peritoneal Tumour Centre included sex, primary tumour detail: site, TNM stage, SACT: adjuvant, peri-operative, operation details: peritoneal cancer index (PCI), cytoreductive score (CC), HIPEC agent, molecular profile: RAS, BRAFV600E, PIK3CA, microsatellite status, date of last follow-up or recurrence/death to 1st July 2022. Univariable and multivariable (MVA) analysis were performed for overall survival (OS) and recurrence free survival (RFS). Outcomes were compared among three patient groups: 1. all comers (all patients who underwent CRS +/- HIPEC), 2. CC0-1 (those who achieved CC0-1) and 3. SACT naïve (CC0-1 and no SACT pre-CRS, adjuvant SACT post primary resection allowed if completed > 6 months). Results: From April 2005 to April 2021, 409 patients received HIPEC: 271 (66%) MMC, 138 (34%) Oxaliplatin; 395 patients (97%) had CRPM (all comers); 336 (85%) achieved CC0-1; 187 (47%) were SACT naïve. Median OS for all comer, CC0-1 and SACT naïve groups were 39, 44 and 47 months respectively. MMC vs Oxaliplatin HIPEC median OS was 44 (95% CI 38-49) vs 50 (95% 40-60) months, p=0.3 in CC0-1. Median OS in SACT naïve was 46 (95% CI 34-58) vs 60 (95% CI 38-82) months, p=0.3. Oxaliplatin HIPEC showed a trend to benefit PCI <15 and SACT naïve (table). OS MVA in CC0-1 and SACT naïve showed Oxaliplatin HIPEC was comparable to MMC HR: 0.85, 95% CI (0.60-1.19) p=0.3, HR: 0.83, 95% CI (0.51-1.35) p=0.5, respectively. Oxaliplatin HIPEC had a significant benefit on local RFS in CC0-1 (MMC vs Oxaliplatin RFS 9 vs 12 months p=0.01; distant RFS 10 vs 12 months p=0.5, local and distant RFS 6 vs 8 months p=0.3). Local RFS MVA showed a HR: 0.64, 95% CI (0.41-0.99), p=0.04 for Oxaliplatin HIPEC when corrected by PCI, N stage and grade. Conclusions: The study shows a trend to better OS with Oxaliplatin HIPEC in selected patients with low volume CRPM not requiring SACT. CRS with Oxaliplatin HIPEC is beneficial in local RFS, suggesting there is a role for local control in CRPM with Oxaliplatin HIPEC. This needs to be further explored in clinical trials. [Table: see text]
Outcomes of transarterial chemoembolization in neoadjuvant therapy of patients with gastric cancer: A multicenter retrospective cohort study.
Authors: Min Jiang , Zhang Wei 
Published: January 2023

410 Background: Gastric cancer is one of the most common cancers globally. About half of new cases were reported in China, and the most cases are advanced gastric cancer. According to treatment guideline, gastric cancers with pT3-4, any N or any pT, N+ are recommended to fluoropyrimidine based preoperative/neoadjuvant chemotherapy, followed by D2 resection and adjuvant chemotherapy, however, the five-years survival rate remain only 30%~50%. Methods: We had a multi-center retrospective cohort study about outcome of 43 gastric cancers with pT3-4, any N treated by Transarterial Chemoembolizaion (TACE) in neoadjuvant chemotherapy between October 2018 and June 2019. The procedure of TACE is that nutrition artery of tumor, usually left, right or right gastroomental artery, was injected into Oxaliplatin (130mg/m2) in DSA, follow by 2ml Iodized Oil Granules. After TACE, patients had S1 from D1 to D14, cycled every 21 days. And then, patients had another above-mentioned TACE+oral S1 procedure, followed by a systemic chemotherapy regimen SOX (Oxaliplatin was injected through vein). After that, a D2 resection (If tumor can be resected) was given to the patients. 3 cycles adjuvant chemotherapy (SOX regimen) were given to patients after operation. Results: 42/43 (97.7%) patients have D2 resection successfully, and 1/42 patient went to systemic chemotherapy because liver metastasis was found before second TACE treatment. According to pathological analysis about the tumor tissues after resection, TRG (Tumor response grade) 0 was 25 in 42 (59.5%); TRG 1 was 10 (23.8%); TRG 2 was 5 (11.9%) and TRG 3 was 2 (4.8%). Anastomotic leak was reported in 3/42 (7.14%); abdominal infection anastomotic leak was in 4/42 (9.5%); no bleeding was reported. All patients were recovered after symptomatic treatment. No death was reported because of the short-term complications. 3-years PFS was 64.2% (95% CI: 60-69), 5 patients had local recurrence, 7 patients had distant recurrence and 3 patients had both. 3-years OS was 71.4% (95% CI: 65-75). Conclusions: TACE used in neoadjuvant therapy of patients with gastric cancer was safe, and shown as a promising method for improving the survival prognosis.
The association between trophoblast cell surface antigen 2 expression and nivolumab monotherapy in patients with advanced gastric cancer.
Authors: Kadono Toru , Shoji Hirokazu , Hirano Hidekazu , Okita Natsuko Okita , Iwasa Satoru , Takashima Atsuo , Kato Ken 
Published: January 2023

438 Background: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is associated with cancer growth. Overexpression of TROP2 in advanced gastric cancer (AGC) is known as a poor prognostic factor. However, the association between TROP2 expression and prognosis in patient with AGC treated with nivolumab (NIVO) is not known. Methods: Patients who received NIVO monotherapy as third- or later-line treatment (NIVO group) and those who received only fluoropyrimidine, platinum and taxanes (non-NIVO group) at our hospital between 2015 and 2019 were enrolled. High TROP2 expression was defined as ≥50% positive tumor cells with weak to moderate membranous staining or ≥10% tumor cells with strong membranous staining using immunohistochemistry. Overall survival from first-line chemotherapy (OS) and progression-free survival (PFS) from starting of NIVO were compared according to TROP2 expression and combined positivity score (CPS). Results: Of 111 patients, 61 were in the NIVO group and 50 were in the non-NIVO group. Patient characteristics in the NIVO/non-NIVO groups were median age 67 (range, 41-83)/64.5 (29-80) years; performance status 0, 20 (33%)/23 (46%); lymph node metastasis 41 (67%)/23 (46%); peritoneal metastasis 32 (53%)/26 (52%); liver metastasis 11 (18%)/6 (12%); lung metastasis 4 (7%)/4 (8%); TROP2 high 55 (90%)/43 (86%). Patient characteristics at starting of NIVO did not differ between TROP2 high and low in the NIVO group. Of 55 patients with TROP2 high, 22 patients (40%) were CPS≥1. In the non-NIVO group, OS from first-line chemotherapy did not differ between TROP2 high and low (median, 16.2 months [95%CI, 13.6-19.2] vs. 26.2 months [95%CI, 7.7-NA], HR 0.97, p=0.946). Meanwhile, in the NIVO group, patients with TROP2 high had significantly longer OS from first line chemotherapy than those with TROP2 low (median survival, 23.5 months [95%CI, 17.2-31.2] vs. 19.2 months [95%CI, 10.7-NA], HR 0.40, p=0.04). Progression-free survival (PFS) from starting of NIVO tended to be longer in TROP2 high group than those in TROP2 low group (median, 1.9 months [95%CI, 1.6-2.3] vs. 0.6 months [95%CI, 0.2-NA], HR 0.62, p=0.26). OS from first-line chemotherapy and PFS from starting of NIVO in patients with TROP2 high did not differ between CPS≥1 and CPS<1 (OS median, 24.0 months [95%CI, 13.8-39.7] vs. 23.2 months [95%CI, 17.0-32.4], HR 0.87, p=0.69; PFS median, 1.9 months [95%CI, 1.6-3.5] vs. 2.0 months [95%CI, 1.4-2.8], HR 0.90, p=0.72). Conclusions: Higher TROP2 expression related to longer survival in the patients with AGC treated with NIVO monotherapy.
The impact of claudin-18.2 expression in patients with advanced gastric cancer treated with nivolumab.
Authors: Kadono Toru , Shoji Hirokazu , Hirano Hidekazu , Okita Natsuko Okita , Iwasa Satoru , Takashima Atsuo , Kato Ken 
Published: January 2023

439 Background: Claudin-18.2 (CLDN 18.2) is the components of tight junction and one of the therapeutic targets in advanced gastric cancer (AGC). It has been reported that the tumor microenvironment in CLDN18.2 high AGC contains more PD-1 negative CD8+ T cells than in CLDN18.2 low, which may make anti-PD-1 antibodies less effective. However, the data on the association between CLDN18.2 expression and prognosis in patients with AGC treated with nivolumab (NIVO) is limited. Methods: Patients who received NIVO monotherapy as third- or later-line treatment (NIVO group) and those who received only fluoropyrimidine, platinum and taxanes (non-NIVO group) at our hospital between 2015 and 2019 were enrolled. High CLDN18.2 expression was defined as ≥40% positive tumor cells with moderate to strong membranous staining on immunohistochemistry. Overall survival (OS) and progression-free survival (PFS) were compared according to CLDN18.2 expression and combined positivity score (CPS). Results: There were 71 and 50 patients in the NIVO and non-NIVO groups, respectively. Patient characteristics at first-line chemotherapy in the NIVO/non-NIVO groups were median age 67 (range, 34-83)/64.5 (29-80) years; performance status 0, 22 (31%)/23 (46%); peritoneal metastasis 38 (54%)/26 (52%); liver metastasis 15 (21%)/6 (12%); CLDN18.2 high 31 (44%)/25 (50%). In the NIVO group, patient characteristics did not differ between CLDN18.2 high and low except for peritoneal metastasis (25 [81%]/22 [55%]). Nine patients (29%) were CLDN18.2 high with CPS≥1, and 14 (35%) were CLDN18.2 low with CPS≥1. OS from first-line chemotherapy did not differ between CLDN18.2 high and low in the non-NIVO group (median, 18.4 months [95%CI, 10.7-32.4] vs. 16.9 months [95%CI, 14.8-21.4], HR 0.94 [95%CI, 0.50-1.78], p=0.847). In the NIVO group, OS from first-line chemotherapy and OS and PFS after starting NIVO did not differ between CLDN18.2 high and low; however, patients with CLDN18.2 high and CPS≥1 had longer OS after starting NIVO (median, 14.8 months [95%CI, 4.2-NR] vs. 3.6 months [95%CI, 2.0-6.9], HR 0.27 [95%CI, 0.11-0.68], p=0.012) and PFS after starting NIVO (median, 3.5 months [95%CI, 0.7-NR] vs. 1.7 months [95%CI, 1.1-3.1], HR 0.38 [95%CI, 0.15-0.97], p=0.033) than those with CLDN 18.2 high and CPS<1. Patients with CLDN18.2 high and CPS≥1 had a trend of longer OS from first-line chemotherapy than those with CLDN 18.2 high and CPS<1 (median, 37.4 months [95%CI, 11.1-NR] vs. 14.8 months [95%CI, 9.4-31.2], HR 0.47 [95%CI, 0.17-1.31], p=0.12). In the CLDN18.2 low group, OS and PFS did not differ between CPS≥1 and <1. Conclusions: With CLDN18.2 high, CPS≥1 was associated with longer survival in AGC treated with NIVO.
Primary results of the ICONIC phase 2 trial of perioperative FLOT plus avelumab (FLOT-A) in operable oesophagogastric adenocarcinoma (OGA).
Authors: Gordon Anderley , Challoner Benjamin , Athauda Avani , Woolston Andrew , Mansukhani Sonia , Dunstan Matt , Petrou Nikoletta , Khabra Komel , Lazaro-Alcausi Retchel , Crux Richard , Borja Victoria , Begum Ruwaida , Rana Isma , Rao Sheela , Kumar Sacheen , Cunningham David , Chau Ian , Starling Naureen , Chaudry M. Asif , Gerlinger Marco 
Published: January 2023

446 Background: ICONIC evaluated 4+4 cycles of FLOT-A (2-weekly standard FLOT with 10mg/kg of the anti-PDL1 antibody avelumab) for perioperative treatment of early-stage OGA. We report R0 resection rates, pathologic complete response rates (pCR), pathologic tumour regression grades (TRG) according to Mandard classification and progression free survival (PFS) data in the modified intention to treat population (mITT), and translational analyses. Methods: ICONIC is a single-arm phase II trial of FLOT-A in patients (pts) with ≥cT2-4 or N+ OGA. The pCR rate in surgical specimens was the primary endpoint. Response evaluation according to Mandard, R0 rates and PFS were among secondary endpoints. PD-L1 expression was assessed according to the combined positive score (CPS) with the 22C3 pharmDx kit. Results: The trial closed early after the pCR rate was 15% (95% CI: 49%-83%) once 34 pts in the mITT population (defined as pts who had 1-4 cycles FLOT-A and surgery) as the pre-specified aim to demonstrate a pCR rate of 25% in 40 pts was unlikely to be met. Baseline characteristics of the mITT population were: median age 64y, 79% male, 79% OG junction, 6% oesophageal, 15% stomach, 65% poorly differentiated, 79% T3/4, 59% N+. 91% of pts received all 4 pre-operative cycles and 97% of pts achieved R0 resections. PDL1 CPS ≥1 and CPS ≥5 were nevertheless associated with increased TRG3 and decreased TRG4/5 rates. 3/34 pts (9%) had hypermutated/MMRd tumours and after their exclusion, the association of higher CPS with better TRG3 and decreased TRG4/5 remained. With a median follow up duration of 15.8 months the 12-month PFS was 93.1% (95% CI: 75.1%-98.2%) which is promising compared to historic results with peri-operative FLOT. Conclusions: Although FLOT-A failed to increase pCR rates to 25%, there is a trend towards higher TRG3 and lower TRG4/5 in pts with PDL1 CPS≥1 and CPS≥5 and promising PFS indicate activity of immunotherapy in combination with FLOT chemotherapy. Translational and biomarker analyses by exome- and RNA-sequencing, and multiplex immune cell staining are ongoing and will be reported. Clinical trial information: NCT03399071 . [Table: see text]
Use of high-dimensional and spatial immune profiling to explore sotigalimab (CD40 agonist) activation of antigen presenting cells and T cells in the tumor microenvironment in patients with esophageal/gastroesophageal junction cancer.
Authors: Soto Maira , Filbert Erin L , Yang Hai , Zhang Li , Starzinski Stephanie , Starzinski Alec , Cheung Alexander , Li Tony , Hsu Frank J. , Ko Andrew H. , Fong Lawrence , Keenan Bridget P 
Published: January 2023

450 Background: Neoadjuvant chemoradiation (CRT) followed by surgical resection is standard of care for patients with locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer. A pathologic complete response (pCR) at surgery is associated with improved survival outcomes. Sotigalimab (sotiga) is a potent CD40 agonist mAb capable of inducing and expanding anti-tumor immune responses. A recently reported non-randomized phase II clinical trial of sotiga combined with CRT in E/GEJ cancer patients showed promising pCR rates that compared favorably to historical data1. Here, deep immune profiling was performed on a subset of patients to gain insight into the mechanism of sotiga. Methods: In the initial safety cohort (n=6) of this phase II E/GEJ clinical trial, tumor and blood samples were obtained pre-treatment and again following a single lead-in dose of sotiga, prior to initiation of CRT. Immune modulation in the tumor microenvironment and blood of patients was examined using high dimensional techniques, including mass cytometry, multiplexed ion beam imaging, and single cell RNA sequencing. Results: Sotiga administration dramatically re-models the tumor microenvironment, inducing immune infiltration and shifting the immune composition predominantly toward an inflammatory phenotype. At baseline, E/GEJ tumors were infiltrated with myeloid cells and T cells, the majority of which were Tregs. Sotiga increased antigen-presenting cell (APC) infiltration in tumors and activated dendritic cells as demonstrated by expression of MHCII and CD86. Sotiga treatment also induced infiltration of activated cytotoxic T cells and decreased the proportion of Tregs. There was also evidence of T cell activation in peripheral blood with increased expression of 4-1BB, CTLA-4, ICOS and PD-L1. Therapeutic responses to sotiga were associated with distinct T cell signatures both at baseline and on-treatment. At baseline, pCR patients (representing 4 of the 6 pts (67%) in this cohort) had a higher ratio of memory CD4+ T cells to Tregs which further increased following sotiga treatment, whereas patients who did not have a pCR had a higher proportion of myeloid cells at baseline and did not show a decrease in Treg cells after sotiga treatment. Conclusions: Sotiga induced dramatic changes in the tumor microenvironment including increased frequency of activated T cells and APCs, and decreased frequency of Tregs. A distinct signature of T cell infiltration in baseline tumor biopsies was observed in patients who achieved a pCR versus those who did not, potentially identifying patients that may benefit from this novel treatment strategy.