bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposal of modified textbook outcome for improving the quality of gastric cancer surgery: A single-center study.
Authors: Kim Sara , Kim Sa-Hong , Choi Jong-Ho , Choe Hwi Nyeong , Park Ji-Hyeon , Kong Seong-Ho , Kwak Yoonjin , Park Do Joong , Lee Hye Seung , Lee Hyuk-Joon , Kim Woo Ho , Yang Han-Kwang 
Published: January 2022

270 Background: Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Since 2014, the national healthcare quality assessment has been implemented for gastric cancer in Korea, which has the highest incidence. The proportion of early gastric cancer through early detection is high in Korea, and gastric cancer surgery has a great influence on outcome index. The aim of this study is to find indicators that can improve Textbook outcome (TO) in patients undergoing gastric cancer surgery. Comparing with Western data, we intended to propose a modified TO (mTO). Methods: Using a prospective clinical database, we included consecutive cases of gastrectomy for primary gastric cancer between 2014 and 2016. TO was achieved when 10 original indicators proposed by the DUCA group were satisfied. We propose to adjust the index of the number of retrieved lymph nodes from 15 to 30 as the modified TO(mTO) indicator for improving the quality of gastrectomy. For comparison with Western data, we calculated TO, mTO and survival in stage I versus Stage II and III. Results: A total of 2,153 patients were included. TO was achieved in 80.1 percents by 10 original indicators. Most of the indicators showed more than 90 percents of TO satisfaction. Five-year survival was significantly different between the TO (90.0%) and non-TO (76.1%) groups ( P < 0.001). For 608 patients in stage II and III, TO was 72.9 percents, which was much higher than the Western publications. Five-year survival were 74.8 percents for the TO group and 56.8 percents for the non-TO group in stage II and III patients. We found that the number of metastatic lymph nodes increases as the stage increases and even the number of metastatic lymph nodes in stage IIIC exceeded 19. The modified textbook outcome (mTO) for stage II and III was 65.3 percents, and five–year survival was significantly different between mTO (74.0%) and mnon-TO (62.1%) groups ( P < 0.001). To prevent R1 resection and minimize the proportion of remnant total gastrectomy, we performed frozen study examinations of the proximal and distal margins as to ensure high oncological safety. Conclusions: Data from a high volume gastric cancer center showed the high textbook outcome rates. It suggests that the minimum number of lymph node retrievals should be at least 30, even in advanced gastric cancer, and routine intraoperative frozen study examination are necessary to increase R0 resection.
X versus XELOX versus PF in definitive concurrent chemoradiotherapy (DCRT) for local-advanced squamous esophageal cancer (ESCC): 2021 update from a multicenter, open-label, randomized III trial, CRTCOESC trial.
Authors: Jia Ruinuo , Shan Tanyou , Wan Lixin , Zheng Anping , Hui Shuang , Xu Zhiqiao , Wang Feng , Zheng Guobao , Lu Ping , Zhang Guifang , Zheng Yingjuan , Cui Yanhui , Luo Xiaoyong , Zhang Weiguo , Li Wanying , Li Ruonan , Zhou Fuyou , Gao Shegan 
Published: January 2022

274 Background: PF (5-fluorouracil plus cisplatin) is the standard regimen for local advanced ESCC with DCRT. CRTCOESC aims to evaluate the effect and safety of X (capecitabine) regimen versus XELOX (capecitabine plus oxaliplatin) and PF in Chinese local advanced ESCC with DCRT by randomized, open-label, multicenter designed. Methods: Patients with ESCC (T2-4N0-2M0) were randomized to 3 groups as X (capecitabine 625mg/m2, bid d1-5, 6 weeks), XELOX (oxaliplatin: 65mg/m2, d1, 8, 22, 29; capecitabine: 625mg/m2, bid d1-5; 6 weeks), or PF (cisplatin: 75mg/m2 d1, 29, 5-Fu: 750mg/m2 CIV24h d1-4, d29-32), Intensity Modulated Radiation Therapy (IMRT) was delivered by 50Gy/2Gy currently. In addition, quadratic randomize were done within all groups to decide whether 2 cycles chemotherapy adding or not after DCRT. 2-year OS and Grade 3-5 AEs were the primary endpoints, 2-year PFS and short-term efficacy (STE) as rates of CR and ORR (CR+PR) (confirmed by gastroscopy biopsy at 16 weeks) were the secondary endpoints. Results: 249 pts successfully were accrued from 13 centers during 2014.10-2020.04. All pts were finished DCRT and evaluated STE at 16 weeks. 229 pts were followed up for 2- years. There were no differences between 3 groups on patients’ baseline characters including age, gender, ECGO score, clinical stage, pathology grade and smoking. In X, XELOX and PF groups, the 2-year OS were 73.8% (59/80), 74.3% (55/47) and 73.3% (55/75) ( P = 0.991), the median OS were 41.43 (3.29), 53.3 (7.686) and 44.6 (4.946) (months, P = 0.896); the incidences of AEs (grade 3-5) were 24.1% (20/83), 31.8% (28/88) and 43.6% (34/78) ( P = 0.03); the 2-year PFS were 63.7% (51/80), 60.8% (45/74) and 61.3% (46/75) ( P = 0.922), the median PFS were 38.467 (2.965), 39.5 (7.619) and 35.8 (4.435) (months, P = 0.87); the CR rate were 36.1% (30/83), 36.4% (32/88), and 35.9% (28/78) ( P = 0.998), and the ORR were 73.5%, 79.5%, and 75.6% ( P = 0.64), respectively. There were no differences on OS, PFS and rates of CR and ORR between 3 groups but the incidence of AEs in X group was the lowest significantly. Subgroup analysis results shown adding 2 cycles chemotherapy after CRT had both OS and PFS advantages but lacked statistically significance. Conclusions: Compared with PF, DCRT with X or XELOX shown lower incidence of AEs and similar OS, PFS and STE. X regimen carried out the lowest AEs incidence. Adding 2 cycles chemotherapy after DCRT seemly had advantages on OS and PFS. Clinical trial information: NCT02025036.
The efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma.
Authors: Xu Weili , Jiang Youhua , Wang Changchun , Wu Jie , Li Jianqiang , Hu Yuqian , Lu Weishan , Shen Dijian , Wang Yinjie , Chen Qixun 
Published: January 2022

278 Background: To explore the efficacy and safety of neoadjuvant camrelizumab and chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by an open label, single-arm, phase 2 clinical trial (ClinicalTrials.gov, Identifier number: NCT04506138). Methods: The eligible patients were arranged to receive 2 cycles of camrelizumab (200mg, day 1) combined with carboplatin (AUC = 5, day 1) and albumin paclitaxel (100 mg/m2, day 1, 8). All treatments were given intravenously in 3-week cycle. Patients underwent surgery within 4-6 weeks after the completion of neoadjuvant treatment. The primary endpoint was pathologic complete response (pCR), and secondary endpoints were major pathological response (MPR), safety and feasibility. The quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scale and EQ-5D-3L scale. Results: A total of 46 patients were recruited, among whom the clinical stage II, III, and IVa at baseline were 11 (23.9%), 33 (71.7%), and 2 (4.3%), respectively. Forty-five patients completed 2 cycles of neoadjuvant treatment. One patient received 1 cycle of neoadjuvant treatment and then lost to be followed up. Eight patients did not receive surgery. Except 1 patient accept exploratory surgery, 37 patients (37/46, 80.4%) achieved R0 resection. Eight patients (8/37, 21.6%) had pCR in both primary tumors and lymph nodes. MPR of primary tumors and lymph nodes was observed in 18 patients (18/37, 48.6%). During neoadjuvant treatment period, all 46 patients presented with treatment-related AEs (TRAEs) of any grade. Seven patients (7/46,15.2%) experienced grade ≥ 3 TRAEs. One patient suffered grade 5 immune-associated pneumonia. The most common TRAEs were anemia (32/46, 70.0%), followed by thrombocytopenia (15, 32.6%), leukopenia (14, 30.4%), neutropenia (13, 28.3%), rash (12, 26.1%), reactive cutaneous capillary endothelial proliferation (RCCEP) (7, 15.2%). The median interval between the first cycle of neoadjuvant treatment and surgery was 64 days (range, 56-77 days). Symptom scores in FACT-E scale were improved by neoadjuvant treatment (t = -2.60, P = 0.01). PD-L1 CPS (< 10 vs ≥ 10), PD-L1 TPS (< 1% vs ≥ 1%) and TMB (split according to top 20% of TMB value) had no effect on the pCR rate and MPR rate. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy achieved a promising pathologic response, which was effective and safe. Meanwhile, neoadjuvant treatment improved QoL of patients. Some larger multi-center trials are undergoing for further confirmation of efficacy and safety. Clinical trial information: NCT04506138.
A multicenter randomized phase III study of albumin-bound paclitaxel combined with S-1 (AS) versus oxaliplatin combined with S-1 (SOX) for first-line treatment of advanced gastric cancer (GAPSO study).
Authors: Dai Yuhong , Yu Xiongjie , Xu Huiting , Zhuang Liang , Zhang Mingsheng , Zou Yanmei , Fu Qiang , Qiu Hong , Yuan Xianglin 
Published: January 2022

282 Background: Albumin-bound paclitaxel has been proven to be an active agent in advanced gastric cancer, and was approved by PMDA Japan for use as a second-line treatment of advanced gastric cancer. The aim of this study was to evaluated the efficacy and safety of AS and SOX in the first-line treatment of advanced gastric cancer. Methods: Patients diagnosed with unresectable locally advanced, recurrent or metastatic human epidermal growth factor receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma were randomized (1:1) to either AS group (albumin-bound paclitaxel 260mg/m2 d1 or 130mg/m2 d1, 8; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks) or SOX group (oxaliplatin 130mg/m2 d1; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks). Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: Between March 2019 and March 2021, 96 patients were enrolled and 85 patients (AS group, n = 43; SOX group, n = 42) who received at least one dose of study drug and had at least one postbaseline efficacy evaluation were included in the final analysis. 34 (79.0%) patients in the AS group and 35 (83.3%) in the SOX group had discontinued treatment. Of these 85 patients, 78.8% had two or more organs involved, 61.2% had peritoneal dissemination, and more than 1/4 had massive ascites. Patient demographics and disease characteristics were generally balanced between arms. With median follow-up 15.4 months (95% CI, 8.8-21.9), the median PFS of AS group vs. SOX group was 9.2 vs.5.1 months (HR = 0.58 [95% CI 0.36-0.96], p = 0.034); and the median OS was 14.4 vs. 15.4 months (HR = 0.73 [95%CI 0.40-1.34], p = 0.375). Tumor response was assessable in 33 patients according to RECIST V1.1 in both cohorts, the ORR and DCR were similar in AS vs. SOX arm (ORR: 54.5% vs. 51.5%, P = 0.805; DCR: 78.8% vs. 78.8%, P = 1.000). The main grade 3 or worse treatment-related adverse events were neutropenia (30.2% vs 23.8%), Leucopenia (11.6% vs 11.9%) and peripheral sensory neuropathy (4.7% vs 7.1%) in AS and SOX group. The study was planned to be adjusted, due to the widespread use of immunotherapy in first-line treatment of gastric cancer. Conclusions: The results of this study indicated that in previously untreated patients with unresectable locally advanced, recurrent or metastatic HER2-negative gastric or GEJ adenocarcinoma, AS achieved better PFS than SOX, with an inadequate power. The toxicities were controllable and consistent with previously reported. Clinical trial information: NCT03801668.
A phase II study of FOLFOX combined with nab-paclitaxel (FOLFOX-A) in the treatment of metastatic or advanced unresectable gastric, gastroesophageal junction adenocarcinoma: Big Ten Cancer Research Consortium—BTCRC-GI15-015.
Authors: Benson Al Bowen , Kocherginsky Masha , Kasi Pashtoon Murtaza , Uboha Nataliya Volodymyrivna , Lou Emil , Chen Yolande , Hochster Howard S. , Kircher Sheetal Mehta , Mulcahy Mary Frances 
Published: January 2022

283 Background: Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/GEJ adenocarcinoma. Previously, anthracycline based triplets have been aborted due to lack of efficacy and toxicity. We hypothesize that the combination of FOLFOX and nab-paclitaxel (FOLFOX-A) will have a higher efficacy, a better tolerability, and enhanced patient reported outcomes. Methods: Phase II single arm trial of FOLFOX + nab-paclitaxel in chemotherapy–naïve unresectable, advanced gastric/GEJ adenocarcinoma. Nab-paclitaxel 150 mg/m2 · Oxaliplatin 85 mg/m2 · Leucovorin 400 mg/m2 · 5-FU 2400 mg/m2 over 46-48 hrs every 14 days. Primary objective was response rate.Evaluable disease according to RECIST v1.1 for solid tumors was required. Her-2 positive gastric tumor patients and those with clinically significant peripheral neuropathy were excluded. A Simon (1989), optimal two-stage design was employed. Response rates and Clopper-Pearson confidence intervals are reported. Progression free (PFS) and overall (OS) survival were estimated using the method of Kaplan-Meier. Results: A 29% response rate was observed in Stage 1 and therefore the study continued enrolling all planned 39 patients. Median age was 63 (range 20-80) years, 29 (74%) were male, 30 patients now are off treatment due to progression (17), initiation of alternative therapy (5) and side effects (3). 38 patients started treatment. Of the 35 patients evaluable for response, 14 (40.0%; 95%CI: 23.9% - 57.9%) had CR/PR as best response, with disease control rate of 80.0%. Progression-free (PFS) and overall survival (OS) were available for 36 patients, with median follow-up duration of 20 months (range: 1.9 - 34.45 months). Median PFS was 6.6 months (95%CI: 5.7 – 13.0), with 28.6% (95%CI: 15.2% - 53.9%) 12-month PFS rate. There were 21 deaths, median OS was 11.0 months (95%CI: 9.6 – 21.7), 12-month OS rate was 46.6% (95%CI: 30.9% - 70.3%). Treatment-related grade 3–4 toxicities included peripheral sensory neuropathy, anemia (18.4% each), decreased neutrophil count (15.8%), and diarrhea (7.9%). One patient died due to multi-organ failure, not treatment-related. 23 patients required dose reductions or discontinuation of at least 1 component of the 3-drug regimen due to toxicity. Median number of cycles completed was 4 (range: 0-30). Conclusions: FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.
Usefulness of an S-1 dosage formula: An exploratory analysis of randomized clinical trial (JCOG1001).
Authors: Kawakami Takeshi , Yasui Hirofumi , Mizusawa Junki , Hasegawa Hiroko , Imazeki Hiroshi , Kano Kazuki , Sato Yuya , Iwasa Satoru , Takiguchi Shuji , Kurokawa Yukinori , Doki Yuichiro , Boku Narikazu , Yoshikawa Takaki , Terashima Masanori 
Published: January 2022

288 Background: Although the S-1 dose is determined by body surface area (BSA), its blood concentration and adverse events are affected by renal function. One study had reported the clinical utility of an S-1 dosage formula for calculating the dose for target blood concentration based on renal function (Booka E. Gastric Cancer 2016;19:876-86.). The present study aimed to explore the usefulness of this formula in adjuvant chemotherapy for gastric cancer. Methods: Ad hoc analyses was performed using data from patients enrolled in a phase III trial, JCOG1001, to evaluate the role of bursectomy for resectable advanced gastric cancer. In the abovementioned trial, patients with stage II/III received adjuvant S-1 chemotherapy based on BSA. The present study calculated the S-1 dose using the following formula: 1447.8 * (14.5+0.301*CLcr+8.23*SEX [male=1, female=0])*BSA (mg/day). Patients were divided into three groups, overdosed (OD), equal dosed (ED), and underdosed (UD), by comparing the initial dosage administered with that recommended by the formula. Results: Among the 686 eligible pts, 324, 304, and 58 were respectively classified as OD/ED/UD, with the following characteristics: median age, 67.5/64/53.5 years; men 188/229/57 (58%/75%/98%); undifferentiated type, 168/172/38 (52%/57%/66%); and pStage III, 212/200/41 (65%/66%/71%). Median relative dose intensity in OD/ED/UD pts was 93.8%/108.8%/75.0% based on the formula-recommended dose. The planned adjuvant S-1 therapy was completed in 69%/74%/74%, dose reduction and treatment schedule alteration were required in 31%/21%/9% and 20%/17%/9%, and treatment was terminated due to adverse events in 25%/18%/12%. The 5-year relapse-free (RFS) and overall survival (OS) OD/ED/UD patients were 66.6%/69.2%/74.0% and 77.0%/74.3%/77.3%, in pStage II 80.2%/85.6%/93.8% and 88.3%/90.1%/100%, and pStage III 59.6%/60.4%/65.8% and 67.0%/70.0%/67.7%, respectively. OD pts had significantly higher incidences of grade 3 or higher anemia, thrombocytopenia, diarrhea, stomatitis than ED and UD pts. Conclusions: Despite no difference in survival, this formula improved treatment compliance in OD patients receiving adjuvant S-1 chemotherapy for gastric cancer.[Table: see text]
Phase II study of SHR1210 and trastuzumab in combination with CAPOX for neoadjuvant treatment of HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Li Ning , Li Zhi , Fu Qiang , Zhang Bin , Zhang Jian , Wan XiangBin , Lu Chaomin , Wang Jinbang , Deng Wenying , Wei Chen , Ma Yijie , Bie Liangyu , Wang Mengyu , Luo Suxia 
Published: January 2022

296 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer. PANTHERA study had showed a significant tumor shrinkage for HER2 positive advanced gastric cancer treated with anti-PD-1 agent, transtuzumab and chemotherapy. SHR1210, a human IgG4 monoclonal antibody that binds to PD-1, has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the addition of SHR1210 and trastuzumab to CAPOX for neoadjuvant treatment of HER2-positive gastric or GEJ adenocarcinoma. Methods: In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable HER2-positive gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of transtuzumab (loading dose of 8mg/kg, with subsequent doses of 6 mg/kg, q3w) and CAPOX (oxaliplatin 130 mg/m2 day 1, capecitabine 1000 mg/ m2 bid po day 1-14, q3w) in combination with 3 cycles of SHR1210 (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of CAPOX. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). This trial is registered with ClinicalTrials.gov, number NCT03950271. Results: Between Jan 20, 2020, and Sept 15, 2021, 22 patients were enrolled and commenced treatment. Four patients had not completed neoadjuvant treatment. Twopatitents refused surgery. Sixteen patients who experienced D2 resection, 9 (56.3%) achieved MPR, including 5 (31.3%) with pCR (ypT0N0M0). The R0 rese-ction rate was 100%. The ORR was 77.3%. The main grade 3 or 4 treatment-related adverse events (TRAEs) included lymphocytopenia (22.7%), neutropenia(13.6%), thrombocytopenia (13.6%) and anaemia (5%). Most frequent grade 1 or 2 TRAEs were Nausea (68.2%), lymphocytopenia (63.6%), leukopenia (59.1%), Anaemia (59.1%), Thrombocytopenia (50%), Serum aspartate aminotransfe-rase increased (45.5%) and hypothyroidism (31.8%). There was no surgical del-ays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of SHR1210, transtuzumab and CAPOX is a safe and efficacious treatment option for patients with HER2-positive gastric or GEJ adenocarcinoma. More importantly, 31.3% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: NCT03950271.
Neoadjuvant PD-1 inhibitor tislelizumab combined with s-1 plus oxaliplatin in patients with local advanced gastric cancer or gastroesophageal junction adenocarcinoma: Interim results of a single-arm, phase II trial.
Authors: Tao Kaixiong , Yin Yuping , Lin Yao , Li Wei , Li Ruidong , Liu Weizhen , Xiong Zhen , Zeng Xiangyu , Cai Ming , Wu Cuanqing , Zhang Peng 
Published: January 2022

300 Background: D2 radical surgery and adjuvant chemotherapy is mainly treatment scheme of Gastric/gastroesophageal junction (G/GEJ) cancer. Nevertheless, the prognosis of patients with G/GEJ cancer still remain variation after normative therapy. Further, neoadjuvant therapy showed highlighted application value and Immuno-oncology therapy is newly prominent in improving prognosis of patients with G/GEJ cancer recently. Methods: We conduct a prospective, single-arm, open-label, non-randomized phase II trials of PD-1 inhibitor Tislelizumab combined with S-1 plus Oxaliplatin (SOX) in Patients with Local Advanced G/GEJ cancer (NCT04890392). Treatment is performed for 3 cycles (21 days/1 cycle) and all patients are evaluated tumor pathology regression after D2 radical surgery performed, and are followed up. The primary endpoints were tumor major pathology response (MPR) and other events of tumor response assessed by tumor regression grade (TRG). We also recode the variation of immunological indicators during treatment and develop a predictive nomogram to predict the probability of patients reached MPR. Results: 13 of 21 patients (61.9%) reached MPR after treatment and 5 of 21 patients had a complete tumor response (23.8%). While 2 of 21 patients were assessed as disease progression (9.5%). there was no significant difference in MPR (TRG = 0&1) between gastric cancer and gastroesophageal junction cancer (6/11 vs. 7/10. P = 0.525). Adverse events occurred in 11 of 21 patients (52.4%) in the cohort. Grade III-IV adverse event occurred in only 1 of 21 patients (4.8%). the variation of CD3+ and CD4+ immune cell counts and TNFα of patients reached MPR was significantly higher than patients not reached MPR during treatment (CD3+, P = 0.044; CD4+, P = 0.042; TNFα, P = 0.048). Further, we developed the predictive nomogram of MPR consisted of age, Hb and TNFα and the AUC of nomogram was 0.890; the C-index was 0.885. Conclusions: Neoadjuvant PD-1 Inhibitor Tislelizumab combined with SOX shows greatly potential of therapeutic application in patients with G/GEJ cancer with no-increasing treatment-related adverse events. While this predictive nomogram may help therapists more accurately apply this scheme and explore improvement. Clinical trial information: NCT04890392.