bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of paclitaxel and cisplatin in combination with anlotinib as first-line treatment for patients with advanced ESCC: A multicenter, single-arm, open-label phase II clinical trial.
Authors: Li Ning , Wu Tao , Hong Yong-Gui , Guo Yanzhen , Cheng Yufeng , Li Baosheng , Wang Junsheng , Luo Suxia 
Published: January 2023

376 Background: Paclitaxel combined with cisplatin regimen has been the standard of care as first-line therapy in advanced ESCC for almost two decades. PD-1 blockades combined with chemotherapy as first line setting exhibited superior efficacy for patients with ESCC recently. Anlotinib was a potential second-line monotherapy for patients with ESCC in China. Therefore, this study was designed to explore the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC. The study had been reported in 2020 ESMO (Abs 1448), 2021 ASCO-GI Symposium (Abs 181), 2021 ASCO (e16013), 2021 ESMO (Abs 1805) and 2022 ASCO-GI Symposium (Abs 315) consecutively and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 4~6 cycles as initial therapy. For those who did not have PD, maintenance treatment was adopted with anlotinib monotherapy (10mg, po, d1~14, q3w) until PD or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. The predefined sample size was 47. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Mar 2021, a total of 47 patients were enrolled, 46 patients included in per-protocol set analysis. The best overall response indicated that there were 4 CR (8.7%), 31 PR (67.4%), 7 SD (15.2%) and 4 NE (8.7%). Consequently, ORR was 76.1% (95%CI: 61.2%-87.4%) and DCR was 91.3% (95%CI: 79.2%-97.6%). At the data cut-off date on Jan 2022, The median PFS and median OS were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. Additionally, safety profile exhibited that the regimen was tolerable. Common grade ≥3 adverse reactions were neutropenia (17.0%), bone marrow suppression (12.8%), nausea (10.6%), and vomiting (10.6%). Conclusions: Regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in phase III clinical trials. Clinical trial information: NCT04063683 .
Retrospective analysis of drug intake affecting the intestinal microbiota and the therapeutic effects of chemotherapy on gastric cancer.
Authors: Nakamura Takeaki , Watanabe Ryosuke , Yamamura Takahiro , Harada Kazuaki , Kawamoto Yasuyuki , Yuki Satoshi , Sakamoto Naoya , Komatsu Yoshito 
Published: January 2023

379 Background: Administration of some medications, such as antibiotics, antacids, and probiotic supplementation, may affects the treatment outcomes of immune checkpoint inhibitors (ICIs), through the change of gut microbiota in cancer patients. Even when ICIs are combined with cytotoxic chemotherapy (Chemo), a use of such medications is expected to be a potential biomarker. However, the impacts of medications that affect gut microbiota on the efficacy of Chemo alone is unclear. Methods: We retrospectively analyzed patients who received fluoropyrimidines and platinum-based therapy for advanced gastric cancer in our institutions between January 2010 and December 2019. Progression-free survival (PFS) and overall survival (OS) by history of antibiotic/antacid/probiotic supplementation, were analysed. Results: A total of 101 pts were analyzed. Median age was 66 years (range, 30-81), female/male; 36/65, 1st-line regimen SP/XP/SOX/XELOX/FOLFOX; 52/2/39/1/7. In all patients, The median PFS for first-line treatment was 5.8 months (95% CI: 5.0-7.3) and the median OS was 15.5 months (95% CI: 12.5-18.6).Univariate analysis for PFS of first-line treatment did not show a significant difference in antibiotic use (median 7.6 vs 5.5 months, HR: 0.79 [95%CI: 0.50-1.24], p=0.31), oral antacids (median 6.6 vs 5.8 months, HR: 0.96 [95%CI: 0.61-1.54], p=0.89) and probiotic supplementation (median 9.1 vs 5.5 months, HR: 0.7 [95%CI: 0.38-1.26], p=0.24). Similarly in OS, the use of antibiotics (median 18.4 versus 13.4 months, HR: 0.85 [95%CI: 0.53-1.37], p=0.49), oral antacids (median 16.3 vs 13.8 months, HR: 1.15 [95%CI: 0.70-1.88], p=0.58), and oral probiotic supplementation (median 20.2 vs 13.8 months, HR: 0.77 [95%CI: 0.42-1.40], p=0.40), with no statistically significant differences. Conclusions: In this study, there were no significant differences in PFS and OS between patients administered with or without antibiotics, antacids, or probiotic supplementation. Future studies are expected to investigate the impacts of these medications on the treatment outcomes of ICIs+Chemo combination.
Adjuvant nab-paclitaxel plus S-1 versus oxaliplatin plus capecitabine after curative D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase 3 open-label, randomized controlled trial
Authors: Pengfei Yu , Du Yian , Xu Zhiyuan , Yang Litao , Ying Jieer , Chen Ping , Wei Yunhai , Wu Yingjie , Yan Zhilong , Xu Hongtao , Zhang Xiaojing , Li Yong , Zheng Zhichao , Chen Zhiheng , Cheng Xiangdong 
Published: January 2023

386 Background: Although adjuvant chemotherapy improvs the survival rate of stage III gastric cancer after curative D2 gastrectomy, the overall benefit is unsatisfactory. Therefore, the study was designed to evaluate the efficacy and safety of adjuvant nab-paclitaxel plus S-1 (AS) versus oxaliplatin plus capecitabine (CAPOX) in the treatment of stage III gastric adenocarcinoma (GAC) after curative D2 gastrectomy. Methods: This phase 3, open-label, randomized study was conducted in patients with stage III GAC after curative D2 gastrectomy. Patients were randomized (1:1) to receive adjuvant AS (100 mg/m2 nab-paclitaxel on days 1 and 8; 40-60 mg oral S-1 twice daily on days 1-14) or CAPOX (130 mg/m2 oxaliplatin on day 1; 1000 mg/m2 oral capecitabine twice daily on days 1-14), repeat every 3 weeks for 8 cycles. The primary endpoint was the 3-year disease-free survival (DFS) rate by intention-to-treat analysis. Secondary endpoints included overall survival (OS) and safety. Results: Between March 2020 and August 2022, 280 patients were screened and 233 were randomly assigned to study treatment (AS, 115; CAPOX, 118). The median age was 62 years (range, 27-77) in AS and 63 years (range, 35-75) in CAPOX. The pathological stages were 42.61% stage IIIA, 34.78% stage IIIB, and 22.61% stage IIIC in AS, while those of CAPOX were 47.46% stage IIIA, 30.51% stage IIIB, and 22.03% stage IIIC. The 1-year DFS rate was 89.0% in AS versus 76.9% in CAPOX. The 1-year OS rate was higher in AS versus CAPOX (100% vs. 95.5%). Seven (6.09%) in AS and 11 (9.32%) in CAPOX experienced recurrence during follow-up; thereinto, one in CAPOX confirmed recurrence with tumor markers and clinical manifestations. Recurrence sites in AS and CAPOX involved the peritoneum (1 vs. 4), locoregional (1 vs. 2), and distant (5 vs. 6), of which, certain patients had 2 simultaneously. Among 6 deaths in CAPOX, 3 died from GAC, 1 died from other diseases and 2 died from unknown. The median relative dose intensity was 96.91% for nab-paclitaxel and 88.00% for S-1 in AS, 82.77% for oxaliplatin and 79.36% for capecitabine in CAPOX. Certain patients in AS (38.26%) and CAPOX (22.03%) experienced grade 3/4 adverse events (AEs). The most common AEs in AS and CAPOX included anemia (20.96% vs. 19.63%), neutropenia (30.70% vs. 21.02%), and thrombocytopenia (1.10% vs. 15.47%). Conclusions: In this study, AS showed longer trends in the DFS rate, OS rate, and manageable safety profile in patients with stage III GAC after curative D2 gastrectomy compared with CAPOX, suggesting a potential therapeutic option for this population. Clinical trial information: NCT04135781 .
Survival results by the prospectively determined clinical staging for locally advanced gastric cancer: An ancillary study of JCOG1302A (JCOG1302A2).
Authors: Hayashi Tsutomu , Mizusawa Junki , Hashimoto Tadayoshi , Fukagawa Takeo , Makuuchi Rie , Hikage Makoto , Misawa Kazunari , Yamada Takanobu , Nomura Takashi , Kawachi Yasuyuki , Kinoshita Takahiro , Kawabata Ryohei , Yabusaki Hiroshi , Sano Takeshi , Sasako Mitsuru , Yoshikawa Takaki , Boku Narikazu , Terashima Masanori 
Published: January 2023

392 Background: Recently, neoadjuvant chemotherapy has been recognized as a promising strategy to improve the survival of patients with advanced gastric cancer. On the other hand, given the adverse events and treatment cost of chemotherapy, the candidate for NAC should be limited to patients who can benefit from NAC. In fact, as previously reported, the proportion of pathological stage I tumors was 50.4% in cT2N0, 38.7% in cT2N(+), 26.7% in cT3N0, 10.6% in cT3N(+), 9.0% in cT4aN0, and 3.0% in cT4aN(+). Therefore, clinical staging before initiation of treatment is increasingly important for determining therapeutic strategy. However, the long-term survival stratified by the prospectively-determined clinical stage has not been fully investigated. Methods: Between July 2013 and November 2014, the JCOG1302A examined 1260 patients with a clinical diagnosis of cT2/T3/T4, cN0/N1/N2/N3, M0, except for diffuse large tumors like linitis plastica and extensive bulky nodal diseases according to the Japanese Classification of Gastric Carcinoma (3rd English edition). The cT diagnosis was made by upper gastrointestinal endoscopy and comprehensive findings on upper abdominal contrast CT scan with 1 or 5 mm slice thickness. Lymph nodes with a shortest dimension greater than 8 mm or a longest dimension greater than 10 mm were defined as positive for metastasis. In this follow-up study, the survival data by stratifying the clinical staging were evaluated. Results: Among 1260 patients, survival data of 1177 were analyzed. With a median follow-up for 821 surviving patients of 6.0 years, the 5y-OS was 82.1% (95% CI, 77.3-85.9) in cT2 (n=319), 72.7% (68.2-76.6) in cT3 (n=450), 60.0% (54.9-64.7) in cT4a (n=401), and 40.0% (5.2-75.3) in cT4b (n=6), while that was 78.0% (74.2-81.2) in cN0 (n=560), 70.6% (65.4-75.2) in cN1 (n=350), 59.1% (52.5-65.1) in cN2 (n=241), and 28.4% (12.7-46.5) in cN3 (n=26), respectively. When combined with cT and cN, 5y-OS was 83.5% (77.8-87.8) in cT2N0 (n=226), 77.2% (71.0-82.2) in cT3N0 (n=232), 66.8% (56.3-75.2) in cT4aN0 (n=100), 100% in cT4bN0 (n=1), 78.7% (68.6-85.8) in cT2N(+)(n=93), 68.0% (61.1-73.8) in cT3N(+)(n=218), 57.7% (51.7-63.2) in cT4aN(+)(n=301), and 25.0% (0.9-66.5) in cT4bN(+)(n=5). Conclusions: Both the survival and the proportion of overdiagnosis of stage I patients in patients with cT4aN0, categorized as cstage IIB, was almost same as in those cT3N(+) categorized as cstage III. In considering the candidate for further treatment development of NAC with high toxic regime in future, cT3N(+) and cT4aN0 should be considered as equivalent category.
A phase II study of paclitaxel and carboplatin plus PD-1 inhibitors combined with anlotinib as first-line treatment for advanced esophageal cancer.
Authors: Xu Mingfang , Pu Yu , Jiang Yuzhu , Liu Hong , Feng Yan , Qian Chengyuan , Dai Nan , Wang Dong , Li Mengxia 
Published: January 2023

395 Background: The combination of anti-PD-1 mAb with chemotherapy is one of the standard first-line therapies for advanced esophageal cancer. Recent studies have shown that anti-PD-1 mAb combined with chemotherapy or targeted treatment can improve the efficacy of immunotherapy. The purpose of this study was to evaluate the efficacy and safety of paclitaxel and carboplatin (TC) combined with anlotinib, an anti-angiogenic TKI, and anti-PD-1 mAb, in the treatment of advanced esophageal cancer. Methods: This study was a parallel, single-center, open-label, phase II trial. A total of 90 patients (pts) with previously untreated, advanced or metastatic ESCC, with an age ranging from 18-75 years old, and an ECOG performance status ≤ 1 were planned to be enrolled into three arms with an allocation ratio of 1:1:1. Arm A received paclitaxel (175 mg/m2, IV, d1, q3w) /nab-paclitaxel (260mg/m2, IV, d1, q3w) + carboplatin (AUC 4-6, IV, d2, q3w) + anti-PD-1 mAb + anlotinib (8mg, PO, d1-14, q3w); Arm B received TC with anti-PD-1 mAb; Arm C received TC only. After 4-6 cycles of induction therapy, arm A and arm B would receive anti-PD-1 mAb plus anlotinib or anti-PD-1 mAb as maintenance therapy until disease progression or intolerable adverse events, respectively. The primary endpoint was ORR. Secondary endpoints included PFS, OS and safety. Results: At data cut-off date (Sep. 20, 2022), a total of 90 pts were enrolled and 88 pts were available for efficacy assessment. 25 of 28 pts achieved partial response (PR) in arm A, 13 of 30 pts PR in arm B, and 7 of 30 pts PR in arm C. The ORR (95% CI) were 89.3% (71.8-97.7) in arm A, 43.3% (25.5-62.6) in arm B, and 23.3% (9.9-42.3) in arm C. The DCR (95% CI) were 100% (87.7-100.0) in arm A, 96.7% (82.8-99.9) in arm B, and 83.3% (65.3-94.4) in arm C. The median PFS was not reached. The rate of treatment related adverse events (TRAEs) of any grade was 100% in all three groups, and grade 3 TRAEs were 23.3%, 16.7% and 13.3%, respectively. The most common grade 3 TRAEs were thrombocytopenia (6.7%), leukopenia (5.6%), neutropenia (5.6%). No grade 4 or 5 TRAEs occurred. Conclusions: The addition of anlotinib to immunotherapy plus chemotherapy as first-line therapy for ESCC demonstrated a high ORR (89.3%), and a manageable safety profile. Clinical trial information: NCT04471480 .
Endoscopic resection of gastrointestinal stromal tumor: The role of clip-and-cut endoscopic full-thickness resection.
Authors: Jung Hwoon-Yong 
Published: January 2023

399 Background: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. We analyzed the results of endoscopic submucosal dissection (ESD) and clip-and-cut endoscopic full-thickness resection (CASE), a modified full-thickness resection method for gastric GISTs to identify the role and its feasibility of CASE. Methods: The medical records of 83 patients diagnosed with GISTs after ER in 2005–2021 were retrospectively reviewed. ESD and CASE were performed in 51 and 32 patients. The clinical characteristics and outcomes were analyzed. Results: The GISTs were mainly found in the upper third of stomach for ESD (52.9%) and CASE (90.6%). In CASE group, there was a tendency that the most of GISTs were in deep muscularis propria or serosal layer (96.9%) compared to ESD group (45.1%). The R0 resection rates were 51.0% in ESD and 84.4% in CASE group, respectively. Perforation during procedure was frequently found in CASE group (25.5% vs. 68.8%), however only three patients were progressed to peritonitis. Seven cases (8.4%) required surgical treatment (6 ESD, 1 CASE) due to residual tumor (n=5), and post-procedure adverse events (n=2). No R0 or R1 resected cases experienced recurrence during the median 14-month follow-up except for one patient in ESD group. Conclusions: CASE showed higher R0 resection rate and was useful and safe in removing small gastric GISTs.
Phase II study of the combination of durvalumab, tremelimumab, and paclitaxel as second-line chemotherapy in biomarker-selected patients with metastatic gastric cancer.
Authors: Lee Keun-Wook , Kim Hark Kyun , Ryu Min-Hee , Zang Dae Young , Kim Ji-Won , Kim Bum Jun , Kim Hyung-Don , Kim Jin Won , Kang Yoon-Koo 
Published: January 2023

401 Background: Currently, ramucirumab plus paclitaxel is the standard second-line chemotherapy in metastatic gastric cancer (mGC), however, its efficacy is very limited. MSI, PD-L1 (CD274), and EBV have been suggested as predictive biomarkers for immune checkpoint inhibitors in mGC. This study was conducted to evaluate efficacy and safety of the combination of durvalumab, tremelimumab, and paclitaxel as a second-line chemotherapy in mGC with potential biomarkers for immune checkpoint inhibitors. Methods: The combination of durvalumab, tremelimumab, and paclitaxel consisted of 1500 mg of i.v. durvalumab on day 1, every 4 weeks for 13 cycles, 75 mg of i.v. tremelimumab on day 1 every 4 weeks for 4 cycles, and 60 mg/m2 of i.v. paclitaxel on days 1, 8, and 15, every 4 weeks until disease progression or unacceptable toxicities. Patients (pts) with MSI-high mGC, EBV-positive mGC, or mGC with CD274 amplification, mutations of mismatch repair or POL gene, or tumor mutation burden (TMB) >5/Mb were included in second-line setting. Results: Forty-eight pts were enrolled. Overall response rate (ORR) was 52.1% with complete response in 4 (8.3%) pts, partial response in 21 (43.8%), stable disease in 14 (29.2%), and progressive disease in 8 (16.7%), and with response not evaluable in 1 (2.0%). With a median follow-up of 18.0 months (range, 7.1-39.4), the median progression-free survival (PFS) and overall survival (OS) were 5.3 months (95% CI, 3.7-6.9) and 13.1 months (95% CI, 5.2-21.0 ), respectively. Compared to mGC with other genetic alterations (n=25), mGC with TMB >20/Mb or MSI-high mGC (n=23) tended to have a higher ORR (56.5% vs 48%), and a prolonged PFS (median 7.2 vs 4.5 months; 44.0 vs 20.8% at 1 year). The combination chemotherapy was generally well tolerable; treatment-related grade 3 or 4 adverse events with frequency >5% included only neutropenia (10.4%) and anemia (8.3%), and there was no treatment-related death. Conclusions: The combination chemotherapy of durvalumab, tremelimumab, and paclitaxel showed encouraging efficacy, especially in mGC with TMB >20/Mb or MSI-high mGC, as a second-line chemotherapy with manageable toxicities in biomarker-selected mGC. Clinical trial information: NCT03751761 .
Outcomes of endoscopic resection for early gastric cancer in very elderly patients: A nationwide population-based study.
Authors: Kim Tae Jun , Lee Hyuk , Kim Jae J. 
Published: January 2023

403 Background: Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients. Methods: Patients with EGC who underwent endoscopic resection from 2006 to 2017 were identified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65–84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and gender. We also evaluated the risk factors for long- and short-term outcomes. Results: A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival (OS) and cancer-specific survival (CSS) rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with CSS. A significantly decreased risk for mortality was observed in all groups (P-value < 0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Further, cerebrovascular disease was associated with mortality within 3 months after endoscopic resection. Conclusions: Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving OS comparable to that of the control group.[Table: see text]
Clinical outcomes of endoscopic resection for gastrointestinal stromal tumor originating from the muscularis propria: A single-center experience.
Authors: Lee Moonwon , Kim Gwang Ha , Lee Bong Eun , Joo Dong Chan 
Published: January 2023

407 Background: With the remarkable advance of endoscopic techniques, endoscopic submucosal dissection (ESD) has become an effective and safe treatment modality for various gastrointestinal tumors (GISTs). However, there is still a lack of evidence on endoscopic treatment of GISTs in the stomach. We aimed to investigate the efficacy and safety of ESD for gastric GISTs and to assess possible predictive factors for incomplete resection. Methods: Between October 2008 and July 2022, a total of 35 patients with gastric GIST underwent ESD at our hospital. Clinicopathologic characteristics of patients and GISTs, therapeutic outcomes, adverse events and follow-up outcomes were evaluated. Results: The overall rates of en bloc resection and complete resection were 77.1% (27/35), 68.6% (24/35), respectively. The median procedure time was 47.3 minutes (range, 15–131 minutes). The procedure-related bleeding and perforation rates were 2.9 % and 17.1%, respectively. In univariate analyses, EUS growth pattern (intraluminal growth, p = 0.027) was independently associated with complete resection. During the median follow-up period of 15.4 months (range, 5.7 – 129 months) in 35 patients except two patients who underwent surgery and one patient who failed to follow up, recurrence occurred in one patient with macroscopically incomplete resection. Conclusions: ESD is an effective, safe, and feasible treatment for gastric GISTs. The frequency of complete resection is increased in EUS with an intraluminal growth pattern. [Table: see text]
The optimal extent of lymph node dissection for gastric cancer with para-aortic lymph node metastases.
Authors: Wada Takeyuki , Yoshikawa Takaki , Ishizu Kenichi , Hayashi Tsutomu , Yamagata Yukinori 
Published: January 2023

413 Background: Gastric cancer (GC) with para-aortic lymph node (PAN) metastasis is diagnosed as stage IV and basically treated with chemotherapy. Recently, D2 and PAN dissection after neoadjuvant chemotherapy (NAC) was reportedly effective when PAN metastasis was limited within #16a2/b1 area. However, PAN dissection is highly invasive surgical procedure and it still remains unclear whether PAN dissection contributes to the survival for these tumors. This study aimed to determine the optimal extent of lymph node dissection for these tumors focusing on survival benefit of PAN dissection. Methods: The study examined patients who received radical gastrectomy with D2 and PAN dissection after NAC for gastric cancer with PAN metastasis (#16a2/b1) from 2004 to 2015. Survival benefit of lymph node dissection was estimated using therapeutic value index (TI). TI was calculated by multiplication of incidence of metastasis and 5-year survival rate of patients with metastasis for each lymph node area. TI of D2 dissection area (TI-D2) and PAN area (TI-PAN) was calculated separately. Overall survival (OS) was calculated in patients who had metastasis to PAN pathologically after surgery (pPAN+ group) and those who had not (pPAN- group). The recurrence site was also examined. Results: Thirty-two patients were analyzed. TI-D2 and TI-PAN were 15.6 and 0.0, respectively. 5y-OS was 81.0% in pPAN- group (21 cases) but was 0.0% in pPAN+ group (11 cases). The most frequent recurrence site was the lymph nodes (82.4% of all recurrences). Among lymph node recurrence, almost all recurrence patterns included the PANs (85.7% of lymph node recurrence). Conclusions: The prognosis was extremely poor when tumor cells remained on PAN after NAC. In these cases, PAN recurrence was seen most frequently even after PANs had been dissected. Patients with PAN could have the chance for the cure only when tumor cells on PAN was completely eliminated by NAC. It is unclear whether they actually needed PAN dissection for pathologically negative PAN. The optimal extent of lymph node dissection after NAC might be D2 for GC with PAN metastasis.