bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study.
Authors: Kato Ken , Ito Yoshinori , Daiko Hiroyuki , Ozawa Soji , Ogata Takashi , Hara Hiroki , Kojima Takashi , Abe Tetsuya , Bamba Takeo , Watanabe Masaya , Kawakubo Hirofumi , Shibuya Yuichi , Tsubosa Yasuhiro , Takegawa Naoki , Kajiwara Takeshi , Baba Hideo , Ueno Masaki , Machida Ryunosuke , Nakamura Kenichi , Kitagawa Yuko 
Published: January 2022

238 Background: Neoadjuvant treatment is the standard care for locally advanced esophageal squamous cell cancer (ESCC). JCOG1109 (UMIN000009482) compared the doublet and triplet of chemotherapy and chemoradiotherapy as neoadjuvant treatment. Methods: Eligible patients (pts) with ESCC of clinical stage IB, II, III (excluding T4) (UICC 7th) from 44 institutions were randomized 1:1:1 to neoadjuvant CF (cisplatin 80 mg/m2 on day1 plus 5-FU 800 mg/m2 on days 1-5 Q3W/2course), DCF (docetaxel 70 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus 5-FU 750 mg/m2 on days 1-5 Q3W/3 course), or CF-RT (cisplatin 75 mg/m2 on day 1 plus 5-FU 1000 mg/m2 on days 1-4 Q4W/2course, radiation 41.4 Gy/23 fr). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), %R0 resection, %objective response by neoadjuvant therapy, %pathological complete response (pCR) and safety. Differences in OS was assessed in the ITT using the stratified log-rank test. The data cutoff date for the analysis was July 20, 2021. Results: Of 601 pts 199 CF, 202 DCF, and 200 CF-RT were enrolled from December 5, 2012 to July 20, 2018, respectively. Among 601 pts, 88.2% were male, median (range) age was 65 (30-75), clinical stage III (nonT4) pts were 62.6%. Median follow-up time (range) was 4.2 years (y) (0-8.5). Median OS in CF, DCF, and CF-RT arm were 4.6 y, not reached (NR), and 6.0y, and 3-year OS was 62.6%, 72.1%, and 68.3%, respectively (stratified log-rank test: p = 0.006 for CF vs. DCF and p = 0.12 for CF vs. CF-RT). By stratified Cox regression analysis for OS, hazard ratios (HR) [95% CI] was 0.68 [0.50–0.92] for CF vs. DCF and 0.84 [0.63–1.12] for CF vs. CF-RT. Median PFS in CF, DCF, and CF-RT arm were 2.7 y, NR, and 5.3 y, and 3-year PFS was 47.7%, 61.8%, and 58.5%, respectively. R0 resection was achieved in 168 (84.4%), 173 (85.6%), and 175 (87.5%), and pCR was 4 (2.1%), 40 (19.8%), and 77 (38.5%), respectively. During neoadjuvant therapy, febrile neutropenia in CF, DCF, and CF-RT arm were 1.0%, 16.3% and 4.7%, and esophagitis (grade>3) were 1.0%, 1.0% and 8.9%, respectively. The treatment-related death was seen in 3 (1.5%), 4 (2.0%), and 2 (1.0%), in CF, DCF, and CF-RT arm, respectively. Conclusions: DCF significantly improved OS over CF as neoadjuvant therapy for locally advanced ESCC, with a manageable toxicity profile. DCF represents a new standard neoadjuvant treatment for ESCC. Clinical trial information: UMIN000009482.
Survival expressed in best-case, typical and worst-case scenarios for patients with nonmetastatic esophagogastric cancer: A population-based study.
Authors: Kuijper Steven , Pape Marieke , Vissers Pauline A.J. , Jeene Paul M. , Kouwenhoven Ewout , Haj Mohammad Nadia , Sosef Meindert , Verhoeven Rob , Van Laarhoven Hanneke W.M. 
Published: January 2022

259 Background: In recent years new treatment options and the centralization of surgery have improved survival for patients with non-metastatic esophageal and gastric cancer. However, it is currently unknown which patients have mostly benefitted from these treatment advances. The aim of this study was to use population-based data to identify best-case, typical and worst-case scenarios in terms of survival time, and to assess if the survival of these scenarios have changed over time. Methods: Patients diagnosed between 2006-2019 with non-metastatic esophageal (including gastro-esophageal junction tumors) or gastric cancer were selected from the Netherlands Cancer Registry. Best-case, typical, and worst-case scenarios were calculated from the 20th (best-case scenario), 40th (upper-typical), 50th (median), 60th (lower-typical) and 80th (worst-case scenario) percentiles of the survival curves. Linear trend analysis was used to investigate the change in survival time for each scenario across diagnosis years. Results: We identified 23350 patients with non-metastatic esophageal cancer and 10150 patients with non-metastatic gastric cancer. Linear trend analyses across diagnosis years showed that for esophageal cancer patients, survival of all scenarios significantly increased over time: the best-case scenario increased from 55 to 112 months (p =.003); the upper typical increased from 18 to 33 months (p <.001); the median increased from 13 to 23 months (p <.001); the lower typical increased from 8 to 15 months (p <.001) and the worst-case scenario increased from 4 to 7 months (p <.001). For patients with gastric cancer, all scenarios also improved significantly: the best-case scenario increased from 73 to 99 months (p =.045); the upper-typical increased from 22 to 33 months (p <.001); the median increased from 14 to 18 months (p <.001); the lower-typical increased from 14 to 18 months (p <.001) and the worst-case scenario increased slightly from 2.9 months to 3.0 (p =.017). Conclusions: All patients with non-metastatic esophageal and gastric cancer have improved their survival over time.The largest survival advantage was among the best-case and upper-typical scenarios. Therefore, treatment advances over the last years have improved survival for all patients with non-metastatic esophagogastric cancer.
Update analysis: Clinical outcomes following regionalization of gastric cancer care in a U.S. integrated health care system.
Authors: Teh Swee H. , Li Robert , Lin Teresa , Shiraga Sharon , Li Yan , Gong I-Yeh , Sundaresan Tilak Kumar , Herrinton Lisa J. 
Published: January 2022

265 Background: The role of laparoscopic gastrectomy and D2 lymphadenectomy is not yet fully defined in patients treated with modern perioperative chemotherapy. In 2016, Kaiser Permanente Northern California regionalized gastric cancer care, introducing a regional comprehensive multidisciplinary care team, standardizing staging and chemotherapy, and implementing laparoscopic gastrectomy and D2 lymphadenectomy for eligible patients with curative-intent surgery. We previously reported a retrospective cohort study comparing treatments and outcomes before and after regionalization, including 2-year overall survival. Here we present updated 3-year overall survival. Methods: As we described previously ( https://ascopubs.org/doi/full/10.1200/JCO.21.00480 ), the study included all 1429 patients with gastric cancer diagnosed during January 2010 to May 2018, of whom 942 were pre-regionalization, and 487 were post. Of the 1429, 650 had Stage I-III disease, and 394 patients underwent curative intent gastrectomy. 34.9% received neoadjuvant chemotherapy, and 18.4 % of patients received laparoscopic gastrectomy in the pre-regionalization period. In contrast, 66.2% received neoadjuvant chemotherapy, and 91.8% received laparoscopic gastrectomy with D 2 lymphadenectomy in the post regionalization period (p < 0.0001). Lymph node metastasis was noted in 50.7% and 45.1% pre- and post-regionalization periods, respectively (p = 0.29). Survival was analyzed using Kaplan-Meier analysis with entry on the diagnosis date, the outcome on the death date, and censoring on disenrollment or the end of the study. In this updated analysis, the end of the study was increased by one year to December 31, 2019. Results: The statistical analysis showed no difference in patients’ selection for surgery between the pre-and post-regionalization period and no change in the rate of surgical complications. At three years, overall survival among Stage I-III patients who received surgery was 66.0% in the pre-regionalization cohort and 83.0% in the post-regionalization cohort (p < 0.002), a more significant difference than was observed at two years. Conclusions: The utilization of laparoscopic surgery and radical D2 lymphadenectomy in the era of perioperative chemotherapy continues to demonstrate improved postoperative overall disease survival.[Table: see text]
First-line treatment with immune checkpoint inhibitors (ICI) for metastatic gastric and esophagogastric junction (EGJ) adenocarcinoma in Latin America: Sociedad Latinoamericana de Gastroenterología Oncológica (SLAGO) evidence-based recommendations.
Authors: Diaz Maria Celeste , Della Valle Adriana , Diaz Consuelo , Mendez Guillermo , O'Connor Juan Manuel , Garrido Marcelo , Montenegro Paola Catherine , Peixoto Renata D'Alpino , Gallardo Jorge 
Published: January 2022

269 Background: Gastric and EGJ cancer in Latin America are associated with a high burden of disease and mortality. Treatment with combination chemotherapy (CT) is the current standard of care for metastatic disease, but with poor benefit. ICI appears as a new option in this setting improving survival and no local guidelines have been found addressing this issue. Methods: We carried out a comprehensive systematic review up to August 2021 and meta-analysis according to PRISMA guidelines and used the GRADE approach to summarize each question in evidence tables. Judgments regarding risk of bias, precision, consistency, directness, and likelihood of publication bias were made and categorized into 4 levels of evidence’s certainty ranging from very low to high. SLAGO formed a guideline panel composed of medical professionals from 6 countries in Latin America and prioritized 2 relevant questions. We provided de novo recommendations for the local setting using the Evidence-to-Decision (EtD) frameworks provided by GRADE to discuss benefits and harms, values and preferences, use of resources, feasibility, acceptability, and equity. Results: The panel agreed on 3 recommendations. For question 1, regarding the use of CT+ICI vs CT, the global certainty of evidence was rated as high. For question 2 (CT vs ICI), the global certainty of evidence was rated as low due to imprecision. The recommendation for question 1 was conditional for the use of CT+ICI among the population with CPS > 1 and strong among those with CPS > 5. For question 2, the recommendation was conditional against the treatment with ICI, regardless of CPS score. Concerns about the lack of economic evidence addressing the treatment's cost-effectiveness were identified. The panel highlighted the complexity of the Latin America health systems for the implementation of CT+ICI and its equity impact. Finally, some research priorities were highlighted (effectiveness in HER2+, CPS 1-4, or MSI-H tumours). Conclusions: The panel agreed on the net clinical benefit of CT+ICI for selected patients (CPS > 5). Nonetheless, cost-effectiveness data are still lacking, especially in Latin America.
Multicenter, randomized double-blind placebo-controlled trial of definitive concurrent chemoradiotherapy plus megestrol acetate/placebo in local-advanced esophageal cancer.
Authors: Jia Ruinuo , Li Wanying , Li Mian , Li Ruonan , Kong Dejiu , Li Shuoguo , Shan Tanyou , Gao Shegan 
Published: January 2022

275 Background: To determine Quality-of-Life (QoL) improvement by Megestrol Acetate (MA) in local advanced esophageal squamous cell carcinoma (ESCC) with definitive concurrent chemoradiotherapy (DCRT). Secondary aims were to examine the safety and the impact of MA on the efficacy of DCRT. Methods: Patients (with previously untreated T1bN+M0 or T2-4aN0-2M0 ESCC) were randomly assigned at a one-to-one ratio to receive MA or placebo (blind). All received 5-FU based chemotherapy with concurrent radiotherapy (50Gy/25F). QoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaires at pretreatment and 3, 6, 16 weeks of DCRT. The good status (GS) rate of appetite loss (AL), nausea and vomiting (NV), weight (WT) and performance status (PS) were chosen as predefined primary end points. GS defined as the score were ≤ 0 for AL or NV and ≥ 0 for WE or PS when the designed time points compared with last one. Secondary end points were the comprehensive QoL (remaining items of QLQ-C30 changes analysis at 16th week), myelosuppression (MS), and deep vein thrombosis (DVT). The exploratory end points were the objective response rate (ORR), 1-year overall survival (OS) and progression-free survival (PFS). Results: 84 completed the follow-up and were analyzed from which 120 patients randomly assigned. The GS rates of AL (3th week: P = 0.011; 6th week: P < 0.001; 16th week: P = 0.001), NV (6th week: P = 0.001) and PS (6th week: P = 0.01) were higher in MA than Placebo. There were no statistical differences between MA and Placebo on WT. At 16th week, the change degree analysis shown the fatigue was worse in MA than Placebo ( p = 0.031). There were no differences on MS, DVT, ORR, OS and PFS between two arms. Nevertheless the rate of DVT was slightly higher in MA than Placebo (12.5% vs. 2.8%, P = 0.113). Conclusions: MA is helpful for ESCC patients receiving DCRT as well as the risk of DVT needed be careful.
Effectiveness of third- or later-line therapy in patients with HER2-positive advanced gastric cancer: Results from an observational retrospective study in Japan.
Authors: Omori Takeshi , Sakai Daisuke , Fumita Soichi , Fujita Junya , Kawabata Ryohei , Matsuyama Jin , Yasui Hisateru , Hirao Motohiro , Kawase Tomono , Kishi Kentaro , Taniguchi Hirokazu , Miyazaki Yasuhiro , Miura Tomoko , Miyake Akimitsu , Kurokawa Yukinori , Yamasaki Makoto , Yamada Tomomi , Satoh Taroh , Eguchi Hidetoshi , Doki Yuichiro 
Published: January 2022

277 Background: The real-world effectiveness of third- or later-line (3L+) therapies in patients (pts) with HER2-positive gastric cancer remains unknown. We report a multicenter, retrospective, observational study at 20 centers in Japan to investigate the outcomes of 3L+ therapy in pts with HER2-positive advanced gastric/gastroesophageal junction (G/GEJ) cancer previously receiving trastuzumab (UMIN000040853). Methods: Pts aged ≥20 years with HER2-positive advanced G/GEJ cancer who were previously treated with trastuzumab and newly initiated on nivolumab, irinotecan, or trifluridine/tipiracil monotherapy as 3L+ therapy (Sep 2017 to Mar 2020) were evaluated for overall survival (OS), progression-free survival (PFS), duration of response (DOR), time to treatment failure (TTF), objective response rate (ORR), and disease control rate (DCR). An exploratory analysis for factors affecting OS was conducted using a multivariate Cox regression model, with HER2 status as a covariate. Results: The overall analysis population was 117 pts (median: age, 71 years; number of prior treatment lines, 2; days since the initiation of first-line treatment, 431 days). Median (95% confidence interval) OS, PFS, and TTF were 6.2 months (4.5–8.0), 1.9 months (1.5–2.3), and 1.8 months (1.5–2.2), respectively, at a median follow-up of 150 days. Outcomes by treatment groups are shown in the Table. ORR and DCR in 100 pts with evaluable target lesions were 9.0% and 32.0%, respectively, and median DOR was 8.4 months. A higher neutrophil-lymphocyte ratio (≥2.540), Glasgow prognostic score (≥1), ECOG PS (≥2), and hepatic metastasis significantly impacted OS. Conclusions: The real-world effectiveness of 3L+ therapies was limited in this study. New HER2 treatment agent is expected to improve outcomes in pts with HER2-positive G/GEJ cancer.[Table: see text]
Randomized, phase 3 study of second-line tislelizumab versus chemotherapy in advanced or metastatic esophageal squamous cell carcinoma, RATIONALE 302: Asia subgroup.
Authors: Zhao Kuaile , Kim Sung-Bae , Kato Ken , Hsu Chih-Hung , Hu Sheng , Wang Feng , Kojima Takashi , Kim Young Saing , Van Cutsem Eric , Ajani Jaffer A. , Li Liyun , Ding Ningning , Tao Aiyang , Shen Lin 
Published: January 2022

279 Background: In the global Phase 3 study RATIONALE 302 (NCT03430843), tislelizumab (TIS) demonstrated statistically and clinically significant improvement in overall survival (OS) vs chemotherapy (chemo) (median OS 8.6 vs 6.3 months; HR 0.70, 95% CI 0.57–0.85; p=0.0001) in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Here, we report data from the Asia subgroup. Methods: Eligible patients who had disease progression after first-line systemic therapy were randomized 1:1 to receive TIS 200 mg intravenously once every three weeks or chemo (paclitaxel, docetaxel, or irinotecan) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS in all randomized patients (Intent-to-treat population). The key secondary endpoint was OS in patients with PD-L1 Tumor Area Positivity Score* ≥ 10%; other secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), health-related quality of life, and safety. Results: Of the 512 randomized patients, 404 (79%) were enrolled from China, Taiwan, Japan, and Korea and constituted the Asia subgroup (n=201 TIS, n=203 chemo). At data cut-off (December 1, 2020), median follow-up was 6.9 months in the Asia subgroup. Median OS was 8.5 months with TIS vs 6.3 months with chemo (HR 0.73; 95% CI 0.59, 0.90). Median PFS was 1.5 months with TIS vs 1.7 months with chemo (HR 0.81; 95% CI 0.64, 1.02). TIS resulted in a higher ORR (20.4% [95% CI 15.1, 26.6] vs 9.4% [95% CI 5.7, 14.2]) and longer median DoR (7.4 vs 4.0 months; HR 0.42, 95% CI 0.21, 0.84) vs chemo. In the safety analysis set (n=201 TIS, n=191 chemo), patients treated with TIS had fewer treatment-related adverse events (TRAEs) (74.1% vs 95.3%), fewer ≥ Grade 3 TRAEs (19.4% vs 57.1%), fewer serious TRAEs (15.4% vs 20.9%), and a similar incidence of TRAEs leading to death (2.5% vs 2.6%) vs chemo. Conclusions: In the Asia subgroup, TIS improved OS and tumor response vs chemo as second-line treatment in patients with advanced or metastatic ESCC and showed a well-tolerated safety profile. These findings were consistent with published results in the overall population. *The TAP score methodology has been previously referred to as visually-estimated combined positive score (vCPS) and was previously presented at the American Society of Clinical Oncology 2021, June 4–8, 2021, ESMO World Gastrointestinal Congress 2021, June 30–July 3, 2021, and The Chinese Society of Clinical Oncology 2021, September 25–29, 2021. Clinical trial information: NCT03430843.
A randomized phase II trial of preoperative chemotherapy of S-1/CDDP with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).
Authors: Tokunaga Masanori , Machida Nozomu , Mizusawa Junki , Yabusaki Hiroshi , Yasui Hirofumi , Hirao Motohiro , Watanabe Masaya , Yasuda Takushi , Kinoshita Takahiro , Imamura Hiroshi , Hihara Jun , Boku Narikazu , Kataoka Tomoko , Yoshikawa Takaki , Sano Takeshi , Sasako Mitsuru , Terashima Masanori 
Published: January 2022

285 Background: The efficacy of trastuzumab has been established for HER2-positive advanced gastric cancer patients with metastatic disease. However, it remains unclear if the addition of trastuzumab to preoperative chemotherapy is effective for treatment of HER2-positive locally advanced gastric cancer. Methods: Eligible patients with HER2-positive gastric cancer with extensive lymph node metastasis were randomized to preoperative S-1/cisplatin (SP) (group A) or SP plus trastuzumab (group B). In both groups, patients received S-1, 80–120 mg/body, on days 1–14 and cisplatin, 60 mg/m2, on day 1, q21, 3-4 courses. Additionally, in group B, patients received infusions of trastuzumab (first course 8 mg/kg followed by 6 mg/kg, day 1). After gastrectomy, adjuvant chemotherapy with S-1 was performed for 1 year in both groups. The primary endpoint was overall survival, and the sample size was planned to be 130 patients in total, expecting a 10% increase in the 3-year overall survival (70% vs 80%) with a 1-sided alpha of 0.2, a power of 0.75. Results: The study was terminated in March 2021 due to slow patient accrual. In total, 46 patients were randomized to either group A (22 patients) or group B (24 patients). Patient characteristics were well balanced between the groups. Planned preoperative chemotherapy was completed in 20 patients (90.9%) in group A and in 23 patients (95.8%) in group B, and R0 resection was achieved in 20 patients (90.9%) in group A and 22 patients (91.7%) in group B. The incidences of grade 3 or 4 hematological/non-hematological adverse events during preoperative chemotherapy were 27.3/18.2% in group A and 4.2/8.3% in group B. Objective response rate (CR/PR) tended to be higher in group B (66.7% [16/24]) than in group A (36.4% [8/22], p = 0.08). Pathological response rate (> grade 1b in Japanese classification, 22.7% [5/22] vs. 50.0% [12/24], p = 0.07) and the proportion of patients achieving downstage to ypStage 0/I/II (22.7% [5/22] vs. 50.0% [12/24], p = 0.07) were also higher in group B than in group A. Conclusions: Preoperative chemotherapy with SP plus trastuzumab was feasible, and tended to show better radiological and pathological response rates. Better survival outcomes are expected by adding trastuzumab to preoperative chemotherapy with SP for locally advanced gastric cancer with extensive nodal metastasis. Clinical trial information: UMIN000016920.