bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, controlled, multicenter study of nab-paclitaxel plus cisplatin followed by surgery versus surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Liu Junfeng , Wang Yan , Cao Bingji , Zhang Shaowei , Cao Fumin , Gao Liping , Sun Nan , Ma Yuquan 
Published: January 2022

310 Background: Taxane is one of the commonly used chemotherapy drugs for ESCC. Nab-paclitaxel, a small particle albumin-bound form of paclitaxel, showed potentially efficacy in metastatic ESCC. This randomized, controlled, multi-center study is conducted to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in neoadjuvant treatment of ESCC. Methods: Two hundred and two patients with resectable locally advanced ESCC which was located in the middle or lower third of the esophagus were enrolled and randomly assigned in a 1:1 ratio to receive neo-adjuvant chemotherapy or surgery alone. Patients were treated with either two 3-week cycles of nab-paclitaxel (125mg/m2, iv, d1, 8) and cisplatin (75mg/m2, iv, d1), followed by esophagectomy 4-6 weeks after neoadjuvant (the treatment arm) or directly underwent esophagectomy (the control arm). The primary endpoint was overall survival (OS), the secondary endpoints included 1-, 2-, and 3-year OS rate, 1-, 2-, and 3-year disease-free survival (DFS) rate, R0 resection rate, reduction stage rate, chemotherapy-related adverse events. Results: Between April 2019 and June 2021, we randomly assigned 67 patients, of whom 31 in the treatment arm and 33 in the control arm were analyzed. There was no difference in baseline characteristics between the two arms. In the treatment arm, 24 patients underwent R0 resection, and 2 did not undergo surgery although chemotherapy was completed. All patients in control arm underwent R0 resection. In the treatment arm, the pathological complete response (pCR) rate was 20.83%, the major pathological response (mPR) rate was 33.33%, and the down-staging rate was 58.33%. No difference in survival benefit was observed between the two arms. The 1- and 2-year DFS rates of the treatment arm and the control arm were 88.99% vs 75.58% (HR = 0.421, 95%CI: 0.087̃2.032, P = 0.281) and 88.99% vs 66.13% (HR = 0.387, 95%CI: 0.082̃1.833, P = 0.231), respectively. The 1-year and 2-year OS rates of the treatment arm and control arm were 93.21% vs 75.32% (HR = 0.293, 95%CI: 0.061̃1.409, P = 0.125) and 86.56% vs 75.32% (HR = 0.444, 95%CI: 0.115̃1.716, P = 0.239). The neoadjuvant chemotherapy was well tolerated. According to NCI-CTC AE V.5.0, the most common adverse events were hematological toxicity, including neutropenia (16.13%), anemia (3.23%) and hypoproteinemia (3.23%), no grade IV adverse events occurred. Conclusions: Nab-paclitaxel plus cisplatin for ESCC reveals a promising efficacy and safety, and has a tendency to prolong DFS and OS compared with surgery alone. The long-term results are worthy of further exploration. Clinical trial information: NCT03964753.
Gastric endoscopic submucosal dissection using a detachable assistant robot.
Authors: Kim Sang Hyun , Choi Hyuk Soon , Lee Jae Min , Keum Bora , Kim Byung Gon , Hong Daehie , Jeen Yoon Tae , Chun Hoon Jai ,   Korea University College of Medicine
Published: January 2022

318 Background: Effective traction and counter-traction for visualizing the dissection plane in endoscopic submucosal dissection (ESD) is difficult to be achieved with a conventional endoscope. We developed a robotic assistive traction device for flexible endoscopy that provides multi-directional traction during ESD. We compared its safety and efficiency in ESD between experienced and novice endoscopists. Methods: Robotic ESD was performed by experienced and novice endoscopist groups (n = 2, each). The outcomes included time to complete each ESD step, total procedure time, size of the dissected mucosa, rate of en bloc resection, and major adverse events. Furthermore, incision and dissection speeds were compared between groups. Results: Twenty gastric lesions were resected from nine live pigs. The submucosal incision speed was significantly faster in the expert group than in the novice group (P = 0.002). There was no significant difference in the submucosal dissection speed between the groups (P = 0.365). No complications were reported in either group. Conclusions: When the robot was assisting in the ESD procedure, the dissection speed improved significantly, especially in the novice surgeons. Our robotic device can provide simple, effective, and safe multidirectional traction during ESD.
Real-world effectiveness of anlotinib in combination with PD-1 inhibitors as second-line or later therapy for advanced or metastatic esophageal squamous cell carcinoma.
Authors: Hong Yonggui , Wu Tao , Lu Ping , Chang Zhiwei , Liang Wei , Zhang Guifang , Wang Junsheng 
Published: January 2022

320 Background: Anti-PD-1 mAb treatment has been shown to be effective in the treatment of esophageal cancer. Anlotinib has been approved in China as a second-line treatment for advanced esophageal cancer because of its good tolerance and efficacy. In the treatment of esophageal cancer, antiangiogenic target therapy combined with immunotherapy has been preliminarily recognized internationally. The purpose of this study is to investigate the efficacy and safety of anlotinib in combination with PD-1 inhibitors in second-line or later therapy during the treatment of esophageal cancer in the real world setting.(A LOT-EC3, NCT04966611). Methods: This is a prospective, multicenter real-world study. The esophageal cancer patients who received anlotinib in combination with PD-1 inhibitors in second-line or later therapy were enrolled. The primary endpoint was PFS (progression-free survival), and secondary endpoints were ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: From Jul 2020 to Sep 2021, 40 patients with a median age of 65.5 (range: 48̃81) were enrolled, in which the metastasis of more than 1 organ occurred in 62.5% of the 40 patients; the metastasis of more than 2 organs occurred in 37.5% (15 patients). 26 (65.0%) and 14 (35.0%) patients received anlotinib combined with PD-1 inhibitors as second line and third & above line therapy, respectively. Among all patients, 1 patient achieved complete response (CR), 11 patients partial response (PR), 23 patients stable disease (SD), illustrating an ORR of 30.0% and a DCR of 87.5%. In the second line therapy, ORR was 30.8 %, DCR was 92.3%. In the third & above line, ORR with 28.6%, DCR with 78.6% was observed. Median PFS was not reached. For all the 40 patients, 27 of which were treated with Camrelizumab, 10 were treated with Sintilimab, other 3 patients were treated with other kinds of PD-1 inhibitors. There was no significant difference in DCR between different PD-1 inhibitors. Treatment related adverse events (trAEs) occurred in 22 (55%) patients. 4 patients had grade 3 or more trAEs. No patient died due to trAE. Conclusions: Anlotinib combined with PD-1 inhibitors is found to be a reasonable option in second-line or later therapy for the treatment of advanced esophageal cancer. To our best knowledge, this is the first summarized real-world study on anlotinib combined with PD-1 inhibitors in advanced esophageal cancer. The treatment effects are similar to the outcomes in comparable clinical trials, which support the further recommendation of anlotinib combined with PD-1 inhibitors in the treatment of esophageal cancer. Clinical trial information: NCT04966611.
Ant-PD-1/PD-L1 inhibitors in metastatic gastroesophageal cancers (GEC): A systematic review and meta-analysis.
Authors: Parmar Kanak , Subramanyam Sai , Appiah Duke , Mukherjee Sarbajit 
Published: January 2022

323 Background: CheckMate 649 and KEYNOTE 590 studies established the role of immune checkpoint inhibitors (ICI) in the frontline setting for unresectable, advanced, or metastatic GEC. However, many GEC patients do not benefit from ICI. The purpose of the study was to evaluate the efficacy of ICI in various subgroups of GEC patients. Methods: We searched MEDLINE/PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase II or III randomized clinical trials (RCTs) testing ICI in metastatic/advanced gastric or gastroesophageal junction or esophageal cancer. Outcome measures included overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed for histology (squamous vs. adenocarcinoma), cancer location (gastric, gastroesophageal junction, and esophageal), age (< 65 years vs. > = 65 years), race (Asians vs. non-Asians), and sex (male vs. females). Random-effects meta-analysis was conducted using the R software. Results: Fourteen RCTs were included for the final analysis with total of 9102 patients. RCTs were divided into three groups: 5 RCTs for ICI+ chemotherapy vs. chemotherapy (Group A), 9 RCTs for ICI vs. chemotherapy (Group B), and 2 RCTs for ICI vs. placebo (Group C). OS was improved in Groups A (HR 0.78, 95% CI 0.71-0.86) and B (HR 0.82, 95% CI 0.73-0.91), but the results were not statistically significant in Group C. PFS was improved in Groups A(HR 0.70 95% CI 0.63-0.78) and C(HR 0.69 95% CI 0.56-0.86) but not statistically significant in Group B. On subgroup analysis for Group A, a statistically significant difference in OS was seen across all subgroups: histology, cancer location, age, and race except gastroesophageal junction cancer (HR 0.83 95% CI 0.66-1.04) and females (HR 0.86 95%CI 0.73-1.01). In Group B, statistically significant differences were only seen in esophageal cancer (HR 0.73 95% CI 0.66-0.81), squamous histology (HR 0.74 95% CI 0.67-0.82), Asian race (HR 0.77 95% CI 0.67-0.88) and men (HR 0.84 95% CI: 0.77-0.92). Conclusions: This study shows evidence for the use of ICI+ chemotherapy in the frontline setting for the management of GEC. While comparing ICI against chemotherapy, esophageal cancer, squamous histology, and the Asian race seemed to benefit more from ICI. Similarly, males, in general, benefited more from ICI than females. We plan to present an updated analysis at the meeting, which will include pending publications of some ongoing clinical trials.
Effect of adding immunotherapy to standard of care on survival in patients with esophageal cancer: Analysis of NCDB database.
Authors: AMIN SABER Ali , Lin Chi 
Published: January 2022

325 Background: Combined immuno-chemotherapy has been shown to be more effective than chemotherapy alone in advanced esophageal cancer. However, the association of immunotherapy and overall survival (OS) of patients with esophageal cancer, regardless of stage and combined therapy, is unknown. The objective is to explore the association of immunotherapy with OS in patients with all stage esophageal adenocarcinoma or squamous cell carcinoma who received any treatment. Subset analysis was conducted on OS for patients who received chemoradiation with and without immunotherapy. Methods: This study included 85,900 adult patients in the National Cancer Database diagnosed between 2004 and 2017 with stage I-IV esophageal adenocarcinoma or squamous cell carcinoma. The association of immunotherapy with OS was assessed with Cox proportional hazards regression, adjusted for age at diagnosis, race, sex, stage, histology, Charlson score, education, income, insurance, hospital type, place of living, region, distance to facility, year of diagnosis and treatment modality. Results: Of 85,900 patients, 69,264 (81%) were men, 85,159 (88%) were White and 7,875 (9%) were Black. The median (range) age at diagnosis was 64 (18-90) years. Overall, 1990 (2.3%) received immunotherapy. Immunotherapy did not improve median OS in stage I-II (31 vs 27M, p >.05) but improved median OS in stage III (from 18 to 30 M, p <.0001) and IV (from 8 to 14 M p <.0001). In the multivariable COX analysis, patients who received immunotherapy had significantly improved OS compared with no immunotherapy (HR 0.756; 95% CI 0.713-0.801; P =.001). Treatment with CRT without surgery plus immunotherapy was associated with significantly improved OS compared with CRT alone (HR 0.817; 95% CI 0.745-0.896; P =.001). Interestingly, addition of immunotherapy to CRT with surgery did not improve OS compared with CRT and surgery. After stratified by stage, immunotherapy was found to be associated with improved OS only in stage IV patients either in all patients (HR 0.685; 95% CI 0.641-0.731, p < 0.001) or in patients who received CRT without surgery (HR 0.758; 95% CI 0.682-0.841). Conclusions: In this study, the addition of immunotherapy to standard of care, especially chemoradiation without surgery was associated with improved OS compared with standard of care (or chemoradiation) alone in patients with advanced stage esophageal cancer.
Induction FOLFOX prior to CROSS chemoradiotherapy and surgery in patients with locally-advanced esophageal and gastroesophageal junction cancer: A phase II study.
Authors: Dunne Richard Francis , Badri Nabeel , Nicolais Maria , Noel Marcus Smith , Baran Andrea M. , Wang Wenjia , Ramsdale Erika E. , Zittel Jason , Qiu Haoming , Katz Alan W. , Jones Carolyn E. , Peyre Christian G. , Lada Michal J. , Hezel Aram F , Tejani Mohamedtaki Abdulaziz 
Published: January 2022

327 Background: In the CROSS trial, neoadjuvant chemoradiotherapy (CRT) prior to surgery for esophageal (E) and gastroesophageal junction (GEJ) cancers was found to improve survival. However, 10-year data did not show benefit in reducing isolated distant metastases. Addition of full-dose induction chemotherapy (CT) prior to CRT could provide early systemic disease control in addition to enhanced local control. We evaluated induction CT with FOLFOX followed by CRT and surgery in patients with E/GEJ cancers. Methods: This single-arm, phase II clinical trial investigated trimodality therapy in clinically staged II/III resectable cancers of the E/GEJ (NCT03110926). Treatment schedule was: 6 weeks of mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) followed by 5.5 weeks of CRT with weekly paclitaxel and carboplatin and 41.4-45 Gy of radiation (RT) and surgery. Primary endpoint was 2-year relapse-free survival (RFS) measured from time of surgery to date of first recurrence or death and was calculated by the Kaplan-Meier method. Overall survival (OS) and key pathologic findings were secondary outcomes. Results: In total, 41 patients enrolled with mean age of 63.1 years; 78% were male. Almost all (95%) were adenocarcinoma. Median duration of follow-up was 2.08 years. Most primary tumors were located in the GE junction (68.3%). Treatment was well tolerated: 95% patients completed all FOLFOX cycles, 98% received the pre-specified RT dose, and 36 of 41 (87.7%) went on to have surgery (1 elected observation after complete clinical response). R0 resection occurred in 97% of those that went on to have surgery. At least partial pathologic response was found in 30 of 36 (83.3%); 8 of 36 (22%, CI 10.1-39.2%) had a pathologic complete response (pCR) and 20 of 36 (55%) had pCR or near-complete response (NCR). At the time of analysis, 2-year RFS was 71.5% (CI 52.1-84.2) and the median RFS was 3.1 years; median OS was not reached. At time of follow-up, 85% (17 of 20) of those with NCR and PCR were relapse-free. Conclusions: Our study demonstrates a high treatment completion rate when FOLFOX was administered prior to CRT and surgery for E/GEJ cancers. Almost all patients had R0 resection and over half had NCR or pCR response. Short-term follow-up RFS and OS demonstrate promising efficacy for this approach in a sample almost exclusively of adenocarcinoma tumors. Strategies to implement induction FOLFOX or FLOT either with or without CRT should continue to be explored in larger studies. Clinical trial information: NCT03110926.
Preclinical evaluation of a dual magnetic and fluorescence-guided approach for sentinel lymph node biopsy in the stomach.
Authors: Shetty Anil , Cousins Aidan , Krishnan Shridhar , Pham Nguyen , Milanova Valentina , Krishnan Giri , Nelson Melanie , Ikoma Naruhiko , Thierry Benjamin 
Published: January 2022

337 Background: Gastrectomy with extended (D2) lymphadenectomy is considered as a standard of care for gastric cancer to provide best possible outcomes and pathologic staging. However, D2 gastrectomy is technically demanding operation and reported to be associated with increased complications, including bleeding, pancreatitis, abscess, chylous ascites, and mortality. Application of sentinel lymph node mapping in gastric cancer has the potential to reduce patient morbidity, while facilitating detailed pathology processing required to accurately identify nodal metastases. However, sentinel lymph node biopsy techniques are not established for gastrectomy because of a lack of practical tracers; an effective and convenient tracer that exclusively accumulates in sentinel lymph nodes is critically needed. Methods: A lymphotropic tracer solution consisting of mannose-labelled magnetic nanoparticles (SPIONs) and a fluorescent dye (indocyanine green, ICG) was injected laparoscopically into the stomach submucosa of 6 healthy female domesticated pigs while under general anaesthesia. Intraoperative laparoscopic fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while a combination of T2-weighted MRI and magnetometer probe detection were used to identify nodes containing SPIONs. Results: Mixing the ICG dye and SPIONs ensured concurrence of fluorescent and magnetic signals in the sentinel nodes. Average tracer accumulation time before dissection was 5 hours. On average 4.5 fluorescent nodes (range 2–7) were removed, of which 2 (average) were also magnetic (range 1–4). Magnetic nodes could be identified using both preoperative MRI and intraoperative magnetometer probe. The mannose label of the SPIONs produced a strong binding affinity to macrophages, and in combination with particle size (80 nm) results in enhanced retention in the sentinel nodes. On average, after 5 hours accumulation time, the sentinel nodes contained 4.1% of the SPION injected dose and 88% of the magnetometer counts. Conclusions: Through the co-injection of fluorescent and mannose-labelled magnetic tracers, lymphatic drainage pathways can be determined preoperatively with MRI, visualised with intraoperative fluorescence cameras, and SLNs confirmed with magnetometer. Although ICG flows through multiple echelons, in doing so it creates a lymphatic roadmap to guide surgeons. The addition of magnetic particles provides sentinel node discrimination, so in combination, these two tracers could greatly enhance the capability to detect SLNs in gastric cancer.
Association of magnitude and consistency of PD-L1 expression and other variables associated with benefit from immune checkpoint inhibition (ICI): Systematic review and meta-analysis of 14 phase 3 trials in advanced gastroesophageal cancer (GEC).
Authors: Yoon Harry H. , Jin Zhaohui , Kour Oudom , Shitara Kohei , Gibson Michael K. , Prokop Larry , Kang Yoon-Koo , Shi Qian , Ajani Jaffer A. 
Published: January 2022

344 Background: ICI with anti-PD-1 therapy was approved by the US FDA as 1st/2nd-line treatment of advanced GEC regardless of PD-L1 status. It is argued that patients (pts) with PD-L1-low GEC do not benefit from ICI. To avoid spurious exclusion of pts, we systematically reviewed phase 3 trials to assess the magnitude and consistency of PD-L1 to predict benefit from ICI. We also examined other potential predictive factors to understand their magnitude and consistency in comparison with PD-L1 status. Methods: MEDLINE, Embase, Scopus, Web of Science, and Cochrane Central Register were searched for all randomized clinical trials (RCT; 2000-2021) in advanced GEC comparing ICI, alone or with chemotherapy, vs standard of care (SOC). The primary endpoint was overall survival (OS). Study screening, data abstraction, and bias assessment were done independently by two reviewers per PRISMA guidelines. The mean HR for ICI vs SOC was calculated by random effects model. The predictive value of a factor was quantified using relative magnitude and consistency (table). Results: 14 RCTs at low risk of bias were included (N = 9,210 pts; KN62, CM649, CM648, ESCORT1st, KN590, ATT4, JAV100, KN181, KN61, ATT3, ESCORT, RATIONALE302, JAV300, ATT2). 6 trials were 1st-line, 8 were after 1st-line. Treatment comparisons were ICI + chemo vs chemo (6 trials), ICI vs chemo (9 trials), and ICI vs placebo (1 trial). ICI was always anti-PD-1/-L1 (1 trial also had anti-CTLA-4). Table shows primary results. To enable head to head comparisons, subgroup analyses of trials containing both levels of a factor or having similar design were done and generally yielded consistent results. Conclusions: PD-L1 CPS is the strongest predictive biomarker, after MSI, for OS benefit from ICI-containing therapy vs SOC. Additional research on gender is warranted.[Table: see text]
Distinct differences in genomic profile of gastric and gastroesophageal junction adenocarcinoma.
Authors: Nakauchi Masaya , Walch Henry S. , Chatila Walid Khaled , Tran Thinh , Vos Elvira Lise , Sihag Smita , Tang Laura H. , Coit Daniel G. , Stadler Zsofia Kinga , Janjigian Yelena Y. , Maron Steven Brad , Ku Geoffrey Yuyat , Ilson David H. , Solit David B. , Schultz Nikolaus , Molena Daniela , Strong Vivian E. 
Published: January 2022

345 Background: Gastroesophageal junction cancer (GEJC) and gastric cancer (GC) are frequently studied together as one disease. Genomic profiles between the two disease sites have not been well characterized. We aimed to characterize molecular differences between the two disease sites. Methods: We collected data between January 2010 and December 2019 from a prospectively maintained database of GEJC and GC at our center. GEJC was defined according to the Siewert type 1 to 3 classification. Patients who underwent surgical resection and had MSK-IMPACT (MSK-Integrated Mutation Profiling of Actionable Cancer Targets) sequencing performed on their primary tumor were included in this analysis. Results: Two hundred and seventy-four samples were analyzed; 156 (56.9%) GEJC and 118 (43.1%) GC patients. Regarding molecular subtypes, the GEJC group had a higher frequency of chromosomally instable tumors compared to the GC cohort (55.1% vs. 25.4%, p < 0.001). The fraction of genome altered (FGA) was significantly higher in the GEJC group (p < 0.001). TP53 (75.3% vs. 31.9%, p < 0.001, q < 0.001), CDKN2A (17.1% vs. 4.3%, p = 0.002, q = 0.02), and MDM2 (6.8% vs. 0%, p = 0.007, q = 0.033) were more frequently altered in the GEJC group, whereas CDH1 (2.7% vs. 9.6%, p = 0.037, q = 0.118) and RHOA (0% vs. 6.4%, p = 0.003, q = 0.02) were more frequently altered in the GC group. The GEJC group also had a higher frequency of alterations in the cell cycle pathway compared to the GC patients (36.3% vs. 11.7%, p < 0.001, q < 0.001). Conclusions: There are distinct differences in genomic profiles between GEJC and GC with a higher frequency of mutations in TP53, CDKN2A, MDM2, and cell cycle pathway in the GEJC patients, that may have potential implications in evaluating optimal treatment strategies with targeted therapy.