bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic versus open esophagectomy for patients with esophageal cancer: Systematic review and meta-analyses of randomized controlled trials.
Authors: Waqar Usama , Ahmed Shaheer , Tauqeer Hasan , Khan Masaab Zaman , Ahmed Kaleem Sohail , Nawaz Waqas , Zafar Syed Nabeel , Jabbar Adnan Abdul 
Published: January 2021

194 Background: There has been an increase in the use of minimally invasive approaches for complex cancer operations. However, its benefit has not been clearly demonstrated for esophageal cancers when compared to open procedures. The purpose of this meta-analysis was to compare operative and postoperative outcomes for partial minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) for patients with esophageal carcinoma. Methods: We conducted a systematic review using CENTRAL, PubMed, Global Index Medicus, ClinicalTrials.gov, EU Clinical Trials Register, and WHO ICTRP until August 30, 2020 without restrictions on publication date, language, or publication status. We included randomized controlled trials evaluating MIEs and partial MIEs including laparoscopic approach with OE for esophageal cancer. All trials including any one of our primary outcome measures -mortality and morbidity- were included. Two authors assessed trials for inclusion. Meta-analyses were conducted for categorical outcomes when heterogeneity was low ( I2< 50%). We reported risk ratios with 95% confidence intervals and GRADE quality of evidence based on our risk of bias assessment. Results: Of 5638 retrieved studies, 10 studies representing 6 trials consisting of 951 patients were included. 347 underwent partial MIE, 106 total MIE, and 498 OE. These were categorized into four cohorts:Co-A: Partial MIE versus OE (4 trials); Co-B: Partial MIE with thoracotomy versus OE (2 trials); Co-C: Partial MIE with cervical incision versus OE (2 trials); Co-D: Complete MIE versus OE (2 trials). Co-A revealed that partial MIE was associated with lower risk of serious adverse events (0.54[0.36-0.83]; 3 trials; 471 participants; I2= 48%), with specifically lower rates of delayed gastric emptying (0.32[0.13-0.80]; 3 trials; 666 participants; I2= 0%), pulmonary complications (0.49[0.29-0.84]; 3 trials; 471 participants; I2= 27%), and mortality (0.67[0.54-0.83]; 4 trials; 692 participants; I2= 0%). Co-B revealed that partial MIE with thoracotomy was associated with lower risk of pulmonary complications (0.61[0.38-0.99]; 2 trials; 231 participants; I2= 0%) and mortality (0.66[0.50-0.87]; 2 trials; 231 participants; I2= 0%). Co-C revealed that partial MIE with cervical incisions were associated with lower risk of serious adverse events (0.38[0.22-0.64]; 1 trial; 240 participants), including pulmonary complications (0.29[0.13-0.65]); 1 trial; 240 participants) and mortality (0.68[0.50-0.94]; 2 trials; 461 participants). Co-D revealed no significant differences between MIE and OE. All significant findings reported originated from high-quality evidence. Conclusions: When compared with completely open esophagectomy, partial MIE is associated with lower risk of mortality and serious adverse events, especially delayed gastric emptying and pulmonary complications.
Selecting the optimal neoadjuvant treatment approach based on the risk of an involved surgical margin in locally advanced adenocarcinoma of the esophagus and esophagogastric junction.
Authors: Spencer Tim , Helbrow Jonathan , Pilsworth Eleanor , Falk Stephen , Winter Helen , Bird Thomas 
Published: January 2021

198 Background: Optimal neoadjuvant (NA) treatment for adenocarcinoma of the esophagus and esophagogastric junction is unknown. This study aims to evaluate an approach of offering NA chemoradiotherapy (CRT) to T3/T4 tumours with a threatened circumferential resection margin (CRM) on staging imaging (computerized tomography/endoscopic ultrasound/positron emission tomography) and NA chemotherapy (CT) to T3/T4 tumours with a non-threatened CRM. Methods: Cases with clinically staged T3/T4 tumours who underwent a radical esophagectomy at a single tertiary referral centre between 2013 and 2019 were retrospectively reviewed. NA CRT was given as 41.4Gqy in 23 fractions with weekly carboplatin/paclitaxel and NA CT was given as a platinum based combination. Survival outcomes are described using the Kaplan-Meier method and calculated from NA treatment start. Results: 81 patients were identified - 18 (22%) received CRT and 63 (78%) received CT. More cases had Stage IVA disease in the CRT group (28% vs. 8%). CT consisted of a platinum/fluoropyrimidine doublet (43%), triplet with epirubicin (51%) or FLOT (6%). Median follow up was 68 months. Median length of post-operative stay (11 days for both) and rate of death within 90 days of surgery (6% vs. 3%) were similar. Rates of R0 resection (100% vs. 67%) and tumour regression grade 1/2 (55% vs. 14%) favoured CRT. There was no difference in overall survival (HR 0.92 (95%CI: 0.45-1.87), p=0.81). Estimated 3 year relapse-free survival was 39% (95%CI: 14-64) for CRT and 45% (95%CI: 33-58) for CT. Location of first relapse was local, distant or both in 0%, 75% and 25% for CRT and 6%, 50% and 44% for CT. In the CT group, overall survival was inferior for patients with an R1 resection (HR: 6.30 (95%CI 3–14), p<0.001). Conclusions: Neoadjuvant chemoradiotherapy for CRM-threatened cases of locally advanced adenocarcinoma of the esophagus and esophagogastric junction resulted in a very low rate of R1 resection and similar survival outcomes to non-CRM-threatened cases treated with neoadjuvant chemotherapy. Tailoring the neoadjuvant approach based on risk to CRM involvement appears feasible and warrants further investigation. [Table: see text]
A phase II study of perioperative capecitabine plus oxaliplatin for clinical SS/SE N1-3 M0 gastric cancer (OGSG1601).
Authors: Yasuda Atsushi , Matsuyama Jin , Terazawa Tetsuji , Goto Masahiro , Kawabata Ryohei , Endo Shunji , Imano Motohiro , Fujita Shoichiro , Akamaru Yusuke , Taniguchi Hirokazu , Tatsumi Mitsutoshi , Lee Sang-Woong , Kawakami Hisato , Kurokawa Yukinori , Shimokawa Toshio , Sakai Daisuke , Kato Takeshi , Fujitani Kazumasa , Satoh Taroh 
Published: January 2021

203 Background: D2 gastrectomy followed by adjuvant S-1 is one of the standard therapy for the patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with clinical SS/SE N1-3 M0 GC. Methods: The eligibility criteria included histopathologically confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of GC (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to JCGC ( ≥Grade 1b). Results: Thirty-seven pts were enrolled from April 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of NAC and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4–68.2) were demonstrated. The relative dose intensity (RDI) of capecitabine and oxaliplatin were 90.5% and 91.9%, respectively. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment, and the RDI of capecitabine and oxaliplatin were 80.9% and 65.1%, respectively. Grade 3–4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%), but no treatment-related death was reported. The overall survival (OS) rate and relapse free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Subgroup analyses according to residual tumor after surgery (R status) showed a 3-year OS and RFS rate of 86.2% (95% CI, 74.5-99.7%) and 75.7% (95% CI, 63.0-90.8%) for R0. Conclusions: Perioperative CapeOx showed good feasibility and favorable prognosis with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations. Clinical trial information: 000021641.
Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).
Authors: Takahari Daisuke , Ohashi Manabu , Takashima Atsuo , Mizukami Takuro , Ishizuka Naoki , Katai Hitoshi , Mikami Shinya , Wakatsuki Takeru , Chin Keisho , Ida Satoshi , Kumagai Koshi , Nunobe Souya , Iwasa Satoru , Ito Miki , Wada Takeyuki , Yamagata Yukinori , Ogura Takashi , Sano Takeshi , Boku Narikazu , Yamaguchi Kensei 
Published: January 2021

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.
SETD1A to induce epithelial-mesenchymal transition to promote invasion and metastasis through epigenetic reprogramming of snail in gastric cancer.
Authors: Wu Jugang , Yu Jiwei , Gu Yan 
Published: January 2021

241 Background: Aberrant epigenetic modification induces oncogenes expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates H3K4, is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study had reported that SETD1A promoted gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. Methods: Transwell migration and invasion assay were performed to determine GC cell migration and invasion. Lung metastasis assay was used to detect GC cell metastasis. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. ChIP assay was performed to investigate the methylation of H3K4. The correlation between SETD1A and EMT associated key genes in GC were performed by bioinformatic analysis. Results: In this study, we found that overexpression of SETD1A promotes GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration, invasion and metastasis. Furthermore, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin, and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin and Vimentin. Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factors snail. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on snail promoter. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, linear correlation between SETD1A and several key EMT genes, including E-cadherin, Fibronectin and snail, in GC specimens obtained from TCGA dataset. Conclusions: In summary, our data reveals that SETD1A mediated EMT process and induced metastasis through epigenetic reprogramming of snail.
Disease-free and overall survival in nonmetastatic esophageal or gastroesophageal junctional cancer after treatment with curative intent: A nationwide population-based study.
Authors: Pape Marieke , Vissers Pauline A.J. , Beerepoot Laurens , Van Berge Henegouwen Mark I. , Lagarde Sjoerd , Mook Stella , Bertwistle David , McDonald Laura , Van Laarhoven Hanneke W.M. , Verhoeven Rob 
Published: January 2021

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.
The interdisciplinary team: Education as a means to exemplify and optimize patient outcomes in gastric/GEJ cancers through collaborative discussions.
Authors: Parikh Kinjal , Cameron Davecia Ragoonath , Peters Pamela M. 
Published: January 2021

248 Background: Care of patients with gastric/GEJ cancer involves multimodality treatment including various systemic and supportive approaches and collaboration of interdisciplinary team members. Optimizing care requires not only adherence to the latest evidence-based and guideline-driven recommendations but also the management of underlying comorbidities or treatment-induced conditions. This complex interplay of factors in treatment planning requires timely education for oncologists and nurses/NPs in both clinically driven topics and interdisciplinary collaboration. Methods: A series of 2 CME/CE-certified activities were launched to educate oncologists and nurses/NPs on the changing paradigms in gastric cancer as well as the interdisciplinary collaboration needed to optimize patient eligibility for treatment. Effectiveness was analyzed using 3 multiple-choice questions measuring knowledge and competence and 1 confidence question were presented as pre-/post- repeated pairs for each of the activities. Oncologists and nurses/NPs who completed both the pre- and post-CME questions were included in the analysis and McNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The CME activities launched in 2/2020 with data collected and reported as of 9/2020. Results: 8034 learners participated in the activities including 1163 oncologists and 3665 nurses/NPs. Analyses from the activities found improvement in knowledge, competence, and confidence. Data from oncologists (n = 94-302) and nurses/NPs (n = 169-510) are reported. Statistically significant changes were seen for oncologists in: Knowledge regarding the impact of nutrition and anemia can have on quality-of-life (QOL) and further treatments (50% pre, 72% post; p < .001); Competence related to implementing strategies to address nutrition and anemia to improve quality-of-life and to advance treatment (45% pre, 72% post; p < .001); Confidence regarding their ability to work together as an integrated, interdisciplinary team to enhance quality of life and treatment outcomes through a holistic treatment approach (68% pre, 83% post; p < .001). And for nurses/NPs in: Knowledge regarding the impact that nutrition and anemia can have on QOL and further treatments (34% pre, 50% post; p < .01). Conclusions: This online, interactive, expert-led, CME/CE-certified educational activity resulted in gains in oncologist and nurse/NP knowledge, competence, and confidence surrounding advanced gastric/GEJ cancer management and team collaboration. As patients with gastric cancer continue to present with poor performance status and require not only systemic interventions but also amelioration of underlying conditions, education remains essential for optimal outcomes to members of the interdisciplinary team.
Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer.
Authors: Kim Daniel W , Lee Grace , Hong Theodore S. , Li Guichao , Roeland Eric , Keane Florence , Eyler Christine Elissa , Drapek Lorraine C. , Ryan David P. , Allen Jill N. , Berger David L. , Parikh Aparna Raj , Mullen John , Klempner Samuel J , Clark Jeffrey William , Wo Jennifer Y 
Published: January 2021

249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.