bluuebunny/crossref_metadata_2025 huggingface dataset:
Double disparities in patients with gastric cancer: Clinicopathology and survival of older adults in a Hispanic-rich population.
Authors: Williams Madison H. , Williams Ryan A. , Hernandez Brian , Michalek Joel , Arora Sukeshi Patel
Published: January 2021

169

Background: Gastric cancer incidence increases with advancing age with a median age at diagnosis of 68. However, older adults (age ≥65) are underrepresented in clinical trials. Additionally, Hispanic populations have a higher incidence of gastric cancer compared with non-Hispanic patients and there is evidence that this population has worse outcomes. Given this double disparity in older Hispanic adults, we evaluated the differences in disease characteristics at diagnosis and survival outcomes in older adults compared to younger adults with gastric cancer at our South Texas cancer center serving a predominantly Hispanic population. Methods: We performed a retrospective analysis of patients with a diagnosis of gastric cancer from 2000 – 2018, who had follow-up at Mays Cancer Center, San Antonio, TX. Older patients were defined as ≥65 years and younger patients were defined as <65 years. Median overall survival (mOS) was estimated from Kaplan-Meier curves and groups were compared using the log-rank test. Results: A total of 190 patients met criteria for analysis. Patients were predominantly younger (age <65), with 128 (67.4%) young and 62 (32.6%) older. Most patients were Hispanic (66.4% of younger and 64.5% of older) and male (51.6% of younger and 66.1% of older). The majority of patients had an ECOG performance status of 0-2, including 61.7% and 64.5% (p = 0.55) of younger and older patients, respectively. At baseline, there was no significant difference in location of primary tumor, grade, stage at diagnosis, or histologic classification between younger and older patients (Table). There was also no significant difference between the two groups in H. pylori status, location of metastases, or HER2 status. Of the 109 patients with follow-up for survival, the mOS was 17 months (95% CI: 15-55) for younger patients versus 14 months (95% CI: 13-NR) for older patients (p = 0.19). Conclusions: In this retrospective analysis of predominantly Hispanic patients with gastric cancer, we found that there were no statistically significant differences in clinicopathologic features at diagnosis or in survival between younger versus older adults. Our study was approximately 2/3 Hispanic, a population for which there is a paucity of data, especially in older adults. Given the limited published research available to guide the management of older patients with gastric cancer, including Hispanics, further prospective real-world studies are needed to evaluate toxicity and quality of life in order to improve the care of older adults with gastric cancer. [Table: see text]
Understanding factors associated with hospital admission for colon cancer diagnosis and staging work up.
Authors: Schriner Jacob B , Arientyl Vanessa , Kopp Adam , Kalam Ali , Friedmann Patricia , Qin Jiyue , In Haejin
Published: January 2021

17

Background: Cancer diagnosis, staging work up and treatment need to be done in a timely manner but are rarely emergencies. Cancer work up during a hospital admission is costly and can take away resources that are needed for more urgent patients. We aim to understand factors related to cancer work up in the hospital inpatient setting. Methods: Patients with a new diagnosis of colon cancer at a single academic institution in 2018 were identified using cancer registry. Patients were excluded if they had cancer other than carcinoma or if data on more than half of their work up was not available for review. A chart review was performed to obtain factors including their demographics, details on their cancer presentation, diagnostic and staging work up and treatment. Patients were considered to have had inpatient work up (Inpt_WU) if 50% or more of their cancer related diagnostic, staging and pre-treatment work up was conducted during a hospital admission, and included imaging, bloodwork, evaluation by consultants. Inpt_WU and non-Inpt_WU patients were compared. Logistic regression model was used calculate odds ratio (OR) and 95% confidence intervals (CI) to identify associations with Inpt_WU. Results: Data on 121 newly diagnosed colorectal cancer patients were analyzed. Inpt_WU occurred in 63 (52%) of the cohort. Inpt_WU and non-Inpt_WU patients required the same median number of work-up events [6, interquartile range (IQR) 5, 6]. Inpt_WU patients were more likely to initially present to the emergency department (ED: 91% vs 16%, p<0.001), have Medicaid insurance (40% vs 17%, p=0.018), be functionally dependent (30% vs 16%, p=0.091), have more defined symptoms (75% vs 45% p=0.001), and have greater cancer severity (metastatic disease 33% vs 17%, p=0.004). The median time between presentation and treatment initiation was markedly less for Inpt_WU compared to non-Inpt_WU [11 days (IQR 5, 24) vs 48 (IQR 37, 81), p<0.001]. The logistic model showed that ED presentation had over 40-fold higher odds of Inpt_WU (OR 41.2, 95% CI 12.1-177.4) after adjusting for comorbidities, insurance, functional status, symptoms, and cancer severity. Conclusions: The cancer diagnostic and pre-treatment work-up process was markedly expedited when done during hospital admission. Most cancers presenting to the ED as the initial location of presentation resulted in admission and cancer work up in the hospital. Further studies are needed to explore whether all of these patients necessitate inpatient admission, and whether healthcare systems can be modified to mimic the efficiency of in-hospital workup.
Incidence of early-onset gastric and esophagus cancers has changed over time with disproportionate impact on Black and Hispanic patients.
Authors: Torrejon Nataly Valeria , Kamath Suneel Deepak , Wei Wei , Tullio Katherine , Khorana Alok A.
Published: January 2021

171

Background: The increased incidence of gastro-esophageal junction adenocarcinoma has been well-described, but how the proportion of early versus older onset cancer has changed over time remains incompletely understood. This study characterized the socioeconomic and pathologic characteristics of early-onset gastro-esophageal malignancies. Methods: All patients with gastric cancer (GC) and esophageal cancer (EC) from 2004-2015 in the National Cancer Database were included and categorized by age under or over 60 years. Differences in demographics, disease stage, treatment characteristics and socioeconomic factors between young and older patients were assessed by Chi-square test. The effect of age, race, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using uni- and multivariable Cox models with Bonferonni correction when indicated. Results: The study population comprised 158,599 patients with GC and 139,210 patients with EC. For GC, 43,146 patients (27.2%) were under age 60. The proportion of patients diagnosed under 60 increased over time: 26.7% in 2004-2006, 26.9% in 2007-2009, 27.6% in 2010-2012 and 27.5% in 2013-2015. Compared to older patients, young patients were more likely to be Black (16.7% vs. 13.2%), Asian (7.6% vs. 6.1%) or Hispanic (15.5% vs. 7.7%), diagnosed with stage 4 disease (43.5% vs. 31.3%) and to have poorly differentiated grade (61% vs. 51.7%), p value < 0.0001 for all. For EC, 38,801 patients (27.8%) were under age 60. The proportion of patients diagnosed under 60, decreased over time: 29.6% in 2004-2006, 28.3% in 2007-2009, 27.6% in 2010-2012 and 26.2 % in 2013-2015. Compared to older patients, young patients were more likely to be Black (12.6% vs. 8.2%) or Hispanic (4.2% vs. 3.1%), diagnosed with stage 4 disease (34.3% vs. 26.1%), p value < 0.0001 for all. There was no difference in histologic grade between younger and older patients (41.1% vs. 40.3%, p = 0.85). Age < 60 years was associated with improved OS in both GC and EC. After adjusting for other demographic, socioeconomic, disease stage and treatment-related factors, Black patients had the worst median OS compared to other races in both malignancies as shown in the Table. Conclusions: Early-onset GC has increased over time while early-onset EC has decreased. Patients with early-onset gastric and esophageal cancer are more likely to be Black or Hispanic and to present with stage 4 cancer. Younger patients with GC are also more likely to have poorly differentiated histology. Most concerning, Black patients have the worst OS compared to other races for both GC and EC. [Table: see text]
Impact of gender on treatment and survival of patients with esophageal cancer in the United States.
Authors: Baumrucker Camille , Franceschi Dido , Livingstone Alan S , Macedo Francis Igor
Published: January 2021

173

Background: Esophageal cancer (EC) is historically a male-predominant disease. Current available evidence on the impact of gender on clinical presentation and survival outcomes of EC is limited by small sample size or single institutional series. Methods: Patients with EC (stage I-III) were identified in the National Cancer Data Base (NCDB, 2004-2016). Clinicopathologic and treatment characteristics of male and female patients were compared using Chi-square analysis. Overall survival (OS) was estimated using Kaplan-Meier method and Cox proportional hazards regression. Results: Of 62,893 patients included, male gender was predominant (77.7% vs 22.3%). Adenocarcinoma was the most common subtype (66.7%); however, squamous cell carcinoma was more predominant in females (57.1% vs. 26.5%, p<0.001). Females were significantly older (68.5 vs. 66.1 years; p<0.001) and more likely African American (AA) (14% vs. 8.1%; p<0.001). Females were more likely to present with local disease (stage I, 19.6% vs. 18.2%; p<0.001), while males presented more likely with locoregional disease (LRD, stage II/III, 80.4% vs 81.8%, p<0.001). Females had worse OS compared to males (18.1 vs. 19.7 mo; p=0.001; cI: 23.5 vs. 31.9mo, p<0.001; cII/III: 17.2 vs 18.3mo, p=0.473). White females had worse OS than white males (18.6 vs. 20.4mo, p<0.001), while AA females had better OS (13.5 vs. 12.6mo, p=0.001). Among patients with LRD, females less frequently received chemotherapy (CT, 75.4% vs. 82.9%, p<0.001), radiation therapy (RT, 78.9% vs. 82.6%, p<0.001), and esophagectomy (28% vs. 40.5%, p<0.001). Females who underwent esophagectomy had improved OS over males (40.3 vs. 32.7mo; p<0.001). More specifically, white females who underwent esophagectomy had improved OS over white males (47.6 vs 38mo, p<0.001); however, AA males and females who underwent esophagectomy had similar OS (33.8 vs 32.6mo, p=0.452). Female gender, advanced age, AA race, high comorbidity score and clinical stage, and lack of access to CT, RT, and esophagectomy were independent predictors of mortality (Table). Conclusions: Females with EC seem to have less access to CT, RT and esophagectomy, which is associated with worse OS compared to males. Healthcare policies should be implemented to increase access to standard of care treatment for female patients with EC. [Table: see text]
Localized diffuse-type gastric adenocarcinoma: Influence of baseline positron emission tomography on survival and therapy response.
Authors: Abdelhakeem Ahmed , Wang Xuemei , Waters Rebecca E , Patnana Madhavi , Estrella Jeannelyn , Blum-Murphy Mariela A. , Trail Allison , Lu Yang , Devine Catherine E , Ikoma Naruhiko , Badgwell Brian D. , Rogers Jane Elizabeth , Ajani Jaffer A.
Published: January 2021

176

Background: Diffuse type of gastric adenocarcinoma (dGAC) confers a poor but variable prognosis compared to intestinal type of GAC. The value of baseline uptake of FDG-PET in localized dGAC is unclear and ~40% are not FDG-PET avid. We analyzed outcomes based on the avidity (high with SUV > 3.5 or low with SUV ≤3.5) of the primary on baseline FDG-PET. Methods: We retrospectively selected 111 localized dGAC cases who had baseline FDG-PET for staging. We compared the FDG-PET avidity with overall survival (OS) and response to preoperative therapy. Standard statistical methods were utilized. Results: The mean age was 59.4 years and with many female patients (47.7%). All patients had dGAC. The high-SUV group (58 [52.3%] patients) and the low-SUV group (53 [47.7%] patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5 – 98.8 months), it was 98.0 months for the low-SUV group and 36.0 months for the high-SUV ( p value = 0.003). While the median PFS for all patients was 38.2 months (95%CI: 27.7 – 97.6 months), it was 98.0 months for the low-SUV group was and 27.0 months for the high-SUV group ( p value = 0.005). Clinical responses before surgery were more common in the low-SUV group but there were only 4 patients with pathologic complete response in the entire cohort. Conclusions: Our unique data suggest that localized dGAC patients with low SUV fare better than those with high SUV meaning highly metabolic GACs consuming glucose confer poor prognosis and overall all dGACs seem resistant to therapy.
A retrospective multicenter study: Clinicopathological factors affecting recurrence-free survival in operable gastric cancer patients.
Authors: Yekeduz Emre , Dogan İzzet , Akbulut Hakan , Karabulut Senem , Utkan Gungor , Urun Yuksel
Published: January 2021

185

Background:Gastric cancer is one of the most common cancers in Asian countries, particularly. However, according to the American Cancer Society, 27,600 new gastric cancer cases and 11,010 deaths due to gastric cancer will be observed in the US in 2020. The rates of 5-year overall survival (OS) are 69.5% and 32% in the localized and regional diseases. Despite surgery and adjuvant treatment, gastric cancer’s recurrence rate is still not reasonable. In this multicenter study, we aimed to identify the clinicopathological factors that affect gastric cancer recurrence. Methods: Clinical and pathological data of the patients performed surgery between the 2009-2018 in the two university hospitals in Turkey was collected retrospectively. Recurrence-free survival (RFS) was estimated using Kaplan-Meier and categorical variables were compared using a log-rank test. After identifying clinicopathological factors affecting RFS, a multivariate analysis was performed using Cox regression analysis. All statistical analyses were performed using IBM SPSS Statistics software, version 27 (IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27 Armonk, NY: IBM Corp.). Results: Three hundred fifty-four patients were included in this study. Two out of three of all patients were male and the median age at diagnosis was 56 years old (Interquartile Range (IQR):48-64). The median follow-up was 25 months (IQR:15-50). The median RFS was 53.2 months (95% Confidence Interval (CI) could not calculated). 5-year survival rate was 64% and the median overall survival (OS) was 136 months (95% CI: 98-173). According to results of multivariate analysis, there was an increased risk for recurrence in patients with preoperative hypoalbuminemia (albumin < 3.5 gr/dl) [Hazard Ratio (HR): 5.3 (95% CI: 1.2-23.4]; p=0.005), and performed R1 resection [HR:5.7 (95% CI:1.2-25.3), p=0.02]. Additionally, patients administered chemoradiotherapy (CRT) had a lower risk for recurrence compared to those administered chemotherapy (CT) alone [HR:0.15 (95% CI:0.04-0.57), p=0.005]. Conclusions: Hypoalbuminemia in the preoperative setting and R1 resection were independent factors that affected gastric cancer recurrence. However, postoperative CRT decreased the recurrence rate of gastric cancer compared to CT alone. Low albumin level is an indicator of a systemic inflammatory response and according to previous studies, hypoalbuminemia was a poor prognostic factor in gastric cancer patients. Although CT alone is considered efficient for patients undergone D2 lymph node dissection, our study showed that CRT decreased the recurrence rates compared to CT alone. This result might be related to the higher number of patients undergone D1 dissection in our study.
Risk factors for gastric cancers in the United States: Variation by anatomic site and race/ethnicity.
Authors: In Haejin , Friedmann Patricia , Sarkar Srawani , Rapkin Bruce , Castle Philip E. , Epplein Meira
Published: January 2021

189

Background: Gastric cancer (GC) is a high mortality cancer in the US. Differences in risk factors by anatomic location and race/ethnicity have been suggested but remain understudied in the US population. Methods: The Multiethnic Cohort (MEC) is a prospective cohort study that collected data on 5 racial/ethnic groups [Whites (W), Blacks (B), Latino (L), Japanese-American (JA), and Hawaiian (HA)] from Hawaii and Los Angeles in 1993-1996. Participants completed a detailed baseline survey and were followed for development of incident cancer. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to identify GC risk factors by anatomic location (cardia, non-cardia) and by race/ethnicity. Results: Data from 192,626 participants was available. The cohort was 25% W, 17% B, 23% L, 28% JA, and 7% HA. During a median follow up of 20.3 years, 1,109 non-cardia and 201 cardia incident GCs were diagnosed. Older age (per year, non-cardia HR 1.08, 95% CI 1.07-1.92; cardia HR 1.06, 95% CI 1.05-1.09), male sex (non-cardia HR 1.6, 95% CI 1.4-1.8; cardia HR 3.0, 95% CI 2.1-4.4), and current (non-cardia HR 1.7, 95% CI 1.5-2.2, cardia HR 3.4, 95% CI 2.2-5.3) or former (non-cardia HR 1.3, 95% CI 1.1-1.5; cardia HR 2.0, 95% CI 1.3-2.9) smoking were associated with both cancer types. Notably, race/ethnicity (ref W: B HR 3.0, 95% CI 2.2-4.0; L HR 2.5, 95% CI 1.8-3.3; JA HR 3.9, 95% CI 3.0-5.1; HA HR 3.9, 95% CI 2.8-5.5), foreign-born (ref: self & parents US born: HR 1.3 95% CI 1.1-1.7), and family history of GC (OR 1.9, 95% CI 1.5-2.3) were associated with non-cardia GC. BMI ≥30 (HR 1.6, 95% CI 1.1-2.3), having ≥1 drink/week (HR 1.6, 95% CI 1.1-2.3), and being JA (ref W: HR 1.9, 95% CI 1.2-2.9) were associated with cardia GC. Risk factors other than age differed by race/ethnicity for non-cardia GC. Male sex was a risk factor for B, L and JA only. Having less than a high school education was a risk factor for B and JA only, smoking a risk factor for L and JA only, and having diabetes a risk factor for B only. Being in the highest sodium intake quartile was a risk factor among W and HA. A family history of GC was a risk factor for W, L, and JA. Having foreign-born parents was a risk factor for W and being foreign-born was a risk factor for JA. Conclusions: GC risk factors differ between subtypes and, for non-cardia, between race/ethnic groups. These differences provide an insight into the etiology of GC and the disproportionate incidence rates in high-risk groups, potentially aiding in the design of targeted intervention strategies.
Is shift-work associated with increased risk of esophageal cancer for males? A meta-analysis.
Authors: Sun Chenyu , Cheng Ce
Published: January 2021

190

Background: Globally, more than 570,000 people are diagnosed of esophageal cancer each year. Shift-work involving circadian disruption was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the relationship between shift-work and esophageal cancer among showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to September 2020 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds risk (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and esophageal cancer risk. Random-effect or fixed-effect model was used to calculate the pooled OR, based on heterogeneity significance. Subgroup analyses were conducted based on night-shift versus rotating-shift. Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: 21 articles were obtained from database searching, and 9 articles were obtained from other sources. 3 articles involving 52,098 participants were included. All studies were considered moderate to high quality. All included studies investigated only males on the association between shift-work and esophageal cancer risk. A statistically significant association between shift-work and increased esophageal cancer risk among males was found (OR 2.09, 95%CI: 1.48, 2.94, P< 0.0001, I 2= 29%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of esophageal cancer (OR 1.56, 95%CI: 0.96, 2.53, P= 0.07, I 2= 0%). In contrast, Rotating-shift was associated with increased esophageal cancer risk (OR 2.80, 95%CI: 1.72, 4.57, P < 0.0001, I 2= 0%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test, and Begg's test found no publication bias of analysis (P = 0.572). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased esophageal cancer risk for males. However, no association between night-shift work and esophageal cancer risk was found. In contrast, association between rotating-shift work and increased esophageal cancer risk was found. Original studies on females regarding shift-work and esophageal cancer risk are lacking. More original studies on this topic for both male and female are needed to further explore shift-work impacts on esophageal cancer risk.
Evaluating the clinical impact of a shortened infusion duration for ramucirumab: A population pharmacokinetic model-based approach.
Authors: Abada Paolo , Lau Yiu-Keung , Wei Ran , O’Brien Lisa , Long Amanda , Piao Yongzhe , Gao Ling
Published: January 2021

191

Background: Ramucirumab is a human recombinant immunoglobin G1 monoclonal antibody (mAb) antagonist of vascular endothelial growth factor receptor-2. Ramucirumab dosed at 8 mg/kg every 2 weeks or 10 mg/kg every 3 weeks, either as monotherapy or in combination with chemotherapy, was initially studied with as an intravenous infusion over 60 minutes following premedication with a histamine-1 receptor antagonist. Lengthy intravenous infusions are inconvenient for patients and increase the workloads of nursing and administrative staff. Shortening the infusion duration of ramucirumab could therefore benefit both patients and healthcare professionals. The current analysis determined the impact such a change could have on the pharmacokinetic (PK) profile of ramucirumab. Additionally, the relationship between infusion rate and incidence of immediate infusion-related reactions (IRRs; occurring on the day of administration), common adverse events associated with mAb infusions, was assessed. Methods: A population pharmacokinetic model was established using concentration–time data collected from 2522 patients who received one of five different ramucirumab regimens involving an intravenous infusion over ~60 minutes in 17 clinical studies. The final PK model was used to simulate concentration–time profiles and exposure parameters following ramucirumab infusion durations of 30 vs 60 min. Phase II/III clinical study data from patients receiving ramucirumab were pooled to assess the association between ramucirumab infusion rate and incidence of immediate IRRs using multivariate logistic regression analysis. Results: Ramucirumab infusions of 30- and 60-min durations resulted in equivalent concentration–time profiles and, hence, equivalent systemic exposure to ramucirumab. Among 3216 patients receiving ramucirumab in phase II/III studies, 254 (7.9%) had at least one immediate any-grade IRR; 17 (0.5%) experienced grade ≥3 immediate IRRs. The incidence of immediate IRRs (any grade or grade ≥3) was similar across infusion rate quartiles. Under multivariate logistic analysis, infusion rate was not significantly associated with an increased risk of an immediate IRR (odds ratio per 1 mg/min increase 1.014, 95% confidence interval 0.999, 1.030; p=0.071). Conclusions: Administering ramucirumab using different infusion durations (30 vs 60 min) did not affect ramucirumab exposure. Analysis of clinical study data showed a faster infusion rate was not associated with an increased risk of immediate IRRs. It is considered unlikely that shortening the infusion duration of ramucirumab will impact its clinical efficacy or overall safety profile, and is now an option for administration in the U.S.
Lymph node mapping in gastric cancer: A pilot study in Western patients.
Authors: Watanabe Akie , Hamilton Trevor D
Published: January 2021

192

Background: Adequate surgical lymphadenectomy is integral to the staging and treatment of gastric cancer. A number of Asian studies have explored the utility of lymph node (LN) mapping in gastric cancer but this in not commonly performed in Western countries. We sought to evaluate the utility and safety of LN mapping in Western patients. Methods: We conducted a pilot study of 13 patients with histologically proven non-metastatic gastric adenocarcinoma that received endoscopic peri-tumoral indocyanine green fluorescence (ICG) injections immediately prior to surgical resection to facilitate LN mapping. Illumination with ICG around the primary tumor, in lymphatic basins, tracts, and lymph nodes were confirmed by the PINPOINT system on recorded videos. Descriptive statistical analysis was performed. Results: Among the 13 patients enrolled, median age was 75 years and 7 were men. On pathologic review, 15% were T1, 54% were T2, and 69% had were node negative. Tumours were located in the proximal third in 1 patient, middle third in 2 patients and distal third in 10 patients. All patients had a laparoscopic subtotal gastrectomy and 10 patients had a D2 lymphadenectomy. 5 patients received preoperative and 7 received postoperative chemotherapy. The median number of LNs harvested was 26 [IQR 24-34]. Video confirmation of ICG mapping of the primary tumor, lymphatic basins, tracts, and LNs were obtained in all patients. All LNs identified with ICG uptake were removed with surgical lymphadenectomy. ICG mapped LNs fell outside the D1 distribution in 100% and outside the D1-plus distribution in 54% of cases. ICG mapped LNs were within the D2 distribution in all cases. No ICG related allergic reactions or procedural complications were observed. Postoperative complications included 2 grade A pancreatic fistulas, 1 gastrointestinal bleed, and 1 NSTEMI. Peri-operative morality was zero. Conclusions: We demonstrate ICG lymph node mapping as a safe and useful technique for identifying regional draining lymph nodes and for primary tumor localization in Western patients. The majority of cases found LNs draining outside the D1 and D1+ distributions, highlighting the importance of appropriate lymphadenectomies in gastric cancer.
Impact of age on outcomes and symptoms in patients with advanced gastroesophageal cancer (GEC).
Authors: Almugbel Fahad , Al-Showbaki Laith , Alqaisi Husam , Suzuki Chihiro , Espin-Garcia Osvaldo , Honório Marta , Jang Raymond Woo-Jun , Alibhai Shabbir M.H. , Elimova Elena
Published: January 2021

193

Background: Although age is a non-modifiable risk factor for most cancers, alone it is not very helpful in deciding on the best treatment for patients. Insufficient data exist in the oldest old ( > 75 years) compared to young-old (65-75 years) and to younger ( < 65 years) patients with de novo metastatic GEC regarding which factors influence response and outcomes. Methods: We retrospectively assessed all patients with de novo metastatic GEC seen from 2006-2015 at the Princess Margaret Cancer Center in Toronto-Ontario, Canada. We used Kaplan-Meier plots and Cox proportional hazards analyses to examine factors associated with progression-free survival (PFS) and overall survival (OS). To examine patient-reported outcomes we used the Edmonton Symptom Assessment System (ESAS) in the first six months of therapy using cross-sectional and longitudinal analyses. Results: A total of 580 de novo metastatic GEC patients were seen between 2006 and 2015. Of these (14%) were oldest old, (31%) were young-old (age 65-75) and 54% were younger ( < 65 years). Most patients (67-80%) were male. Median OS for the entire cohort was 9.1 mo. (95% confidence interval (CI) 8.0 – 10.1); the shortest OS was in the oldest old group at 4.5 mo. compared to 8.7 mo. in young-old and 9.8 mo. in younger group, p < 0.001. PFS was also significantly different among the age groups (4.4 mo., 6.1 mo., and 6.5 mo., respectively), p = 0.0145. In a multivariate model predictors for OS were age (young-old group), number of metastasis, and Eastern Cooperative Oncology Group (ECOG) performance scale (PS). Similar predictors were found for PFS; however, age was not a significant factor. Of the 55 patients who provided ESAS data, 58% were < 65 and 42% were age≥ 65. The most common symptoms at presentation were fatigue, appetite, and well-being. There were no differences by age group (all p > 0.05). Conclusions: Patients age > 75 have poorer OS compared to younger age groups but PFS does not differ, suggesting similar benefits with treatment in appropriately selected older adults with advanced GEC. Symptom profiles were similar with age. Further comprehensive care is needed for older patients with advanced GEC to improve their survival.
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.