Esophagogastric Adenocarcinoma Patients Research Articles

Incidence trends and survival in early-onset esophagogastric adenocarcinoma: A Swedish population-based cohort study.

Early-onset adenocarcinomas of different sites are increasing in high-income countries, data on esophagogastric adenocarcinoma are sparse. We performed a Swedish population-based cohort study over 1993-2019 to delineate differences in incidence and survival in early-onset (age 20-54 years) compared to later-onset (55-99 years) esophageal, cardia, and non-cardia gastric adenocarcinoma. Temporal incidence trends were quantified as annual percentage changes (APC) and survival differences as excess mortality rate ratios (EMRR) using Poisson regression and including 95% confidence intervals (CI). Among 27,854 esophagogastric adenocarcinoma patients, 2576 were early-onset whereof 470 were esophageal, 645 were cardia, and 1461 were non-cardia gastric. Except non-cardia gastric, the male predominance was larger in early- compared to later-onset disease. Advanced stage and signet ring cell morphology were more common among early-onset patients. Early- and later-onset APC estimates were comparable and esophageal adenocarcinoma incidence increased, cardia remained stable, and non-cardia gastric decreased. Early-onset patients had better survival than later-onset, which was amplified when adjusting for prognostic factors including stage (adjusted EMRR 0.73 [95% CI 0.63-0.85] in esophageal, 0.75 [95% CI 0.65-0.86] in cardia, and 0.67 [95% CI 0.61-0.74] in non-cardia gastric adenocarcinoma). The early-onset survival advantage was more pronounced in localized stages 0-II (all sites) and women (esophageal and non-cardia gastric). We found no major differences in incidence trends comparing early- and later-onset esophagogastric adenocarcinoma. Despite unfavorable prognostic features, early-onset esophagogastric adenocarcinoma survival was better than later-onset, particularly in localized stages and women. Our findings suggest delayed diagnosis in younger individuals and especially men.

Immune responses against shared antigens are common in esophago-gastric cancer and can be enhanced using CD40-activated B cells

BackgroundSpecific immune response is a hallmark of cancer immunotherapy and shared tumor-associated antigens (TAAs) are important targets. Recent advances using combined cellular therapy against multiple TAAs renewed the interest in...

378. FLOT VS ECX: A COMPARISON OF TWO NEOADJUVANT CHEMOTHERAPY REGIMEN’S EFFECTS ON SARCOPENIA IN ESOPHAGOGASTRIC ADENOCARCINOMA PATIENTS

Abstract Sarcopenia is defined as a loss of skeletal muscle mass and function. It is prevalent amongst patients with esophagogastric adenocarcinoma (EGA) and associated with adverse treatment outcomes. Neoadjuvant chemotherapy (NAC) may contribute to sarcopenia development. FLOT, although superior to ECX in terms of survival, has been reported to have higher toxicities. The aim of this study was to compare the effect of ECX and FLOT on sarcopenia and lean body mass (LBM) in EGA patients. Patients diagnosed with EGA between January 2017 and December 2020 and undergoing ECX/FLOT NAC followed by esophagectomy from a single tertiary center in the UK had their pre- and post-NAC CT scans assessed for radiological sarcopenia. Skeletal muscle index (SMI) was calculated from muscle area measured on CT scans at the level of third lumbar vertebra. Previously published SMI cut off values for radiologically defined sarcopenia were used (52.4cm2/m2 for men and 38.5cm2/m2 for women). LBM (kg) was calculated using a previously published formula. 153 patients were included in the analysis. Sarcopenia increased from 77/153 (50.3%) pre-NAC to 98/153 (64.1%) post-NAC (p < 0.005). There were 48/82 (58.5%) ECX and 29/65 (44.6%) FLOT patients sarcopenic pre-NAC. 60/82 (73.2%) ECX and 38/65 (58.5%) FLOT patients were sarcopenic post-NAC and pre-operatively. There was no statistically significant difference observed for development of sarcopenia after NAC between the two NAC regimens (p = 0.793). Similarly, LBM significantly decreased during NAC (p = 0.007), but this effect did not vary between NAC regimen (p = 0.917). Radiological sarcopenia is highly prevalent in EGA patients and significantly increases during NAC. However, this study suggests that there is no difference in the degree of sarcopenia between ECX and FLOT NAC regimens. Impact of pre- and post-FLOT related sarcopenia on treatment outcomes needs to be established alongside strategies to treat this syndrome and prevent its further development.

460. SARCOPENIA AFTER NEOADJUVANT CHEMOTHERAPY IS ASSOCIATED WITH DEVELOPMENT OF MODERATE TO SEVERE POST-OPERATIVE COMPLICATIONS IN ESOPHAGOGASTRIC ADENOCARCINOMA PATIENTS

Abstract Sarcopenia is defined as a loss of skeletal muscle mass and function. Preoperative sarcopenia amongst patients with esophageal cancer has been linked to various postoperative complications and to the degree of severity of these complications. The majority of this evidence comes from populations with squamous cell carcinoma or where neoadjuvant chemoradiotherapy was used. Whether sarcopenia pre- or post-neoadjuvant chemotherapy (NAC) for esophagogastric adenocarcinoma (EGA) is associated with postoperative complications is not fully understood. Patients diagnosed with EGA between January 2017 and December 2020 and undergoing NAC followed by esophagectomy from a single high-volume center had their pre- and post-NAC CT scans assessed for radiological sarcopenia. Skeletal muscle index (SMI) was calculated from muscle area measured on CT scans at the level of third lumbar vertebra. Previously published SMI cut off values for radiologically defined sarcopenia were used (52.4cm2 for men and 38.5cm2 for women). Post-operative complications were prospectively evaluated and classified using the Clavien-Dindo (CD) classification system. Patients were grouped as either CD 0-I (no-mild complications) or CD II-V (moderate–severe complications). There were 144 patients included in the analysis. 62 patients had FLOT NAC and 82 patients had ECX NAC. Pre-NAC sarcopenia was not associated with the development of moderate–severe postoperative complications (p = 0.075). However, sarcopenia assessed on restaging scan post-NAC was found to be associated with moderate–severe postoperative complications (p = 0.044). EGA patients with sarcopenia post-NAC are more likely to develop moderate–severe post-operative complications than those without sarcopenia. Strategies to treat sarcopenia and prevent its further development are desperately needed in order to reduce post-operative complications.

Irinotecan with or without capecitabine as a beyond 2nd line regime for esophago-gastric adenocarcinomas.

e16545 Background: Purpose: The aim of this retrospective study was to assess the efficacy and toxicity of irinotecan +/- capecitabine for patients with metastatic esophago-gastric (EG) adenocarcinomas previously treated with at least two chemotherapy regimens including platinum-based, fluoropyramidines and taxanes. Introduction: Treatment for metastatic EG cancer beyond 2nd line remains controversial. Recently, the TAGS phase III trial (Shitara et al., 2018) showed overall survival benefit with Trifluridine/tipiracil of 2.1 months compared to placebo as a third line. Apatinib is also approved for use as third line in China (Li et al., 2013). Based on minimal evidence (Kang et al., 2013), irinotecan in combination with capecitabine is used in the UK. We performed a retrospective study to assess the efficacy and toxicity of irinotecan as a beyond 2nd line regime in metastatic EG adenocarcinomas in one of Europe’s largest cancer centres, The Christie. Methods: Data was collected retrospectively from all metastatic EG adenocarcinoma patients who were treated with irinotecan +/- capecitabine as a beyond 2nd line palliative treatment at the Christie Hospital from January 2014 to December 2019. Irinotecan was either given 2 or 3 weekly at dose of 180 mg/m² with or without capecitabine 800 mg/m². Response rate (RR) was calculated according to RECIST version 1.1, overall survival measured and toxicity data collected. Results: Fifty-six patients received irinotecan as beyond 2nd line palliative chemotherapy. Out of the thirty-seven patients with measurable disease on their scans, the overall response rate was 8.1% and the disease control rate was 51.4% as per RECIST 1.1. Median overall survival was 5 months (95% CI 4.2-5.8). The presence of grade 3-4 toxicities was 16% (9 patients) and included neutropenia, fatigue, nausea and diarrhea. On average, 3.7 cycles were administered, 32% (18 patients) required dose reductions, mainly secondary to grade 2 diarrhea and fatigue. Conclusions: Irinotecan in combination with capecitabine is efficacious as a beyond 2nd line regime in metastatic EG with an acceptable toxicity profile with a limited role in patients with resistant disease to first line platinum-based chemotherapies with fluoropyramidines.

Rapid stromal remodeling by short-term VEGFR2 inhibition increases chemotherapy delivery in esophagogastric adenocarcinoma.

Anti‐angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient‐derived xenograft (PDX) models of EAC were subjected to long‐term and short‐term treatment with anti‐VEGFR2 therapy followed by chemotherapy injection or multi‐agent dynamic contrast‐enhanced (DCE‐) MRI and vascular casting. Long‐term anti‐VEGFR2‐treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short‐term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short‐term anti‐angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long‐term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti‐angiogenic therapy combined with chemotherapy in EAC patients.

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8+ T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients.

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1NEG CD8+ T cell populations.

Prognostic stratification in esophagogastric adenocarcinoma in the revised AJCC staging (7th edition).

92 Background: AJCC esophageal staging assigns prognostic groups based on tumor, node, and metastasis classifications. In 2010, AJCC 7th ed. separated adenocarcinoma from squamous cell histology and added tumor grade and number of involved regional nodes. Our study aim was to compare survival prognostication for esophagogastric adenocarcinoma between AJCC 7 and AJCC 6thed. stage groupings. Methods: We abstracted pathology and survival for surgically-resected esophagogastric adenocarcinoma patients (n=836; 1997 to 2011); 256 received induction therapy. AJCC stage was assigned; overall survival in months (esophagectomy to death or most recent alive contact) was analyzed. Discriminatory ability and homogeneity, by stage, was assessed with Kaplan-Meier (KM) curves. Monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) was used to assess model fit. Results: Compared to AJCC 6, AJCC 7 restaged 165 patients. (Table) KM log-rank statistic indicated stronger differentiation in AJCC 7 curves compared to AJCC 6 (166.128 vs 185.523 overall). Cox likelihood ratio (162.957 vs. 173.951 overall) and AIC (4,831.011 vs 4,820.016 overall) indicated better model fit to the survival data for AJCC 7 versus AJCC 6, overall and for induction subgroups (data not shown). As stage group increases, stronger linear trends for survival were observed at 24, 36 and 60 months using AJCC7 stage groupings, overall and for induction subgroups, compared to AJCC 6. Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected esophagogastric adenocarcinoma patients, including patients who received induction therapy. [Table: see text]

Retrospective analysis of adjuvant chemotherapy for curatively resected gastric cancer

To determine the efficacy of adjuvant chemotherapy for gastric cancer in clinical practice, a retrospective analysis was conducted in a high-volume Chinese cancer center. Between November 1995 and June 2007, a total of 423 gastric or esophagogastric adenocarcinoma patients who did (Arm A, n = 300) or did not (Arm S, n = 123) receive radical gastrectomy followed by postoperative chemotherapy were enrolled in this retrospective analysis. In Arm A, monotherapy(fluoropyrimidines, n = 25), doublet (platinum/fluoropyrimidines, n = 164), or triplet regimens [docetaxel/cisplatin/5FU (DCF), or modified DCF, epirubicin/cisplatin/5FU (ECF) or modified ECF, etoposide/cisplatin/FU, n = 111] were administered. Disease-free survival (DFS) and overall survival (OS) were compared between the two arms. A subgroup analysis was carried out in Arm A. A multivariate analysis of prognostic factors was conducted. Stage I, II and III cancers accounted for 9.7%, 35.7% and 54.6% of the cases, respectively, according to the American Joint Committee on Cancer (AJCC) staging system, 7(th) edition. Only 178 (42.1%) patients had more than 15 lymph nodes harvested. Hazard ratio estimates for Arm A compared with Arm S were 0.47 (P < 0.001) for OS and 0.59 (P < 0.001) for DFS. The 5-year OS rate was 52% in Arm A vs 36% in Arm S (P = 0.01); the adverse events in Arm A were mild and easily controlled. Ultimately, 73 patients (26.5%) who received doublet or triplet regimens switched to monotherapy with fluoropyrimidines. The OS and DFS did not differ between monotherapy and the combination regimens, however, both were statistically improved in the subgroup of patients who were switched to monotherapy with fluoropyrimidines after doublet or triplet regimens as well as patients who received ≥ 8 cycles of chemotherapy. In clinical practice, platinum/fluoropyrimidines with adequate treatment duration is recommended for stage II/III gastric cancer patients according to the 7(th) edition of the AJCC staging system after curative gastrectomy even with limited lymphadenectomy.