Systemic treatment offers only modest survival benefits in previously treated metastatic gastroesophageal adenocarcinoma (GEA). Treatment monitoring using imaging-based response assessments are often delayed and imprecise, highlighting the need for biomarkers to guide early treatment decisions. We evaluated the value of circulating tumor DNA (ctDNA) for prognosis, patient selection, and on-treatment monitoring in patients with previously treated GEA. This retrospective study aimed to investigate whether baseline ctDNA levels and early ctDNA changes assessed by ctDNA-RECIST were associated with survival outcomes in a randomized Phase 2 trial comparing trifluridine-tipiracil plus bevacizumab or trifluridine-tipiracil alone. Plasma samples were collected at baseline and during treatment (weeks 4 and 8). ctDNA was quantified by a tumor-agnostic methylation-specific digital droplet PCR (ddPCR) assay. Plasma samples were available in 86 patients out of a total of 103 patients included in the trial. Patients with the highest baseline ctDNA levels (top 20

343 Background: In MATTERHORN (NCT04592913), D + FLOT significantly improved event-free survival (EFS) vs placebo (P) + FLOT in participants (pts) with resectable G / GEJ adenocarcinoma (Janjigian et al. N Engl J Med 2025). Dose modifications for each FLOT component could be made per local standard clinical practice. Here, we report rates of FLOT discontinuation along with EFS based on FLOT completion status. Methods: In this global, double-blind, Phase 3 study, pts with resectable G / GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT every 2 weeks on Days 1 and 15 for 4 cycles (2 cycles neoadjuvant and 2 cycles adjuvant), followed by D 1500 mg or P on Day 1 Q4W for 10 additional cycles. Rates of discontinuation of any FLOT component are reported in pts who received ≥1 dose of study treatment. EFS (time from randomization to progression, local or distant recurrence, or death) according to RECIST v1.1 per BICR and / or locally by pathology testing is reported in pts who completed all FLOT, stopped some (≥1–3 components) FLOT and stopped all FLOT. Results: Of the 944 pts who received ≥1 dose of study treatment, the proportion of pts who received all administrations of ≥1 FLOT component was similar in the D + FLOT vs P + FLOT arms in the neoadjuvant (96.0% vs 95.1%) and adjuvant (61.5% vs 64.4%) periods. The overall rate of discontinuation of ≥1 FLOT component due to adverse events (AEs) was 25.5% in the D + FLOT arm vs 20.3% in the P + FLOT arm, with higher discontinuation rates in the adjuvant (21.4% vs 15.1%) than the neoadjuvant (6.5% vs 7.7%) period (Table). The most common AEs causing FLOT discontinuation were peripheral neuropathy and neutropenia (Table). EFS was improved with D + FLOT vs P + FLOT in pts who completed all FLOT (n=228 vs 243; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.49–0.94), stopped some FLOT (n=63 vs 60; HR, 0.35; 95% CI, 0.16–0.71) or stopped all FLOT (n=183 vs 167; HR, 0.72; 95% CI, 0.55–0.95). Conclusions: MATTERHORN was designed for pts to receive the full perioperative FLOT regimen. In this exploratory analysis, the addition of D to FLOT did not notably impact the ability to receive FLOT; no new safety concerns were identified. EFS was improved with D + FLOT vs P + FLOT regardless of FLOT completion. Clinical trial information: NCT04592913 . Neoadjuvant Adjuvant Overall D + FLOT (n=475) P + FLOT (n=469) D + FLOT (n=365) P + FLOT (n=351) D + FLOT (n=475) P + FLOT (n=469) ≥1 FLOT component discontinuation due to AEs, n (%) 31(6.5) 36(7.7) 78(21.4) 53(15.1) 121(25.5) 95(20.3) Peripheral neuropathy* 14(2.9) 16(3.4) 7(1.9) 5(1.4) 25(5.3) 27(5.8) Neutropenia* 1(0.2) 1(0.2) 10(2.7) 7(2.0) 15(3.2) 8(1.7) Infusion-related reaction* 1(0.2) 0 12(3.3) 5(1.4) 13(2.7) 5(1.1) Hypersensitivity* 2(0.4) 1(0.2) 9(2.5) 6(1.7) 11(2.3) 7(1.5) *Occurring in ≥2% of pts in either arm overall.

Background: Evidence of treatment of patients with relapse following multimodal treatment for oesophageal, gastro-oesophageal junctional and gastric adenocarcinoma is almost absent. Methods: In a nationwide consecutive cohort of 202 patients, radically resected after perioperative chemotherapy (CTx) and followed-up without scheduled imaging, we identified 89 patients with recurrence within 12 years. We registered prior clinico-pathological and treatment characteristics, alarming symptoms, work-up, recurrence patterns, treatment of recurrence, and outcome. Results: Median time to recurrence was 15.2 months, 91% of relapses occurred within 3 years. Frequent alarming symptoms were pain, weight loss and loss of appetite. Fifty-four percent recurred at multiple sites, 36% at a single anatomic site, and 10% were solitary. Recurrence was a 99% fatal event with a median overall survival (OS) of only 4.6 months. Older age, ypN3 at surgery, poor performance status, weight loss, non-solitary recurrence, no postoperative CTx, and no palliative CTx, were associated with short OS. Three patients had initial surgery, but all progressed; one additional patient was cured by salvage surgery after palliative CTx. Sixty percent (53 patients) were treated with CTx yielding a median progression-free survival and OS of 4.0 and 5.8 months, respectively; the overall response rate was 35%. Pleuroperitoneal metastases predicted poor prognosis. Non-platinum-based, first-line palliative CTx was used in 38%, mostly in patients with short treatment-free interval. Interpretation: In this national cohort, recurrence was a 99% fatal event and only 60% of patients received palliative CTx. Efficacy of palliative CTx at relapse after multi-modal treatment is poor and needs further investigations.

The prognostic value of lymph node (LN) yield in esophageal and gastric cancer remains controversial, especially in the context of modern perioperative treatment. This multicenter Danish cohort study evaluates the association between LN yield and survival outcomes. This study included 3092 patients who underwent curative-intent resection for esophageal (n = 2402) or gastric cancer (n = 690) between 2013 and 2021 at four Danish upper GI centers. All cases were registered in the Danish Esophagogastric Cancer Group database, covering 99% of all Danish esophageal and gastric cancer cases. Patients were stratified by nodal status (pN0/pN+) and categorized into five LN yield groups. Survival analyses were performed using Kaplan-Meier curves and multivariable Cox regression. In node-negative esophageal cancer, higher LN yields (20-29, 30-39, and 40+) were significantly associated with improved survival (hazard ratio: 0.47-0.58, P < 0.001) compared with the reference group (16-19). No survival benefit was seen beyond 16-19 nodes in node-positive esophageal or gastric cancers. Perioperative chemotherapy improved survival in node-positive esophageal cancer but had no effect in node-negative esophageal and gastric cancer. Discrepancies between clinical and pathological nodal staging were frequent and influenced both survival estimates and treatment allocation. LN removal was associated with survival in esophageal and gastric cancer. Node-negative patients showed increased survival if ≥20 nodes were removed, while node-positive esophageal cancer and gastric cancer patients showed no difference in survival beyond 16-19. Lastly, discrepancies between clinical and pathological staging underscore the need for more accurate preoperative diagnostics and highlight the impact of modern perioperative chemotherapy.

PURPOSE:The bispecific antibodies lomvastomig and tobemstomig block the immune checkpoint receptor PD-1 and either TIM-3 or LAG-3, respectively. This phase 2 study assessed their efficacy compared with nivolumab in CPI-naïve patients with unresectable advanced or recurrent ESCC who were refractory or intolerant to one prior line of chemotherapy. PATIENTS AND METHODS:This active-controlled, blinded, multicenter study randomized patients (1:1:1) to treatment with lomvastomig (2100 mg Q2W), tobemstomig (2100 mg Q2W), or nivolumab (240 mg Q2W). The primary endpoint was overall survival, secondary endpoints included objective response, progression-free survival, pharmacodynamic changes, safety/tolerability, immunogenicity, and pharmacokinetics. RESULTS:190 patients were randomized, 27 to lomvastomig (this group was discontinued early), 82 to tobemstomig, and 81 to nivolumab. The median overall survival was lower in the lomvastomig (4.8 months; 80%CI, 2.8-5.8) and tobemstomig (6.7 months; 80%CI, 5.4-8.7) arms than in the nivolumab arm (8.1 months; 80%CI, 6.7-9.0). The objective response rate was 3.7%, 9.8%, and 8.6%, respectively. An exploratory biomarker analysis of tobemstomig-treated patients showed improved survival in the PD‑L1‑high (CPS≥10) versus the PD-L1-low (CPS<10) subgroup, with the greatest benefit in patients with concurrent high expression of PD-L1 and LAG-3 (>median). Adverse events with lomvastomig and tobemstomig were manageable, and the safety profiles of all three compounds remained consistent with their known immune-mediated side effects profiles. CONCLUSIONS:Neither lomvastomig nor tobemstomig improved survival compared to nivolumab in the overall patient population. However, in the PD-L1-high (CPS≥10) and PD-L1-high/LAG3-high subgroups, tobemstomig was associated with prolonged survival, supporting PD-L1-guided treatment selection for tobemstomig in ESCC.

In recent years, the utility of positron emission tomography/magnetic resonance imaging (PET/MRI) has become increasingly significant in diagnostic settings. This study provides a five-year follow-up on a previous pilot study that demonstrated the feasibility of PET/MRI in predicting the resectability of adenocarcinoma of the esophagogastric junction (AEG). We aimed to evaluate whether this imaging modality could further serve as a prognostic tool for survival in AEG patients. A total of 22 patients were included in the initial pilot study, with 17 of them undergoing surgery. All patients underwent three series of neo-adjuvant chemotherapy (NT). This follow-up study retrospectively analyzed the correlation between the apparent diffusion coefficient (ADC) and standard uptake value (SUV) measurements of the primary tumor from the original study with overall survival and recurrence. ADC and SUV values were measured prior to initiation of NT, and again 17–21 days into the first cycle of NT-administration, and the differences between the scans were calculated as ∆SUVmax, ∆ADCb0, and ∆ADCb50. Early treatment response was assessed using the Response Evaluation Criteria In Solid Tumors (RECIST). Binary logistic regression was employed to evaluate the predictive values of ADC and SUV parameters, and receiver operating characteristic (ROC) curves were generated to determine sensitivity, specificity, and area under the curve (AUC). As of January 7, 2022, 8 of the 22 patients were still alive. The AUC was calculated to assess the association of imaging parameters with long-term survival: ∆SUVmax: AUC = 0.74, sensitivity, 87.5

Gastric cancer remains a major clinical challenge with poor prognosis. This study investigated survival outcomes based on treatment strategy, tumor stage, and histology in Danish gastric cancer patients. From January 2013 to December 2021, 2,156 gastric cancers were registered in the Danish Esophagogastric Cancer Group database, covering 99

Introduction: Older patients with gastroesophageal (GE) cancer are at increased risk of low treatment tolerability and poor outcome. Dose reduced chemotherapy has been shown to improve tolerability without compromising efficacy in advanced GE cancer. However, the impact of reduced dose preoperative chemotherapy in the curative setting of older patients is unknown. The primary aim of this study was to investigate if dose reduction during preoperative chemotherapy impacts survival in older patients aged >= 70 >= 70 years with resectable GE cancer. Materials and Methods: This cohort study included consecutive patients referred to perioperative chemotherapy treated from November 2016 until October 2021. The primary endpoint was overall survival (OS) estimated by Kaplan-Meier analysis. The log-rank test was used to compare survival rates. A multivariate analysis was made to control for potentially interacting covariates. Results: A total of 548 patients (age >= 70, 179; age < 70, 369) were included. Fewer older compared to younger patients had Eastern Cooperative Oncology Group Performance Status 0 at baseline (50 % vs 63 %, p = 0.007). Preoperative chemotherapy was more often initiated at reduced dose in older patients compared to younger (37 % vs 14 %, p < 0.001). Older patients who did not receive a reduce dose in the second or subsequent cycles of preoperative chemotherapy were less likely to complete preoperative chemotherapy when compared to the younger patients (75 % vs 85 %, p = 0.03). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with significantly better OS for the older patient population (HR = 0.54, 95 % CI: 1.2-2.9, p = 0.006) but not for the younger (HR = 0.97, 95 % CI: 0.75-1.4, p = 0.83). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with lower mortality risk in the multivariate analysis for the older patients (HR = 0.56, 95 % CI: 0.33-0.97, p = 0.04). Discussion: Dose reduction in the second or subsequent preoperative chemotherapy cycles seems safe and feasible in older patients without compromising survival and may result in a benefit in OS. This finding should be validated in an independent cohort or a randomized trial.

Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC). Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4. ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56

Background Trifluridine-tipiracil has shown a survival benefit compared with placebo in patients with chemorefractory metastatic esophago-gastric adenocarcinoma. We aimed to compare the efficacy of trifluridine-tipiracil plus bevacizumab vs trifluridine-tipiracil monotherapy in pre-treated patients with metastatic esophago-gastric adenocarcinoma. Methods This investigator -initiated, open -label, randomized trial enrolled patients with metastatic esophago-gastric adenocarcinoma. The main inclusion criteria were patients with pre-treated metastatic esophago-gastric adenocarcinoma, and WHO performance status 0 or 1. Participants were randomly assigned (1:1) to receive oral trifluridine-tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 every 28 days) alone or combined with bevacizumab (5 mg/kg on days 1 and 15) until progression, unacceptable toxicity, or patient decision to withdraw. Randomisation was stratified by sex and treatment line. The primary endpoint was investigator -evaluated progression -free survival. All analyses were based on intention to treat. This trial is registered with EudraCT, 2018-004845-18. Findings From Oct 1, 2019, to Sept 30, 2021, 103 patients were enrolled and randomly assigned to trifluridine-tipiracil (n = 53) or trifluridine-tipiracil plus bevacizumab (n = 50). The clinical cut-off date was March 1st, 2023, after a median follow-up of 36.6 months. Median progression -free survival was 3.1 months (95% CI 2.0-4.3) in the trifluridine-tipiracil group vs 3.9 months (3.0-6.3) in the trifluridine-tipiracil plus bevacizumab group (hazard ratio 0.68, 95% CI 0.46-1.02; p = 0.058). The most frequent grade 3 or worse adverse event was neutropenia, observed in 26 (49%) patients in the trifluridine-tipiracil group vs 23 patients (46%) in the trifluridine-tipiracil plus bevacizumab group. At least one hospitalization was observed in 21 patients (40%) in the trifluridine-tipiracil group and 22 patients (44%) in the trifluridine-tipiracil plus bevacizumab group. No deaths were deemed treatment related. Interpretation In patients with pre-treated metastatic esophago-gastric cancer, trifluridine-tipiracil plus bevacizumab, compared to trifluridine-tipiracil monotherapy, did not significantly prolong progression -free survival. The combination of trifluridine-tipiracil with bevacizumab was well tolerated without increase in severe neutropenia and no new safety signals. Funding Servier, Roche.

Background and purpose: Perioperative 5 -FU, leucovorin, oxaliplatin, and docetaxel (FLOT) is recommended in resectable esophagogastric adenocarcinoma based on randomised trials. However, the effectiveness of FLOT in routine clinical practice remains unknown as randomised trials are subject to selection bias limiting their generalisability. The aim of this study was to evaluate the implementation of FLOT in real -world patients. Methods: Retrospectively collected data were analysed in consecutive patients treated before or after the implementation of FLOT. The primary endpoint was complete pathological response (pCR) and secondary endpoints were margin -free resection (R0), overall survival (OS), relapse -free survival (RFS) tolerability of chemotherapy and surgical complications. Results: Mean follow-up time for patients treated with FLOT ( n = 205) was 37.7 versus 47.0 months for epirubicin, cis- or oxaliplatin, and capecitabine (ECX/EOX, n = 186). Surgical resection was performed in 88.0% versus 92.0%; pCR were observed in 3.8% versus 2.4%; and R0 resections were achieved in 78.0% versus 86.0% ( p = 0.03) in the ECX/EOX and FLOT cohorts, respectively. Survival analysis indicated no significant difference in RFS ( p = 0.17) or OS ( p = 0.37) between the cohorts with a trend towards increased OS in performance status 0 (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.50-1.04). More patients treated with ECX/EOX completed chemotherapy (39% vs. 28%, p = 0.02). Febrile neutropenia was more common in the FLOT cohort (3.8% vs. 11%, p = 0.0086). 90 -days mortality (1.2% vs. 0%) and frequency of anastomotic leakage (8% vs. 6%) were equal and low. Interpretation: Patients receiving FLOT did not demonstrate improved pCR, RFS or OS. However, R0 rate was improved and patients in good PS trended towards improved OS.

Background The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).Methods Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m(2) epirubicin on day 1 plus intravenous 60 mg/m(2) cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m(2) fluorouracil daily or oral 625 mg/m(2) capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m(2) fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m(2) leucovorin, and 50 mg/m(2) docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41.4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m(2) paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452.Findings Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38 center dot 8 months (IQR 16.3-55.1), median overall survival was 48 center dot 0 months (95% CI 33.6-64.8) in the perioperative chemotherapy group and 49 center dot 2 months (34.8-74.4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1.03 [95% CI 0.77-1.38]; log-rank p=0.82). Median disease-free survival was 32.4 months (95% CI 22.8-64.8) in the perioperative chemotherapy group and 24 center dot 0 months (18 center dot 0-40.8) in the trimodality therapy group [hazard ratio 0.89 [95% CI 0.68-1.17]; log-rank p=0.41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1.35 [95% CI 0.63-2.91], p=0.44). Pathological complete response (odds ratio 0.33 [95% CI 0.14-0.81], p=0.012), major pathological response (0.21 [0.12-0.38], p<0.0001), and R0 rates (0.21 [0.08-0.53], p=0.0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years.Interpretation Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise.

Background: In this randomized clinical trial, we compared endoscopic-assisted electrochemotherapy (ECT) with argon plasma coagulation (APC) in patients suffering from esophageal cancer. We hypothesized that an initial, local tumor treatment could prevent or prolong the time to severe, obstructive dysphagia. Previous studies suggest that ablative therapies might have survival advantages compared with placing an esophageal stent. Methods: We aimed to include 50 patients with non-curable esophageal cancer. Patients were randomized to ECT or APC (1:1) as an upfront treatment and hereafter referred for standard treatment. The primary endpoint was the difference in time to interventional treatment demanding dysphagia. Secondary endpoints included side effects, symptom palliation, tumor response, and survival. Results: Ten patients were included (the study was prematurely terminated due to recruitment challenges), and the results are, therefore, mainly exploratory. Five patients received ECT, and four patients received APC. The median survival time among all patients was ten months. Two patients in the APC group and no patients in the ECT group had an esophageal stent placed during the follow-up period. One month after treatment, dysphagia relief was observed in five patients (two patients in the ECT group), and four patients had a partial response evaluated from CT imaging (three patients from the ECT group). No severe adverse events were registered in either group. Conclusion: ECT and ACP were administrated as initial therapy with few side effects, and none of the patients in the ECT group developed interventional treatment demanding dysphagia during their remaining lifetime. Future studies with ECT should focus on both symptom palliation, the need for re-intervention, and survival.

Purpose In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment. Methods In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples. Results Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21 , ANGPTL4 , and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased. Conclusion This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.

Egeland, Charlotte; Baeksgaard, Lene MD, PhD; Gehl, Karen MD, DMSci, PhD; Gogenur, Ismail MD, DMSci, PhD; Patrick, Michael Author Information

295 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) remains controversial, specifically whether multimodal therapy or perioperative chemotherapy is superior. Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multimodal CROSS regimen (carboplatin/paclitaxel, 41.4Gy radiation therapy) with a modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) regimen (pre-2018) and more latterly the FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin) regimen. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5% for peri-operative chemotherapy. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 34.2 (0.43-111.8) months, there were 186 deaths, 91 CROSS and 95 MAGIC/FLOT arm, with 3-year estimated survival probability of 57% (95% CI 49,64) and 55% (95% CI 47,62), respectively [(HR 1.03 (95%CI. 0.77-1.38))]. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy in the primary outcome of overall survival, notwithstanding greater proxy markers of local tumor response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in clinical decision making in modern practice. Clinical trial information: NCT01726452 . [Table: see text]

Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.

A majority of the patients with esophageal cancer (EC) suffer from dysphagia. Several endoscopic treatment options are available such as stent placement, argon plasma coagulation, and esophageal dilatation. This study aimed to map the use of endoscopic dysphagia relieving interventions and secondly investigate possible impact on survival. Data was collected at the Dept. of Surgery Transplantation, Rigshospitalet, Denmark. Patients with non-curable EC referred from 2016 to 2019 were included. Type of dysphagia treatment, complications and the need for repeated treatments, and survival were registered. In the study, 601 patients were included. Forty-five percent were treated with an endoscopic procedure due to dysphagia (82