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Background: Meta‐analyses have primarily focused on the effects of exercise‐based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition‐based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. Methods: Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni‐ or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. Results: Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66–0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66–0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = −0.77, 95% CI = −1.46 to −0.09). Conclusions: Nutrition‐based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation. [ABSTRACT FROM AUTHOR]

Background: Long-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs. Methods: A patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software. Results: Prolonged DC101 treatment induced deposition of HA (p

Abstract Background Meta‐analyses have primarily focused on the effects of exercise‐based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition‐based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. Methods Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni‐ or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. Results Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66–0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66–0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = −0.77, 95% CI = −1.46 to −0.09). Conclusions Nutrition‐based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation.

Background: Treatment of metastatic and locally advanced unresectable esophagogastric adenocarcinoma (EGA) after first-line therapy has limited efficacy. Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) linking a TROP-2-directed antibody to the topoisomerase-I inhibitor SN-38. EGA has a high TROP-2 positivity rate and is sensitive to topoisomerase inhibition. Thus far, limited data on the efficacy and safety of SG in this patient population are available. Aim: To evaluate the safety and efficacy of SG in patients with metastatic EGA who progressed under previous treatment. Objective response rate (ORR) is the primary endpoint. Trial design: SAGA is a single-arm, non-randomized, open-label multicenter phase Ib/II study. Patients after prior treatment with a fluoropyrimidine-platinum-containing chemotherapy with or without targeted therapy or immunotherapy will be treated with SG intravenously at a dose of 10 mg/kg body weight on days 1 and 8 of a 21-day treatment cycle. After a run-in phase of 20 patients, safety and efficacy will be evaluated and the trial will proceed to a recruitment goal of 56 patients when at least two tumor responses are documented in the run-in phase. A hypothesis of an ORR of 16% is tested against a null hypothesis of an ORR of 5%. Trial identifiers: EU CT 2023-505257-40-00, NCT06123468, AIO-STO-0123/ass., IKF-t065

Simple Summary: The management of adenocarcinomas of the gastroesophageal junction is rapidly evolving, making it an interesting and important subject for review. In this review article, we provide a brief overview of the anatomic considerations that impact management and discuss the questions of true biologic nature, incidence, and prognosis that still persist. We discuss the choice of non-operative modalities—chemotherapy, chemoradiation, and immunotherapy—and describe key results from major trials that guide the current standard of care for treatment. We describe in more detail the surgical techniques for esophagectomy, including the advantages and disadvantages of each method, as well as newer surgical techniques for proximal gastrectomy that are especially applicable to Siewert type II tumors. Gastroesophageal (GE) junction adenocarcinoma is an aggressive malignancy of growing incidence and is associated with public health issues such as obesity and GERD. Management has evolved over the last two decades to incorporate a multidisciplinary approach, including endoscopic intervention, neoadjuvant chemotherapy/chemoradiation, and minimally invasive or more limited surgical approaches. Surgical approaches include esophagectomy, total gastrectomy, and, more recently, proximal gastrectomy. This review analyzes the evidence for and applicability of these varied approaches in management, as well as areas of continued controversy and investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophagogastric cancer remains a devastating diagnosis, even when it is caught early the likelihood of its recurrence remains significant. Treatment prior to surgery, or neoadjuvant therapy, has been a mainstay of management for esophagogastric cancers over the past decade. In this review we discuss how this treatment paradigm has evolved and the trials and pertinent results that shape our management today. Unlike traditional methods that focus solely on surgery, radiotherapy or chemotherapy, immunotherapy uses drugs that stimulate the body's immune system to fight cancer. By administering these drugs before surgery, clinicians aim to shrink tumors, making them easier to remove, and potentially preventing cancer from spreading or returning in the future. We discuss recent studies investigating its use before surgery that have shown promising results indicating improved outcomes and reasonable safety. Although more research is needed to fully understand its long-term benefits, neoadjuvant immunotherapy represents a hopeful advancement in the quest for more effective treatments against this type of cancer. Despite advances in treatment strategies and surgical approaches in recent years, improving survival outcomes in esophagogastric cancer (EGC) patients treated with curative intent remains a significant area of unmet need. The recent emergence of adjuvant immunotherapy as the standard of care for resected EGC demonstrates the impact of immunotherapy in improving recurrence-free survival. Neoadjuvant and perioperative immunotherapies represent another promising approach with potential advantages over adjuvant therapy. Despite the promising results of early neoadjuvant immunotherapy studies, there are several challenges and future research needs. The optimal timing, duration and number of doses in relation to surgery and the optimal combination of immunotherapies are still unclear. In addition, rigorous correlative studies need to be performed to identify biomarkers for patient selection and treatment response prediction to maximize the benefits of neoadjuvant immunotherapy. In this review, we provide a concise summary of the current standard of care for resectable EGC and discuss the rationale for the use of immune checkpoint inhibitors in this setting and the pre-clinical and early clinical data of these novel therapies. Finally, we will examine the potential role and future direction of immunotherapy in the treatment paradigm and the perceived challenges and opportunities that lay ahead. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of unimodal or multimodal prehabilitation on patients undergoing surgery for esophagogastric cancer. Methods: We conducted a systematic search of the PubMed, Embase, CINAHL, Web of Science, and Cochrane Library (CENTRAL) databases from database inception to May 5, 2023, for randomized controlled trials (RCTs) and cohort studies that investigated prehabilitation in the context of esophagogastric cancer. A random-effects model was used for meta-analysis. Results: We identified 2,994 records and eventually included 12 studies (6 RCTs and 6 cohort studies) with a total of 910 patients. According to random-effects pooled estimates, prehabilitation reduced the incidence of all complications (RR = 0.79, 95% CI: 0.66 to 0.93, P = 0.006), pulmonary complications (RR = 0.61, 95% CI: 0.47 to 0.79, P = 0.0002), and severe complications (RR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002), and shortened the length of stay (MD = -1.92, 95% CI: -3.11 to -0.73, P = 0.002) compared to usual care. However, there were no statistically significant differences in 30-day readmission rates or in-hospital mortality. Subgroup analysis showed that multimodal prehabilitation was effective in reducing the risk of all complications and severe complications, while unimodal prehabilitation was not. Conclusions: Our findings suggested that prehabilitation may be beneficial in reducing postoperative complications and length of stay. We recommend preoperative prehabilitation to improve postoperative outcomes and hasten recovery following esophagogastric cancer surgery, and multimodal prehabilitation seems to be more advantageous in reducing complications. However, further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: This study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities. Patients and Methods: Patients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed ≥ 2 questionnaires from the time intervals prior to resection and 0–3, 3–6, 6–9, and 9–12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately. Results: The study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0–3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9–12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity. Conclusions: This study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship. [ABSTRACT FROM AUTHOR]

BackgroundThe impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial.MethodsTwo independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated.ResultsOut of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61–1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21–1.74; p

Abstract Background After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. Methods The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. Discussion We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients’ nutritional status than no pyloroplasty. Trial registration UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 .

Background: After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. Methods: The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. Discussion: We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty. Trial registration: UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346. [ABSTRACT FROM AUTHOR]

Purpose: Perioperative systemic treatment has significantly improved the outcome in locally advanced esophagogastric cancer. However, still the majority of patients relapse and die. Data on the optimal treatment after relapse are limited, and clinical and biological prognostic factors are lacking. Methods: Patients with a relapse after neoadjuvant/perioperative treatment and surgery for esophagogastric cancer were analyzed using a prospective database. Applied treatment regimens, clinical prognostic factors and biomarkers were analyzed. Results: Of 246 patients 119 relapsed. Among patients with a relapse event, those with an early relapse (< 6 months) had an inferior overall survival (OS 6.3 vs. 13.8 months, p < 0.001) after relapse than those with a late relapse (> 6 months). OS after relapse was longer in patients with a microsatellite-unstable (MSI) tumor. Systemic treatment was initiated in 87 patients (73% of relapsed pat.); among those OS from the start of first-line treatment was inferior in patients with an early relapse with 6.9 vs. 10.0 months (p = 0.037). In 27 patients (23% of relapsed pat.), local therapy (irradiation or surgical intervention) was performed due to oligometastatic relapse, resulting in a prolonged OS in comparison to patients without local therapy (median OS 35.2 months vs. 7.8 months, p < 0.0001). Multivariate analysis confirmed the prognostic benefit of the MSI status and a local intervention. Conclusion: Patients relapsing after multimodal treatment have a heterogeneous prognosis depending on the relapse-free interval (if systemic treatment applied), extent of metastatic disease as well as MSI status. The benefit of additional local intervention after relapse should be addressed in a randomized trial. [ABSTRACT FROM AUTHOR]

Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab-acquired resistance. FGFR inhibition could be a potential mechanism as a second-line treatment. In this Simon's two-stage phase 2, single arm study, patients with advanced EG cancer refractory to trastuzumab-containing therapies received pemigatinib, an inhibitor of FGFR. The primary end point was the 12-week progression-free survival rate. Translational analyses were performed on tissue and plasma samples. Eight patients were enrolled in the first stage. Although the 6-week disease control rate was 25%, only one patient achieved a stable disease after 12 weeks of treatment. The trial was discontinued before the second stage. Two out of six evaluable tumor samples expressed FGFR3. No FGFRs amplification was detected. HER2 amplification was lost in three out of eight patients. Three patients had an high Tumor Mutational Burden, and two of them are significantly long-term survivors. These results do not support the therapeutic efficacy of targeting FGFR in unselected patients with advanced EG cancer, who are refractory to trastuzumab-containing therapies. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.

Long-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs. A patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software. Prolonged DC101 treatment induced deposition of HA (p<0.01) and collagen (p<0.01). HA was effectively degraded by PEGPH20 (p<0.001), but not by NTG as expected. Both PEGPH20 (p<0.05) and NTG (p<0.01) dilated vessels collapsed in response to long-term DC101 treatment. However, only PEGPH20 (rather than NTG) was found to significantly inhibit tumor growth (p<0.05) in combination with NPTX and DC101. These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC. [Display omitted] • Anti-angiogenesis enhances drug delivery but causes desmoplasia with long-term use. • Dense stroma and vascular regression reduce the efficacy of the cytotoxic agent. • PEGPH20 can restore the long-term benefits of anti-angiogenesis. [ABSTRACT FROM AUTHOR]

Currently, one of the most common causes of death worldwide is cancer. The development of innovative methods to support the early and accurate detection of cancers is required to increase the recovery rate of patients. Several studies have shown that medical Hyperspectral Imaging (HSI) combined with artificial intelligence algorithms is a powerful tool for cancer detection. Various preprocessing methods are commonly applied to hyperspectral data to improve the performance of the algorithms. However, there is currently no standard for these methods, and no studies have compared them so far in the medical field. In this work, we evaluated different combinations of preprocessing steps, including spatial and spectral smoothing, Min-Max scaling, Standard Normal Variate normalization, and a median spatial smoothing technique, with the goal of improving tumor detection in three different HSI databases concerning colorectal, esophagogastric, and brain cancers. Two machine learning and deep learning models were used to perform the pixel-wise classification. The results showed that the choice of preprocessing method affects the performance of tumor identification. The method that showed slightly better results with respect to identifing colorectal tumors was Median Filter preprocessing (0.94 of area under the curve). On the other hand, esophagogastric and brain tumors were more accurately identified using Min-Max scaling preprocessing (0.93 and 0.92 of area under the curve, respectively). However, it is observed that the Median Filter method smooths sharp spectral features, resulting in high variability in the classification performance. Therefore, based on these results, obtained with different databases acquired by different HSI instrumentation, the most relevant preprocessing technique identified in this work is Min-Max scaling. [ABSTRACT FROM AUTHOR]

Purpose: Regorafenib monotherapy, a multikinase inhibitor of angiogenesis, tumor microenvironment, and tumorigenesis, showed promising results in gastric cancer. We aimed to assess the tolerability of regorafenib and paclitaxel in patients with advanced esophagogastric cancer (EGC) refractory to first-line treatment, and explore potential biomarkers. Methods: Patients received paclitaxel (80 mg/m2) on days 1, 8, and 15 of a 28-day cycle and regorafenib (80/120/160 mg) on days 1–21 in the dose-escalation cohort, and the maximum-tolerated dose (MTD) in the dose-expansion cohort. Exploratory, overall survival (OS) and progression-free survival (PFS) were compared to a propensity-score matched cohort receiving standard second-/third-line systemic treatment. Paclitaxel pharmacokinetics were assessed using samples from day 1 (D1) and day 15 (D15). We performed enzyme-linked immunosorbent assay measurements of galectin-1, RNA sequencing, and shallow whole-genome sequencing of metastatic tumor biopsies for biomarker analyses. Results: In the dose-escalation cohort (n = 14), the MTD of regorafenib was 120 mg. In all, 34 patients were enrolled in the dose-expansion cohort. Most common toxicities (all grades; grade ⩾ 3) were fatigue (79%; 4%) and sensory neuropathy (63%; 4%). Best responses achieved were partial response (28%) and stable disease (54%). Median OS and PFS were 7.8 and 4.2 months, respectively (median follow-up: 7.8 months). OS (p = 0.08) and PFS (p = 0.81) were not significantly improved compared to the matched cohort. Paclitaxel concentrations were significantly increased with regorafenib (D15) compared with paclitaxel only (D1; p < 0.05); no associations were observed with toxicity or efficacy. An increase in circulating galectin-1 compared to baseline was associated with shorter OS (p < 0.01). Enrichment of angiogenesis-related gene expression was observed in short survivors measured by RNA sequencing. Chromosome 19q13.12-q13.2 amplification was associated with shorter OS (p = 0.02) and PFS (p = 0.02). Conclusion: Treatment with regorafenib and paclitaxel is tolerable and shows promising efficacy in advanced EGC refractory to first-line treatment. Galectin-1 and chromosome 19q13.12-q13.2 amplification could serve as negative predictive biomarkers for treatment response. Registration: Clinicaltrials.gov, NCT02406170, https://clinicaltrials.gov/ct2/show/NCT02406170 [ABSTRACT FROM AUTHOR]

Abstract Background Substantial postoperative complications occur after tumor resection for esophagogastric cancers. Physical prehabilitation programs aim to prepare patients for surgery by improving their functional status with the aim of reducing postoperative complications. This systematic review aims to summarize the effects of physical prehabilitation programs on exercise capacity, muscle strength, respiratory muscle function, postoperative outcomes, and health-related quality of life and to determine the optimal design of such a program to improve these outcomes in esophagogastric cancer patients undergoing tumor resection. Methods A systematic literature review was conducted using PubMed, The Cochrane Library, Scopus, and PEDro databases to identify studies evaluating the effects of physical prehabilitation program on exercise capacity, muscle strength, respiratory muscle function, postoperative complications, length of hospital stay, mortality, and health-related quality of life in patients with esophagogastric cancer awaiting surgery. Data from all studies meeting the inclusion criteria were extracted. The quality of each selected study was determined using the Downs and Black checklist. Results Seven studies with 645 participants were included. The preoperative exercise program consisted of respiratory training alone in three studies, a combination of aerobic and resistance training in two studies, and a combination of respiratory, aerobic, and resistance training in two studies. Training frequency ranged from three times a day to twice a week and each session lasted between 20 and 75 min. Four studies were of fair quality and three of good quality. Some studies reported improvements in maximal inspiratory pressure, inspiratory muscle endurance, postoperative (pulmonary) complications, and length of hospital stay in the preoperative exercise group compared to the control group. Conclusion This systematic review reports the current evidence for physical prehabilitation programs in patients with esophagogastric cancer awaiting surgery. However, due to the limited number of randomized controlled trials, the significant heterogeneity of exercise programs, and the questionable quality of the studies, higher quality randomized controlled trials are needed. Trial registration PROSPERO Registration Number: CRD42020176353 .

Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Esophagogastric (EG) malignancies in patients who have had a prior bariatric procedure have not been fully characterized. To characterize EG malignancies after bariatric procedures. University Hospital, United Kingdom. We performed a retrospective, multicenter observational study of patients with EG malignancies after bariatric surgery to characterize this condition. This study includes 170 patients from 75 centers in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years, and the mean weight 128.8 ± 28.9 kg. Women composed 57.3% (n = 98) of the population. Most (n = 64) patients underwent a Roux-en-Y gastric bypass (RYGB) followed by adjustable gastric band (AGB; n = 46) and sleeve gastrectomy (SG; n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years, and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One third of patients presented with metastatic disease. The majority of tumors were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under 1 year for most patients who died over the intervening period. The Oesophago-Gastric Malignancies After Obesity/Bariatric Surgery study presents the largest series to date of patients developing EG malignancies after bariatric surgery and attempts to characterize this condition. ▪ This is the largest series of patients developing OG cancer after bariatric surgery. ▪ OG cancers were diagnosed at a mean of 9.5 ± 7.4 years (range 1 – 44 years) from BS. ▪ One-third of the patients presented with distant metastasis at the time of diagnosis. ▪ Approximately 1 in 5 patients underwent palliative treatment. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC. [ABSTRACT FROM AUTHOR]

Purpose: In total gastrectomy, Roux-en-Y reconstruction with esophagojejunal anastomosis has been widely used in gastrointestinal reconstruction. In the case of anastomotic leakage of RY reconstruction, esophagojejunal anastomosis should be paid attention, and esophageal fragility is considered the reason for the leakage. Here, we introduce an atraumatic and innovative technique for esophagojejunostomy. Methods: We prospectively performed routine novel esophagojejunal anastomosis using circular stapler device and reviewed the records of 14 consecutive patients with gastric cancer who underwent open total gastrectomy at Kitasato University Hospital from April 2019 to March 2020. By placing about 10 stay sutures around the entire esophageal stump, the esophageal stump can be opened to the maximum diameter. The forceps grasping the tissue was not necessary for these procedures, consequently preventing either tears the esophageal stump tissue or narrowing the esophageal lumen. Results: These 14 cases were far advanced cases of gastric cancer, 6 cases of splenectomy and 3 cases of distal pancreatectomy. No technical problems such as esophageal tear were observed in all cases. Postoperative complications were observed in 6 patients (42.9%), and their contents varied. However, they all improved conservatively. Regarding anastomotic complications, anastomotic leakage of Clavien-Dindo-II was observed in one case, but it improved conservatively. Conclusion: Our new atraumatic anastomosis technique could abolish problems such as tear of esophagus wall due to introduce a larger-sized anvil, trauma of esophageal wall by grasping with forceps such as Alice or Babcock. Consequently, the atraumatic and innovative technique might make the esophagojejunostomy safe. This method might prevent anastomotic leakage and other complications effectively. [ABSTRACT FROM AUTHOR]

Although the number of nationwide clinical registries in upper gastrointestinal cancer is increasing, few of them perform regular clinical audits. The Spanish EURECCA Esophagogastric Cancer Registry (SEEGCR) was launched in 2013. The aim of this study was to assess the reliability of the data in terms of completeness and accuracy. Patients who were registered (2014–2017) in the online SEEGCR and underwent esophagectomy or gastrectomy with curative intent were selected for auditing. Independent teams of surgeons visited each center between July 2018 and December 2019 and checked the reliability of data entered into the registry. Completeness was established by comparing the cases reported in the registry with those provided by the Medical Documentation Service of each center. Twenty percent of randomly selected cases per hospital were checked during on-site visits for testing the accuracy of data (27 items per patient file). Correlation between the quality of the data and the hospital volume was also assessed. Some 1839 patients from 19 centers were included in the registry. The mean completeness rate in the whole series was 97.8% (range 82.8–100%). For the accuracy, 462 (25.1%) cases were checked. Out of 12,312 items, 10,905 were available for verification, resulting in a perfect agreement of 95% (87.1–98.7%). There were 509 (4.7%) incorrect and 35 (0.3%) missing entries. No correlation between hospital volume and the rate of completeness and accuracy was observed. Our results indicate that the SEEGCR contains reliable data. [ABSTRACT FROM AUTHOR]

Abstract Background Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10–26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells. Methods We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC). Results We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p = 0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC = 0.707, 95% CI 0.593–0.821, p = 0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p = 0.04). Conclusions We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.

Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Trastuzumab for Gastric Cancer (ToGA) trial marked a pivotal moment in the adoption of trastuzumab for treating advanced human epidermal growth factor receptor 2 (HER2)-positive esophagogastric (EG) cancer. The KEYNOTE-811 trial brought to light the synergistic effect of immune modulation and HER2 targeting. Additionally, the emergence of trastuzumab deruxtecan (T-DXd) highlighted the potential of new pharmaceutical technologies to extend response, particularly for patients who have advanced beyond initial HER2-targeted therapies. This review aims to navigate through both the successes and challenges encountered historically, as well as promising current trials on innovative and transformative therapeutic strategies, including promising first-in-class and novel first-in-human agents., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial. Methods: Patients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA). Results: Thirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p<0.05). Conclusions: Exercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer. Impact: Exercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors. Clinical Trial Registration: ClinicalTrials.gov (NCT03314311). [ABSTRACT FROM AUTHOR]

BackgroundThe Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial.MethodsPatients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA).ResultsThirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p

Esophagogastric cancer (EGC) is a heterogeneous group of malignancies that collectively represent the 2nd leading cause of cancer deaths worldwide. While surgery in combination with chemotherapy and/or radiation therapy represents the primary curative treatment for early stage disease, survival outcomes for the majority of patients with later-stage disease remain poor. Cytotoxic chemotherapy with platinum doublets such as 5-FU/leucovorin/oxaliplatin is the mainstay of treatment with incremental benefits provided by targeted therapy (trastuzumab, trastuzumab deruxtecan, ramucirumab) and immunotherapy (pembrolizumab, nivolumab). In this article, we provide an updated review and perspectives on the management of advanced EGC. We examine the distinct epidemiological, etiological and molecular features of each disease entity comprising EGC. After reviewing the critical studies that established conventional systemic cytotoxic and targeted therapeutics, we elaborate on recent promising and complex data with immune checkpoint inhibition focusing on implications of tumor histology and PD-L1 expression in the tumor microenvironment. We also highlight novel diagnostic and therapeutic strategies to build on these recent advances. [ABSTRACT FROM AUTHOR]

Introduction: Esophagogastric cancers remain a considerable health burden and among the top causes of global cancer-related deaths. Chemotherapy remains the cornerstone of treatment for patients with advanced disease. Doublet platinum/fluoropyrimidine therapy is established as first-line treatment with the option of adding a taxane in selected patients. Irinotecan, taxanes, and ramucirumab are approved as second-line treatments. Results from the trials KEYNOTE-059, ATTRACTION-2, and TAGS have established the use of immune checkpoint inhibitors and trifluridine/tipiracil as a third-line treatment. High PD-L1 expression, microsatellite instability, tumor mutational burden, and Epstein-Barr virus status may also be used to enrich for responses to immunotherapy.Areas Covered: In this review, we discuss the outcome of recent trials in the later lines of therapy for esophagogastric cancer and place these in the context of current treatment paradigms. We also discuss the biology of esophagogastric cancers and how this might inform the development of new treatments. Finally, we comment on promising new drugs in development.Expert Opinion: Recent advances in the treatment of chemo-refractory esophagogastric cancer add to the improving survival of patients with this disease. Further research is needed to improve patient selection to therapies and the earlier incorporation of these agents in the treatment journey. [ABSTRACT FROM AUTHOR]

Background: Substantial postoperative complications occur after tumor resection for esophagogastric cancers. Physical prehabilitation programs aim to prepare patients for surgery by improving their functional status with the aim of reducing postoperative complications. This systematic review aims to summarize the effects of physical prehabilitation programs on exercise capacity, muscle strength, respiratory muscle function, postoperative outcomes, and health-related quality of life and to determine the optimal design of such a program to improve these outcomes in esophagogastric cancer patients undergoing tumor resection. Methods: A systematic literature review was conducted using PubMed, The Cochrane Library, Scopus, and PEDro databases to identify studies evaluating the effects of physical prehabilitation program on exercise capacity, muscle strength, respiratory muscle function, postoperative complications, length of hospital stay, mortality, and health-related quality of life in patients with esophagogastric cancer awaiting surgery. Data from all studies meeting the inclusion criteria were extracted. The quality of each selected study was determined using the Downs and Black checklist. Results: Seven studies with 645 participants were included. The preoperative exercise program consisted of respiratory training alone in three studies, a combination of aerobic and resistance training in two studies, and a combination of respiratory, aerobic, and resistance training in two studies. Training frequency ranged from three times a day to twice a week and each session lasted between 20 and 75 min. Four studies were of fair quality and three of good quality. Some studies reported improvements in maximal inspiratory pressure, inspiratory muscle endurance, postoperative (pulmonary) complications, and length of hospital stay in the preoperative exercise group compared to the control group. Conclusion: This systematic review reports the current evidence for physical prehabilitation programs in patients with esophagogastric cancer awaiting surgery. However, due to the limited number of randomized controlled trials, the significant heterogeneity of exercise programs, and the questionable quality of the studies, higher quality randomized controlled trials are needed. Trial registration: PROSPERO Registration Number: CRD42020176353. [ABSTRACT FROM AUTHOR]

The prognosis of patients with advanced oesophageal cancer (EC) and gastric cancer (GC) is poor. Circulating microRNAs (ci-miRNAs) may have prognostic and predictive value to improve patient selection for palliative treatment. The purpose of this study is to assess the prognostic and predictive value of specific ci-miRNAs in plasma of patients with EC and GC treated with first-line palliative gemcitabine and cisplatin. Droplet digital PCR (ddPCR) was used to quantify miR-200c-3p, miR-375, miR-21-5p, miR-148a-3p, miR-146a-5p, miR-141-3p and miR-218-5p in plasma from 68 patients. ci-miRNA expression was analyzed in relation to overall survival (OS), progression-free survival (PFS), and response to chemotherapy. ci-miRNA levels were detectable in 36 baseline (71%) samples and in 14 (47%) follow-up samples. Increased circulating miR-200c-3p in GC showed a trend (p = 0.06) towards a shorter OS. High circulating miR-375 was associated with a longer OS (p = 0.02) in patients with esophageal adenocarcinoma (EAC). No significant difference was observed in ci-miRNA expression between paired pre- and on-treatment samples. ci-miRNA expression was not associated with response to chemotherapy. ci-miRNAs can be measured in plasma samples of patients treated with first-line palliative chemotherapy using ddPCR despite prolonged storage in heparin. Elevated circulating miR-375 might be a prognostic marker for patients with EAC.

Objective: To investigate if prolonged TTS after completed nCRT improves postoperative outcomes for esophageal and esophagogastric junction cancer. Summary of Background Data: TTS has traditionally been 4–6 weeks after completed nCRT. However, the optimal timing is not known. Methods: A multicenter clinical trial was performed with randomized allocation of TTS of 4–6 or 10–12 weeks. The primary endpoint of this sub-study was overall postoperative complications defined as Clavien-Dindo grade II-V. Secondary endpoints included complication severity according to Clavien-Dindo grade IIIb-V, postoperative 90-day mortality, and length of hospital stay. The study was registered in Clinicaltrials.gov (NCT02415101). Results: In total 249 patients were randomized. There were no significant differences between standard TTS and prolonged TTS with regard to overall incidence of complications Clavien-Dindo grade II–V (63.2% vs 72.6%, P = 0.134) or regarding Clavien-Dindo grade IIIb–V complications (31.6% vs 34.9%, P = 0.603). There were no statistically significant differences between standard and prolonged TTS regarding anastomotic leak (P =0.596), conduit necrosis (P = 0.524), chyle leak (P = 0.427), pneumonia (P = 0.548), and respiratory failure (P = 0.723). In the standard TTS arm 5 patients (4.3%) died within 90 days of surgery, compared to 4 patients (3.8%) in the prolonged TTS arm (P = 1.0). Median length of hospital stay was 15 days in the standard TTS arm and 17 days in the prolonged TTS arm (P =0.234). Conclusion: The timing of surgery after completed nCRT for carcinoma of the esophagus or esophagogastric junction, is not of major importance with regard to short-term postoperative outcomes. INSET: è ò Ò á à è é á è.. [ABSTRACT FROM AUTHOR]

Background: Metastatic esophagogastric cancers (EGCs) have a poor prognosis with an approximately 5% 5‐year survival. Additional treatment approaches are needed. c‐MET gene‐amplified tumors are an uncommon but potentially targetable subset of EGC. Clinical characteristics and outcomes were evaluated in patients with MET‐amplified EGC and compared with those without MET amplification to facilitate identification of these patients and possible treatment approaches. Patients and Methods: Patients with locally advanced or metastatic MET‐amplified EGC at Massachusetts General Hospital (MGH) were identified using fluorescent in situ hybridization analysis, with a gene‐to‐control ratio of ≥2.2 defined as positive. Non–MET‐amplified patients identified during the same time period who had undergone tumor genotyping and treatment at MGH were evaluated as a comparison group. Results: We identified 233 patients evaluated for MET amplification from 2002 to 2019. MET amplification was seen in 28 (12%) patients versus 205 (88%) patients without amplification. Most MET‐amplified tumors occurred in either the distal esophagus (n = 9; 32%) or gastroesophageal junction (n = 10; 36%). Of MET‐amplified patients, 16 (57%) had a TP53 mutation, 5(18%) had HER2 co‐amplification, 2 (7.0%) had EGFR co‐amplification, and 1 (3.5%) had FGFR2 co‐amplification. MET‐amplified tumors more frequently had poorly differentiated histology (19/28, 68.0% vs. 66/205, 32%; p =.02). Progression‐free survival to initial treatment was substantially shorter for all MET‐amplified patients (5.6 vs. 8.8 months, p =.026) and for those with metastatic disease at presentation (4.0 vs. 7.6 months, p =.01). Overall, patients with MET amplification had shorter overall survival (19.3 vs. 24.6 months, p =.049). No difference in survival was seen between low MET‐amplified tumors (≥2.2 and <25 MET copy number) compared with highly amplified tumors (≥25 MET copy number). Conclusion: MET‐amplified EGC represents a distinct clinical entity characterized by rapid progression and short survival. Ideally, the identification of these patients will provide opportunities to participate in clinical trials in an attempt to improve outcomes. Implications for Practice: This article describes 233 patients who received MET amplification testing and reports (a) a positivity rate of 12%, similar to the rate of HER2 positivity in this data set; (b) the clinical characteristics of poorly differentiated tumors and nodal metastases; and (c) markedly shorter progression‐free survival and overall survival in MET‐amplified tumors. Favorable outcomes are reported for patients treated with MET inhibitors. Given the lack of published data in MET‐amplified esophagogastric cancers and the urgent clinical importance of identifying patients with MET amplification for MET‐directed therapy, this large series is a valuable addition to the literature and will have an impact on future practice. New treatment approaches are needed for esophagogastric cancer. c‐MET gene‐amplified tumors are a potential new target. This article compares patients with and without MET‐amplified esophagogastric cancer to identify possible treatment approaches. [ABSTRACT FROM AUTHOR]

Summary: Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2, MET, or FGFR2 or mutations in PIK3CA, EGFR, or BRAF. Ganetespib which is a novel triazolone heterocyclic inhibitor of HSP90, is a potentially biologically rational treatment strategy for advanced EG cancers with these gene amplification. This multicenter, single-arm phase 2 trial enrolled patients with histologically confirmed advanced EG cancer with progression on at least one line of systemic therapy. Patients received Ganetespib 200 mg/m2 IV on Days 1, 8, and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints included: Progression Free Survival (PFS); to correlate the presence of HSP clients with ORR and PFS; evaluating the safety, tolerability and adverse events profile. In this study 26 eligible patients mainly: male 77%, median age 64 years were enrolled. The most common drug-related adverse events were diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response and stayed on treatment for more than seventy (70) months. Median PFS and OS was 61 days (2.0 months), 94 days (3.1 months) respectively. Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single-agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. [ABSTRACT FROM AUTHOR]

A 66-year-old man was diagnosed with advanced esophagogastric junction cancer and referred to our institution (Department of Gastroenterological Surgery, Chiba Cancer Center) for treatment. Computed tomography imaging confirmed the presence of a tumor, extending from the lower thoracic esophageal to the esophagogastric junction, with swelling of the upper mediastinal lymph nodes. Based on the criteria of the International Union against Cancer Committee (UICC, 8th Edition), the staging was confirmed as follows: 101R, 107 and 106 pre. Based on these findings, a clinical diagnosis of EGJ cancer was made, with a UICC 8th classification of cT3N1M0 c-stage-III. Preoperative chemotherapy was performed, with tumor shrinkage obtained after three courses of chemotherapy (using S-1 plus oxaliplatin). Subsequently, esophagectomy with three-field lymph node dissection and gastric tube reconstruction, via the intrathoracic route, was performed. On postoperative day 2, the patient developed an idiopathic pneumothorax, with brown-green drainage from the chest tube. A repeat thoracotomy was performed, confirming the presence of brown-green pleural fluid and necrosis of esophageal tissue. The area of necrosis was situated 4 cm on the oral side of the anastomosis, with greater necrosis of the right than left side. There was no evidence of necrosis of the gastric tube. The necrotic residual esophagus was excised and reconstructed, as an external fistula on the left side of the neck. On day 38, after the second surgery, reconstruction of the esophageal conduit and gastric tube, via the jejunum, was performed. At 7 months after discharge, the patient was symptom free, with no evidence of cancer recurrence. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first‐line chemotherapy in metastatic esophagogastric cancer. Materials and Methods: Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5‐fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14‐day cycle. The primary endpoint was 6‐month progression‐free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. Results: Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single‐center phase II study (NCT01913639). The most common grade 3–4 treatment‐related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6‐month PFS was 53% (95% confidence interval [CI], 38%–71%), the objective response rate was 54% (95% CI, 37%–70%), and the disease control rate was 77% (95% CI, 67%–94%). Next‐generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum‐based chemotherapy. Conclusion: Regorafenib (one week on–one week off schedule) is well tolerated in combination with first‐line FOLFOX but does not improve 6‐month PFS relative to historical control. Implications for Practice: Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first‐line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD‐1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible. This phase II trial was conducted to determine the activity of regorafenib combined with FOLFOX in chemotherapy‐naïve patients with esophageal and gastric cancers. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Methods The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. Discussion MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. Trial registration NCT02128243 (date of registration: 29–04-2014).

Purpose: To evaluate the effects of unimodal or multimodal prehabilitation on patients undergoing surgery for esophagogastric cancer., Methods: We conducted a systematic search of the PubMed, Embase, CINAHL, Web of Science, and Cochrane Library (CENTRAL) databases from database inception to May 5, 2023, for randomized controlled trials (RCTs) and cohort studies that investigated prehabilitation in the context of esophagogastric cancer. A random-effects model was used for meta-analysis., Results: We identified 2,994 records and eventually included 12 studies (6 RCTs and 6 cohort studies) with a total of 910 patients. According to random-effects pooled estimates, prehabilitation reduced the incidence of all complications (RR = 0.79, 95% CI: 0.66 to 0.93, P = 0.006), pulmonary complications (RR = 0.61, 95% CI: 0.47 to 0.79, P = 0.0002), and severe complications (RR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002), and shortened the length of stay (MD = -1.92, 95% CI: -3.11 to -0.73, P = 0.002) compared to usual care. However, there were no statistically significant differences in 30-day readmission rates or in-hospital mortality. Subgroup analysis showed that multimodal prehabilitation was effective in reducing the risk of all complications and severe complications, while unimodal prehabilitation was not., Conclusions: Our findings suggested that prehabilitation may be beneficial in reducing postoperative complications and length of stay. We recommend preoperative prehabilitation to improve postoperative outcomes and hasten recovery following esophagogastric cancer surgery, and multimodal prehabilitation seems to be more advantageous in reducing complications. However, further studies are needed to confirm these results., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to investigate the association between short-term outcome indicators and long-term survival after esophagogastric resections. Summary Background Data: Short-term outcome indicators are often used to compare performance between care providers. Some short-term outcome indicators concern the direct quality of care, that is, complications, others are used because they are expected to be associated with long-term outcomes. Method: For this national cohort study, all patients who underwent esophagectomy or gastrectomy for cancer with curative intent between 2011 and 2016 and were registered in the Dutch Upper gastrointestinal Cancer Audit were included. Primary outcome was conditional survival (under the condition of surviving the first postoperative 30 days and hospital admission). Cox regression modeling was used to study the independent association between "textbook outcome" with survival. "Textbook outcome," a composite quality indicator, was defined as a pathological complete resection with at least 15 retrieved lymph nodes, an uneventful postoperative course, and no hospital readmission. Results: In total, 4414 and 2943 patients with esophageal or gastric cancer, respectively, were included. The 1-, 2-, and 3-year overall survival rates were 76%, 62%, and 54%, and 71%, 56%, and 49% for esophageal and gastric cancer, respectively. Textbook outcome was achieved in 33% and 35% of patients respectively. "Textbook outcome" was independently associated with longer conditional survival [hazard ratio: 0.75 (95% confidence interval, 0.68-0.84) and 0.69 (0.60-0.79), respectively]. Conclusion: This study showed that the short-term outcome indicator textbook outcome is associated with long-term overall survival and therefore may accentuate the importance of using these indicators in clinical audits. [ABSTRACT FROM AUTHOR]

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68–0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67–0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21–0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays. [ABSTRACT FROM AUTHOR]