Search Results (59)

Adenocarcinoma of the gastroesophageal junction (AEG) is an aggressive cancer with rising incidence and poor long-term survival despite multimodal treatment. Reliable preoperative prognostic markers are lacking. Methods: The study is based on data from a prospectively maintained institutional database, which was retrospectively analyzed. In total, 211 patients were analyzed who underwent curative resection for AEG to evaluate the association of SII and LVI and their combined prognostic value. Results: LVI was present in 45% of patients and was significantly associated with higher median SII values compared to patients without LVI (943 vs. 652; p < 0.001). Both high SII and the presence of LVI were independently associated with worse overall survival (p < 0.001 for both). In patients treated with primary surgery (65%), the combined presence of high SII and LVI identified a subgroup with particularly poor prognosis (pseudo-R² increased from 0.451 to 0.524; likelihood-ratio test p < 0.001). Among patients who received neoadjuvant therapy (NT) (35%), SII remained a strong prognostic factor (pseudo-R² = 0.432), while LVI alone was not statistically significant (p = 0.135), and its addition to the SII model did not improve prognostic performance (p = 0.377). Conclusions: The combined assessment of SII and LVI may improve prognostic stratification in AEG, especially in patients undergoing upfront surgery. These findings suggest that combined assessment of SII and LVI enhances prognostic stratification, particularly in patients treated with upfront surgery, and may aid personalized treatment and follow-up planning in AEG. To the best of our knowledge, this is the first study investigating the association of SII and LVI in AEG. Full article

Background/Objectives: Human epidermal growth factor receptor 2–negative (HER2-negative), locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (advanced G/GEJa) is associated with poor survival outcomes, and there is an unmet need for targeted therapy. This study, conducted in the pre-immunotherapy era, aimed to describe the characteristics and management, and compare the survival, of HER2-negative and HER2-positive patients initiating first-line (1L) treatment for advanced G/GEJa in Spain and estimate the number of HER2-negative patients eligible for 1L polychemotherapy. Methods: Patients from the AGAMENON-SEOM registry who initiated 1L polychemotherapy for advanced G/GEJa (2015–2019) in Spain were included. Results: In total, 1357 patients were included (951 [70.1%] HER2-negative; 315 [23.2%] HER2-positive; 91 [6.7%] unknown HER2 status). Most patients (56.3%) received one line of therapy; 27.6% received two lines; and 16.1% received three lines. Among HER2-positive patients, 92.7% received trastuzumab as part of 1L treatment. The use of FOLFOX and CAPOX increased over the study period (2015–2019). HER2-negative patients had significantly shorter progression-free survival (median, 5.92 months [95% CI, 5.59–6.38] vs. 7.37 months [95% CI, 6.55–8.29]; log-rank p < 0.0001) and overall survival (median, 10.49 months [95% CI, 9.74–11.05] vs. 13.82 months [95% CI, 12.30–14.74]; adjusted time ratio, 0.812 [95% CI, 0.722–0.913]; p = 0.0005) than HER2-positive patients. Per probabilistic sensitivity analyses, an estimated 2856 (95% CI, 1619–4134) Spanish patients with HER2-negative advanced G/GEJa were eligible for 1L polychemotherapy in 2024. Conclusions: The survival difference between HER2-positive and HER2-negative patients underscores the critical need for targeted therapies for HER2-negative patients in the 1L setting. Full article

Background: Zolbetuximab, a monoclonal antibody targeting claudin-18.2 (CLDN18.2), which was recently approved as first-line treatment for advanced gastric cancer (AGC), presents unique safety challenges, particularly infusion-related gastrointestinal toxicity and hypoalbuminemia. This study aimed to present our experience with zolbetuximab administration in patients with AGC, focusing on the safety and management effectiveness of our adapted protocol in routine clinical practice. Methods: This study presents our single-institution real-world experience implementing a proactive management protocol (“Project VYLOY”) using zolbetuximab to mitigate these toxicities. We adopted a standardized stepwise infusion protocol and antiemetic premedication to reduce infusion-related nausea and vomiting. Patients with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received zolbetuximab combined with chemotherapy were included. Results: Twenty-four patients were included. The median infusion duration was 215 min, with an interruption rate of 25.0%. In cycle 1, 62.5% experienced infusion-associated adverse events, primarily grade 1 nausea (54%) and vomiting (25%). Hypoalbuminemia (grade ≥ 2) occurred in 57% of first-line patients, potentially linked to zolbetuximab-induced gastritis and gastrointestinal protein loss. Proactive antiemetic support and infusion rate adjustments substantially reduced infusion interruptions in subsequent cycles (10.9%). Patients without prior gastrectomy had higher nausea and vomiting rates, confirming the stomach’s role in mediating toxicity. Conclusions: Our results suggest that proactive management can improve the safety and tolerability of zolbetuximab, especially by reducing infusion-related toxicity in real-world practice. Full article

Background/Objectives: Adenocarcinomas of the esophagogastric and gastric areas are often managed with a multimodal treatment including neoadjuvant chemotherapy and surgery. The impact of neoadjuvant chemotherapy on the host’s antitumoral immune response remains largely unknown. Methods: A retrospective review of a single-institution cohort of patients with adenocarcinoma of the stomach or esophagogastric area undergoing curative intent surgery after neoadjuvant chemotherapy FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) was reviewed. After institutional ethics approval, pathologic slides were re-reviewed and tumor-infiltrating lymphocyte scores were calculated. Tumor-infiltrating lymphocytes (TILs) were studied in conjunction with tumor regression scores (TRG) and the degree of regression in the involved lymph nodes as well as in correlation with the lymph node ratio (the ratio of involved lymph nodes over the total number of lymph nodes resected). Results: A total of 106 patients were reviewed. No statistical correlation could be established between the tumor-infiltrating lymphocyte scores and the degree of regression in the primary tumor as well as with the partial response to chemotherapy of pathologically involved lymph nodes. The TIL score also did not correlate with the lymph node ratio in our patient cohort. A strong correlation was noted between TILs and lymph nodes that completely regressed after neoadjuvant chemotherapy. Conclusions: Tumor-infiltrating lymphocytes do not correlate with the response of the primary tumor or the partial response of the involved lymph nodes, but only with the complete response to neoadjuvant chemotherapy of tumor-involved lymph nodes. Our study focuses on the effects of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes compared to the effects on the primary tumor and the involved lymph nodes. Full article

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer. Full article

Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas. Full article

In patients with gastric, gastroesophageal junction or esophageal adenocarcinoma (GOC), peri-operative multimodal therapies have improved survival; however, prognosis remains underwhelming. Pre-operative nutritional decline and weight are linked with poorer patient outcomes. This study retrospectively analyzed the impact of peri-operative nutritional status (as assessed by patient-generated subjective global assessment, PG-SGA), and weight loss on the survival of patients undergoing curative surgery for GOC (2013 to 2022). Of the 148 patients who underwent surgery, PG-SGA and weight data were available for 107 (72%) and 121 (82%), respectively. At presentation, 44% (n = 47) of patients were well nourished, dropping to 17% (n = 18) post-operatively. Lower post-operative nutritional status correlated to worse overall survival (OS) (p < 0.001). Patients who stayed well nourished or improved their nutritional status had better survival outcomes (HR: 2.7; 95%CI: 1.2–6.1; p = 0.01). Significant weight loss (>10%) was ubiquitously observed in 54% (n = 64) of patients, and this group had shorter OS (HR: 2.2; 95%CI: 1.2–4.1; p = 0.009). In conclusion, both nutritional decline and weight loss negatively impacted survival. Maintenance of nutritional status over the peri-operative period resulted in better outcomes. This study highlights the need for improved nutritional support during curative treatment in GOC. Full article

Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic esophagectomy with two-field lymphadenectomy were included from the Dutch Upper Gastro-intestinal Cancer Audit registry. After 1:1 propensity score matching of patients with and without paratracheal lymphadenectomy within histologic subgroups, short-term outcomes and overall survival were compared between the two groups. Results: A total of 1154 patients with adenocarcinoma and 294 patients with squamous cell carcinoma were matched. Lymph node yield was significantly higher (22 versus 19 nodes, p < 0.001) in patients with paratracheal lymphadenectomy for both tumor types. Paratracheal lymphadenectomy was associated with more recurrent laryngeal nerve injury (10% versus 5%, p = 0.002) and chylothorax in patients with adenocarcinoma (10% versus 5%, p = 0.010) and with more anastomotic leakage in patients with squamous cell carcinoma (42% versus 27%, p = 0.014). The 3- and 5-year survival in patients with and without a paratracheal lymphadenectomy were for adenocarcinoma, respectively, 58% versus 56% and 48% in both groups (log rank: p = 0.578) and for patients with a squamous cell carcinoma, 62% in both groups and 57% versus 54% (log rank: p = 0.668). Conclusions: The addition of paratracheal lymphadenectomy significantly increases lymph node yield in transthoracic esophagectomy but did not result in improved survival for esophageal cancer patients in the current dataset. However, there was an increase in postoperative morbidity in patients who underwent a paratracheal lymphadenectomy. Full article

Background: The purpose of this retrospective study was to evaluate the value of contrast-enhanced computed tomography (CE-CT) image features at baseline and after neoadjuvant chemotherapy in predicting histopathological response in patients with adenocarcinoma of the gastroesophageal junction (GEJ). Methods: A total of 105 patients with a diagnosis of adenocarcinoma of the GEJ were examined by CE-CT at baseline and preoperatively after neoadjuvant chemotherapy. All patients underwent surgical resection. Histopathological parameters and tumor regression grading according to Becker et al. were collected in 93 patients. Line profiles of the primary tumor area in baseline and preoperative CE-CT were generated using ImageJ. Maximum tumor density and tumor-to-wall density delta were calculated and correlated with the histopathological tumor response. In addition, tumor response was assessed according to standard RECIST measurements in all patients and by endoscopy in 72 patients. Results: Baseline and change in baseline to preoperative CE-CT parameters showed no significant differences between responders (Becker grade 1a, 1b) and non-responders (Becker grade 2, 3). After neoadjuvant therapy, responders and non-responders showed significant differences in maximum density and tumor-to-wall density delta values. Line profile measurements showed excellent inter-rater agreement. In comparison, neither RECIST nor endoscopy showed significant differences between these groups. Conclusions: Posttreatment CE-CT can predict histopathological therapy response to neoadjuvant treatment in adenocarcinoma of GEJ patients with high accuracy and thus may improve patient management. Full article

Here, we describe the case of a 74-year-old male patient with a high-risk prostate carcinoma who underwent positron-emission tomography/computed tomography (PET/CT) with [⁶⁸Ga]Ga-prostate-specific membrane antigen ([⁶⁸Ga]Ga-PSMA-11) for staging. [⁶⁸Ga]Ga-PSMA-11 PET/CT detected an extensive area of increased tracer uptake at the prostatic level, involving both lobes. Additionally, a rounded lesion approximately 4 cm in diameter was identified in the celiac region adjacent to the stomach, exhibiting moderate tracer uptake. Based on these imaging findings, the patient underwent radiation therapy applied to the prostate and pelvis and a biopsy of the suspected lesion adjacent to the stomach, which was positive for Siewert type III gastroesophageal junction adenocarcinoma (HER2-negative, PDL-1 60%). This case demonstrates the importance of not overlooking incidental tracer uptakes in PSMA PET/CT imaging in the stomach, as they could represent neoplastic lesions. Full article

Introduction: Transhiatal esophagectomy (THE) is used for specific gastroesophageal junction adenocarcinomas. THE is a high-risk surgical procedure. We aimed to assess the impact of postoperative sepsis (sepsis or septic shock) on the 1-year mortality after THE and to determine the risk factors associated with these outcomes. Secondly, we aimed to assess the impact of postoperative sepsis and other risk factors on 1-year cancer recurrence. Method: A retrospective, observational study was undertaken at the Paoli-Calmettes Institute, Marseille, from January 2012 to March 2022. Results: Of 118 patients, 24.6% (n = 29) presented with postoperative sepsis. Their 1-year mortality was 11% (n = 13), and their 1-year cancer recurrence was 23.7% (n = 28). In the multivariate analysis, independent factors for 1-year mortality were the following: postoperative sepsis (OR: 7.22 (1.11–47); p = 0.038), number of lymph nodes removed (OR: 0. 78 (0.64–0.95); p = 0.011), recurrence at one year (OR: 9.22 (1.66–51.1); p = 0.011), mediastinitis (OR: 17.7 (1.43–220); p = 0.025) and intraoperative driving pressure (OR: 1.77 (1.17–2.68); p = 0.015). For postoperative sepsis, independent factors were low-dose vasopressors (OR: 0.26; 95% CI: 0.07–0.95; p = 0.049), a cervical abscess (OR: 5.33; 95% CI: 1.5–18.9; p = 0.01), bacterial pneumonia (OR: 11.1; 95% CI: 2.99–41.0; p < 0.001) and a high SOFA score on day 1 (OR: 2.65; 95% CI: 1.36–5.19; p = 0.04). For 1-year cancer recurrence, independent factors were the number of lymph nodes removed (sHR: 0.87; 95% CI: 0.79–0.96; p = 0.005), pTNM stages of III or IV (sHR: 8.29; 95% CI: 2.71–25.32; p < 0.001) and postoperative sepsis (sHR: 6.54; 95% CI: 1.70–25.13; p = 0.005). Conclusions: Our study indicates that after THE, postoperative sepsis influences survival and cancer recurrence. We identified the associated risk factors, suggesting an early diagnosis might decrease mortality and recurrence. Full article

Gastric cancer is common globally and has a generally poor prognosis with a low 5-year survival rate. Targeted therapies and immunotherapies have improved the treatment landscape, providing more options for efficacious treatment. The use of these therapies requires predictive biomarker testing to identify patients who can benefit from their use. New therapies on the horizon, such as CLDN18.2 monoclonal antibody therapy, require laboratories to implement new biomarker tests. A multidisciplinary pan-Canadian expert working group was convened to develop guidance for pathologists and oncologists on the implementation of CLDN18.2 IHC testing for gastric and gastroesophageal junction (G/GEJ) adenocarcinoma in Canada, as well as general recommendations to optimize predictive biomarker testing in G/GEJ adenocarcinoma. The expert working group recommendations highlight the importance of reflex testing for HER2, MMR and/or MSI, CLDN18, and PD-L1 in all patients at first diagnosis of G/GEJ adenocarcinoma. Testing for NTRK fusions may also be included in reflex testing or requested by the treating clinician when third-line therapy is being considered. The expert working group also made recommendations for pre-analytic, analytic, and post-analytic considerations for predictive biomarker testing in G/GEJ adenocarcinoma. Implementation of these recommendations will provide medical oncologists with accurate, timely biomarker results to use for treatment decision-making. Full article

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes. Full article

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24–31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel. Full article

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation. Full article