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MATTERHORN Spotlight—Shaping the Treatment Horizon for Gastric/Gastroesophageal Junction (GEJ) Cancers - Episode 1

Understanding GC/GEJC: Disease Overview and Current Treatment Practices

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Panelists discuss how gastric cancers (GC) and gastroesophageal junction cancers (GEJC) present with nonspecific symptoms, affect approximately 1.2 million patients worldwide annually, and are managed with perioperative FLOT chemotherapy as the established standard of care for resectable disease.

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    GC and GEJC represent significant global health challenges, with approximately 1.2 million cases worldwide, ranking as the fifth most common cancer and the fifth-leading cause of cancer death. These malignancies are more prevalent in developing countries and among men, often presenting with nonspecific symptoms including unintentional weight loss, fatigue, abdominal pain, and anemia. The disease encompasses various subtypes with distinct risk factors, including HER2-positive tumors (20% of patients) associated with worse outcomes, intestinal-type cancers, and challenging signet ring cell variants.

    The current standard of care for resectable GC and GEJC has evolved toward a perioperative chemotherapy approach, moving away from historical paradigms of neoadjuvant chemoradiation or up-front surgery with adjuvant therapy. The FLOT regimen (fluorouracil, leucovorin, oxaliplatin, docetaxel) has emerged as the globally accepted standard for perioperative therapy, administered before and after surgical resection. This 3-drug combination provides active systemic treatment that addresses micrometastatic disease, which is crucial given that most patients present with at least regional disease involvement.

    The management approach requires careful multidisciplinary coordination between medical oncologists and surgeons to determine surgical candidacy, which serves as a critical branch point in treatment decisions. Despite advances in perioperative chemotherapy and surgical techniques, cure rates remain suboptimal at approximately 50% for node-positive patients, highlighting significant unmet medical needs. The complexity of these cancers, combined with challenges in early detection due to a lack of screening programs in most countries and nonspecific early symptoms, underscores the importance of continued research efforts to improve outcomes for patients with these aggressive malignancies.

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