CANCER OF THE STOMACH AND GASTROESOPHAGEAL JUNCTION OVERVIEW

CANCER OF THE STOMACH AND GASTROESOPHAGEAL JUNCTION OVERVIEW

  • For stomach cancer in the United States, the expected incidence in 2012 was 21,320 cases and 10,540 deaths.
  • These cancers are usually adenocarcinomas.
  • In the United States, the site of origin is shifting as more proximal lesions are diagnosed.
  • Prognostic factors relate to tumour extent and include nodal involvement and extension beyond the gastric wall.
  • Ploidy may be an independent prognostic factor.
  • Staging should always include history and physical examination, complete blood cell count, liver chemistries, chest x-ray film, endoscopy with biopsy, ultrasound (determine degree of direct tumour extensions), and computed tomography (CT) of the abdomen (define extragastric disease).
  • Additional studies that may help define extent of disease include upper gastrointestinal imaging, CT of the chest (for gastroesophageal junction [GEJ] lesions), laparoscopy (to rule out peritoneal seeding or early liver metastases), and positron emission tomography.
  • Surgical resection is the primary therapy of resectable gastric and GEJ cancers.
  • Cure rates of 80% or higher are achieved only with early lesions (patients with nodes negative, confined to mucosa or submucosa), which are uncommon in the United States.
  • Role for extended node dissection has not been found in randomized trials.
  • Adjuvant therapy (chemotherapy, irradiation) is indicated on the basis of patterns of relapse and survival results with surgery alone (high rates of local-regional relapse and distant metastases).
  • Adjuvant chemotherapy has a modest, significant benefit and has become the standard in Asia.
  • Irradiation alone reduced local-regional relapse and improved overall survival (OS) in a Beijing trial of 370 patients testing preoperative irradiation versus surgery alone (5-year OS 30% vs. 20%, = 0.009).
  • The U.S. intergroup phase III trial of 556 patients found a survival benefit for combined-modality postoperative irradiation plus chemotherapy versus surgery alone (3-year relapse-free survival 48% vs. 31%, = 0.001; 3-year OS 50% vs. 41%, = 0.005).
  • A British phase III trial of 503 patients demonstrated a survival advantage for perioperative ECF chemotherapy (epirubicin, cisplatin, 5-fluorouracil [5-FU]) when compared with surgery alone (5-year OS 36% vs. 23%, = 0.009).
  • A French phase III trial of 224 patients demonstrated a survival advantage for perioperative cisplatin and 5-FU compared with surgery alone (5-year OS 38% vs. 24%, P= 0.02).
  • The POET trial of 120 patients with GEJ lesions tested preoperative chemotherapy versus chemoradiotherapy (CRT); outcomes trends favoured preoperative CRT over chemotherapy alone for both OS ( = 0.07) and local control ( = 0.06).
  • Combined external beam radiation therapy (EBRT) plus chemotherapy or intraoperative radiation therapy (IORT) produced long-term survival in 10% to 20% of patients in most randomized and nonrandomized trials.
  • Neoadjuvant chemotherapy studies reveal possible increase in resection rates but high incidence of local-regional relapse (consider addition of IORT alone or with EBRT and concurrent chemotherapy to neoadjuvant chemotherapy regimens).
  • Palliative resection of gastric component of disease may be indicated.
  • European phase III trials demonstrate a trend toward improved quality and duration of life with palliative chemotherapy versus supportive care.
  • Multiple-drug chemotherapy regimens have response rates of 30% to 50%, and provide some improvement in OS, including the two- and three-drug regimens ECF, EOX (epirubicin, oxaliplatin, capecitabine), and DCF (docetaxel, cisplatin, 5-FU).
  • A phase III trial of 594 patients showed a significant improvement in OS with the addition of trastuzumab to chemotherapy in patients with HER-2-positive tumours (median OS 13.8 vs. 11.1 months, = 0.0046)

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