Radiation Oncology/Stomach/Overview

Gastric Cancer Overview

Epidemiology

 * In 2010: 21,000 cases and 10,570 deaths in US (NCI).
 * Incidence in men is 8.4 per 100,000 in North America. Sharp decrease in incidence in Western countries over the past 60 years (by a factor of about 5). (However, incidence of GE junction and proximal gastric tumors is increasing.)
 * More common in men by 1.5 to 1.
 * Third most common cancer in the world and 2nd leading cause of cancer deaths. Common in Japan (78 per 100,000 men), China, other East Asian countries, Eastern Europe and South America.
 * Risk factors:
 * smoked and salted food, low fruit/vegetable intake, low socioeconomic status, pernicious anemia (5-10% patients develop gastric ca.).
 * H.pylori infection (3-6X risk), confined to distal cancers and intestinal type malignancy)
 * No increased risk found with gastric ulcers.
 * 2nd generation Japanese have similar risk factor to general U.S. population and not Japanese population

Location
Most commonly antrum/distal stomach (40%), followed by proximal stomach or GE junction (35%), then body (25%). The incidence of proximal lesions has increased (used to be the least common site).

Borrmann type

 * Type I: polypoid or fungating
 * Type II: ulcerating lesions surrounded by elevated borders
 * Type III: ulceration with invasion of the gastric wall
 * Type IV: diffusely infiltrating (linitus plastica)
 * Type V: unclassifiable

Patterns of spread
Lymph node drainage is to nodes along the greater and lesser curvatures (gastroepiploic and gastric nodes respectively), to the celiac axis (includes porta hepatis, splenic, suprapancreatic, pancreaticoduodenal LN), paraaortics, distal paraesophageal.
 * left gastric LNs (largest drainage) - from lesser curvature
 * gastro-epiploic LNs - from greater curvature
 * right gastric LNs - from pyloris

Venous drainage is by the portal system to the liver. Metastases to liver in 30% of cases at presentation.

By location of primary site:
 * Proximal / GE junction - may spread to mediastinal and pericardial lymph nodes, have a low chance of spreading to gastric antrum, periduodenal, and porta hepatic nodes.
 * Body - can spread to all nodal sites; most likely to spread to the greater and lesser curvature nodes
 * Distal / antrum - periduodenal, peripancreatic, porta hepatis nodes; low chance of spread to cardia, periesophageal, mediastinal, or splenic hilum nodes

Anatomy of lymphatics and lymphadencomy extent

 * N1 lymph nodes: perigastric
 * Along lesser curvature (Stations 1, 3, and 5)
 * Along greater curvature (Stations 2, 4, and 6)


 * N2 lymph nodes: along celiac and its three branches (left gastric, common hepatic, and splenic)
 * Along left gastric artery (Station 7)
 * Along common hepatic artery (Station 8)
 * Along celiac artery (Station 9)
 * Along splenic artery (Station 10, and 11)


 * N3 (hepatoduodenal, peripancreatic, root of mesentery)


 * N4 (periaortic, middle colic)

Lymph node stations:
 * 1 - R paracardial
 * 2 - L paracardial
 * 3 - Lesser curvature
 * 3a - along L gastric A
 * 3b - along R gastric A (2nd branch and distal part of artery)
 * 4 - Greater curvature
 * 4sa - along short gastric vessels, left (perigastric area)
 * 4sb - along L gastroepiploic vessels (perigastric area)
 * 4d - along R gastroepiploic vessels (2nd branch and distal part of R gastroepiploic A)
 * 5 - suprapyloric (along 1st branch and proximal part of R gastric A)
 * 6 - infrapyloric (along 1st branch and proximal part of R gastroepiploic A down to confluence of R gastroepiploic V and anterior superior pancreatoduodenal V)
 * 7 - trunk of left gastric A between its root and the origin of its ascending branch
 * 8 - common hepatic A
 * 8a - anterosuperior group
 * 8p - posterior group
 * 9 - Celiac A
 * 10 - Splenic hilum (including those LN adjacent to the splenic artery distal to the pancreatic tail, and those on the roots of the short gastric arteries and those along the left gastroepiploic artery proximal to its 1st gastric branch)
 * 11 - Splenic A
 * 11p - Proximal splenic artery LNs from its origin to halfway between its origin and the pancreatic tail end
 * 11d - Distal splenic artery LNs from halfway between its origin and the pancreatic tail end to the end of the pancreatic tail
 * 12 - Hepatoduodenal ligament
 * 12a - Hepatoduodenal ligament LNs along the proper hepatic artery, in the caudal half between the confluence of the right and left hepatic ducts and the upper border of the pancreas
 * 12b - Hepatoduodenal ligament LNs along the bile duct, in the caudal half between the confluence of the right and left hepatic ducts and the upper border of the pancreas
 * 12p - Hepatoduodenal ligament LNs along the portal vein in the caudal half between the confluence of the right and left hepatic ducts and the upper border of the pancreas
 * 13 - LNs on the posterior surface of the pancreatic head (cranial to the duodenal papilla)
 * 14 - Root of mesentery
 * 14a - SMA
 * 14v - SMV
 * 15 - middle colic vessels
 * 16 - paraaortic
 * 17 - LNs on the anterior surface of the pancreatic head beneath the pancreatic sheath
 * 18 - LNs along the inferior border of the pancreatic body
 * 19 - Infradiaphragmatic LNs predominantly along the subphrenic A
 * 20 - Paraesophageal LNs in the diaphragmatic esophageal hiatus
 * 110 - Paraesophageal LNs in the lower thorax
 * 111 - Supradiaphragmatic LNs separate from the esophagus
 * 112 - Posterior mediastinal LNs separate from the esophagus and the esophageal hiatus

Stations 1-12 and 14v are regional LNs. Any other nodes are distant (M1). For tumors invading the esophagus, stations 19, 20, 110, and 111 are included as regional LNs.

Lymphadenectomy extent:
 * See also: Radiation Oncology/Stomach/Resectable


 * D1 dissection:
 * For total gastrectomy: all of stations 1-7
 * For distal gastrectomy: 1, 3, 4sb, 4d, 5, 6, 7 (2, 4sa are excluded)
 * For pylorus preserving gastrectomy: 1, 3, 4sb, 4d, 6, 7 (2, 4sa, 5 are excluded)
 * For proximal gastrectomy: 1, 2, 3a, 4sa, 4sb, 7 (3b, 4d, 5, 6 are excluded)
 * D1+ dissection:
 * For total gastrectomy: D1 plus 8a, 9, 11p
 * For distal gastrectomy: D1 plus 8a, 9
 * For pylorus preserving gastrectomy: D1 plus 8a, 9
 * For proximal gastrectomy: D1 plus 8a, 9, 11p
 * D2 dissection:
 * For total gastrectomy: D1 plus 8a, 9, 10, 11p, 11d, 12a
 * For distal gastrectomy: D1 plus 8a, 9, 11p, 12a
 * For pylorus preserving gastrectomy or proximal gastrectomy: N/A

See:
 * PMID 21573742 (2010) - "Japanese gastric cancer treatment guidelines 2010 (ver. 3)." (Japanese Gastric Cancer Association, Gastric Cancer. 2011 Jun;14(2):113-23.)
 * PMID 21573743 (2011) - "Japanese classification of gastric carcinoma: 3rd English edition." (Japanese Gastric Cancer Association, Gastric Cancer. 2011 Jun;14(2):101-12.)

Work-up

 * EUS accuracy: 77% T stage, 69% N stage
 * Should include CT scan to aid in radiation planning, assess for nodes.

Treatment Overview

 * Localized disease (Stage IA) is treated by primary surgery, with 5-year OS 70-95%
 * Disease penetrating through submucosa (Stage II+) has higher chance of nodal involvement, and poor outcomes (5-year OS 20-30%) with surgery alone.
 * In the US, INT-0116 (surgery followed by +/- 5-FU/RT) showed survival benefit to CRT (median survival 27 vs. 36 months), and CRT became standard of care following a curative-intent resection
 * In Europe, CRT following surgery has not become widespread. Instead, MRC MAGIC neoadjuvant chemotherapy trial (surgery only vs. neoadjuvant/adjuvant chemotherapy) has shown similar survival benefit as INT-0116
 * It is currently not clear what the best treatment plan is, as the 2 trials intervened at different treatment time points, but both strategies (surgery + CRT, or neoadjuvant CT + surgery + adjuvant CT) appear reasonable

Survival

 * Early stage: 83% or more 5-year survival
 * Node positive: 10-30% survival