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SWOG
ONCOLOGY RESEARCH PROFESSIONAL (ORP) MANUAL
VOLUME II
GASTROINTESTINAL
CHAPTER 4
REVISED: OCTOBER 2014
Disease Information
Gastrointestinal cancers occur along the tubular alimentary tract, including esophagus,
stomach, small intestine, colon, rectum and anus, as well as supporting organs including the
liver, pancreas, bile ducts and gallbladder. They may also arise from abdominal mesentery or
omentum. Adenocarcinoma and squamous cell carcinoma (epidermoid carcinoma) are the
most frequently occurring histologies, though sarcomas (especially gastrointestinal stromal
tumors) and carcinoid are common as well.
Gastrointestinal cancers account for about 23% of all cancers and 24% of all cancer deaths. As
most lesions do not produce symptoms until late in the course of the disease, patients generally
have advanced disease on initial presentation. As a result, gastrointestinal adenocarcinomas
have a poor prognosis in general, although the colorectal tumors have a somewhat better
prognosis.
Gastrointestinal Sites
Esophagus
A muscularized tube through which food passes to the stomach; it begins at the level of the fifth
cervical vertebra. This is just below the pharynx where the pharynx branches into the larynx. At
the far end it extends down to a valve which opens into the stomach.
Treatment is based on clinical stage at presentation. Strategies do not vary significantly based
on histology (adenocarcinoma vs. squamous carcinoma). For low stage disease (Stage I)
surgery alone is recommended, though irradiation is often used in frail patients. For higher
stage, non-metastatic but potentially resectable disease (usually stages II or III), surgery alone
remains standard of care. However, the combination of radiation and chemotherapy is often
used neoadjuvantly to surgery, and dual-modality therapy (chemotherapy plus irradiation) alone
may be as effective as surgery. For Stage IV disease, treatment often consists of systemic
chemotherapy, with irradiation being reserved for palliation of pain and refractory dysphagia.
Nutritional support is important for all groups of patients.
Stomach
A muscularized bag-like organ which secretes juices during bulky food digestion, it lies mainly
on the left side of the upper abdomen and its contents empty into the small intestine. It stores
ingested food and prepares it for eventual treatment by the small intestine. The inside of the
stomach has a lining that acts as a protective coat and that also secretes some of the digestive
juices.
Gastric cancer is linked to a number of dietary factors (intake of fatty, smoked and salted foods)
and is more prevalent in countries where these foods are commonly eaten.
Ninety-five percent of gastric cancers are of adenocarcinoma histology. For potentially
resectable (early stage) disease, surgical resection has been the standard therapy. A recent
SWOG study demonstrated improved survival after resection with the addition of chemo
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ONCOLOGY RESEARCH PROFESSIONAL (ORP) MANUAL
VOLUME II
GASTROINTESTINAL
CHAPTER 4
REVISED: OCTOBER 2014
radiation. Additionally, a recent UK study demonstrated improved outcomes with chemotherapy
alone preceding and following surgery. There is no standard chemotherapeutic regimen for
advanced disease; however systemic therapy does improve survival in general.
Small Intestine
A tubular organ which absorbs nutrients and water into the bloodstream, the small intestine can
be divided into three parts: the duodenum, jejunum, and ileum. Digestive juices from other
organs flow through the common bile duct that opens into the duodenum. The jejunum has thick
walls and many blood vessels to carry away the nutrients and water into the bloodstream. At the
far end the small intestine opens into the large intestine. Therapeutic principles for small bowel
cancers generally mirror those for the colon, though there are very few published trial data.
Large Intestine
Also called the colon, the large intestine is a tubular organ which collects the solid wastes of the
digestive tract. It also absorbs water, minerals and certain vitamins. The nutrients are then
transmitted to the liver via the hepatic portal system. The large intestine is approximately five
feet in length, and consists of the cecum, ascending, transverse, descending, and sigmoid
colon, the rectum, and anus. The vermiform appendix is a wormlike diverticulum of the cecum.
Surgery is the primary curative treatment in early disease (except anus). Stage I colon and
rectal cancers are treated with surgery alone. Treatment of stage II colon cancer is
controversial, though some experts offer fit patients adjuvant chemotherapy following resection.
Stage III colon cancers are commonly treated with postoperative FOLFOX (5FU , leucovorin,
and oxaliplatin). Most stage II and III rectal cancers are treated preoperatively with irradiation
and a fluoropyrimidine, followed by surgery, and then more adjuvant systemic therapy. Newer
chemotherapy strategies, plus or minus biologic agents, are being tested in clinical trials. In
advanced disease of either the colon or rectum, combination chemotherapy plus the
antiangiogenesis agent bevacizumab prolongs survival, though several different
chemotherapeutic regimens may be combined with the biologic . Anal cancer is most
commonly treated with chemoradiation without surgery (except biopsy).
Digestive Organs
The digestive organs provide secretions that help in food digestion. There are three major
digestive organs: the liver, the gallbladder and the pancreas. The liver's major functions include
the filtration and extraction of toxic material from the blood, the secretion of bile juices that aid
digestion, the regulation of the blood's sugar content by a reversible chemical storage process,
and the storage and alteration of nutrients absorbed by the large intestine. It lies to the right of,
and above the stomach. Tumors of the liver are in general difficult to treat, owing to the
underlying chronic non-malignant disease sustained by most patients with hepatocellular
carcinoma. Early tumors may be treated with surgical resection, liver transplant, or ablation of
the cancer (with alcohol, radiofrequency waves, or cold therapy). More advanced tumors,
whether confined to the liver or metastatic, may be treated with chemotherapy, but no specific
drug has been shown to affect survival. Many patients are merely offered hospice.
Chemoembolization has had mixed results in late phase trials.
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ONCOLOGY RESEARCH PROFESSIONAL (ORP) MANUAL
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GASTROINTESTINAL
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REVISED: OCTOBER 2014
The gallbladder stores extra bile; it resides below the liver and to the right of the stomach. The
pancreas produces juices which aid in digestion and insulin which helps to make use of sugars;
the pancreas lies below the stomach. The juices from these three organs flow into the common
bile duct that opens into the small intestine. Treatment for early stage gall bladder cancers
consists of surgical resection alone. Adjuvant therapy of any kind remains experimental.
Unresectable disease is commonly treated with chemoradiation (fluoropyrimidine based).
Metastatic disease is incurable and the potential benefit of chemotherapy on survival is not welldefined. Many patients are treated with gemcitabine-based combination chemotherapy,
however.
Seventy-five percent of pancreatic cancers are adenocarcinoma. Usually the disease is not
resectable for cure upon presentation. Currently, patients with surgically resectable disease are
managed with surgery, often in combination with chemoradiation administered after surgery.
Neoadjuvant chemoradiotherapy remains experimental. For patients with locally advanced
(unresectable) or metastatic disease there is no highly effective therapy, though combined
radiation and chemotherapy may improve survival. For patients with metastatic disease,
gemcitabine chemotherapy, gemcitabine with capecitabine, and gemcitabine with erlotinib
improve survival and/or quality of life.
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ONCOLOGY RESEARCH PROFESSIONAL (ORP) MANUAL
VOLUME II
GASTROINTESTINAL
CHAPTER 4
REVISED: OCTOBER 2014
Staging
The staging system most often used for SWOG gastrointestinal protocols is the TNM system of
the American Joint Committee, Version 7 (2010). The specific staging criteria for each disease
site are detailed in the tables that follow.
AJCC Staging - Esophagus
Primary Tumor
TX
Primary tumor cannot be assessed.
T0
No evidence of primary tumor.
Tis
High-grade dysplasia.*
T1
Tumor invades lamina propria, muscularis mucosa or submucosa.
T1a
Tumor invades lamina propria or muscularis mucosa.
T1b
Tumor invades submucosa.
T2
Tumor invades muscularis propria.
T3
Tumor invades adventitia.
T4
Tumor invades adjacent structures.
T4a
Resectable tumor invading pleura, pericardium, or diaphragm.
T4b
Unresectable tumor invading other adjacent structures, such as aorta, vertebral
body, trachea, etc.
*Note: High grade dysplasia includes all neoplastic epithelium that was formerly called
carcinoma in situ, a diagnosis that is no longer used for columnar mucosa anywhere in the
gastrointestinal tract.
Regional Lymph Nodes
NX
Regional lymph nodes cannot be assessed.
N0
No regional lymph node metastasis.
N1
Regional lymph node metastasis involving 1 to 2 nodes.
N2
Regional lymph node metastasis involving 3 to 6 nodes.
N3
Regional lymph node metastasis involving 7 or more nodes.
Distant Metastasis
MX
Presence of distant metastasis cannot be assessed.
M0
No distant metastasis.
M1
Distant metastasis present.
For selected protocols, M1 disease may be subdivided by:
Tumors of the lower thoracic esophagus:
M1a Metastasis in celiac lymph nodes.
M1b Other distant metastasis.
Tumors of the midthoracic esophagus:
M1a Not applicable.
M1b Nonregional lymph nodes and/or other distant metastasis.
Tumors of the upper thoracic esophagus:
M1a Metastasis in cervical nodes.
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CHAPTER 4
REVISED: OCTOBER 2014
M1b Other distant metastasis.
Esophagus staging groups – Version 7 of the AJCC Staging Manual includes a differentiation
between squamous cell carcinoma (or mixed histology) and adenocarcinoma for primary tumors
of the esophagus as illustrated below:
Squamous Cell Carcinoma*
GROUP
T
0
Tis (HGD)
IA
T1
IB
T1
T2-3
IIA
T2-3
T2-3
IIB
T2-3
T1-2
IIIA
T1-2
T3
T4a
IIIB
T3
IIIC
T4a
T4b
Any
IV
Any
N
N0
N0
N0
N0
N0
N0
N0
N1
N2
N1
N0
N2
N1-2
Any
N3
Any
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
Grade
1
1,X
2-3
1, X
1, X
2-3
2-3
Any
Any
Any
Any
Any
Any
Any
Any
Any
Tumor Location**
Any
Any
Any
Lower, X
Upper, middle
Lower, X
Upper, middle
Any
Any
Any
Any
Any
Any
Any
Any
Any
* or mixed histology including a squamous component or NOS
** Location of the primary cancer site is defined by the position of the upper (proximal) edge of
the tumor in the esophagus
Adenocarcinoma
GROUP
0
IA
IB
IIA
IIB
IIIA
IIIB
IIIC
IV
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T
Tis (HGD)
T1
T1
T2
T2
T3
T1-2
T1-2
T3
T4a
T3
T4a
T4b
Any
Any
N
N0
N0
N0
N0
N0
N0
N1
N2
N1
N0
N2
N1-2
Any
N3
Any
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
Grade
1, X
1-2, X
3
1-2, X
3
Any
Any
Any
Any
Any
Any
Any
Any
Any
Any
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AJCC Staging - Stomach
Primary Tumor
TX
Primary tumor cannot be assessed.
T0
No evidence of primary tumor.
Tis
Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria.
T1
Tumor invades lamina propria or submucosa.
T1a
Tumor invades lamina propria or muscularis mucosa
T2b
Tumor invades submucosa
T2
Tumor invades the muscularis propria
T3
Tumor penetrates subserosal connective tissue without invasion of visceral
peritoneum or adjacent structures. * ** ***
T4
Tumor invades serosa (visceral peritoneum) or adjacent structures. * ** ***
T4a
Tumor invades serosa (visceral peritoneum)
T4b
Tumor invades adjacent structures
* A tumor may penetrate the muscularis propria with extension into the
gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum,
without perforation of the visceral peritoneum covering these structures. In
this case, the tumor is classified T3. If there is perforation of the visceral
peritoneum covering the gastric ligaments or the omentum, the tumor should
be classified T4.
**The adjacent structures of the stomach include the spleen, transverse colon,
liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small
intestine, and retroperitoneum.
***Intramural extension to the duodenum or esophagus is classified by the
depth of the greatest invasion in any of these sites, including the stomach.
Regional Lymph Nodes
NX
Regional lymph nodes cannot be assessed.
N0
No regional lymph node metastasis.
N1
Metastasis in 1 to 2 regional lymph nodes.
N2
Metastasis in 3 to 6 regional lymph nodes.
N3
Metastasis in 7 or more regional lymph nodes.
N3a Metastasis in 7 to 15 regional lymph nodes.
N3b Metastasis in 16 or more regional lymph nodes.
Distant Metastasis
MX
Presence of distant metastasis cannot be assessed.
M0
No distant metastasis.
M1
Distant metastasis.
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Stomach Stage Groupings
GROUP
0
IA
IB
IIA
IIB
IIIA
IIIB
IIIC
IV
T
Tis
T1
T2
T1
T3
T2
T1
T4a
T3
T2
T1
T4a
T3
T2
T4b
T4b
T4a
T3
T4b
T4b
T4a
Any T
N
N0
N0
N0
N1
N0
N1
N2
N0
N1
N2
N3
N1
N2
N3
N0
N1
N2
N3
N2
N3
N3
Any N
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
AJCC Staging - Pancreas
Primary Tumor
TX
Primary tumor cannot be assessed.
T0
No evidence of primary tumor.
Tis
carcinoma In situ.
T1
Tumor limited to the pancreas 2 cm or less in greatest dimension.
T2
Tumor limited to the pancreas more than 2 cm in greatest dimension.
T3
Tumor extends beyond the pancreas but without involvement of the celiac axis or
the superior mesenteric artery.
T4
Tumor involves the celiac axis or the superior mesenteric artery (unresectable
primary tumor).
Regional Lymph Nodes
NX
Regional lymph nodes cannot be assessed.
N0
No regional lymph node metastasis.
N1
Regional lymph node metastasis.
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Distant Metastasis
MX
Presence of distant metastases cannot be assessed.
M0
No distant metastasis.
M1
Distant metastasis
Stage Grouping - Pancreas
Stage 0
Stage IA
Stage IB
Stage IIA
Stage III
Stage IV
Tis
T1
T2
T3
T2
T3
T4
Any T
N0
N0
N0
N0
N1
N1
Any N
Any N
M0
M0
M0
M0
M0
M0
M0
M1
AJCC Staging - Colon/Rectum
Primary Tumor
TX
Primary tumor cannot be assessed.
T0
No evidence of primary tumor.
Tis
Carcinoma in situ: intraepithelial or invasion of the lamina propria.*
T1
Tumor invades the submucosa.
T2
Tumor invades the muscularis propria.
T3
Tumor invades through the muscularis propria into pericolorectal tissues.
T4a
Tumor penetrates to the surface of the visceral peritoneum.^**
T4b
Tumor directly invades or is adherent to other organs or structures. and/or
perforates the visceral peritoneum.
*Note Includes cancer cells confined within the glandular basement membrane
(intraepithelial) or lamina propria (intramucosal) with no extension through the
muscularis mucosa into the submucosa.
^Note: Direct invasion in T4 includes invasion of other organs or other segments of the
colorectum as a result of direct extension through the serosa, as confirmed on
misroscopic examination (for example, invasion of the sigmoid colon by a
carcinoma of the cecum) or, for cancers in a retro-peritoneal or subperitoneal
location, direct invasion of other organs or structures by virtue of extension
beyond the muscularis propria (i.e., respectively, a tumor on the posterior wall of
the descending colon invading the left kidney or lateral abdominal wall; or a mid
or distal rectal cancer with invasion of prostate, seminal vesicles, cervix or
vagina).
**Note Tumor that is adherent to other organs or structures, macroscopically, is
classified cT4b. However, if no tumor is present in the adhesion,
microscopically, the classification should be pT1-4a depending on the anatomical
depth of wall invasion. The V and L staging system should be used to identify
the presence or absence of vascular or lymphatic invasion whereas the PN site
specific factor should be used for perineural invasion.
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Colon and Rectum Lymph Nodes
NX
N0
N1
N1a
N1b
N1c
N2
N2a
N2b
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in 1 to 3 regional lymph nodes
Metastasis in 1 regional lymph node
Metastasis in 2-3 regional lymph nodes
Tumor deposit(s) in the subserosa, mesentery, or non-peritonealized
pericolic or perirectal tissues without regional nodal metastasis
Metastasis in 4 or more regional lymph nodes
Metastasis in 4 to 6 regional lymph nodes
Metastasis in 7 or more regional lymph nodes
Note: A satellite peritumoral nodule in the pericolorectal adipose tissue of a primary carcinoma
without histologic evidence of residual lymph node in the nodule may represent discontinuous
spread, venous invasion with extravascular spread (V1/2) or a totally replaced lymph node
(N1/2). Replaced nodes should be counted separately as positive nodes in the N category,
whereas discontinuous spread or venous invasion should be classified and counted in the SiteSpecific Factor category Tumor Deposits (TD).
Distant Metastasis
MX
Presence of distant metastasis cannot be assessed.
M0
No distant metastasis.
M1
Distant metastasis.
Colon and Rectum Stage Groups
GROUP
0
I
IIA
IIB
IIC
IIIA
IIIB
IIIC
IVA
IVB
T
Tis
T1
T2
T3
T4a
T4b
T1-T2
T1
T3-T4a
T2-T3
T1-T2
T4a
T3-T4a
T4b
Any T
Any T
N
N0
N0
N0
N0
N0
N0
N1/N1c
N2a
N1/N1c
N2a
N2b
N2a
N2b
N1-N2
Any N
Any N
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1a
M1b
Dukes*
A
A
B
B
B
C
C
C
C
C
C
C
C
-
MAC*
A
B1
B2
B2
B3
C1
C1
C2
C1/C2
C1
C2
C2
C3
-
*Dukes B is a composite of better (T3 N0 M0) and worse (T4 N0 M0) prognostic groups, as is
Dukes C (Any TN1 M0 and Any T N2 M0). MAC is the modified Astler Collier classification
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