Transcript Overview of Colorectal Cancer - American Medical Technologists

Colorectal Cancer and
Gastrointestinal Stromal
Tumor: Disease State
Overview and New
Treatment Approaches
Robin M Ross, PharmD
Medical Science Liasion
Colorectal Cancer (CRC) Epidemiology
 CRC is the fourth most frequently diagnosed
cancer and the second leading cause of
cancer death in the US1
 143,460 new cases of CRC are estimated for
20122
 ~72% of cases arise in the colon and ~28%
arise in the rectum3
 CRC incidence rate is more than 15x higher
in adults aged ≥50 than in adults aged
20-493
 ~20% of patients have metastatic CRC
(mCRC) when first diagnosed4
1.
2.
3.
4.
NCCN Colon Cancer: Version 1, 2013.
American Cancer Society. http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf. Accessed August 31, 2012.
American Cancer Society. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-028323.pdf.
Accessed August 31, 2012.
National Cancer Institute. http://www.seer.cancer.gov/statfacts/html/colorect.html. Accessed August 31, 2012.
2
Signs and Symptoms of CRC
 Not all cases of CRC present with symptoms1
 However, a variety of clinical symptoms can be associated with CRC1,2
Systemic
Local
Fatigue
Peritonitis
Anemia
Ulcerations
Palpitations
Decreased appetite
Weight loss
Pale skin
Changed bowel habits
Abdominal pain and distension
Rectal tenesmus
Mucus and blood in stools
Deep vein thrombosis
Melena
1.
2.
Abeloff. 2008.
DeVita. 2011.
3
Screening for CRC
 Goals of screening are to detect cancer at an early, curable stage, and to detect and
remove adenomatous polyps1
 National Comprehensive Cancer Network (NCCN) guidelines recommend screening
based on one’s risk status1
 The following are applicable to asymptomatic adults ≥50 of age2
Screening Method
Frequency
Colonoscopy
Every 10 years
Flexible sigmoidoscopy
Every 5 years
Double-contrast barium enema
Every 5 years
Computed tomographic colonography
Every 5 years
Guaiac-based fecal occult blood test
Annually
Fecal immunochemical test
Annually
Stool DNA
Unspecified
 Although the US Preventive Services Task Force (USPSTF) recommends screening
for people aged 50-75, it does not recommend screening for adults >753
1.
2.
3.
NCCN Colorectal Cancer Screening: Version 1, 2013.
Levin B, et al. CA Cancer J Clin. 2008;58:130-160.
US Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf08/colocancer/colcancs.pdf. Accessed August 31, 2012.
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Diagnosing CRC
 An accurate diagnosis depends on the implementation of a range of clinical
evaluations:1,2
 Complete personal and family history
 Physical examination
 Laboratory tests (including blood, liver, and kidney tests)
 Colonoscopy
 Computed tomography scan (for the detection of possible metastases)
1.
2.
Abeloff. 2008.
DeVita. 2011.
5
Staging CRC (1)
 Following a CRC diagnosis, a pathological review of an endoscopically removed
biopsy sample can determine the stage of CRC, which measures the anatomic
extent of disease1,2
 The American Joint Committee on Cancer/Tumor Node Metastasis (AJCC/TNM)
system is the most prominent and highly regarded:3
Invasiveness (T)
Tis: confinement to the basement membrane or
lamina propria
T1: invasion into the submucosa but not through
it
T2: invasion into, but not through the muscularis
propria
T3: invasion through the muscularis propria
T4a: invasion into other organs or structures
T4b: perforation of the visceral peritoneum
1.
2.
3.
NCCN Colon Cancer: Version 1, 2013.
Abeloff. 2008.
DeVita. 2011.
Local-regional lymph nodes
containing metastatic cancer (N)
Distant metastatic
disease (M)
N0: all lymph nodes negative
N1: 1 positive regional lymph
node
N1b: 2 or 3 positive regional
lymph nodes
N1c: positive areas of fat near but
not in lymph nodes
N2a: 4-6 positive regional lymph
nodes
N2b >7 positive regional lymph
nodes
M0: no distant
metastases
M1a: metastasis to
1 distant organ or
distant set of lymph
nodes
M1b: metastases to
>1 distant organ or
distant set of lymph
nodes
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Staging CRC (2)
Stage
1.
T
N
M
0
Tis
N0
M0
I
T1-T2
N0
M0
IIA
T3
N0
M0
IIB
T4a
N0
M0
IIC
T4b
N0
M0
IIIA
T1-T2
N1 or N2a
M0
IIIB
T3-T4a
T2-T3
T1-T2
N1
N2a
N2b
M0
IIIC
T4a
T3-T4a
T4b
N2a
N2b
N1-N2
M0
IVA
T any
N any
M1a
IVB
T any
N any
M1b
DeVita. 2011.
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CRC Stage and Five-Year Survival
1.
Abeloff. 2008.
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Prognoses for Patients with mCRC Remain Poor
 5-year relative survival rate for patients with CRC was 67% for 1999-2006
 Localized: 90%
 Regional: 70%
 Distant: 12%
 5-year CRC-specific survival by stage and race/ethnicity, 1999-2006:
Men
1.
Women
American Cancer Society. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-028323.pdf.
Accessed August 31, 2012.
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CRC Risk Factors
Non-Modifiable Risk Factors
Modifiable Risk Factors
Age
Diet high in red meats and processed
meats
Personal history of colorectal polyps or
CRC
Physical inactivity
Personal or family history of inflammatory
Obesity
bowel disease
Inherited syndromes (eg, familial
adenomatous polyposis, hereditary
non-polyposis colon cancer)
Smoking
Racial and ethnic background
Heavy alcohol use
Type 2 diabetes
1.
American Cancer Society. http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf. Accessed August 31, 2012.
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Biomarkers in CRC: Improving Outcomes
 Biomarkers in CRC allow:
 Identification of patients who will benefit most from a specific treatment
 Improved outcomes
 Sparing of needless treatment-related toxicity
 Reduced costs
 Prognostic biomarkers provide information about overall outcome
 Predictive biomarkers give information about the effects of treatment
1.
Tejpar S, et al. Oncologist. 2010;15:390-404.
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Biomarkers in CRC: Current Status
 Several candidate biomarkers have been identified:


1.
Prognostic
Shortened survival or no value
Predictive
Negative outcome with anti-EGFR agents in mCRC
Prognostic
Poor prognosis
Predictive
Negative outcome with anti-EGFR agents in mCRC
KRAS mutation
BRAF mutation
Tejpar S, et al. Oncologist. 2010;15:390-404.
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KRAS Mutations in CRC
 Present in 35-45% of CRC1
 May be associated with shortened survival1
 Predictive marker of response to EGFR therapy in CRC:1
 Only patients with wild-type KRAS benefit from cetuximab/panitumumab
 Patients should be screened for KRAS status at the time of diagnosis of stage IV
disease, prior to treatment2
1.
2.
Tejpar S, et al. Oncologist. 201;15:390-404.
NCCN Colon Cancer: Version 1, 2013.
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