Cancer colon introduction

2. Colon and rectal cancer are
the 3rd leading cause of
cancer death in men and
women

3. Risk Factors
1- Genetic Predisposition
2- IBD
3- Tobacco
4- Sedentary life style
5- Obesity
6- Diet
7- Family history

4. Risk Factors
• Age 50 or older.
• A family history of cancer of the colon or rectum.
• A personal history of cancer of the colon, rectum, ovary,
endometrium, or breast.
• A history of polyps (small pieces of bulging tissue) in the
colon.
• A history of ulcerative colitis (ulcers in the lining of the large
intestine) or Crohn disease.
• Certain hereditary conditions, such as familial adenomatous
polyposis and hereditary nonpolyposis colon cancer.

5. Prevention Strategies
1- Fiber Supplementation ….
Decreases Fecal bile acids; decreases transit
time, binds to fecal mutagens, dilutes fecal
material.

6. Prevention Strategies
2- Dietary fat Reduction
Decreases fecal bile
acids; may reduce
consumption of
carcinogenic heterocyclic
amines associated with
meat preparation.

7. Prevention Strategies
3- Calcium supplementation
Reduces the proliferative response to fatty
acids and bile acids.
4- Cyclooxygenase inhibition
Decreases cox-2 mediated free radical
formation; may inhibit growth factor
synthesis in response to tumor promoters
Chan AT, Giovannucci EL, Meyerhardt JA et al. Long-term use of aspirin and nonsteroidal anti-inflammatory
drugs and risk of colorectal cancer. JAMA. 2005; 294:914-23.
Wactawski-Wende J, Kotchen JM, Anderson GL, Calcium plus vitamin D supplementation and the risk of
colorectal cancer. N Engl J Med. 2006; 354:684-96.
Hawk ET, Levin B. Colorectal Cancer Prevention. J Clin Oncol. 2005; 23:378-91.

8. Possible signs of colon cancer include a change
in bowel habits or blood in the stool
• A change in bowel habits.
• Blood (either bright red or very dark) in
the stool.
• Diarrhea, constipation, or feeling that the
bowel does not empty completely.
• Stools that are narrower than usual.
• Frequent gas pains, bloating, fullness, or
cramps.
• Weight loss for no known reason.
• Feeling very tired.
• Vomiting.

9. Signs & Symptoms
A. Clinical presentation depends
on the site and extent of tumor
involvement
B. Right colon
1. Vague abdominal pain
2. Anemia secondary to chronic blood loss,
blood will be mixed in w/ stool so harder to
detect
3. Weakness
4. Weight loss
5. No obstruction, secondary to stool is liquid
here so more diarrhea

10. Signs & Symptoms
C. Left colon
1. Constipation alternating with diarrhea secondary to obstruction
2. Secondary to pressure against the obstruction that causes stool to liquefy
3. Blood will be on the stool (coating)
4. Abdominal pain
5. Obstructive symptoms (nausea/vomiting)
D. Rectum
1. Changes in bowel movements
2. Rectal fullness
3. Urgency,
4. Bleeding (bright red blood)

11. Diagnosis
A. Medical and family history for:
1. Signs/symptoms
2. Inflammatory bowel disease
3. Colorectal cancer or polyps
B. Physical examination for:
1. Lymphadenopathy
2. Hepatomegaly
3. Masses or ascites
4. Women should undergo appropriate evaluations to rule out breast,
ovarian, endometrial cancers
C. Colonoscopy
D. Biopsy of any detected lesions
E. CT scan of chest/abdomen/pelvis

12. Diagnosis
F. PET scan only if potential surgically curable metastatic disease
G. CBC with platelets, LFTs, creatinine

13. Diagnosis
H. Carcinoembryonic antigen (CEA)
level
1. May be useful in monitoring
colorectal cancer response to
treatment
2. Normal < 3
3. Normal in smokers 0-6
4. CEA can be higher with ↑ SrCr,
hepatic dysfunction or chemo (5-FU) so
may see an increase in CEA and then a
decrease after a few months of
treatment

14. Diagnosis
I. Anatomy
1. Proximal (Ascending and Transverse Colon)-35-45% of cancers
diagnosed
2. Descending colon-5% of cancers diagnosed
3. Distal (Sigmoid colon and Rectum)-45-55% of cancers diagnosed

15. Diagnosis
J. Pathology
1. Adenocarcinomas make up 90-95% of large bowel neoplasms
2. Mucinous adenocarcinomas characterized by large amount of
extracellular mucus within the tumor
3. Signet ring cell carcinoma

16. Diagnosis
4. Pathology review for KRAS,
BRAF and MMR

17. Diagnosis
5. Microsatellite Instability (MSI)
testing
• NCCN recommends that all
patients < 50 years of age or with
stage II disease be tested for
mismatch repair. Patients with a
stage II MSI-H cancer may have a
good prognosis and do not benefit
from adjuvant therapy.

18. Diagnosis
• MMR as well as other high risk features for recurrence are to
be evaluated when determining whether adjuvant therapy is
indicated for stage II colorectal cancers and do not benefit
from 5-FU adjuvant therapy.
• Several studies have demonstrated that colorectal
adenocarcinomas demonstrating microsatellite instability
(MSI) exhibit loss expression of one or more of the mismatch
repair (MMR) enzymes MLH1, MSH2, PMS2 and MSH6, which
can be assessed by IHC.

19. Defective DNA mismatch repair (dMMR)
1) Associated with colon cancers in the proximal (right side) colon,
poor differentiation, mucinous histology, lymphocytic infiltration
and diploid DNA contents
2) Measured by microsatellite instability (MSI) or testing for loss of
genes involved in DNA mismatch repair – MLH1, SMH2, MSH6, and
PMS2
• High-level MSI (MSI-H) and loss of protein expression of MLH1
and MSH2 have similar prognostic ability
3) Stage II colorectal cancers with dMMR (MSI-H, loss of MLH1 or
MSH2) do not benefit from 5-fluororuacil based adjuvant
chemotherapy.
4) MMR as well as other high risk features for recurrence are to be
evaluated when determining whether adjuvant therapy is indicated
for stage II colorectal cancers

20. Tests and procedures for diagnosis
• Physical exam and history : An exam of the body to check
general signs of health.
• Digital rectal exam : The doctor or nurse inserts a lubricated,
gloved finger into the rectum to feel for lumps or anything
else that seems unusual.
• Fecal occult blood test: A test to check stool.
• Barium enema : A series of x-rays of the lower gastrointestinal
tract. A liquid that contains barium is put into the rectum. The
barium coats the lower gastrointestinal tract and x-rays are
taken. This procedure is also called a lower GI series.

21. • Sigmoidoscopy: A procedure to look inside
the rectum and sigmoid colon for polyps
(small pieces of bulging tissue), abnormal
areas, or cancer.

22. • Colonoscopy : A procedure to look inside the
rectum and colon for polyps, abnormal areas,
or cancer.

23. • Virtual colonoscopy (CT Colonography): A
procedure that uses a series of x-rays called
computed tomography to make a series of
pictures of the colon.

24. • Biopsy : The removal of cells or tissues so
they can be viewed under a microscope by a
pathologist to check for signs of cancer.

25. The prognosis
• The stage of the cancer.
• Whether the cancer has blocked or
created a hole in the colon.
• Whether there are any cancer cells
left after surgery.
• The blood levels of
carcinoembryonic antigen (CEA)
before treatment begins.
• Whether the cancer has recurred.
• The patient’s general health.

26. Treatment ‘depends on the following’
• The stage of the cancer.
• Whether the cancer
has recurred.
• The patient’s general
health.

27. Tests and procedures used in the
staging process
• CT scan.
• MRI (magnetic resonance imaging)
• PET scan (positron emission tomography scan)
• Chest x-ray
• Lymph node biopsy
• Complete blood count (CBC)
• Carcinoembryonic antigen (CEA) assay

37. I- Surgery
Surgery is the most common treatment for all
stages of colon cancer.
• Local excision: in very early stage.

38. I- Surgery
• Resection: If the cancer is larger
• perform a partial colectomy (removing the cancer and a small
amount of healthy tissue around it).
• perform an anastomosis (sewing the healthy parts of the colon
together).
• Usually remove lymph nodes near the colon.

39. • Radiofrequency ablation: The use of a special probe
with tiny electrodes that kill cancer cells.
• Cryosurgery (Cryotherapy): A treatment that uses an
instrument to freeze and destroy abnormal tissue.
I- Surgery

40. II-Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-
rays or other types of radiation to kill cancer cells or keep them
from growing.

41. II-Radiation therapy
a. Administered prior to or following surgery in patients with
curable disease
1) Neoadjuvant - utilized to improve resectability of primary
tumor (decrease risk for positive margins and increase
opportunity for LAR resection) and to decrease risk of local
recurrence.
2) Adjuvant – used to decrease risk of local recurrence
a) Radiation alone after surgery has been found to be inferior to
concurrent radiation and chemotherapy in rectal cancer
3) Utilized in patients with metastatic disease for symptom
reduction (pain, bleeding) for both colon and rectal cancer

42. II-Radiation therapy
Complications
a. Acute toxicity
1) Thrombocytopenia/leukopenia
2) Dysuria, diarrhea, abdominal cramping, proctitis
b. Chronic toxicity
1) Can be persist for months following discontinuation of
XRT
• Diarrhea
• Small bowel disease
• Proctitis
• Enteritis

43. III- Chemotherapy

44. III- Chemotherapy
Treatment Regimens for adjuvant Colon Cancer
Stage I
• Surgical excision of primary tumor and removal of regional
lymph nodes
• No adjuvant chemotherapy

45. High risk Stage II Disease
The NCCN guidelines include :
1- Grade 3, 4 histology.
2- lymphovascular invasion.
3- Perineural invasion.
4- < 12 lymph nodes examined.
5- Positive margins after surgical resection.
6- Bowel obstruction, or localized perforation.

46. High risk Stage II Disease
• the number of lymph nodes:
• If fewer than 12 lymph nodes are removed and examined, the
risk of recurrence is higher and the overall survival lower. In
studies, the 5-year overall survival (OS) correlates to the
number of lymph nodes removed (1-7 LNs = 49.8% OS, 8-12
LNs = 56.2%, >12 LNs = 63.4%).
• It is not clear if this is because examining more lymph nodes
in these patients would have found their tumors to be stage
III, or because the surgical removal was less than complete, or
perhaps both. We don't know for sure, but this finding often
drives the decision to use adjuvant chemotherapy in patients
with fewer than 12 LNs removed.

47. High risk Stage II Disease
• Positive margin:
A positive margin has been defined as
1) Tumor <1 mm from the transected margin.
2) Tumor <2 mm from the transected margin
3) Tumor cells present within the diathermy of the transected
margin.

48. III- Chemotherapy
Treatment Regimens for adjuvant Colon Cancer
Stage II
• Surgical excision of primary tumor and removal of regional lymph nodes
• Role of adjuvant chemotherapy still unclear for stage II
• Stage II disease to be evaluated for MMR. Adjuvant therapy is not recommended for
stage II MSI-H tumors
High Risk IIA & Stage IIB,IIC
• FOLFOX
•CapeOx - flox
• Capecitabine or 5 – fluorouracil plus leucovorin.
•Clinical trials
Low Risk IIA
• Observation or clinical trial.
•Capecitabine, 5- fu/leuc.

49. Treatment Regimens for adjuvant Colon Cancer
Stage III IIIA (T3, N1, M0), IIIB (T4, N1, M0), IIIC (T1-4, N2, M0)
Surgical excision of primary tumor and removal of regional lymph nodes
Adjuvant therapy – FOLFOX and CapeOx preferred, Flox, capecitabine, 5-FU/LV
Good Performance Status (PS)
• FOLFOX and CapeOx preferred
• Capecitabine, Flox or 5 – fluorouracil plus leucovorin.
Poor Performance Status
• Capecitabine.

52. PRINCIPLES OF ADJUVANT THERAPY
5-FU-based regimens standard of care
1) Schedule of 5-FU/LV administration does not affect efficacy, but toxicities may
be different
i. Mayo Clinic regimen - more commonly associated with leucopenia and
stomatitis
ii. Roswell Park regimen - more commonly associated with diarrhea
iii. Infusional 5-FU/LV may have less toxicity vs. bolus
iv. Capecitabine equally effective to bolus 5-FU/LV
v. Addition of oxaliplatin increased benefit
(a) FOLFOX is superior to fluoropyrimidine therapy alone for stage III
(b) FOLFOX is reasonable for high-risk stage II
vi. Irinotecan not used in the adjuvant setting
vii. No targeted agents are approved for use in the adjuvant setting

53. PRINCIPLES OF ADJUVANT THERAPY
• Adjuvant therapy begins 4 to 8 weeks after surgery and lasts
for 6 months
• FOLFOX is superior to 5-FU/leucovorin for patients with stage
III colon cancer.
• Capecitabine/oxaliplatin is superior to bolus 5-FU/ leucovorin
for patients with stage III colon cancer.

54. PRINCIPLES OF ADJUVANT THERAPY
• FLOX is an alternative to FOLFOX or CapeOx but FOLFOX or
CapeOx are preferred.
• Capecitabine appears to be equivalent to bolus
5FU/leucovorin in patients with stage III colon cancer.
• A survival benefit has not been demonstrated for the addition
of oxaliplatin to 5-FU/leucovorin in stage II colon cancer.
• FOLFOX is reasonable for high-risk stage II patients and is not
indicated for good- or average-risk patients with stage II.

55. PRINCIPLES OF ADJUVANT THERAPY
• A benefit for the addition of oxaliplatin to 5-FU/leucovorin in
patients age 70 and older has not been proven.
• Bevacizumab, cetuximab, panitumumab, or irinotecan should
not be used in the adjuvant setting for patients with stage II or
III colon cancer outside the setting of a clinical trial.

57. Treatment Options for Metastatic Colon Cancer (Stage IV)
Resectable synchronous liver only or lung only metastases
Colectomy with synchronous resection of liver or lung metastases followed by adjuvant
chemotherapy with FOLFOX or CapeOx (preferred)
• Neoadjuvant to increase curative resection rates and to convert patients from unresectable
to resectable disease (for 2-3 mnths)
• Combination chemotherapy for 2-3 months followed by chemoradiation with 5-FU or
capecitabine and then resection of metastases and rectal primary
i. FOLFIRI, CapeOx, or FOLFOX ± bevacizumab
ii. FOLFIRI or FOLFOX + panitumumab ( Vectibix®) if KRAS wild type (WT)
iii. FOLFIRI + cetuximab if KRAS WT
Adjuvant First-Line Therapy Adjuvant Second-Line Therapy
Good Performance Status
• FOLFOX with or without Bevacizumab.
• FOLFIRI with or without Bevacizumab.
• 5-FU + Leucovrin with bevacizumab
If first line Irinotecan
• FOLFOX with or without Bevacizumab.
• Irinotecan ???? with or without Cetuximab.
• Capecitabine or 5-FU + Leucovorin
Poor Performance Status
• Capecitabine or 5-FU + Leucovorin with or
without Bevacizumab.
If first line Oxaliplatin
• FOLFIRI with or without Bevacizumab.
• Irinotecan with or without Cetuximab.

58. Treatment Options for Metastatic Colon Cancer (Stage IV)
Resectable synchronous liver only or lung only metastases
1- Colectomy with synchronous resection of liver or lung metastases
followed by adjuvant chemotherapy with FOLFOX or CapeOx
(preferred)
2- Neoadjuvant chemotherapy
Neoadjuvant chemotherapy given for 2-3 months
Colectomy with synchronous resection of metastatic disease
Observation or shortened course adjuvant chemotherapy with FOLFOX or CapeOx
3- Colectomy followed by 2-3 months of chemotherapy and staged
resection of metastatic disease

59. Treatment Options for Metastatic Colon Cancer (Stage IV)
Unresectable liver or lung only lesions
Treated with chemotherapy and evaluated every 2 months to
assess resectability of liver and/or lung metastases.
Consider colon resection if risk of obstruction or significant
bleeding.
1) FOLFIRI, CapeOx, or FOLFOX + bevacizumab
2) FOLFIRI or FOLFOX + panitumumab if KRAS WT
3) FOLFIRI + cetuximab if KRAS WT
4) FOLFOXIRI + bevacizumab
5) For patients that are able to undergo resection of metastatic
disease , they should
receive 6 months of adjuvant therapy with an active regimen for
advanced disease,
observation, or shortened course of chemotherapy

60. Based on the information presented, create a care plan for this
patient’s colon cancer; includes:
a)The patient’s drug and non drug-related needs and problems
b)The goals of therapy
c)A treatment plan specific to the patient that includes strategies to
prevent adverse effects of chemotherapy
d)A follow-up plan to determine whether the goals have been
achieved and the adverse effects of chemotherapy have been
minimized.
e)A plan for treatment options when the initial therapy is no longer
achieving the goals of therapy.
Creating a care plan

61. Scenarios

62. Scenario 1
• MM 55 years old patient admitted to the hospital
complaining of non- stop diarrhea after
investigations patient diagnosed as Cancer colon
with no signs of metastatic disease.
• Q 1, it is appropriate for him to undergo surgical
resection for his colon cancer??
Yes
No

63. Scenario 1
• MM 55 years old patient admitted to the hospital
complaining of non- stop diarrhea after
investigations patient diagnosed as Cancer colon
with no signs of metastatic disease.
• Q 1, it is appropriate for him to undergo surgical
resection for his colon cancer??
Yes
No

64. Scenario 1
• After surgery .. The surgical wound has completely healed. He
presents to the medical oncologist’s office for a discussion
about whether or not he should receive adjuvant
chemotherapy. The pathology for the primary tumor was
determined to be a Stage IIIA (T2 N1 M0). His performance
status is a 1.
• Q 2, Should he receive adjuvant Chemotherapy ??
 Yes
 No

65. Scenario 1
• After surgery .. The surgical wound has completely healed. He
presents to the medical oncologist’s office for a discussion
about whether or not he should receive adjuvant
chemotherapy. The pathology for the primary tumor was
determined to be a Stage IIIA (T2 N1 M0). His performance
status is a 1.
• Q 2, Should he receive adjuvant Chemotherapy ??
 Yes
 No

66. Scenario 1
• Q 3, What adjuvant therapy do you recommend LD
receive?
FOLFOX
FOLFIRI
FOLFOX + bevacizumab
FOLFIRI + bevacizumab

67. Scenario 1
• Q 3, What adjuvant therapy do you recommend LD
receive?
FOLFOX
FOLFIRI
FOLFOX + bevacizumab
FOLFIRI + bevacizumab

68. Answer Explanation
• Given that MM has stage III disease, the recommendation is for MM to
receive adjuvant chemotherapy for 6 months with either FOLFOX or
CapeOx(preferred regimens). Other options include FLOX, capecitabine, or
5-FU/LV.
• Observation and clinical trials are not recommended for stage III disease.

69. Scenario 1
• Q 4, Would your recommendation change if
the pathology revealed a stage IIA (T3 N0
M0)? What additional information is needed
to make this decision?

70. THANK YOU
Cancer