its for colon ca treatment

1. Solid Tumors
Yazan Momani
Medical oncologist

2. Definition
. Malignant growth of tumor that begins from the inner
wall of the colon or rectum.

3. EPIDEMIOLOGY
. The 3rd most common malignancy worldwide ( ≥ 1.2
million new cases annually).
. The incidence is greatest among males (37.4 per
100,000 vs. 29.9 per 100,000)
. 3
rd leading cause of cancer-related deaths in US.
. Highest incidence rates in economically developed
countries
. Invasive CA of rectum occurs less frequently (<1/3
cases)

4. Age & Colorectal CA
Relationship:
An individual’s risk of developing cancer of the
colon or rectum increases with advancing age.
The likelihood of cancer diagnosis ↑ after 40
years of age and rising progressively after age 50.
The median age at diagnosis is 69 years.
< 20% of patients are less than 50 years of age at
the time of diagnosis.

5. SURVIVAL :
5-year survival rate:
Disease Stage 5- Year
survival
Early stages (localized/stage I, II) of colon
Early stages rectal cancer.
91 %
88%
70%
Regional disease/Stage III:
Colon & rectal cancer after the tumor has spread
regionally to adjacent LNs or tissues
Metastatic disease ≤ 12%

6. Pathophysiology
. The formation of colorectal CA is a multistep process.
. Begins with an abnormal growth of tissue known as a
polyp (precursors to the disease) originating from the
innermost wall of the colon.

7. A stalked colon
polyp
 The process of
transformation from polyp
to malignant disease
takes years.
 Once transformation
occurs, cancer begins to
spread through the wall
of colon/rectum.
 It can eventually invade
blood, L.Ns, or other
organs directly.

8. 95% are adenocarcinoma (glandular tissue).
The disease can be prevented by removal of precancerous
tissue.

9. Anatomy
The large intestine consists of the cecum; the ascending,
transverse, descending, and sigmoid colon; and the rectum
Ascending colon (22% of colorectal carcinomas)
Transverse colon (11% of colorectal carcinomas)
Descending colon (6% of colorectal carcinomas)
Sigmoid colon (55% of colorectal carcinomas)
4 major tissue layers, from the lumen outward, form the large
intestine:
The mucosa
Submucosa
Muscularis propria
Serosa

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12. Aetiology
Aetiology is complex, involving:
. Patient- specific factors
. Environmental factor
. Genetic factors
Genetic mutations associated with colorectal cancer:
. APC mutation/loss (Tumour suppressor gene).
. P53 mutation
. COX-2 overexpression (growth factor signalling
pathways)
. K-RAS mutation 35%, BRAF mutation 5% (oncogenes)

13. Risk Factors
Increase age: Age >50 (90% of patients)
Male sex
Family history.
Personal history:
(history of colon polyps; multiple adenomas or size
≥10 mm)
IBD (Ulcerative colitis, Crohn’s disease):
↑ 5- to 10-fold
Risk ↑ with increasing extent of bowel involvement &
disease duration.

14. Risk Factors
Environmental factors/ Lifestyle:
. Physical inactivity & obesity
. Diet:
fatty food
Red meats
processed meats
(hot dogs and some luncheon meats)
low fibers
. Alcohol (excessive)
. SMOKING:
Rectal > colon
Dose relationship (pack/year)
Duration

15. Particularly smoking in early life.
As compared to never-smokers, the risks of
colorectal cancer and mortality in smokers were
18% and 25% higher, respectively.
Early tobacco use influence risk of cancer
recurrence and mortality among colon cancer
survivors.

16. Factors may ↓ colorectal CA risk:
. Fiber (Fruit & Vegetables)
. Physical activity
. Regular consumption of milk/Calcium & Vitamin D
(May have antiproliferative effects )
. Hormone replacement therapy (HRT). Persist over
10 y

17. NSAID (Celecoxib) and Aspirin Use:
. Regular use (2 x wk), over 10-15 year.
. Inhibition of COX-2 & free radical formation.
. COX-2 overexpression is seen in pre-cancerous &
cancerous lesions in the colon
. COX-2 overexpression is associated with:
Decreased colon CA cell apoptosis
Increased production of angiogenesis-promoting
factors.

18. Signs & Symptoms
1. Subtle & nonspecific (generalised symptoms)
2. Asymptomatic (early stage).
3. **Persistent/sudden change in bowel habits:
(*Prolong constipation
*or diarrhea.
*pencil thin stool)
4. Bleeding from rectum or blood
In stool.
5. Vague Cramping or abdominal pain/discomfort,
bloating , N, V 2ndry obstruction, perforation,
bleeding.

19. Signs and symptoms
6. Weakness and tiredness
(advanced stage).
7. Iron-deficiency anemia.
8. Unintentional weight loss
9. Increased liver enzymes
(sign of liver metastasis) (AST/ALT)
10. Jaundice in advanced disease.

20. DIAGNOSIS
. Signs and symptoms
. Entire Large bowel evaluation:
Colonoscopy
Double-Contrast Barium Enema
CT Colonography (detect adenomas at least 6 mm).
Flexible sigmoidoscopy (FSIG) : examine lower half of
the bowel to the splenic flexure, capable to detect
50%-60% of CA.

21. . Biopsy
(during colonoscopy)
. Ultrasound: Determines
depth of tumor penetration,
assessing L.Ns
. CT scan: same as ultrasound + useful in assessing for
metastasis
. Blood tests: bld count, PT, PTT, Liver function test.
. CEA (carcinoembryonic antigen) Tumour marker
Non-sensitive, non specific in early stage
Usually elevated in metastatic or recurrent colon CA
Normal 0-3 ng/mL
Monitor the recurrence.

22. SCREENING
A. Colonoscopy/ Barium enema/ CT scan
(alternative for individuals who don’t wish to
undergo /not suitable for colonoscopy.)
B. Fecal occult blood testing (FOBT)

23. 2. Fecal immunochemical test (FIT)
Can be used to replace FOBT
Sensitivity 60-85%
Specificity > 97%
No drug or food interactions
Uses ABs to detect globin protein Hg in stool
D. Digital Rectal Exam (DRE):
Can detect anorectal
palpable mass

24. Screening guidelines for early detection of colorectal
CA with the goal of cancer prevention:
Risk Screening recommendation
Average risk
(R.F ≥ 50 ys)
both M/F
. Annual DRE and FOBT/FIT and one of the following:
– Sigmoidoscopy every 5 years
– CT colonography every 5 years
– Colonoscopy every 10 years
– Barium enema every 5 years
Family History Begin screening at age of 35-40 years or 10 years younger from
first-degree relative colorectal cancer diagnosis
IBD Begin screening at 8–15 years after diagnosis
FAP Begin screening at 10-12 years
HNPCC Begin screening at age of 20–25 years or 10 years younger
from 1st-degree relative colorectal CA diagnosis

25. Staging:
TNM Staging System
T – (tumor size), based on DEPTH (penetration) invasion
into mucosa
T1 – Tumour invades the submucosa
T2 – Invades the muscularis propria
T3 – Invade through the muscularis propria into
subserosa
T4 – Tumors invading or adhering other local
organs/structures/segments/ surface of visceral
peritoneum
N – lymph node involvement
N1 – 1-3 +ve L.N
N2 – ≥ 4 or more +ve L.N
M – distant metastasis
M0 – no other organs involved
M1 – distant metastases are present

27. Simplified Staging System
Stage
Stage I Tumors that either invade into or through the
submucosa with NO (+) LN
Stage II Tumors that invade through the muscularis propria or
into local organs with NO (+) LN
Stage III
Stage IV
Any T with nodal involvement (+) LN
Tumor with nodal involvement and with distant
metastasis (usually liver, followed by lungs, then
bones)
25% of patients present with stage IV

28. 34

29. Treatment
I. Surgery
II. Radiation
III. chemotherapy
IV. Targeted molecular therapies.
Treat Depend on the location & extent of disease.
Prognosis depend on extent of tumour
penetration/LNs involvement, Metastases.
Goals:
Curative therapy for localized CA
Palliative therapy for metastatic CA.

30. Rectal CA is more difficult to resect with wide margins.
Local recurrence of rectal CA is more common
compared to colon CA
If lies closer to the anal sphincter, so the risk of
localized treatment failure & recurrence at the initial
site of disease is increased
Radiation (XRT) is usually reserved for rectal cancer
Adjuvant XRT + chemo. are standard for stage II/III
rectal CA
Neo- Adjuvant therapy before rectal surgery to:
Shrink the tumour & make it resectable, prevent local
recurrence in rectal CA.

31. In metastasis disease, radiotherapy will reduce the
symptoms
Stage I colon or rectal cancer are cured by surgical
resection alone, adjuvant therapy is not indicated.
Adjuvant chemotherapy in –ve L.N (stage II) colon
cancer is controversial
Adjuvant chemotherapy should be considered for
stage II disease with pts. at higher risk for relapse :
(inadequate LN sampling, bowel obstruction/ perforation of the
bowel at presentation, poorly differentiated tumors, perineural
invasion, and T lesions (stage IIB/IIC).
4

32. Adjuvant chemotherapy is standard therapy
for patients with stage III colon cancer
(decreases risk of cancer recurrence & death)
 Combined neo-adjuvant therapy + radiation
therapy (chemoradiation) and surgery for
patients with stage II or III rectal cancer is
considered standard of care to decrease risk
of local and distant disease recurrence.

33. Stage
Stage I
Management
Surgery
Stage II
Stage III
Stage IV
Colon: Surgery (observation +/- chemo.)
Rectal: Surgery + XRT + chemo.
Colon: Surgery + Chemotherapy
Rectal: Surgery + XRT + chemo.
+/- surgery (selected pt.)+ chemo. + MoAB ,
Palliative care