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Colon

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Colon & Rectal Cancers Imran Ahmad, MD., Clinical Assistant Professor. Medical Oncology, Saskatoon Cancer Centre. Colon & rectal cancers Management of metastatic CRC ... – PowerPoint PPT presentation

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Title: Colon


1
Colon Rectal Cancers
  • Imran Ahmad, MD.,
  • Clinical Assistant Professor.
  • Medical Oncology,
  • Saskatoon Cancer Centre.

2
Faculty Declaration
  • Will discuss an unapproved/investigative use of a
    commercial product/device
  • I have/had a financial arrangement or affiliation
    with one or more organizations
  • Research Support Hoffman La-Roche

3
Colon rectal cancers
  • Objectives
  • - Colon and rectal ca statistics in Canada.
  • - Prevention and screening.
  • - Medical management of localized and advanced
    stage cancer.

4
Colon rectal cancers
  • Statistics
  • - An estimated 153,000 new cases 70,000 deaths
    from cancer will occur in 2006 in Canada1.
  • - An estimated 20,000 new cases 8,500 deaths
    from colorectal cancer will occur in 2006 in
    Canada1.
  • 1Canadian cancer statistics, 2006.

5
Percentage Distribution of Estimated New Cases
for Selected Cancer Sites, Males, Canada, 2006.
6
Percentage Distribution of Estimated Deaths for
Selected Cancer Sites, Males, Canada, 2006
7
Percentage Distribution of Estimated New Cases for
Selected Cancer Sites, Females, Canada, 2006
8
Percentage Distribution of Estimated Deaths for
Selected Cancer Sites, Females, Canada, 2006
9
Age-Standardized Incidence Rates (ASIR) for
Selected Cancer Sites, Males, Canada, 1977-2006
10
Age-Standardized Mortality Rates (ASMR) for
Selected Cancer Sites, Males, Canada, 1977-2006
11
Age-Standardized Incidence Rates (ASIR) for
Selected Cancer Sites, Females, Canada, 1977-2006
12
Age-Standardized Mortality Rates (ASMR) for
Selected Cancer Sites, Females, Canada, 1977-2006
13
Selected Causes of Potential Years of Life Lost
(PYLL), Canada, 2002
14
Actual Data for New Cases for the Most Common
Cancer Sites by Sex
And Geographic Region, Most Recent Year1, Canada
1 2001 for Canada, Quebec 2002 for Ontario
2003 for Newfoundland, Prince Edward Island, Nova
Scotia, New Brunswick, Manitoba, Saskatchewan,
Alberta, British Columbia 199-2003 average for
Yukon, Northwest Territories, Nunavut
15
Canadian Cancer Stats 2004
16
Colon rectal cancers
  • Risk factors
  • (I) Sporadic (70)
  • - Age Risk increases significantly b/w ages of
    40 and 50, in each succeeding decade
    thereafter1.
  • - Lifetime incidence is about 5.
  • 1Eddy, DM et al. Ann Intern Med 1990.

17
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18
Colon rectal cancers
  • Risk factors (Sporadic)
  • - Inflammatory bowel disease (Pancolitis ,5-15
    fold increased risk )1
  • - Alcohol
  • - Diabetes mellitus
  • - Cigarette smoking.
  • 1Ekbom,A et al. NEJM 1990.

19
Colon rectal cancers
  • (II) Risk factors, inherited (5-10)
  • (a) Germ line mutations.
  • (1) Polyposis syndromes
  • - Familial adenomatous polyposis.
  • - Less than 1 of CRC.
  • - Germ line mutations in APC gene on ch 51.
  • 1Burt, RW et al. Ann Rev Med 1995.

20
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21
Colon rectal cancers
  • (II) Risk factors, inherited (5-10)
  • (a) Germ line mutations.
  • (2) Non Polyposis syndromes
  • - Hereditary nonpolyposis CRC.
  • - Autosomal dominant.
  • - More common than FAP1.
  • 1Lynch, HT et al. Gastroenterology 1993.

22
Colon rectal cancers
  • (III) Risk factors, familial (20-25)
  • - Affected pts have family history, but pattern
    is different from inherited one.
  • - Having an affected 10 relative increases the
    risk 1.7 fold.
  • - Genetic abnormalities
  • ? Mutated APC gene, ? loss of DNA, ?mismatch
    repair genes.

23
Adenoma carcinoma
sequence
24
Genetic model of CRC carcinogenesis
25
Colon rectal cancers
  • Protective factors
  • - Diet high in fruits and vegetables.1
  • (? Fiber, antioxidants, FA, Selenium)
  • - ASA / NSAIDS2.
  • - HMG-CoA reductase inhibitors3.
  • 1Kim et al. Nutr Rev 1996.
  • 2Giovannucci et al. NEJM 1999
  • 3Sacks et al. NEJM 1996.

26
Colon rectal cancers
  • CASE 1
  • 63 yr old asymptomatic man with no family h/o
    colorectal ca, presented for first annual
    physical exam, by family MD.
  • Physical exams including rectal exam was normal.
    Fecal occult blood testing was negative.
  • What should be further recommendations for
    colorectal cancer screening in future?

27
Colon rectal cancers
  • Screening
  • Canadian Association of Gastroenterology
    Canadian Digestive Foundation. Guidelines on
    Colon Ca Screening. 2004.
  • - Begin screening at age 40 if
  • One 10 relative gt60 yrs has CRC or AP, or gt
    one 20 relative has CRC or AP.
  • Otherwise begin screening at age 50.
  • www.cag-acg.org/www.screencolons.ca

28
Colon rectal cancers
  • Choices of screening methods include1
  • - FOB atleast every 2 years.
  • - Flex sig (w/wo FOB) every 5 yrs.
  • - Double contrast BE every 5 yrs.
  • - Colonoscopy every 10 yrs.
  • Screening method should be determined by its
    availability after discussion b/w pt
    physician
  • 1Leddin et al. Can J Gastroenterol 2004.

29
Colon rectal cancers
  • CRC Screening Practices opinions of primary
    care physicians1.
  • lt 42 of physicians were familiar with
    guidelines.
  • Only 35.6 of physicians offered screening to at
    least 75 of their average risk pts.
  • 1McGregor et al. Preventive Medicine 2004.

30
Colorectal Cancer Screening Percentage of Men
and Women Aged
50 Years and Over Reporting a Screening Fecal
Occult Blood Test
(FOBT Within the Last 2 Years, by Province.
Regions (Within SK, ON), 2003
Based on selected sampling units (regions)
where relevant data were collected 7 of 11
units in Saskatchewan
(63 of SK population) and 14 of
37 units in Ontario (27 of ON population
Toronto not included)
31
Colon rectal cancers
  • Diagnosis
  • Presenting symptoms 1(resectable cancer)
  • - Abdominal pain (44)
  • - Change in bowel habit (43)
  • - Haematochezia or melena (40)
  • - Fe def anemia, w/o other GI symp (11)
  • - Weight loss (6)
  • 1Steinberg et al. Cancer 1986.

32
Colon rectal cancers
  • Diagnosis
  • Presentation of metastatic disease
  • - 15-20 of pts have metastatic disease on
    presentation.
  • - Common sites are LN, liver, lungs and
    peritoneum.

33
Mesenteric Lymphadenopathy in a pt with colon ca
34
Liver mets in a pt with colon cancer
35
Colon rectal cancers
  • Diagnostic procedures
  • - Colonoscopy.
  • - Double contrast barium enema.

36
Colon rectal cancers
  • CASE 2
  • 65 yr old woman, with no significant medical
    history presented to family doctor with h/o
    tiredness and easy fatigue.
  • Blood studies showed evidence of hypochrmic
    microcytic anemia secondary to iron deficiency.
  • What inv will be needed to r/o colorectal ca as
    the cause of problem?

37
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38
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39
Colon rectal cancers
  • Stages of disease at presentation
  • Dukes classification AJCC staging
  • - Localized to mucosa and submucosa (Dukes A or
    TNM stage I) 23.
  • - Extending through muscle layer without LN
    involvement (Dukes B or TNM stage II) 31.
  • - LN involvement (Dukes C or TNM stage III) 26.
  • - Distant mets (Dukes D or TNM stage IV) 20.

40
Colon rectal cancers
  • Pre op staging
  • - Essential workup
  • H P, CT scan of abd pelvis.
  • Chest xray, Serum CEA.
  • - Other tests
  • LFTs, PET scan, EUS.

41
Five yr survival rates for rectal cancer
42
Colon rectal cancers
  • Other prognostic features
  • - Lymphovascular invasion.
  • - Pre op CEA Level.
  • - Presence of microsatellite instability loss
    of the Deleted in Colon Cancer (DCC) gene.

43
Colon rectal cancers
  • Adjuvant therapy for colon cancer
  • Monotherapy. 5 Fluorouracil. (no improvement in
    5 yr survival)1
  • Combination chemo (NSABP C-01 trial)2.
  • - 1166 pts.
  • - Arm A Surgery, Arm B BCG, Arm C MOF
  • - Result Significant improvement in 5 yr OS with
    MOF.
  • 1Buyse et al, JAMA 1988. 2Wolmark et al, JNCI
    1988

44
Colon rectal cancers
  • CASE 3
  • Lady in case 2 underwent colonoscopy followed by
    laparotomy for cecal cancer.
  • She was found out to have a 5 cm mod
    differentiated adenocarcinoma, with one out of 11
    lymph node positive.
  • She is 3 wks out of surgery, and asking for
    further recommendations?

45
Colon rectal cancers
  • Adjuvant therapy for colon cancer
  • (NCCTG trial)1
  • - 5 FU levamisole vs surgery alone.
  • - 40 reduction in risk of recurrence.
  • - OS benefit only in lymph nodes positive
    disease.
  • 1Laurie et al JCO 1989.

46
Colon rectal cancers
  • Adjuvant therapy for colon cancer
  • Trials using combination of 5FU leucovorin.
  • (NSABP C-03, IMPACT report1, NCCTG trial2)
  • - 5 FU leucovorin for at least 6 mo.
  • - Approx 20 reduction in death, 5 benefit in 3
    yr OS.
  • - Benefit limited to node positive disease.
  • 1Impact investigators Lancet 1995.
    2OConnell et al JCO 1997

47
Colon rectal cancers
  • Adjuvant therapy for colon cancer
  • 1990 NIH consensus conference1,
  • Adjuvant 5 FU containing chemotherapy is the
    standard of care for resected node positive
    (stage III) colon cancer.
  • 1NIH consensus conf JAMA 1990.

48
Colon rectal cancers
  • New developments in adjuvant therapy
  • Oxaliplatin containing regimens.
  • (MOSAIC trial)1
  • - 2246 pts.
  • - 5FU and Leucovorin /- Oxaliplatin.
  • - 3 yr DFS 78 vs 73 (plt 0.05).
  • - OS was similar.
  • 1Andre T et al. NEJM 2004.

49
Colon rectal cancers
  • New developments in adjuvant therapy
  • Use of oral Capecitabine
  • (X-ACT study)1
  • - 1987 pts.
  • - 5FU and LV vs oral Capecitabine
  • - Capecitabine was at least as effective as 5FU
    and LV, but better tolerable.
  • 1Scheithauer W et al. Ann Oncol 2003.

50
Colon rectal cancers
  • Current options for adjuvant therapy for colon
    ca
  • Oxaliplatin based regimen.
  • - Oral capecitabine.

51
Colon rectal cancers
  • Adjuvant therapy for Stage II (Duke B) colon
    cancer
  • ASCO 2004 recommendation
  • - Recommend against routine administration of
    chemo in stage II colon ca.
  • - Adjuvant chemo can be considered for
  • lt6 LN in surgical specimen, T4 lesions,
    perforation, poorly differentiated histology.

52
Adjuvant therapy for rectal cancer
53
Colon rectal cancers
  • Adjuvant therapy for rectal ca
  • Pattern of relapse (local)1
  • - T1-2 lt10.
  • - T3N0 15-35
  • - T3-4,N1-2 45-65.
  • 1Willett et al. Cancer 1992.

54
Colon rectal cancers
  • Adjuvant therapy for rectal ca
  • Post op radiation therapy1
  • - Better local control
  • - no survival benefit
  • 1GITSG. NEJM1985.

55
Colon rectal cancers
  • Adjuvant therapy for rectal ca
  • Post op chemo and radiation
  • (GITSG TRIAL)1
  • - 227 Pts.
  • - Obs vs chemo vs xrt vs xrt chemo.
  • - Significant lower local recurrence.
  • - Improvement in OS.
  • 1NEJM 1985.

56
Colon rectal cancers
  • Adjuvant therapy for rectal ca
  • Our Practice at SCC
  • 5FU bolus?5FU cont inf xrt? 5FU bolus
  • (2 mo) (6 wks) (2
    mo)

57
Colon rectal cancers
  • Pre op vs post op chemoxrt for rectal ca1
  • Pts T3, T4 or Node , (n823)
  • Pre op Post op
  • 5 yr OS 76 74 p0.80
  • Local relapse 6 13 p0.006
  • Toxicity 27 40
    p0.001
  • 1Sauer et al NEJM, Oct 2004.

58
Colon rectal cancers
  • Pre op vs post op chemoxrt for rectal ca
  • Critiques
  • Primary end point (OS) was not statistically
    different.
  • Similar rates of sphincter preservation.
  • Possibility of over treating early stage tumors.
  • EUS neither perfectly accurate nor universally
    available.

59
Colon rectal cancers
  • Management of metastatic CRC
  • - Regional treatment.
  • - Systemic chemotherapy.

60
Colon rectal cancers
  • Management of metastatic CRC
  • Regional treatment.
  • - Surgical resections
  • - Local tumor ablation (Ethanol, RFA).
  • - HIA chemo (chemoembolization)

61
Colon rectal cancers
  • Management of metastatic CRC
  • Surgical resections
  • - 5 yr RFS ranges from 24-581.
  • - Only potentially curative option for isolated
    liver mets.
  • - lt10 of pts are surgical candidates.
  • 1Fong et al. Ann Surg 1999.

62
Colon rectal cancers
  • Management of metastatic CRC
  • Systemic chemotherapy.
  • (Meta-analysis of seven randomized trials1)
  • Palliative chemo vs BSC
  • - N 866
  • Median OS 3.7 mo longer for palliative chemo.
  • With use of newer drugs (like avastin) along with
    chemo median overall surv of 20 months has been
    reported2
  • 1Simmonds, PC et al. BMJ 2000.
  • 2H. Hurwitz et al. NEJM 2004.

63
Colon rectal cancers
  • Management of metastatic CRC
  • Infusional vs bolus 5 FU meta- analysis1
  • - RR 22 vs 14
  • - Median OS 12 vs 11mo
  • - Different Toxicity pattern
  • 1Meta-analysis. JCO 1998.

64
Colon rectal cancers
  • Management of metastatic CRC
  • Combination of 5 FU LV with
  • - Irinotecan
  • - Oxaliplatin
  • - Capecitabine
  • - Targeted therapies

65
Colon rectal cancers
  • Management of metastatic CRC
  • 5 FU LV Irinotecan/Oxaliplatin1,2
    vs 5 FU LV
  • RR 40-50 vs 20-30
  • TTP 6.7 mo vs 4.4
    mo
  • Median OS 17.4 mo vs 14.1mo
  • 1Douillard et al. Lancet 2000. 2Saltz et al.
    NEJM 2000.

66
Colon rectal cancers
  • Management of metastatic CRC
  • Targeted therapies Cetuximab (Erbitux)
  • - Human/mouse chimeric monoclonal antibody.
  • - Binds to EGFR expressed on cells.
  • - 80 -90 of CRC expresses EGFR.
  • - In an open label study1 RR 9 in chemo
    refractory pts.
  • - With or without chemotherapies (Trials open).
  • 1Saltz et al. JCO 2004.

67
Colon rectal cancers
  • Management of metastatic CRC
  • Targeted therapies Bevacizumab (Avastin)
  • - Anti-VEGF MoAb.
  • - No molecular markers predict efficacy.
  • - Studied in combination with chemo with some
    success1.
  • - Further trials underway.
  • 1Kabbinavar et al. JCO 2003.

68
Colon rectal cancers
  • Conclusions
  • Colorectal ca is the second common cause of ca
    deaths in males and third common cause of ca
    deaths in females.
  • Risk increases significantly b/w ages of 40 and
    50, in each succeeding decade thereafter.

69
Colon rectal cancers
  • Conclusions
  • 3.Adjuvant 5 FU containing chemotherapy is the
    standard of care for resected node positive
    (stage III) colon cancer.
  • 4. For rectal cancer chemo should be combined
    with XRT in adjuvant setting.

70
Colon rectal cancers
  • Conclusions
  • 5. Treatment of metastatic colon and rectal
    cancer provides good palliation with some
    progression free survival.

71
Colon rectal cancers
  • ..end of beginning.
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