COLON CANCER

Presenter: Dr. Harrison R. Chuwa, Click to edit Master subtitle style M.Med Clinical Oncology Resident Special thanks to Dr. Maunda, Consultant Oncologist

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Key Issues/Lay-out

Introduction Anatomy Epidemiology Natural history Pathology Mode of Spread Clinical Presentation Diagnostic Work-up

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Introduction

Is the 2nd leading

cause of cancer death in the western world.

Develops over

a number of years & normally begins as a polyp. 4/13/12

Anatomy

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Arterial Supply

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Venous Supply

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Lymphatic Drainage

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Cross-section of Colon

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Epidemiology

Approximately 6% of individuals in the US will develop a cancer of the colon or rectum within their lifetime Male: female = 1.37:1 The incidence in developing countries is increasing At ORCI, 60 cases (0.55%) were Rxed for colon ca from 2008 to 2010. 70% male
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Etiology & Risk Factors

Aging Hereditary Risk Factor Environmental Life style and Dietary Factor Inflammatory Bowel Diseases

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Genetic Susceptibility Syndromes

Familial Adenomatous Polyposis (FAP)- APC Hereditary Nonpolyposis Colorectal Cancer (HNPCC)- hMLH1/hMSH2 Turcot syndrome Peutz-Jeghers syndrome-STK11 MUTYH-associated polyposis
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Colon Cancer
Sporad ic (average risk) (65% 85%) Fami ly histo ry (10% 30%)

Ra re syndrom es (<0.1 %) Familial adenomatous polyposis (FAP) (1%) 4/13/12

Hereditary nonpolyposis colorectal cancer (HNPCC) (5%)

Pathogenesis of Colon Cancer

i. Tumour suppressor gene mutations

APC gene defect DCC p53 K-ras : Proto-oncogene

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ii. Proto-oncogene amplification

Natural History of Colon Cancer

Loss of APC Activati Deletio Loss on n of of of K-ras 18q P53
Early adeno ma Intermediat e adeno ma Late adeno ma

Other alteratio ns
Metast asis

Normal epithel ium

Hyperprolifera tive epitheliu m

Carcino ma

4/13/12 from Fearon ER. Cell 61:759, Adapted

1990

Pathology

Macroscopically

ulcerative, polypoid, annular, or infiltrative

Microscopically

Adenocarcinoma >95% Carcinoid tumours Gastrointestinal stromal tumours (GITS)

Lymphomas 4/13/12

Distribution of Cancer along the Colon

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Mode of Spread

Direct extension Peritoneal seeding Lymphatic drainage Hematogeneous

Note: skip metastasis (retrograde spread) occurs in 1-3% of node positive pts
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Clinical Presentation

Early sign

A change in bowel habits fatigue Colon obstruction Ribbon-like stool Hematochezia Cachexia (wasting syndrome)

Late sign

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Diagnostic Work-up
H&P

Colonoscopy or sigmoidoscopy

Bx Imaging
-

Ba enema CXR US CT scan MRI PET scan

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Blood testing

Staging
1. Dukes classication for staging in colorectal cancer:

Stage A: Tumour confined w/in bowel wall -Prevalence at Dx: 10% - 5yr survival rate: > 90%

Stage B: Extension through bowel wall Prevalence at Dx: 35%

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TNM Staging

Stage O (in situ) The tumor is small and limited to The 4/13/12 mucosa

Stage I The tumor has spread to the muscularis, but not to the outer wall

Stage II The tumor has spread to the outer wall of the colon, but not to

Stage III The tumor has spread into nearby lymph nodes, but not to other

Stage IV The tumor has spread to other organs such as the liver,

Management

Surgery Chemotherapy Targeted therapy

Sometimes used in combination with standard chemotherapy

Radiation

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Treatment by Stage

Stage O:

Local surgery (polypectomy or removal of larger tumors) Surgery followed by observation Surgery followed by chemotherapy or observation

Stage I:

Stage II:

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Stage III:

Surgery

Polypectomy Laser or diathermy therapy Radical surgery

Total colectomy Transverse colectomy Rt hemicolectomy Lt hemicolectomy

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Lymphadenectomy

chemotherapy

Neoadjuvant down staging

1st line 1st line 2nd line + targeted therapy

Adjuvant micro remnants

Palliative metastatic disease

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Chemotherapy cont...

1st line regimen

5-FU +LV 5-FU + LV + OX (FOLFOX 4/6) 5-FU + LV + Irinotecan (FOLFIRI) Irinotecan + 5-FU + LV (IFL) Capecitabine 5-FU + LV+ OX + Irinotecan (FOLFOXIRI) FOLFOX + bevacizumab/cetuximab

2nd line regimen

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Radiation

No clear evidence of survival benefit with RT Mainly for stage 4 tumours fixed to abdominal lining Adjuvant EBR +/- chemo i.e. Adjuvant chemoradiation Brachytherapy has no role in colon ca
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XRT also has a role for metastatic

XRT Techniques

Field should include margin around tumor bed, LNs and residual disease based on pre-op imaging and/or surgical clips. 3D simulation to define the tumour volume Bladder distension & prone position Dose 50.4Gy/1.8Gy/28# OR 46Gy/2Gy/23#

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Follow-up

Follow-up visits Serial (CEA) measurements are recommended Colonoscopy one year after removal of colon cancer Surveillance colonoscopy every three to five years to identify new polyps and/or cancers
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Prognostic factors
-

Stage and grade of disease.

- Pre op CEA Level. - Presence of microsatellite instability & loss of DCC gene.

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Screening

FOBT Colonoscopy Sigmoidoscopy Ba enema

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THANK YOU FOR LISTENING

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