Preventative Oncology

Question 1

What is the metastatic cascade?

Answer 1

• in situ ca
• detachment
• invasion
  
  • migration
  • protease secretion
• intravasation
• detachment from endothelium
• circulation
• reattachment
• extravasation
• invasion
  
  • migration
  • protease secretion
• attachment
• proliferation
• distant mass

Question 2

What are the risk factors of colon and rectal cancer?

Answer 2

• Average risk: age >50
• Increased risk:
  
  • adenomatous polyps/sessile serrated polyps
  • Prior CRC
  • smoking
• Genetics:
  
  • positive family history of CRC
  • Cancer family syndromes
  • Lynch syndrome (aka, hereditary nonpolyposis colorectal cancer; HNPCC): defect in DNA mismatch repair enzymes
  • familial adenomatous polyposis: mutated APC gene
• Inflammatory bowel disease: ulcerative colitis or Crohn’s disease

Question 3

What are the screening modalities for colorectal cancer?

Answer 3

• fecal occult blood test (FOBT)
• Colonoscopy
• Sigmoidoscopy/FOBT
• Stool DNA testing (research)
• Virtual colonoscopy (research)
• Measure carcinogenesis itself (research)

Question 4

What are some modalities for CRC risk reduction?

Answer 4

• Smoking cessation
• Diet and lifestyle
• NSAIDs:
  
  • aspirin (COX1/2): risks outweigh benefits
  • celecoxib (COX2): APC patients
  • Vitamin D3 and Calcium
• Increased screening/early detection

Question 5

What is the role of chemoprevention in colorectal cancer?

Answer 5

• Chemoprevention is the use of specific chemical, compounds to prevent, inhibit or reverse carcinogenesis
• Chemoprevention represents the corner stone of primary prevention
• Challenge: Required to have minimal toxicity because used for long periods in healthy people
• Risk versus benefit

Question 6

What is familial adenomatous polyposis? What is the standard treatment?

Answer 6

• FAP: 100’s of adenomas occur in colon , rectum (<1% colorectal cancers)
  
  • Treatment: colectomy with ileorectal anastomosis
  • Sulindac: NSAID, causes regression adenomas in retained rectal segment.
    
    • 22 FAP pts randomized to placebo versus sulindac for 6 month.
    • 44% decrease in no., 35% in mean diameter from baseline.
  • A subsequent prospective cohort confirmed long term use of sulindac in FAP
    
    • 76% reduction at 1 year, sustained ( 74%) through 63 months of follow up

Question 7

What is the effect of celecoxib in FAD?

Answer 7

• A double blind placebo controlled trial, celecoxib, selective COX-2inhibitor, in FAP, for 6 months
• In the high dose arm, 28% reduction in number of polyps compared to placebo(4.5%)
• FDA approved celecoxib as adjunct therapy FAP, only chemopreventive agent approved to date

Question 8

What is the role of aspirin in prevention of colorectal adenomas?

Answer 8

• Aspirin decreases the risk of adenomas compared to placebo
  
  • 81 mg is the most effective dose, especially in advanced lesions
• USPSTF reccomendation is against using aspirin as prevention, but may be useful for more advanced cases