Colon cancer

Question 1

Treatment of Stage I (T1-2, N0, M0) colon cancer

Answer 1

Surgery then surveillance

Adjuvant therapy

• Start 6-8 weeks post operatively
• in high risk stage 2 or stage 3/4 (for micro-metastatic disease)
• FOLFOX (5FU with oxaliplatin) CAPOX (capecitabine + oxaliplatin)
• MOSAIC trial - better to add oxaliplatin
• IDEA trial - 3 months not inferior to 6m CAPOX (but not FOLFOX), high risk groups 6 months

Question 2

Microsatellite instablity (MSI-H)

Answer 2

No benefit of adjuvant chemo in stage II CRC

Question 3

Implications of microsatellite stability in CRC

Answer 3

• Most colon cancers are microsatellite stable (MSS)
• MSI is measured best by checking for the 4 MMR genes:
  
  • MLH 1, MSH2, MSH 6, PMS2
• A deficiency (dMMR) in 1 or more of these genes makes a tumour have microsatellite instability in it (i.e MSI-H = HIGH)
• MSI-H is seen in Lynch syndrome (HNPCC) but it is commonly seen in sporadic colon cancer as well due to MLH1 hypermethylation
• Having a MSI-H Stage II tumour confers LACK OF BENEFIT with adjuvant 5FU/capecitabine chemotherapy

Question 4

Treatment of Stage III CRC

Answer 4

• Standard adjuvant chemotherapy: 6 months of FOLFOX
• Single agent 5FU should not be used in stage II dMMR CRC
• Low risk stage III bowel cancer is 3 months of CAPOX, high risk patients 6 months oxaliplatin based chemo (SCOT trial and IDEA analysis)

FOLFOX (5FU with oxaliplatin)

CAPOX (capecitabine + oxaliplatin)

Question 5

Left or right sided CRC - which agent

Answer 5

Left - EGFR (osimetinib, gemfitinib)
Right - Bevacizumab (VEGF)

Question 6

Colorectal Ca - screening guidelines

Answer 6

Question 7

Colonic polyps surveillance

Answer 7

Question 8

CRC Screening

• general population
• high risk, inc what defines high risk

Answer 8

Question 9

Treatment of Colon Cancer

Answer 9

Question 10

Fluorouracil (5FU) Drug info

Answer 10

Question 11

Most common extracolonic manifestation of Lynch syndrome

Answer 11

Endometrial cancer!

Question 12

Recommended Screening in Lynch Syndrome

Answer 12

Question 13

Colorectal Cancer: Risk Factors

Answer 13

Question 14

Management of Early Stage CRC

Answer 14

Adjuvant chemotherapy in stage II CRC - limited benefit

• Consider if high risk:
  
  • T4 Primary tumour
  • Perforation/obstruction
  • lympho-vascular and perineural invasion
  • poorly differentiated tumou
  • inadequatelt sampled nodes (<12 LN)
  • High pre op CEA?
• Single agent fluoropyrimidine (5FU or capecitabine)

Question 16

Screening in FAP

Answer 16

Question 17

FAP

Answer 17

Question 18

Indications for Colectomy in FAP

Answer 18

Question 19

Familial CRC syndromes - comparison

Answer 19

Question 21

Surveillance after early stage CRC

Answer 21

ASCO guidelines

Main purpose: early detection of asymptomatic recurrence to increase the likelihood of curative surgical resection

• Several meta-analyses support modest but significant survival benefit from an intensive surveillance after resection of CRC
• Those who haven’t had a full colonoscopy at diagnosis require one at the conclusion of treatment –> Then at 3 years, then 5 yearly
• Physical exam, with CEA (expressed in 70% of CRC) 3 monthly for 3 years, then 6 monthly
• CT CAP annually for 3 years.

Question 22

Bevacizumab
-?requirements for use
-mechanism
-side effects
Cetuximab
-requirements for use
-mechanism
-side effects

Answer 22

Question 24

Management of Stage 3 CRC

Answer 24

Question 25

Lynch Syndrome Adenomas vs Sporadic Adenomas

Answer 25

Question 26

Treatment of Metastatic CRC

Answer 26

Question 27

Aspirin and CRC risk

Answer 27

Question 28

What is the most common cause of inherited colorectal cancer? Is it associated with anything else?

Answer 28

**HNPCC** * **Autosomal dominant,** several genes, most families have unique mutations * MMR in **MLH1,** MLH3, **MSH2** (most common), **MSH6, PMS1**, PMS2 (absence on immunohistochemistry staining = diagnosis) * Loss of expression of MSH 2nd deletion in EPCAM * DNA mismatches occur in regions of repetitive nucleotide sequences called microsatellites * **Lifetime 70% risk of CRC, usually younger/right sided** * 7-10% have \>1 cancer at dx, 20-60% develop metachronous CRC after initial non-total colectomy **3% of all newly diagnosed CRC** **Associated with** * Endometrial (most common) ~40% * Ovarian ~10% * Stomach * Small bowel * Hepatobiliary * TCC of renal pelvis and ureter * Glioma (Turcot syndrome) * Sebaceous neoplasm Amsterdam criteria * **3-2-1 rule. 3 affected, 2 generations, 1 under 50**

Question 29

What is the prognosis like in oesophageal cancer? Risk factors? Is chemoradiotherapy of benefit?

Answer 29

**Risk factors** * **SCC:** chronic irritation, low SES, Plummer Vinson Syndrome, non-epidermolytic palmoplantar keratoderma (95% SCC risk by 70yrs) * **Adenoca: GORD, obesity, Barrett's** * Both: smoking, RTx **Poor Prognosis overall** * depends on stage, like always * 10% survival at 5yrs post diagnosis * Only 45% totally surgically resectable. 20% survival at 5yrs if they survive the resection * Oesophagectomy associated with significant morbidity/mortality (5-12%) **Chemo** * Mass decrease in 15-25% given single; 30-60% given combo including **cisplatin** * Increased benefit for **trastuzumab (herceptin) in the 15% of adenocarcinomas expressing HER2/neu gene** * **Chemoradiotherapy of benefit, especially neoadjuvant**