Colon cancer Flashcards
Treatment of Stage I (T1-2, N0, M0) colon cancer
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
Microsatellite instablity (MSI-H)
No benefit of adjuvant chemo in stage II CRC
Implications of microsatellite stability in CRC
- 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
Treatment of Stage III CRC
- 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)
Left or right sided CRC - which agent
Left - EGFR (osimetinib, gemfitinib)
Right - Bevacizumab (VEGF)
Colorectal Ca - screening guidelines
Colonic polyps surveillance
CRC Screening
- general population
- high risk, inc what defines high risk
Treatment of Colon Cancer
Fluorouracil (5FU) Drug info
Most common extracolonic manifestation of Lynch syndrome
Endometrial cancer!
Recommended Screening in Lynch Syndrome
Colorectal Cancer: Risk Factors
Management of Early Stage CRC
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)
Screening in FAP
FAP
Indications for Colectomy in FAP
Familial CRC syndromes - comparison
Surveillance after early stage CRC
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.
Bevacizumab
-?requirements for use
-mechanism
-side effects
Cetuximab
-requirements for use
-mechanism
-side effects
Management of Stage 3 CRC
Lynch Syndrome Adenomas vs Sporadic Adenomas
Treatment of Metastatic CRC
Aspirin and CRC risk
What is the most common cause of inherited colorectal cancer? Is it associated with anything else?
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
What is the prognosis like in oesophageal cancer? Risk factors? Is chemoradiotherapy of benefit?
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
