Colorectal Cancer - Block 4 Flashcards
What are the RF of CRC?
- > 50YO
- Family hx
- Colon polyps
- T2DM
- IBD
- Genetic predisposion
- Hx of other cancers
What is the hereditary autosomal dominant predisposition of CRC?
- Familial adenomatous polyposis (FAP)
- Lynch syndrome
When should you screen for FAP?
- Starts between 10-11 YO
- Total colectomy when polyps are found
What are the risks of having lynch syndrome?
- Increased risk for endometrial, overain, stomach, and colon
Gene that codes for lynch syndrome?
Germline mutation in MMR gene
When is lynch syndrome most suspected?
- Early age of diagnosis or family hx
- Multiple generations in a family can be affected
What lifestyle factors increase the risk of CRC?
- Western diet
- Alcohol
- Smoking
- Sedentary lifestyle
- Obesity/overweight
What lifestyle factors decrease the risk of CRC?
- NSAIDs/ASA
- Calcium
- Vit D
- Postmenopausal hormone use
Who should be screened and what does screen look like? Which does not require bowel prep?
Starting at age 50:
* Colonoscopy every 10 yrs
* Fecal occuly blood test (FOBT): yearly
* Fecal immunochemical test (FIT-No bowel prep): yearly
What are the presentations of CRC?
- Change in bowel habits
- Rectal bleeding
- Abdominal pain
- Weight loss
Wha is the tumor marker used for CRC?
CEA (Carcinoembryonic antigen): oncofetal protein expressed in embryonic development
* Elevation -> metastatic
* However, not all CRC produce CEA therefore it is not used for screen only treatment
How many nodes should be biopsied for CRC diagnosis?
12 minimum
Differentiate the gene mutations tested for CRC diagnosis?
KRAS/NRAS: wild type = normal
* Mutated is unresponsive to EGFR inhibitors
BRAF: EGFR inhibitors can still be used, but it provided the worst prognosis
How do the stages of CRC differ in terms of curability?
Stage 1-3: potentially curable
Stage 4: incurable unless metastases is resectable
Tx options for CRC?
- Surgery
- Chemotherapy
- Radiation
What is the tx option for Stage 1 CRC?
- Watch and wait based on polyptype
- Surgery (90% cure rate as monotx)
- Adjuvant chemotherapy NOT indicated
How often should you follow up for stage 1?
Colonoscopy 1 yr after tx
* Advanced adenoma: repeat colonoscopy in 1 yr
* Not advanced adenoma: repeat colonoscopy in 3 yrs, then 5 yrs
What are the recommended tx options for Stage 2-3?
Surgery and neoadjuvant chemotherapy:
Stage 2: may not require adjuvant chemo
Stage 3: Adjuvant starts right after surgery for 3-6 months
What is the preferred adjuvant chemo for Stage 3?
FOLFOX
What are the components of FOLFOX? How long is the course?
- Oxaliplatin on day 1
- Leucovorin on day 1
- 5-FU on day 1 after leucovorin
Repeat every 2 weeks for 24 weeks
What are the components of CapeOx? How long is a course?
- Oxaliplatin on day 1
- Capecitabine BID on days 1-14
Cycle lasts 3 wks for 24 wks
What is the tx plan for capecitabine monotherapy for adjuvant stage 3 tx?
Capecitabine BID on days 1-14
Cycle lasts 14 days and repeats every 3 wks for 24 wks
What are the tx options for metastatic/stage 4?
- Surgery then adjuvant chemo
Describe the progression of resectable metastases?
Mets to the liver are most common then progress to the lungs and bones
* May require to neoadjuvant chemo
What are the chemo regimens for Stage 4?
FOLFIRI and FOLFOX
Follow-up for Stage 4?
After every 2 months of tx reassess for possible resection
* All metastatic tumors should be genotypes for RAS and BRAS mutations
What are the components of FOLFOX-B?
5-FU, leucovorin, oxaliplatin, bevacizumab
What are the components of FOLFIRI?
5-FU, leucovorin, irinotecan
What are the components of FOLFIRI-B?
5-FU, leucovorin, irinotecan, bevacizumab
What are the components of FOLFOXIRI?
5-FU, leucovorin, oxaliplatin and irinotecan
Why would FOLFIRI be preferred over FOLFOX?
FOLFOX has more PN due to oxaliplatin
MOA of bevacizumab?
VEGF inhibitors and homanized monoclonal antibodies
ADR of bevacizumab?
HTN, bleeding, VTE, proteinuria
* Interferes with wound healing
When should not bevacizumab be administered?
Surgery should not occur within 6 wks of last dose
* Don’t re-start for 6-8 wks after surgery due to increased bleeding risk and complications with wound healing
What are examples of EGFR inhibitors?
Cetuximab/Panitumumab
Indications for Cetuximab/panitumumab?
Wild-type RAS, wild-type BRAF tumors, left sided tumors
* DON’T use in patients with mutated RAS and BRAF
ADR of Cetuximab/panitumumab?
Infusion rx, rash, increased risk for VTE
* No benefit combining biologics
What are the tx options that are only used because of first line tx failure?
- Ramucirumab
- Regorafenib
- Afibercept
- Immunotherapy
What are the tx options for hepatic mets?
Hepatic artery infusion (HAI):
* Chemo infused directly into liver
* Limits tox while being high dose
Hepatic transarterial chemoembolization
What needs to be considered prior to irinotecan dosing?
Test for genetic variants in UGT1A1
* Reduce dose of irinotecan if homozygous for UGT1A1*28
How is rectal cancer treated?
May use radiation