Colon Cancer EXAM 3 Flashcards
What are the risk factors for colon cancer?
-Western diet: high fat, refined carbs
-Sugar-sweetened beverages
-obesity/inactivity
-alcohol and tobacco
-gut microbiome dysbiosis (difference in risk for cancer, it also affects immune checkpoint inhibitors chemo)
-IBS: UC or Crohn’s disease, also chronic GERD, Barret’s esophagus, chronic colitis
-Genetics: FAP, HNPCC (mutation in DNA mismatch repair -> responds well to immune checkpoint inhibitors)
What are the protective factors of colon cancer?
-Dietary fiber (whole grains)
-Calcium + Vitamin D
-Aspirin/NSAIDs (high dose -> protective against colon cancer)
-Hormone replacement therapy (HRT)
What is the Pathophysiology of Colon cancer?
OBJECTIVE !!!
oncogenic mediators turned ON
-MSI, CIN, BRAF, KRAS, PIK3CA, PTEN
tumor suppressor genes that are turned OFF
-APC, TP53, BAX, SMAD4, TGFBR4
What is the most common presenting sign of colon cancer?
-Blood in the stool
other signs:
-Positive guaiac stool (microscopic blood) - Iron deficiency anemia, some blood loss in the stool
-changes in bowel habits (increase or decrease, constipation)
-N/V, abdominal discomfort
-Elevated carcinoembryonic antigen (CEA), a tumor marker
-Hepatomegaly, jaundice, elevated LFT (metastatic liver disease)
What is the most important treatment option for colon cancer?
Surgery (since it is a solid tumor)
-> for Stage I
Stage II, III, IV need adjuvant therapy
Which drugs are used for Stage II colon cancer?
What is the duration?
Surgery +
-5-fluorouracil (5-FU) + leucovorin for 6 months (in cycles)
OR
Surgery +
-Capecitabine (oral prodrug of 5-FU) for 6 months
Which drugs are used for Stage III colon cancer?
What is the duration?
Surgery+
-FOLFOX
[FOL]: Folinic acid (Leucovorin) infusion
[F]: 5-FU bolus, then 46h infusion
[OX]: Oxalplatin
OR
Surgery +
-CapeOx (3 months are ok for some patients)
Capecitabine and Oxaliplatin
for 3 to 6 months
When do we start screening patients for colon cancer?
at the age of 45
Higher-risk patients:
-FAP (gene mutation): at puberty
-HNPCC: age 2
-IBD: 8 to 15 y after symptoms
What is the preferred screening tool?
Colonoscopy
others:
-Sigmoidoscopy (sigmoid colon)
-fecal blood test (annually)
-stool DNA, RNA test
-Cell-free DNA blood test (cfDNA)
blood and stool tests are less effective in finding precancerous lesions
What is the BBW for Capecitabine and 5-FU?
CYP2C9 inhibition
increase in Warfarin level -> increase in INR
-change to a LMWH or DOAC
What are the unique toxicities of a FOLFOX cycle?
-5-FU: -diarrhea
-Oxaliplatin: neuropathy (gets worse with cold)
A patient was diagnosed with colon cancer. The cancer was removed with surgery. After 7 cycles of adjuvant therapy, he developed a DVT, how should he be treated for the DVT?
DOAC is fine despite the higher risk of GI bleeding (bc the cancer was removed)
-LMWH (Lovenox) would also be fine but less preferable bc of the injections
Which genetic testing is required for EGFR-monoclonal antibodies Cetuximab and Panitumumab?
k-RAS and N-RAS
they have to be wild-type for the drugs to be effective
What is Microsatellite Instability (MSI)?
often duplication mutations that accumulate in a cell with less mismatch repair (mismatch repair deficiency)
Why are MSI-high tumors less susceptible to 5-FU?
because they cant cause cyclic arrest and apoptosis when treated with 5-FU (due to missing mismatch repair enzymes)
5-FU causes false base pairing, then cyclic arrest and apoptosis in cancer cells
Which drugs are effective against MSI-high tumor cells?
immune checkpoint inhibitors
less mismatch repair leads to more mutations -> more non-self antigens that can be detected by the immune system
Immunotherapy works well in which type of cancer?
-Melanoma (UV-light)
-Lung cancer (smoking)
-Renal cell carcinoma (smoking)
-Bladder cancer (smoking)
-MSI-high/dMMR colon cancer
-rich in mutations: inherited or due to carcinogens
How are rectal and colon cancer different?
differ in treatment:
in rectal:
-neoadjuvant chemoradiation +/- surgery + chemo
in the colon: No role for radiation !!!
both are adenocarcinoma
What is the benefit of radiation in rectal cancer?
-lower rates of required colostomy in patients
the rectum is close to the end of the GI pipe, causing less damage to other parts of the colon?
