Colon Flashcards
Age to start screening for regular risk, 1st degree relative with CRC, HNPCC, and FAP
Regular risk- recently changed to 45 from 50
1st degree relative- 40 or 10 years younger than youngest 1st degree relative with CRC
HNPCC- 20-25
FAP- as early as 10 years old
HNPCC (Lynch syndrome) mutations
Mutation in DNA mismatch repair enzyme (MSH-2, MLH-1, PMS-2, MSH-6, and EPCAM)
HNPCC (Lynch syndrome) cancers
Colorectal Ovarian Endometrial Pancreatic Biliary Gastric/small bowel GU
Familial adenomatous polyposis mutation
Mutation in APC gene
Stage I definition and treatment
Stage I = T1 (invades submucosa) or T2 (invades muscularis propria), N0 M0
Treatment is surgery
Stage II definition
T3-T4b N0 M0
Invades subserosa or into pericolorectal tissues
Stage II higher risk features
T4 disease (invades visceral peritoneum or invades/adheres to adjacent organs)
+LVI, +PNI
Clinical obstruction or perforation
<12 nodes sampled
Stage II adjuvant treatment indications and options
High risk = T4, perforation/obstruction, <12 nodes removed, +LVI/PNI
Adjuvant chemo usually given for BRAF mutant
Low risk patients generally observed
MSI-H/dMMR tumors should be observed
Adjuvant options:
3 months CAPEOX
6 months capecitabine or 5-FU or FOLFOX
*No benefit to oxaliplatin if > 70yrs
Stage III definition
Node positive disease
N1 = 1-3 nodes N2 = 4+ nodes
Stage III adjuvant treatment indications and options
All stage III should get adjuvant
CapeOx or FOLFOX x 3-6 months
If T4 and/or N2, give 6 months
If giving 3 months, use CapeOx
If > 70 years, no proven benefit for addition of oxali to cape/5-FU
*Don’t substitute irinotecan for oxali
1st line metastatic tx for left sided RAS/RAF WT
FOLFOX/IRI + cetuximab/panitumumab
*Don’t use anti-EGFR if potentially resectable
1st line metastatic tx for right sided RAS/RAF WT
FOLFOX/IRI + bev
1st line metastatic tx for any side, RAS mutated
FOLFOX/IRI + bev
Indication for anti-EGFR antibody tx
Only patients that are WT for KRAS exons 2,3,4 and NRAS exons 2,3,4
BRAF V600E unlikely to respond even if RAS WT
1st line metastatic MSI-H/dMMR
Pembro
1st line metastatic BRAF mutated
FOLFOXIRI + bev
2nd line metastatic BRAF V600E mutated
Encorafenib + cetuximab
Same median OS as encorafenib + binimetinib + cetuximab
2nd line metastatic treatment
Switch FOLFOX FOLFIRI
Continue bev
Switch anti-EGFR to bev
Can consider anti-EGFR +/- irinotecan for right sided RAS WT
Treatment of metastatic disease in patients treated with fluoropyrimide, oxali, iri, VEGF, and EGFR (if RAS WT)
Regorafenib
Trifluridine-tipiracil (TAS 102)
Treatment options for metastatic Her2+ disease
Trastuzumab + pertuzumab
Trastuzumab + lapatinib
Trastuzumab deruxtecan
Only patients with RAS WT/Her2+ seem to respond to Her2 targeted therapy
Generally consider 2nd line or later
5-FU/capecitabine AEs
Diarrhea Myelosuppression Mucositis Hyperbili Coronary vasospasm
*If severe diarrhea, myelosuppression, mucositis, consider DPD deficiency
Adjust 5-FU for hepatic dysfunction
Adjust capecitabine for renal and hepatic dysfunction
Irinotecan AEs
Cholinergic toxicity- acute onset salivation, diarrhea, diaphoresis. Can treat with atropine
Myelosuppression
Diarrhea
Alopecia
- Reduce dose in UGT1A1*28 homozygous or Gilbert’s
- Avoid if bilirubin > 2
Oxaliplatin AEs
Peripheral neuropathy/cold sensitivity
Diarrhea
Myelosuppression
Elevated LFTs
Reduce dose for renal dysfunction (Cr Cl < 30)
Cetuximab/panitumumab AEs
Hypersensitivity reactions (alpha gal)
Acneiform skin rash
Diarrhea
