Lecture 14 - Colorectal Cancer Flashcards
(55 cards)
Colorectal is ____ most common in incidence and death rates
3rd
Epidemiology
incidence is increased in industrialized nations with males having slightly increased incidence
Risk factors
age - increases starting after age 40 and is greater after 50 years of age; family history of colon cancer
dietary factors: high fat, low fiber, reduced folate, reduced calcium; polyps; smoking, alcohol, obesity; ulcerative colitis or crohn’s disease (chronic inflammation)
hereditary syndromes: familial adenomatous polyposis (FAP), autosomal dominant disorder, mutation of adenomatous polyposis coli gene on chromosome 5, hereditary nonpolyposis colorectal cancer
development of 100’s-1000’s of adenomatous polyps (nearly 100% lifetime risk of developing
Pathophysiology
malignant polyps tend to grow from inner basement membrane of bowel wall outward into mucosa, submucosa, muscularis, and serosa
metastatic spread via lymphatic and hematogenous routes to lymph nodes, lungs, liver, and bone
>95% are adenocarcinomas
Presentation
may be asymptomatic; rectal bleeding, anemia, N/V, change in bowel habits
some present with metastatic disease: jaundice, hepatomegaly, weight loss
Additional testing-work up
defective DNA mismatch repair (dMMR)
test for microsatellite instabilit (MSI) or test for loss of genes involved in DNA MMR
Early stage disease and MMR
dMMR or MSI-H tumor predicts decreased benefit from adjuvant 5-FU based therapy for stage II disease: chemo won’t work!!
stage III patients with dMMR or MSI-H disease can benefit from adjuvant 5-FU: chemo will be of benefit!
All pts with colon cancer diagnosis should be tested for
mismatch repair or microsatellite instability
Treatment options
surgery: early stage disease
radiation therapy: well established for rectal cancer, but more controversial in colon cancer; can be used to alleviate pain and decrease bleeding
chemo
Treatment goals for stage I,II, and III
considered potentially curable; achieve remission and avoid disease recurrence
Treatment goals for stage IV
incurable/palliation
decrease sx and avoid disease related complications
Localized therapy (stage I and II)
surgery alone is definitive therapy: partial or total colectomy + lymph nodes
no proven benefit with chemo in stage II; guidelines recommend against adjuvant chemo in stage II, can recommend if pt is high risk
if MSI-H or dMMR, then will NOT benefit from chemo in stage II
Stage II disease (chemo)
FOLFOX: reasonable for high risk or intermediate risk stage II pts - 5-FU, leucovorin, oxaliplatin
CapeOX also an option - capecitabine, oxaliplatin
Stage III disease
surgery including regional lymph node removal
chemo indicated for this stage
Stage III disease: chemotherapy
principles of adjuvant therapy: capecitabine appears to be = to bolus 5-FU/leucovorin in stage III pts
bevacizumab, cetuximab, panitumumab, and irinotecan DO NOT play a role in this setting
FOLFOX
FOLFOX = 5-FU, oxaliplatin, leucovorin
decrease in recurrence, increased 5-year disease free survival
toxicities with oxaliplatin (paresthesia, neutropenia, GI)
Adjuvant chemo options
mFOLFOX6: oxaliplatin, leucovorin, 5-F; pts take chemo pump home
CapeOX: oxaliplatin, capecitabine
Current recommendations by NCCN
low risk: CapeOX for 3 mo or FOLFOX for 3-6 mo
high risk: CapeOX for 3-6 mo or FOLFOX for 6 mo
IDEA trial conclusions
risk-based approach
with CapeOX: 3 mo as effective as 6 mo, especially in low-risk pts
with FOLFOX: 6 mo was more effective than 3 mo, especially in high risk pts
How to implement in practice: stage III colon cancer
low risk: CapeOX for 3 mo
high risk: FOLFOX for 6 mo
FOLFOX and CapeOX considerations
FOLFOX: requires port, 2-day pump, more infusions overall, increased myelosuppression and mouth sores; repeated every 2 weeks
CapeOX: port not required (oral agent), less infusions overall (not continuous), increased hand foot syndrome and diarrhea; capecitabine requires renal dose adjustments, adherence, copay, look into drug/drug interactions; repeat every 3 weeks
Metastatic disease colon cancer
chemo is mainstay of therapy
survival has increased from 12 mo with 5-FU monotherapy to ~2 years with the addition of irinotecan, oxaliplatin, and newer biologics
surgery could play a role in isolated disease
radiation therapy for palliation of sx
Which chemo regimen to use for mestatic disease
pt performance status
co-morbidities that determine therapy: neuropathy, UGT1A1 deficiency
Advanced disease and MMR
predict benefit to PD-L1 inhibitors: pembrolizumab and nivolumab shown benefit in metastatic setting, both approved for pts unresectable or metastatic, with dMMR or MSI-H tumors after FOLFOX and FOLFIRI
