Colorectal cancer Flashcards
relevance of RAS in CRC
Benefit from MoAbs targeting the EGFR is restricted to patients whose tumors do not contain mutated RAS genes (eg RAS wild type).
microsatelite stability and relationship to prognosis
MSS tumors are characterized by changes in chromosomal copy number and show worse prognosis, on the contrary the less common MSI tumors (about 15%) are characterized by the accumulation of a high number of mutations and show predominance in females, proximal colonic localization, poor differentiation, tumor-infiltrating lymphocytes and a better prognosis.
relevance of microsatelite stability and treatment
Benefit from PD-1 inhibitors is limited to tumors with MSI-H/dMMR.
significance of Ki-67
Prognostic marker in breast cancer. Measure of tumor cell proliferation.
Ki-67 interpretation
A result of less than 10% is considered low, 10-20% borderline, and high if more than 20%.
Higher the score = more likely to be aggressive.
her2 positive treatment
Trastuzumab + pertuzumab + taxane (docetaxel or paclitaxel)
trastuzumab trade name
Herceptin
xeleri is
capecitabine plus irinotecan
doxorubicin trade name
adriamycin
biomarkers to test for in CRC
KRAS + BRAF + MMR/MSS status
relevance of BRAF in CRC
- Negative prognosticator
Moreover, BRAF V600E mutations also appear to predict response to EGFR-targeted agents is unlikely in patients whose tumors harbor BRAF V600E mutations, even if they are RAS wild type.
BRAF pathway?
component of the RAS-RAF-MAPK signaling pathway.
why trend CEA
A rise in CEA predicts recurrence, so if you see a rise, you should order imaging earlier.
downside to capeox
- wide variability in pricing
- some variation in response based off genetic profile (asians tend to tolerate fluoropyrimidines better)
FOLFOX is
Folinic acid “FOL”, Fluorouracil “F”, and Oxaliplatin “OX”.
bevacizumab/avastin SE profile
epistaxis, headache, hypertension, rhinitis, proteinuria,
taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, and
exfoliative dermatitis
cetuximab indication
KRAS + BRAF wild type and left sided
general SE of pembro and other checkpoint inhibitors
most people do well, but they can do anything
why do you give leucovorin with FOLFOX
It enhances the activity of 5-FU. It is folinic acid.
Common SE’s of 5-Fu
myelosuppression + mucositis + palmar/plantar erythrodysesthesia + diarrhea + cardiotoxicity + neurotoxicity
term for effect on cold liquids of oxaliplatin
cold hypersensitivity
RF’s
(think of things that are going to cause inflammation in colon)
IBD, drinking, smoking, obesity
Consumption of red and processed meats
Diabetes
Screening colonoscopy recommendation
average risk = 50
IF FH – 10 years prior to age of earliest occurrence or beginning at age 40
clinical workup recommended for patients who develop CRC before age 50
MSI testing, (test for mismatch repair if MSI high)
Until what age is screening recommended
Up to 10 years prior to a patients life expectancy
Interventions to reduce risk of CRC and protective factors
Increase physical activity polypectomy Reduce fat and meat intake Daily use of ASA + NSAIDs Metformin possibly
sensitive and specific markers of adenocarcinoma
CK20 + CDX2
Signs/symptoms
Change in bowel habits (74 percent), rectal bleeding in combination with change in bowel habits, (51 percent of all cancers and 71 percent of those presenting with rectal bleeding), rectal mass (24.5 percent) or abdominal mass (12.5 percent), iron deficiency anemia (9.6 percent)
prognostic significance of MSI
positive prognosticator
Management of oligometastatic disease
Metastastectomy, particularly if liver mets, (can lead to long term survival)
Name some of the common chemo regimens
CapeOX
FOLFOX
FOLFIRI
Targeted agents approved for CRC
(VEGF TKI) Bevacizumab (EGFR TKI's) Cetuximab Regorafenib Panitumumab
Panitumumab mechanism
EGFR TKI
Prior to use of cetuximab or panitumumab what testing must be performed?
Test for mutations in KRAS and NRAS that confer resistance to anti-EGFR therapy
Polyp with the greatest malignant potential
Serrated
Higher villous histology
surgical management of colon cancer
Hemicolectomy
IF tumor in distal one third of rectum and invades anal sphincter –> abdominoperineal resection (APR), leading to permanent colostomy.
IF tumor in proximal two thirds of rectum –> low anterior resection
Regimen that is standard of care for neoadjuvant and adjuvant treatment of CRC
FOLFOX or CapeOX
Role for targeted agents for CRC
Reserved for advanced-stage metastatic disease
General approach to locoregionally advanced CRC
IF resectable –> surgery followed by adjuvant chemo
IF nonresectable –> chemo, re-evaluate for surgery
Use of cetuximab or panitumumab
Addition to FOLFIRI or FOLFOX in metastatic CRC in patients with KRAS and NRAS wild-type tumors
Stage I definition
tumor restricted to muscularis propria + no nodal or distal mets
Stage II definition
Muscle invasive + node negative
Stage III definition
nodal mets
Clinical significance of MMR testing
IF positive, no benefit from 5-Fu
Initial workup
Detailed family history CMP CT chest + abdomen/pelvis IF suspicious but not well defined lesion on CT → liver MRI (or intraoperative biopsy) Pretreatment CEA MMR/MSI testing
Initial workup
Detailed family history CMP CT chest + abdomen/pelvis IF suspicious but not well defined lesion on CT → liver MRI (or intraoperative biopsy) Pretreatment CEA MMR/MSI testing
Molecular testing needed if metastatic
RAS, BRAF, HER2
Trends in incidence of CRC
Overall incidence and mortality are decreasing but incidence is increasing among younger people
Explanation for increasing incidence of CRC in young people
Unknown but thought to be genetically dissimilar, so may need different treatment strategies
genetic syndromes associated with CRC
Lynch syndrome
FAP
MMR vs. MSI
MMR positive means patient has a germline mutation in mismatch repair protein. Microsatelite instability results from MMR mutation.
Classification of mets in CRC (meaning of M1A and M1B)
M1A = Mets limited to one site/solid organ M1B = Mets to multiple sites
What are tumor deposits?
Discrete tumor deposits in the pericolic or perirectal fat without lymph node tissue but being within lymphatic drainage system. Associated with reductions in OS and PFS.
Management of single malignant polyp
IF negative margins + no high risk features (grade 1 or 2 and no angiolymphatic invasion), no further management
CT contrast management for CRC evaluation
Should always be with PO + IV contrast.
Management of patient with contrast contraindication
MRI with contrast
Stage at which adjuvant chemotherapy is indicated
Stage II with high risk features
High risk features of stage II CRC warranting chemo
- T4 tumors
- poorly differentiated histology
- lymphovascular invasion
- bowel obstruction
- lesion with localized perforation
- close, indeterminate, or positive margins
- inadequately sampled nodes (less than 12)
preferred adjuvant treatment options for Stage III and duration of treatment
3 months of CAPEOX
OR
3-6 months of FOLFOX
Timing of adjuvant therapy
ASAP. There is a survival benefit to starting chemo ASAP
Cause of death in most people who die of CRC
Metastatic liver disease
Term for tumor in the peritoneum
Peritoneal carcinomatosis
Tumor marker in colorectal cancer
CEA
term for pain, swelling, erythema associated with 5-Fu
palmar/plantar erythrodysesthesia
subset of tumors that have shown benefit from CPIs
mismatch repair deficient
Contraindications to surgical resection of hepatic mets
1) Tumor involvement of common artery or portal vein or CBD 2) more than 70% liver involvement 3) more than 6 involved segments 4) involvement of all 3 hepatic veins
Difference in SE profile between infusional and bolus 5-FU
Cardiotoxicity more commonly found with infusional 5-FU compared to bolus (causes vasospasm)
Management of coronary vasospasm from infusional 5-FU
Drop infusional, give bolus
Significance of MSI-H disease in stage II colon
positive prognosticator, don’t need adjuvant treatment
alternative term for lynch syndrome
Hereditary nonpolyposis colorectal cancer (refers to patients who fulfill amsterdam criteria)
N1 disease in colon cancer
1-3 nodes involved
Adjuvant for elderly for stage III
5-FU alone without oxaliplatin
Likely SOC for early stage dMMR
neoadjuvant IPI/nivo
When is 3 month capeox preferred?
Low risk Stage III it is preferred
For high risk 3-6 months
Systemic therapy for stage II disease
5-Fu alone for 6 months
First line for HER2+ colon
trastuzumab + tucatinib
Drugs targeting TRK fusion-positive tumors
Entrectinib, larotrectinib
