Colorectal cancer Flashcards by Ned Jones

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).

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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.

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relevance of microsatelite stability and treatment

Benefit from PD-1 inhibitors is limited to tumors with MSI-H/dMMR.

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significance of Ki-67

Prognostic marker in breast cancer. Measure of tumor cell proliferation.

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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.

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her2 positive treatment

Trastuzumab + pertuzumab + taxane (docetaxel or paclitaxel)

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trastuzumab trade name

Herceptin

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xeleri is

capecitabine plus irinotecan

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doxorubicin trade name

adriamycin

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biomarkers to test for in CRC

KRAS + BRAF + MMR/MSS status

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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.

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BRAF pathway?

component of the RAS-RAF-MAPK signaling pathway.

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why trend CEA

A rise in CEA predicts recurrence, so if you see a rise, you should order imaging earlier.

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downside to capeox

wide variability in pricing

- some variation in response based off genetic profile (asians tend to tolerate fluoropyrimidines better)

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FOLFOX is

Folinic acid “FOL”, Fluorouracil “F”, and Oxaliplatin “OX”.

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bevacizumab/avastin SE profile

epistaxis, headache, hypertension, rhinitis, proteinuria,
taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, and
exfoliative dermatitis

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cetuximab indication

KRAS + BRAF wild type and left sided

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general SE of pembro and other checkpoint inhibitors

most people do well, but they can do anything

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why do you give leucovorin with FOLFOX

It enhances the activity of 5-FU. It is folinic acid.

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Common SE’s of 5-Fu

myelosuppression + mucositis + palmar/plantar erythrodysesthesia + diarrhea + cardiotoxicity + neurotoxicity

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term for effect on cold liquids of oxaliplatin

cold hypersensitivity

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RF’s

(think of things that are going to cause inflammation in colon)
IBD, drinking, smoking, obesity
Consumption of red and processed meats
Diabetes

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Screening colonoscopy recommendation

average risk = 50

IF FH – 10 years prior to age of earliest occurrence or beginning at age 40

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clinical workup recommended for patients who develop CRC before age 50

MSI testing, (test for mismatch repair if MSI high)

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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