Colorectal cancer 2 Flashcards by Ned Jones

Recommended interval for c-scope in surveillance setting

1 year, then 3 years if normal, then 5 years if normal

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clinical features of palmar-plantar erythrodysesthesia

redness, swelling, skin peeling and pain on the palms of the hands and/or the soles of the feet.

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Tumor marker for CRC

CEA

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What is the idea of total neoadjuvant therapy (TNT) in rectal cancer?

Using all systemic chemo + radiation in preoperative setting to downstage rectal cancer

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Neoadjuvant vs. surgery concept for CRC

Surgery is the only curative modality, so if patient has resectable disease and are anticipated to have negative margins, they should proceed to surgery rather than upfront chemo.

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What is the goal of adjuvant chemotherapy for colon cancer?

Eradicate micrometastases

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Duration of adjuvant therapy

6 months (BUT IDEA collaboration which involved 6 trials suggest that you lose some disease free survival with 3 months but it is suitable in patients with low risk disease)

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high risk stage II features per ASCO and NCCN

1) fewer than 12 nodes sampled
2) ***T4 tumor
3) perforated
3) obstruction
4) poorly differentiated tumor histology
5) LVI
6) PNI
7) close/indeterminate margins

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Therapy that is controversial for use in older people

Oxaliplatin

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Access for 5 Fu

Need central access

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Role for RT in rectal vs colon

Postop RT not used for colon, as opposed to rectal

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most common distant metastatic sites

Liver, lungs, lymph nodes, peritoneum

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Survival in metastatic CRC

30 months (around 3 years)

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In what sites can metastasectomy be performed

Liver and lung

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Is long term survival possible with metastasectomy?

Yes, but most people are alive at 5 years with active disease

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How to predict 5 year survival rate for solid tumors

Memorial sloan kettering has nomograms on their websites

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What does presence of synchronous CRC cancers suggest?

Lynch syndrome or FAP

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Clinical significance of microsatelite instability

Predicts lack of response to fluoropyrimidine therapy

- Predicts response to CPIs

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Liver test abnormality associated with liver mets

Elevated alk phos
- Elevated liver enzymes are not a reliable marker for exclusion of liver involvement (may be normal in the setting of small hepatic mets)

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When do you start adjuvant chemo in stage III?

Await until recovery following surgery (typically 6-8 weeks)

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FOLFOX vs CAPEOX in terms of toxicity

CAPEOX probably more toxic

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Biochem interaction and physiology of PD-1 and PD-L1

PD-1 is upregulated on activated T cells, and upon recognition of tumor via the T cell receptor, PD-1 engagement by programmed death ligand 1 (PD-L1) results in T cell inactivation.

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Initial combination or single chemo for mCRC?

initial combination chemo

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What is “conversion therapy”?

Giving chemo with the hope of converting unresectable mets to resectable

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Best metric for response to therapy in palliative setting

PFS (trying to delay tumor progression for as long as possible)

Is chemo typically modified in obese patients?

Doses are often reduced because of concern for excess toxicity due to a larger body surface area (guidelines recommend against this for mCRC though)

Response assessment in mCRC

Scans every 2-3 months + CEA every 1-3 months

Management of rising CEA level in mCRC

Confirm disease progression with scan prior to changing therapy

Clinical utility of PET/CT for CRC

Low, not indicated generally | Can be considered in Stage IV for potentially curable M1 disease

Stage II adjuvant treatment options

``` *Depends on risk factors Capecitabine 5-Fu FOLFOX CAPEOX Observation ```

Imaging if recurrence suggested by elevated CEA

Chest/abdomen/pelvis CT with contrast

Next step if elevated CEA prompts imaging in surveillance and imaging is negative

Consider PET/CT | Re-evaluate chest/abdomen/pelvis CT with contrast in 3 months

Surveillance imaging for stage II and III

Chest, abdomen, pelvis CT q6 months for a total of 5 years

Surveillance imaging for stage I

Imaging only if symptomatic

Surveillance imaging for stage IV

chest/abdomen/pelvis CT q3 months x 2 years, then q6 months for total 5 years

When MRI is indicated for liver mets

Indeterminate, potentially resectable mets

What is tumor budding + clinical significance

ON path -- single or cluster of cells at advancing edge of invasive carcinoma. Negative prognostic factor

Number of lymph nodes required to pathologically stage nodal status of CRC

Clinical significance of KRAS or NRAS mutations

No treatment with cetuximab or panitumumab

Clinical significance of BRAF mutation

Response to panitumumab or cetuximab is highly unlikely unless given with a BRAF inhibitor

How testing for MSI status is performed

PCR or NGS

Testing for HER2

IHC, FISH, or NGS

Is re-resection of lung mets possible?

Can be considered in selected patients

Role for bevacizumab

Usually added to FOLFOX or CAPEOX

Indication for cetuximab or panitumumab

KRAS/NRAS/BRAF WT + left-sided only

Bevacizumab formulation

What does m in mFOLFOX stand for?

Modified FOLFOX

Percentage of cases of CRC associated with familial clustering

20%

How is a malignant polyp defined?

Cancer invading the submucosa

Surgical management of lymph nodes for resectable non-metastatic CRC

Colectomy with en bloc removal of the regional lymph nodes

Adjuvant therapy for Stage II depends on

Depends on risk (low vs high)

Adjuvant therapy options for low-risk stage II?

Observation OR capecitabine OR 5-FU/leucovorin

Adjuvant therapy options for low-risk stage III disease

3 months CAPEOX 3-6 months FOLFOX IF oxaliplatin inappropriate --> single agent capecitabine or 5-FU/LV

Adjuvant therapy options for high-risk stage III disease

6 months FOLFOX | 3-6 months CAPEOX CONFIRM

MSI classification

MSI-High or MSI-low

NCI preferred FOLFOX regimen for adjuvant and metastatic treatment?

mFOLFOX

Reversibility of peripheral neuropathy with oxalaplatin

Reversible in most patients, irreversible in a small percentage

Cause of death in most patients with mCRC

Metastatic liver disease

Local therapies for metastases

Surgical resection is the standard of care, but in patients who aren't surgical candidates, image-guided ablation is used. SBRT is an option for patients who can't be ablated.

Goal of treatment of peritoneal metastases

Palliative

What is HIPEC?

Hyperthermic intraperitoneal chemotherapy - treatment fit or peritoneal metastases - works but morbidity high and didn't change long term survival

Potential upside + downside to neoadjuvant chemo as

- elimination of micro metastatic disease | - may miss "window of opportunity" for resection

Why don't you test for EGFR?

Hasn't been shown to predict response to EGFR inhibitors

When should you drop oxaliplatin?

After 3 months of therapy or sooner if unacceptable neurotoxicity

EGFR-targeted therapies for CRC

cetuximab, panitumumab

Need to rebiopsy tumor if metastatic recurrence and retest mutational status?

No (RAS mutations occur early in carcinogenesis so mutation status of primary tumor and subsequent recurrence are very concordant)

Stage III means

Mets to local-regional lymph nodes

Stage IIIC means

Mets to four or more nodes

epidemiology of CRC

- incidence is going down due to screening but incidence of early onset is rising

who among CRC patients are tested for Lynch syndrome?

everyone

*Indications for adjuvant therapy

High risk Stage II | Stage III

Duration of adjuvant treatment for Stage III

- Intermediate risk = 3 months CAPOX or 6 months FOLFOX - High risk = 6 months FOLFOX or 3-6 months CAPOX * so 6 months except data for 3 months CAPOX with intermediate risk

Adjuvant therapy regimens and duration for Stage II

3 months CAPOX OR 5-Fu/LV OR capecitabine

Stage II patients who you should avoid giving chemo to in CRC

MSI-H patients

CEA level that is thought to predict adverse impact on survival

Equal to or greater than 5

Initial management of CRC presenting with hepatic mets

- SURGERY -- hemicolectomy + surgical resection of liver disease, followed by adjuvant chemo - NO biopsy (hepatic mets in CRC are diagnosed by noninvasive imaging and tumor markers. Hepatic biopsy adds little diagnostic information and may reduce long term survival)

Contraindications to surgery for hepatic mets

- inadequate liver reserve for resection - extensive liver mets (greater than 70%, over 6 segments, involving all 3 hepatic veins) - vascular involvement: involvement of hepatic artery, major bile ducts, or main portal vein

Clinical significance of dMMR tumors in CRC

1) Patients experience clinical benefit from PD-1 inhibitors and can have durable responses 2) chemo resistant

IO for GBCs?

- frequency of dMMR tumors is around 5% for GBC - pembro is FDA approved for MSI-H tumors for tumors progressing following prior treatment - PD-L1 may predict response

what is the pathophysiologic mechanism of VEGF inhibitors?

- angiogenesis inhibitors (vascular endothelial growth factor)

Clinical relevance of MSI -- MMR status

1) eligibility for checkpoint inhibitor immunotherapy | 2) predicts responsiveness to fluoropyrimidines,

Benefit of chemo with stage II colon cancer

- somewhat muted. NCCN basically accepts relative benefit of adjuvant therapy in stage III disease

prognostic + clinical relevance of MSI status in Stage II colon cancer

1) MSI-High patients do not benefit from adjuvant fluoropyrimidines 2) Responsive to immunotherapy

clinical significance of MSI-H**

1) Response to immunotherapy | 2) Unresponsive to fluoropyrimidines

When is adjuvant chemotherapy indicated in stage II disease indicated

pT3 with high risk features pT4 disease *must be pMMR

what defines stage II colon cancer

Any T stage | No nodal involvement

EGFR inhibitors you can add to front line systemic therapy

Cetuximab OR *panitumumab

when EGFR inhibitors are indicated

KRAS + NRAS + BRAF wild type

Efficacy of capecitabine vs. 5-Fu

EQUIVALENT, choose based on SE profile

second line for colon after first line FOLFOX

FOLFIRI (if FOLFOX first line)

High risk features for Stage II colon cancer

- bowel obstruction - less than 12 lymph nodes sampled - LVI - close/positive margins - PNI - *poorly differentiated histology - perforation

N1c disease in CRC

- nodal deposits in the subserosa, mesentery, pericolic, perirectal, mesorectal tissues

significance of tumor deposits in the subserosa, mesentery, pericolic, perirectal, mesorectal tissues in CRC

Stage III disease, not metastatic

High risk features of Stage III colon cancer

1) T4 disease w/ N1-2 2) T any, N2

Differences in duration of treatment for low and high risk stage III colon

Capeox 3 months for low risk, noninferiority of 3 months of FOLFOX vs. 6 months has not been shown

What is pseudomyxoma peritonei?

Diffuse mucinous peritoneal involvement from appendiceal cancer. This is not peritoneal carcinomatosis.

Are hepatic mets typically biopsied with CRC?

NO biopsy (hepatic mets in CRC are diagnosed by noninvasive imaging and tumor markers. Hepatic biopsy adds little diagnostic information and may reduce long term survival)

Utility of PET/CT in colon cancer

Not indicated

When is neoadjuvant therapy indicated aside from nonresectable disease?

T4b disease

What has been shown to reduce risk of colon cancer recurrence?

Exercise

Second line for BRAF V600 mutant metastatic colon

encorafenib + cetuximab

What is high risk in Stage III

T4 and or N2 disease

Abnormality associated with severe symptoms from 5-Fu

dihydropyrimidine dehydrogenase (DPD; encoded by DPYD) deficiency.

MSI vs. MMR in terms of testing

dMMR = loss of expression on IHC MSI-H = PCR

Med contraindicated with capecitabine

PPIs

Adjuvant therapy for low risk

3 months FOLFOX or CAPOX

Continue Bev at progression in second line?

Yes, shown to have a benefit of a couple months

Mutation associated with delayed clearance of irinotecan

UGT1a1

Colonoscopy recommended surveillance interval

- 1 yr after curative resesction - 3 years later if no high-risk adenomas