Lec 31 Colorectal Cancer

What screening modalities are available for colorectal cancer? How often do these modalities need to happen?

When should screening begin for average risk patients?

Age 45 for men and women

Which molecular tests need to be obtained for colorectal cancer to guide treatment decisions?

• KRAS/NRAS mutation: Damage to growth-control genes that makes cancer cells grow out of control.

• BRAF mutation: A broken signal gene that tells cells to divide too much.

• dMMR/MSI-H: dMMR means the cell’s DNA repair system is broken, leading to high microsatellite instability (MSI-H) and lots of DNA errors. A broken DNA repair system that lets lots of mistakes build up.

• HER2 amplification: Too many HER2 signals making cells grow way too fast

What treatment modalities can be used for rectal cancer stages I, II, III?

• Surgery

  • Resection of primary tumor 

• Radiation

  • Neoadjuvant: Improves resectability of primary tumor

  • Adjuvant: decreases risk of local recurrence 

• Chemotherapy

  • Combined with radiation or alone

  • Neoadjuvant:  improves resectability of primary tumor (TNT)

  • Adjuvant: eradicate micrometastatic disease, improve disease free survival (DFS)

In rectal cancer, doctors use a mix of surgery, chemo, and radiation (before or after surgery) to shrink the tumor, remove it, and prevent it from coming back.

What are the common chemotherapy regimens used for adjuvant treatment of colon cancer? (Based on risk and stage)

Stage I & Low risk II MSI-H	Surveillance, no adjuvant tx
Low risk II	Surveillance OR  Consider adjuvant chemo:  Capecitabine, 5-FU/leucovorin 6 months
High risk II	Adjuvant chemo Capecitabine, 5FU/leucovorin 6 months FOLFOX (6 mo), CapeOX (3mo) Observation
Low Risk III	Adjuvant chemo FOLFOX OR CapeOX (3 mo) FOLFOX (6 mo)
High risk III	Adjuvant chemo FOLFOX (6 mo) CapeOX (3-6 mo)

High risk colorectal cancer feature

Grade ¾ tumors, lymphovascular invasion, perineural invasion, bowel obstruction, localized perforation, positive margins, <12 lymph nodes dissected

What unusual side effects can occur with oxaliplatin?

• Peripheral neuropathy

• Chemo induced nausea/vomiting

• Hepatotoxicity

• Pulmonary fibrosis

What therapies can be used with the KRAS/NRAS G12C mutation and KRAS/NRAS wild type in stage IV colon cancer

KRAS/NRAS G12C mutation:

• Adagrasib (with cetuximab)

• Sotorasib (with panitumumab)

KRAS/NRAS wild type

• Panitumumab/Cetuximab

What therapies can be used with the HER2 amplification mutations in Stage IV colon cancer?

HER2 amplification

• Trastuzumab + [pertuzumab, lapatinib, or tucatinib]

• Fam-Trastuzumab deruxtecan-nxki

What therapies can be used with the BRAF mutations in Stage IV colon cancer?

BRAF mutation

• Encorafenib (always in combo with pani)

What therapies can be used with the dMMR/MSI-H mutations in Stage IV colon cancer?

dMMR/MSI-H:

• Pembrolizumab

• Nivolumab (with or without ipilimumab)

Treatment algorithm for Stage IV cancer based on mutations

What regimens could be considered for first-line treatment in a patient with stage IV RAS mutated rectal cancer?

What regimens could be considered for first-line treatment in a patient with MSI-H Stage IV rectal cancer?

How do you manage acute diarrhea from irinotecan? How do you manage delayed diarrhea from irinotecan?

Acute Phase: Within 24 hours of infusion	Delayed Phase: 24 hours after infusion
During tx: Atropine IV or SubQ After tx: diphenoxylate/atropine (Lomotil) tablets 1-2 PO QID PRN	Loperamide + Fluids & Electrolytes

How is the hand-foot syndrome arising from capecitabine  and 5FU best prevented, and how is it treated if it occurs?

Prevention: Prophylactic moisturizer BID, avoid hot water, excessive friction, and constrictive footwear

Treatment:

• Grade 1: 

  • Cont capecitabine

  • Start clobetasol 0.05% cream apply 

Why is leucovorin added to colorectal chemotherapy regimens that include 5FU or capecitabine?

• Tightens the binding of 5FU metabolite (fdump) to thymidylate synthase → promotes anticancer effect of FOLFOX 

• Not necessary with capecitabine because it’s a prodrug of 5FU so slower metabolism → longer exposure to anticancer effect

What drugs are most commonly tried for the treatment of oxaliplatin-induced neuropathy?

• Duloxetine 

• Gabapentin

What is the preemptive management of EGFR-inhibitor rash? How does it differ from the treatment of rash from Immune Checkpoint Inhibitors?