Gastrointestinal and Hepatobiliary Oncology
What this domain tests
This domain tests site-specific adjuvant and metastatic algorithms across colorectal, esophagogastric, pancreatic, hepatocellular and biliary cancers, with heavy emphasis on molecular selection (RAS/BRAF, MSI-H, HER2, FGFR2, IDH1) and on liver-directed therapy in hepatocellular carcinoma.
Core rules
- Colon: stage III and high-risk stage II receive adjuvant FOLFOX or CAPOX; three months of CAPOX is acceptable for low-risk stage III (IDEA). Molecular testing includes RAS, BRAF V600E and MSI status. Left-sided RAS/BRAF wild-type tumors benefit from anti-EGFR antibodies; right-sided tumors do not and are treated with chemotherapy plus bevacizumab. MSI-H disease responds to checkpoint inhibition.
- Rectal: locally advanced disease is managed with total neoadjuvant therapy, with watch-and-wait reserved for complete clinical responders in protocol settings.
- Esophagogastric: perioperative FLOT for resectable gastric and junctional adenocarcinoma; HER2 testing mandatory; CROSS-trial chemoradiation for esophageal cancer; adjuvant nivolumab for residual disease after chemoradiation (CheckMate 577).
- Pancreas: adjuvant modified FOLFIRINOX in fit patients (PRODIGE 24), gemcitabine–capecitabine or gemcitabine alone otherwise; metastatic first line is FOLFIRINOX or gemcitabine–nab-paclitaxel.
- Hepatocellular carcinoma: BCLC stage guides therapy; atezolizumab plus bevacizumab (IMbrave150) or lenvatinib/sorafenib for advanced disease; TACE for intermediate stage; transplant for selected early disease within Milan criteria.
- Biliary tract: gemcitabine/cisplatin plus durvalumab (TOPAZ-1); targeted options include pemigatinib for FGFR2 fusion and ivosidenib for IDH1 mutation.
Worked example
A 62-year-old with a left-sided sigmoid adenocarcinoma and liver-limited metastases. RAS and BRAF are wild-type, MMR is proficient. First-line FOLFOX plus cetuximab is appropriate: left-sided primaries derive an overall survival benefit from EGFR blockade (FIRE-3, CALGB 80405), while the same regimen in a RAS-mutant tumor would be harmful.
Traps
- Giving an anti-EGFR antibody to a right-sided primary, a RAS-mutant tumor, or one with a BRAF V600E mutation.
- Assuming all MSI-H tumors need chemotherapy; pembrolizumab is first line in metastatic MSI-H colorectal cancer.
- Offering sorafenib before testing whether the patient is a candidate for atezolizumab–bevacizumab, which is now preferred.
- Forgetting DPD testing before fluoropyrimidines in patients with severe prior toxicity.