Análisis genómico en el colangiocarcinoma intrahepático (CCAi)

Biopsy³

• A core biopsy should be obtained for diagnostic pathology and molecular profiling before any non-surgical treatment

Molecular profiling³

• Discussion with a molecular pathologist or the molecular tumour board is strongly recommended when considering molecular profiling
• Molecular profiling should be performed before or during first-line therapy using NGS
• NGS can be performed on formalin-fixed and paraffin-embedded tumour tissue and is well suited for tissue biopsies
• Alternatively, liquid biopsies using cell-free circulating DNA may be considered, if not enough tumour tissue is available for NGS
• Results may help to inform treatment decisions in first-line or to determine eligibility for second-line targeted therapies, should the patient experience disease progression on first-line therapy

DNA-based NGS³

• NGS gene panels that include isocitrate dehydrogenase 1 (IDH1), human epidermal growth factor receptor 2 (HER2/neu) and B-Raf proto-oncogene (BRAF) should be used to test for hotspot mutations, but owing to the evolving landscape of drug targets and predictive biomarkers, this may soon necessitate larger panels
• DNA-based NGS assays should ideally employ hybrid capture or anchored multiplex PCR technology

RNA-based NGS³

• For tissue-based testing, gene fusions involving the fibroblast growth factor receptor 2 (FGFR2) and neurotrophic tyrosine receptor kinase (NTRK) genes should preferably be interrogated at the RNA level using a panel-based method that can identify fusion transcripts of known and unknown fusion partners
• RNA-based NGS assays should ideally employ hybrid capture or anchored multiplex PCR technology

^*Durvalumab in combination with gemcitabine and cisplatin is indicated for the first-line treatment of adults with unresectable or metastatic BTC; ^†Clinical trial recommended when available; ^‡Molecular profiling should be performed before/during first-line therapy. Gene panel should include FGFR2, IDH1, HER2/neu and BRAF to test for hotspot mutations, but may also include genes such as NTRK and c-MET; ^§Cisplatin–gemcitabine ± durvalumab is recommended for first-line treatment; consider gemcitabine monotherapy in patients with a compromised PS or significant debility who are at risk of toxicity from platinum-containing chemotherapy regimens; ^¶Reconsider surgery in the event of adequate response to treatment.

5-FU, fluorouracil; BRAF, B-Raf proto-oncogene; BTC, biliary tract cancer; c-MET, mesenchymal epithelial transition; dMMR, mismatch repair deficient; ESMO, European Society for Medical Oncology; FGFR2, fibroblast growth factor receptor 2; FOLFOX, fluorouracil plus oxaliplatin; HER2, human epidermal growth factor receptor 2; iCCA, intrahepatic cholangiocarcinoma; IDH1, isocitrate dehydrogenase 1; MDT, multidisciplinary team; MSI-H, microsatellite instability-high; NTRK, neurotrophic tyrosine receptor kinase; PS, performance status.