Abstract
Background: FGFR2 fusions/rearrangements and IDH1 mutations are implicated in CCA pathogenesis and are targetable. Tissue adequacy for molecular profiling is challenging and dependent on tissue acquisition methods.
Methods: This retrospective study included consecutive patients (pts) with advanced CCA referred for systemic therapy to a tertiary referral centre (‘22-‘24). Aim: Assess molecular testing success rate based on tumour acquisition method. Categorical variables were analysed by Fisher’s exact test and survival by Kaplan Meier and log rank tests.
Results: One hundred and fifty-seven pts (54% male) were seen [98 (62%) fit for active palliative treatment; remaining: 59 (38%) Best Supportive Care (BSC)]. Median age at diagnosis: 70 years (IQR 60-76), intrahepatic CCA: 99 (63%), distal and perihilar CCA: 30 (19%) and 28 (18%), respectively. Diagnosis by percutaneous biopsy in 105 (67%), endoscopic ultrasound fine needle aspiration (EUS-FNA) in 11 (7%), EUS-fine needle biopsy (FNB) in 12 (9%) and brushings in 27 (17%); tumour cellularity provided in 75 (48%). Two pts had imaging only-based diagnosis. Molecular profiling was requested for 96 (61%) pts [Multigene panels: 21 (22%), NHS Genomics (FGFR2, IDH1, MSI, NTRK): 75 (78%)]; successful in 81 (84%): all alterations analysed in 65 (68%). Analysis failed for at least one targetable alteration: 16 (17%). Main reason for not testing was BSC: 43/61 (71%). FNB had the highest molecular testing success rate: 100%, followed by percutaneous biopsy: 86%, brushings: 80% and FNA: 63%, P = .26. Median survival from diagnosis of pts who received targeted treatment with pemigatinib (N=4) or ivosidenib (N=3) was 21.6 mo (95% CI 19.6-22.6); 8.8 mo (95% CI 5.7-14.4) for those on other active palliative treatment (HR=0.3, 95% CI 0.09 – 0.96, P = .04) and 5.2 mo (95% CI 2.6-7.4) for BSC (median follow-up: 7.4 mo).
Conclusions: FNB or percutaneous biopsy offered best chance of molecular profiling success in those fit for active treatment. Molecular profiling was unsuccessful in one sixth due to inadequate tissue. Pts with identified alterations receiving targeted treatment had favourable survival, highlighting importance of tissue adequacy from initial diagnostic method.
Methods: This retrospective study included consecutive patients (pts) with advanced CCA referred for systemic therapy to a tertiary referral centre (‘22-‘24). Aim: Assess molecular testing success rate based on tumour acquisition method. Categorical variables were analysed by Fisher’s exact test and survival by Kaplan Meier and log rank tests.
Results: One hundred and fifty-seven pts (54% male) were seen [98 (62%) fit for active palliative treatment; remaining: 59 (38%) Best Supportive Care (BSC)]. Median age at diagnosis: 70 years (IQR 60-76), intrahepatic CCA: 99 (63%), distal and perihilar CCA: 30 (19%) and 28 (18%), respectively. Diagnosis by percutaneous biopsy in 105 (67%), endoscopic ultrasound fine needle aspiration (EUS-FNA) in 11 (7%), EUS-fine needle biopsy (FNB) in 12 (9%) and brushings in 27 (17%); tumour cellularity provided in 75 (48%). Two pts had imaging only-based diagnosis. Molecular profiling was requested for 96 (61%) pts [Multigene panels: 21 (22%), NHS Genomics (FGFR2, IDH1, MSI, NTRK): 75 (78%)]; successful in 81 (84%): all alterations analysed in 65 (68%). Analysis failed for at least one targetable alteration: 16 (17%). Main reason for not testing was BSC: 43/61 (71%). FNB had the highest molecular testing success rate: 100%, followed by percutaneous biopsy: 86%, brushings: 80% and FNA: 63%, P = .26. Median survival from diagnosis of pts who received targeted treatment with pemigatinib (N=4) or ivosidenib (N=3) was 21.6 mo (95% CI 19.6-22.6); 8.8 mo (95% CI 5.7-14.4) for those on other active palliative treatment (HR=0.3, 95% CI 0.09 – 0.96, P = .04) and 5.2 mo (95% CI 2.6-7.4) for BSC (median follow-up: 7.4 mo).
Conclusions: FNB or percutaneous biopsy offered best chance of molecular profiling success in those fit for active treatment. Molecular profiling was unsuccessful in one sixth due to inadequate tissue. Pts with identified alterations receiving targeted treatment had favourable survival, highlighting importance of tissue adequacy from initial diagnostic method.
| Original language | English |
|---|---|
| Article number | 348P |
| Pages (from-to) | S136 |
| Number of pages | 1 |
| Journal | Annals of Oncology |
| Volume | 36 |
| Issue number | Supplement 1 |
| DOIs | |
| Publication status | Published - 16 Jul 2025 |
| Event | ESMO GI 2025 - Barcelona, Spain Duration: 2 Jul 2025 → 5 Jul 2025 |
Keywords
- cholangiocarcinoma
- molecular profiling
- Tissue adequacy