Findings from the ARCAGEN study (EORTC-1843) performed within the EORTC-SPECTA platform point to identification of targetable alterations in majority of patients with advanced rare gastrointestinal malignancies. However, only few alterations have matched targeted treatments approved in Europe. The alterations were found in all tumour subtypes, not only in intrahepatic cholangiocarcinoma, suggesting that molecular profiling utilising wide gene next-generation sequencing panels is recommended in all patients diagnosed with advanced rare gastrointestinal malignancies. Further development of ctDNA-based molecular profiling options should be pursued. The results are published by Dr. Angela Lamarca of the Department of Oncology – OncoHealth Institute, Fundación Jiménez Díaz University Hospital in Madrid, Spain and colleagues on 31 July 2022 in the Annals of Oncology.  

The ARCAGEN study was initiated within the EORTC-SPECTA platform in June 2019 with aim to assess the prevalence of genomic alterations, tumour mutation burden (TMB), microsatellite instability (MSI), and actionability in patients diagnosed with advanced rare gastrointestinal malignancies. Analysis was performed on tumour formalin-fixed paraffin-embedded (FFPE) tissue samples if available and less than 2 years old or blood sample, using the Foundation Medicine (FMI)® platform.

In total, 87 patients from 9 centres across Europe were included. Slightly more than half of included patients were male (50.6%), median age was 62 years (range, 14-88). Majority of patients (72) had cholangiocarcinoma of which 47 intrahepatic, 16 extrahepatic, and 9 not specified, followed by 5 patients with small bowel carcinoma, 4 patients with ampullar carcinoma, 3 patients with carcinoma of appendix including goblet cell, ex-goblet cell, and non-mucinous carcinoma, 1 patient with pancreato-biliary carcinoma (not otherwise specified), and 1 patient with fibrolamellar carcinoma.

FFPE samples were used for molecular profiling in 52 patients. However, testing failed in 11 patients (21.16%) due to poor tumour representation. Blood sample was utilised for molecular profiling in 35 patients, of which in 11 as rescue due to failure on FFPE and in 24 because FFPE tissue did not meet inclusion criteria of being less than 2 years old. Most patients for whom blood sample was used were patients with intrahepatic cholangiocarcinoma: 25 patients, 71.4% of all blood samples utilised and 53.2% of all intrahepatic cholangiocarcinoma.

Results of molecular profiling showed 3.5% TMB-high and 2.3% MSI-high tumours. Targetable alterations were identified in 76.4% patients with cholangiocarcinoma, 83.3% patients with small bowel and in 77.8% patients with other tumours. The most common were FGFR alterations in 13 cases (14.9%) and IDH mutations in 12 cases (13.8%). The results are in line with prior literature, with a wide spectrum of targetable alterations identified.

Most of identified alterations had no available treatments approved for rare gastrointestinal cancers in Europe. Nine patients had their treatment adapted according to the results of the molecular profiling. The high rate of FFPE failure highlights the issue about sample quality and encourages further development of ctDNA-based molecular profiling options to enable access of larger proportion of patients to molecular profiling and to the potentially available treatments.

The EORTC SPECTA platform is supported by Alliance Healthcare, a member of the AmerisourceBergen group. The ARCAGEN study (EORTC-1843) is supported by F. Hoffman-La Roche Ltd. Dr. Angela Lamarca received funding from the grant of the European Union’s Horizon 2020 Research and Innovation Programme.


Lamarca A, Morfouace M, Tejpar S, et al. Molecular profiling and precision medicine in rare gastrointestinal cancers within EURACAN in the SPECTA Arcagen study (EORTC-1843): too few patients treated in Europe. Annals of Oncology; Published online 31 July 2022. DOI: