First results of the EORTC-SPECTA/Arcagen study exploring the genomics of rare cancers in collaboration with the European reference network EURACAN

Abstract

PurposeRare cancers are defined by an incidence of <6 out of 100 000 cases per year. They are under-represented in clinical research including tumour molecular analysis. The aim of Arcagen is to generate a multinational database integrating clinical and molecular information of patients with rare cancers.Patients and methodsWe present the retrospective feasibility cohort of patients with rare cancers, with previously collected tumour samples available from any stage. Molecular analysis was performed using FoundationOne CDx for all histologies except for sarcoma where FoundationOne Heme was used. Clinical data including demographic data, medical history, malignant history, treatment and survival data were collected.ResultsEighty-seven patients from three centres were screened; molecular data were obtained for 77 patients (41 sarcomas, 9 yolk sac tumours, 14 rare head and neck cancers, 13 thymomas). The median age at the time of diagnosis was 48 (range 28–85). Most patients had reportable genomic alterations (89%). The most common alterations were linked to cell cycle regulation (TP53, RB1, CDKN2A/B deletions and MDM2 amplification). Multiple activating single-nucleotide variants (SNVs) could be detected in the RAS/RAF family. The tumour mutational burden status was globally low across all samples with a median of 3 Muts/MB (range 0–52). Only 4 cases (ie, 4.7% of tumours) had direct actionable mutations for a treatment approved in Europe within the patient’s tumour type.ConclusionThe Arcagen project aims to bridge the gap and improve knowledge of the molecular landscape of rare cancers by prospectively recruiting up to 1000 patients.

Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform

“…For thymic malignancies, we were unable to confirm findings from TCGA as GTF2I was not part of any of the panels used in SPECTAlung and the sample size was very small. Moreover, we were also unable to repeats the molecular profile of the Arcagen studies (n = 23) for which several mutations were found in the RAS/RAF pathway 15 , similarly to what was found in the TCGA cohort. This clearly highlight the need for further fundamental and clinical research for rare cancers and possibly NGS panels adaptations.…”

Clinical Impact of Prospective Whole Genome Sequencing in Sarcoma Patients

“…These results are largely in line with the potential of broad molecular profiling in sarcoma patients that has been widely recognized previously. Actionable variants have been reported in 40–50% of sarcoma patients [ 30 , 31 ], germline variants are prevalent in 10–15% patients [ 7 ], and the utility of molecular profiling for accurate tumor classification has been established in previous clinical trials [ 4 , 5 ]. The extensive pathology testing to appropriately diagnose sarcoma patients is usually employed iteratively, while complete genomic characterization with WGS incorporates detection of all possible genomic events within one diagnostic test.…”

Biology-guided precision medicine in rare cancers: Lessons from sarcomas and neuroendocrine tumours

“…In addition, these and other similarly designed protocols have proven to be important "signal finding" endeavours from which interventional trials are increasingly emerging, including some that use composite biomarkers and evaluate combination therapies (ClinicalTrials.gov: NCT03127215, NCT04551521) [80]. In any case, progress in precision therapy of rare cancers, whether through interventional or registry studies, requires the consistent collaboration of multiple institutions in coordinated national networks or even international alliances such as the EORTC [81,82] and Cancer Core Europe [83].…”