Abstract 45: Screening somatic genomic alteration for rare adult cancers: the SPECTA-ARCAGEN project of the EORTC/EURACAN
Authors: Morfouace Marie , Stevovic Aleksandra , Oliveira Julio , Penel Nicolas , Péron Julien , Casali Paolo G. , SECKL Michael J. , GIETEMA Jourik A. , de HERDER Wouter , WYRWICZ Lucjan , de la FOUCHARDIERE Christelle , LICITRA Lisa , GIRARD Nicolas , PIPERNO-NEUMANN Sophie , KAPITEIJN Ellen , IDBAIH Ahmed , Blay Jean-Yves 
Published: June 2022

Introduction: Rare cancers are defined as having an incidence lower than 6 per 100,000 new cases per year. Despite advances in treatments and personalised medicine for cancer, rare cancers are often left behind due to limited knowledge regarding molecular characterization, heterogeneity of the population and poor access to screening platform or interventional trials.To bridge this gap, EORTC, in collaboration with EURACAN, has developed a project within the EORTC-SPECTA platform to assess the molecular landscape of rare cancers in Europe and the actionability of the different findings.

Material and Methods: The pan-European Arcagen project is prospectively analyzing tumor material or blood of patient with rare cancers, using Foundation Medicine NGS panels, while collecting baseline and follow-up clinical data.

Results: At the cut-off date of 10/10/2021, 629 patients were evaluable (baseline clinical data and successful molecular profiling performed by a Foundation Medicine test), molecular alterations were found in 620 patients, theoretically actionable ones in 421 patients. Importantly, approved treatment in the right tumor type was proposed in 58 patients (9.2%). Longer follow-up is needed to assess treatment adaptation and response. Most analyses were performed based on FFPE material (451 out of 629), but in case of low sample quality, low content of tumor cells, or old sample, rescue analysis was performed on liquid biopsy (177 out of 629). The main reason for switching to liquid biopsy was due to low FFPE tissue quality (90 out of 178). This rescue pathway was used on average in 28.1% of cases, ranging from 14.7% in salivary gland cancers to 48% for Cancer of Unknown Primary. Comparing per tumor type the molecular profile obtained either with FFPE or blood analysis, we noticed that SNVs are nicely detected in both compartments. However, copy number loss and amplifications are mainly detected when FFPE material is used. This is especially true for copy number loss of CDKN2A/B (cholangiocarcinoma, mesothelioma and salivary gland), or MTAP (mesothelioma), and MYC amplification (brain and rare skin cancer).As expected according to other datasets, some clonal hematopoiesis of indeterminate potential (CHIP) was observed on liquid biopsy, with DNMT3A being in the top ten mutations detected in the blood of patients with salivary gland tumors, endocrine tumors, Merkel cell carcinoma and uveal melanoma.

Conclusion: This project highlights the clear need for more collaboration, research and clinical trials on rare cancers, to improve the treatment accessibility for targeted therapy for these patients. The use of liquid biopsy, despite its limitations, is an ideal candidate to gain understanding of a patient tumor molecular profile, while being non-invasive and easily performed longitudinally.

Citation Format: Marie Morfouace, Aleksandra Stevovic, Julio Oliveira, Nicolas Penel, Julien Péron, Paolo G. Casali, Michael J. SECKL, Jourik A. GIETEMA, Wouter de HERDER, Lucjan WYRWICZ, Christelle de la FOUCHARDIERE, Lisa LICITRA, Nicolas GIRARD, Sophie PIPERNO-NEUMANN, Ellen KAPITEIJN, Ahmed IDBAIH, Jean-Yves Blay. Screening somatic genomic alteration for rare adult cancers: the SPECTA-ARCAGEN project of the EORTC/EURACAN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 45.