Abstract 2005: First results of the EORTC-SPECTA project on comprehensive molecular profiling of adolescent and young adult sarcoma patients
Authors: Morfouace Marie , Horak Peter , Kreutzfeldt Simon , Shenjere Patrick , Wardelmann Eva , Denisova Evgeniya , Stevovic Aleksandra , Bautista Francisco J. , Oliveira Julio , van der Graaf Winette , Fröhling Stefan , McCabe Martin G. 
Published: June 2022

Introduction: Yearly, around 45,000 new diagnoses of cancer in the adolescent and young adult (AYA) population are made in Europe, with sarcoma and brain tumors being some of the most prevalent tumor types.Despite great progress being made in understanding the molecular landscape of cancer in children and adults, AYA cancer biology is still poorly understood.

Material and Methods: To identify clinically relevant molecular alterations in this patient population, we aimed to recruit 50 evaluable patients aged between 12 and 29 with high-risk, sarcoma at initial diagnosis or relapse, using the EORTC-SPECTA platform (deRojas et al. IJC, 2020) and perform in depth molecular analysis (WES, RNAseq, array-based DNA methylation profiling) and central pathology review. Between April 2019 and July 2020, 71 patients were recruited from nine sites within six European countries. In total, 48 patients were evaluable. The remainder (32%) failed quality control, mainly due to poor quality of the formalin-fixed and paraffin-embedded tumor tissue. Median age at diagnosis was 19 years (range 6 to 28 years), including 25 cases of newly diagnosed sarcoma and 23 cases of recurrent sarcoma.

Results: Central pathology review was performed for all evaluable patients. The local diagnosis was confirmed in 41 cases (85.4%) and changed in 7 cases (14.6%), including new diagnoses of BCOR sarcomas (n=3) and teratoma (n=1). DNA methylation analysis was performed for all cases with adequate DNA (n=46), and profiles were categorized according to the Heidelberg classifier (Koelsche et al., Nature Communication, 2021). The classifier confirmed the diagnosis of central pathology in 32 cases (69.6%). The remaining cases showed discrepancies mainly due to poor DNA quality. Whole-exome and RNA sequencing were performed on all samples where DNA and/or RNA quality permitted (98% and 48% respectively).Pathology and molecular profiling results were discussed at a monthly combined clinico-pathological tumor board, with the goal of adapting treatment strategies based on molecular profile either for this treatment episode or for future progression. Actionable molecular alterations were identified in 39 cases. Treatment was adapted in 3 cases and confirmed in 1. Treatment was not adapted in the remainder because they were undergoing primary treatment (n=14), undergoing an alternative treatment for progression (n=10), due to death prior to molecular tumor board (n=10) or loss to follow-up (n=1).

Conclusion: Despite expected logistic challenges associated with sample quality and analysis, actionable alterations were identified in 81.2% of evaluable patients, confirming that there is an unmet clinical need in this population. Moreover, we have identified remediable organizational factors to reduce sample failures and increase the turnaround speed of recommendations in this overlooked AYA cancer population.

Citation Format: Marie Morfouace, Peter Horak, Simon Kreutzfeldt, Patrick Shenjere, Eva Wardelmann, Evgeniya Denisova, Aleksandra Stevovic, Francisco J. Bautista, Julio Oliveira, Winette van der Graaf, Stefan Fröhling, Martin G. McCabe. First results of the EORTC-SPECTA project on comprehensive molecular profiling of adolescent and young adult sarcoma patients [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 2005.