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The ¹û¶³Ó°Ôº/¹û¶³Ó°ÔºH Cancer 2.0 Translational Research and Surgical Innovation Program introduces novel technologies to improve the diagnosis, classification and therapy, and thereby the survival of patients.

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Project Lead: Ellie Crossley (Research Fellow) andÌýMs Yuju Ahn (Grade 7 Bioinformatician)

Key PublicationsÌý

1. The European Network for Sinonasal Cancer Research (EUSICA) – a pan-European initiative targeting a group of orphan tumours. M. Hermsen, … & M. Lechner. European Journal of Cancer. 2024; in print.

2.International consensus statement on allergy and rhinology: Sinonasal tumors. E.C. Kuan, E.W. Wang, N.D. Adappa, D.M. Beswick, N.R. London Jr, S.Y. Su, M.B. Wang, W.M. Abuzeid, B. Alexiev, J.A. Alt, P. Antognoni, … , M. Lechner, … J.N. Palmer. International Forum of Allergy and Rhinology. 2023; doi: 10.1002/alr.23262. Epub ahead of print. PMID: 37658764.

3. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing; G.M. Frampton, A. Fichtenholt, …, M. Lechner, C. Boshoff, …, R. Yelensky; Nature Biotechnology. 2013, 10.1038/nbt.2696.

4.ÌýDNA methylation-based classification of central nervous system tumours. D. Capper, D.T.W. Jones, …, M. Lechner, ... , A. von Deimling, Pfister SM; Nature. 2018; 555(7697):469-474.

5. DNA methylation-based reclassification of olfactory neuroblastoma. D. Capper, N.W. Engel, D. Stichel, M. Lechner, …, M. Meinhardt, U. Schüller. Acta Neuropathol. 2018. doi: 10.1007/s00401-018-1854-7.

6. The genomics and epigenetics of olfactory neuroblastoma: A systematic review. R.P. Kaur, E. Izumchenko, D.M. Blakaj, N. Mladkova, M. Lechner, T.L. Beaumont; Laryngoscope Investigative Otolaryngology. 2021; doi.org/10.1002/lio2.597

7. Signatures of copy number alterations in human cancer. C.D. Steele, A. Abbasi, S.M.A. Islam, A.L. Bowes, A. Khandekar, K. Haase, S. Hames-Fathi, D. Ajayi, A. Verfaillie, P. Dhami, A. McLatchie, M. Lechner, N. Light, A. Shlien, D. Malkin, A. Feber, P. Proszek, T. Lesluyes, F. Mertens, A.M. Flanagan, M. Tarabichi,, P. Van Loo, L.B. Alexandrov, N. Pillay; Nature. 2022; doi: 10.1038/s41586-022-04738-6.

8. Precision medicine in rare tumors and the need for multicenter trials and international collaboratives: Sinonasal cancer as paradigm. P. Bossi, M. Hermsen, M. Lechner, A. Franchi. Oral Oncology. 2020;104737. doi:10.1016/j.oraloncology.2020.104737

9. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. M. Lechner, et al.; Nature Communications. 2020; 12(1):117. doi: 10.1038/s41467-020-20308-8.

10. SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. O. Emanuel, J. Liu, V.H. Schartinger, W.L. Nei, Y.Y. Chan, C.M. Tsang,ÌýH. Riechelmann, L. Masterson, J. Haybaeck, U. Oppermann, S.M. Willems, M.L. Ooft, G. Wollmann, D. Howard, B. Vanhaesebroeck, V.J. Lund, G. Royle, M.L.K. Chua, K.W. Lo, P. Busson, and M. Lechner; Cancers. 2021; 13(19), 4944;Ìý

11. C. Schatz, … , M. Lechner, M. Hermsen, J. Haybaeck. Dysregulation of Translation Factors EIF2S1, EIF5A and EIF6 in Intestinal-Type Adenocarcinoma (ITAC). Cancers (Basel). 2021 Nov 11;13(22):5649. doi: 10.3390/cancers13225649. PMID: 34830804; PMCID: PMC8616251.

12. DNA methylation-based classification of sinonasal tumors. P. Jurmeister, … , M. Lechner, ... , D. Capper. Nature Communications. 2022; 13(1):7148. doi: 10.1038/s41467-022-34815-3..

13. Clinical Outcomes, Kadish-INSICA Staging and Therapeutic Targeting of SSTR2 in Olfactory Neuroblastoma. M. Lechner, et al.; European Journal of Cancer. 2022; 162:221-236; doi: 10.1016/j.ejca.2021.09.046.

14. Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review. M. Turri-Zanoni, G. Dalfino, M. Lechner, I. Dallan, P. Battaglia, C. Facco, F. Franzi, G. Gravante, M. Ferrari, D. Terzakis, A. Jay, M.D. Forster, A.L. Ambrosoli, M. Bignami, C. Georgalas, P. Herman, P. Nicolai, V.J. Lund, P. Castelnuovo. Acta Otorhinolaryngol Ital. 2022; 42(6):545-553. doi: 10.14639/0392-100X-N2087.Ìý

15. Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers. A. Esposito, … , M. Lechner & P. Bossi. Journal of Clinical Medicine. 2022;11(22):6787. doi: 10.3390/jcm11226787.Ìý

16. International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System. M. Lechner, et al. Journal of Neurological Surgery—Part B: Skull Base. 2022; DOI: 10.1055/s-0042-1750178.

17. EUSICA/COST IMMUNO-model workshop fostering collaboration to advance sinonasal cancer research: A meeting report. M.A. Hermsen, M. Lechner, L. Oliveira Ferrer, A. Trama, P.R.G. Eriksen, E. Martinez-Balibrea, C. von Buchwald. Oral Oncology. 2023; 146:106543. doi: 10.1016/j.oraloncology.2023.106543.

Diagnosis of many rare cancers in the UK is often delayed and highly challenging due to overlapping histopathological characteristics, leading to frequent misdiagnoses. For sinonasal cancers, skull base tumours, and brain tumours, evidence shows that initial misdiagnoses result in poorer outcomes and incorrect treatment recommendations. Molecular analysis can classify these tumours into subgroups with distinct clinical outcomes and treatment options. There is unmet clinical need to provide comprehensive molecular analysis allowing for the above in the clinical setting for patients with these cancers in the UK currently.

Genomics England’s 100,000 Genomes project has laid the foundation for the NHS Genomic Medicine Service (NHS GMS) through which molecular testing is already offered. Matt has served as National Co-Lead of the Head and Neck Domain of the 100,000 Genomes Project since 2016.

Genomic testing is now delivered routinely for many NHS patients as part of the commitment outlined in the NHS Long Term Plan. However, genomic analysis alone does not overcome the above challenges which are faced by many histopathologists.

There is clear evidence that the analysis of epigenetic/DNA methylation marks (‘methylation classifier’) can classify brain tumours and sinonasal cancers into subgroups, each associated with specific treatment options and clinical outcomes. This technology has not been introduced into routine clinical care.

This programme introduces this technology at ¹û¶³Ó°ÔºH, i.e. the ¹û¶³Ó°Ôº/¹û¶³Ó°ÔºH Cancer 2.0 Translational Research and Surgical Innovation Programme, and beyond, with a focus on improving the diagnosis, classification and therapy, and thereby the survival of patients affected by these tumours.

This programme is linked with international research network, including the European Network for Sinonasal Cancer Research (EUSICA; ) and the International Network for Research on Sinonasal Cancer, Nasopharyngeal Cancer, Skull Base Tumors and Brain Cancers (INSICA-Brain). Together with INSICA-Brain we offer a platform for international collaboration under the umbrella of an IRB approval for multi-center data analysis from the ¹û¶³Ó°Ôº IRB/Research Ethics Committee with further local approval from all institutions. This allows us to publish the largest datasets on sinonasal cancers, nasopharyngeal cancer, skull base tumors and brain cancers in order to inform on clinical outcomes, improved staging systems and novel biomarkers.

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