Surgical Innovation

Background

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 clinical need to provide comprehensive molecular analysis allowing for the above in the clinical setting for patients with these cancers in the UK.

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 UCLH, i.e. the UCL/UCLH 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.

The programme is linked with international research networks, 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 University College London 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.

Key publications

1. Hermsen M, Bossi P, Capper D ... Lechner M. The European Network for Sinonasal Cancer Research (EUSICA) - A pan-European initiative targeting a group of orphan tumours. Eur J Cancer. 2024 May;202:113939.
2. Kuan EC, Wang EW, Adappa ND, Beswick DM ... Lechner M, et al. International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors. Int Forum Allergy Rhinol. 2024 Feb;14(2): 149-608.
3. Frampton GM, Fichtenholtz A, Otto GA ... Lechner M, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov;31(11): 1023-31.
4. Capper D, Jones DTW, Sill M ... Lechner M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018 Mar 22;555(7697): 469-474.
5. Capper D, Engel NW, Stichel D, Lechner M, et al. DNA methylation-based reclassification of olfactory neuroblastoma. Acta Neuropathol. 2018 Aug;136(2): 255-271. Erratum in: Acta Neuropathol. 2018 Sep;136(3): 505.
6. Kaur RP, Izumchenko E, Blakaj DM, Mladkova N, Lechner M, et al. The genomics and epigenetics of olfactory neuroblastoma: A systematic review. Laryngoscope Investig Otolaryngol. 2021 Jun 7;6(4): 721-728.
7. Steele CD, Abbasi A, Islam SMA ... Lechner M, et al. Signatures of copy number alterations in human cancer. Nature. 2022 Jun;606(7916): 984-991.
8. Bossi P, Hermsen M, Lechner M, Franchi A. Precision medicine in rare tumors and the need for multicenter trials and international collaboratives: Sinonasal cancer as paradigm. Oral Oncol. 2020 Oct;109: 104737.
9. Lechner M, Schartinger VH, Steele CD, et al. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. Nat Commun. 2021 Jan 5;12(1): 117.
10. Emanuel O, Liu J, Schartinger VH, Nei WL ... Lechner M. SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. Cancers (Basel). 2021 Sep 30;13(19): 4944.
11. Schatz C, Sprung S, Schartinger V, Codina-Martínez H, Lechner M, et al. Dysregulation of Translation Factors EIF2S1, EIF5A and EIF6 in Intestinal-Type Adenocarcinoma (ITAC). Cancers (Basel). 2021 Nov 11;13(22): 5649.
12. Jurmeister P, Glöß S, Roller R ... Lechner M, et al. DNA methylation-based classification of sinonasal tumors. Nat Commun. 2022 Nov 28;13(1): 7148.
13. Lechner M, Takahashi Y, Turri-Zanoni M, et al. Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma. Eur J Cancer. 2022 Feb;162: 221-236.
14. Turri-Zanoni M, Dalfino G, Lechner M, et al. Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review. Acta Otorhinolaryngol Ital. 2022 Dec;42(6): 545-553.
15. Esposito A, Stucchi E, Baronchelli M ... Lechner M, Bossi P. Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers. J Clin Med. 2022 Nov 16;11(22): 6787.
16. Lechner M, Takahashi Y, Turri-Zanoni M, et al. 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. J Neurol Surg B Skull Base. 2022 Jul 10;84(4): 307-319.
17. Hermsen MA, Lechner M, Oliveira Ferrer L, et al. EUSICA/COST IMMUNO-model workshop fostering collaboration to advance sinonasal cancer research: A meeting report. Oral Oncol. 2023 Nov;146: 106543.

Funding