Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences

Authors

  • Erika Tóth National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest https://orcid.org/0000-0003-2054-8447
  • Zsófia Kürönya National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0001-8500-5924
  • Edina Soós National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology
  • Tamás Pintér National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0001-7462-9424
  • Henriett Butz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary; Central Biobank, National Institute of Oncology, Budapest https://orcid.org/0000-0003-1664-409X
  • Zsolt Horváth National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology https://orcid.org/0000-0002-5376-7737
  • Erzsébet Csernák National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • Vince Kornél Grolmusz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary https://orcid.org/0000-0002-5677-895X
  • Judit Székely National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary
  • Tamás Straussz National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • József Lövey National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0001-6467-191X
  • Levenete Jánvári National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary
  • László Báthory-Fülöp National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
  • Péter Nagy National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0003-3393-235X
  • Csaba Polgár National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary https://orcid.org/0000-0001-7245-0762
  • Attila Patócs National Institute of Oncology, National Tumor Biology Laboratory, Budapest, Hungary; Department of Molecular Genetics, National Institute of Oncology; HUN-REN Hereditary Cancer Research Group, Budapest, Hungary https://orcid.org/0000-0001-7506-674X

DOI:

https://doi.org/10.2340/1651-226X.2024.39918

Keywords:

Tumour mutation profile, molecular tumour board, targeted therapy

Abstract

Recent developments in molecular genetic testing methods (e.g. next-generation sequencing [NGS]-panels) largely accelerated the process of finding the most appropriate targeted therapeutic intervention for cancer patients based on molecularly targetable genetic alterations. In Hungary, a centralized approval system following the recommendation of the National Molecular Tumor Board was launched for the coordination of all aspects of comprehensive genetic profiling (CGP) including patient selection and therapy reimbursement.

Aim: The study aims to evaluate the clinical benefit of CGP in our Comprehensive Cancer Center

Methods and patients: CGP was introduced into our routine clinical practice in 2021. An NGS-based large (> 500 genes) gene panel was used for cases where molecular genetic testing was approved by the National Molecular Tumor Board. From 2021 until August 2023 163 cases were tested. The majority of them were ECOG 0–1 patients with advanced-stage diseases, histologically rare cancer, or cancers with unknown primary tumours.

Results: Seventy-four cases (74 of 163, 45%) had clinically relevant genetic alterations. In 34 patients, the identified variants represented an indication for an approved therapy (approved by the Hungarian authorities, on-label indication), while in 40 cases the recommended therapy did not have an approved indication in Hungary for certain tumour types, but off-label indication could be recommended. Based on our CGP results, 24 patients (24/163; 14.7%) received targeted therapy. Treatment duration was between 1 and 60 months. In total 14 (14/163; 8.5% of the tested cases) patients had a positive clinical response (objective response or stable disease) and were treated for more than 16 weeks.

Interpretation: NGS-based CGP was successfully introduced in our institution and a significant number of patients benefited from comprehensive genetic tests. Our preliminary results can serve as the starting point of Drug Rediscovery Protocol (DRUP) studies.

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Published

2024-06-16

How to Cite

Tóth, E., Kürönya, Z., Soós, E., Pintér, T., Butz, H., Horváth, Z., … Patócs, A. (2024). Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences. Acta Oncologica, 63(1), 433–440. https://doi.org/10.2340/1651-226X.2024.39918

Issue

Vol. 63 (2024): Acta Oncologica

Section

Short report

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Copyright (c) 2023 Erika Tóth, Zsófia Kürönya, Edina Soós, Tamás Pintér, Henriett Butz, Zsolt Horváth, Erzsébet Csernák, Vince Kornél Grolmusz, Judit Székely, Tamás Straussz, József Lövey, Levenete Jánvári, László Báthory-Fülöp, Péter Nagy, Csaba Polgár, Attila Patócs

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