Cargando…

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhib...

Descripción completa

Detalles Bibliográficos
Autores principales: Nenadić, Ilija, Staber, Janine, Dreier, Susanne, Simons, Guus, Schildgen, Verena, Brockmann, Michael, Schildgen, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532624/
https://www.ncbi.nlm.nih.gov/pubmed/28696381
http://dx.doi.org/10.3390/cancers9070088
_version_ 1783253497056067584
author Nenadić, Ilija
Staber, Janine
Dreier, Susanne
Simons, Guus
Schildgen, Verena
Brockmann, Michael
Schildgen, Oliver
author_facet Nenadić, Ilija
Staber, Janine
Dreier, Susanne
Simons, Guus
Schildgen, Verena
Brockmann, Michael
Schildgen, Oliver
author_sort Nenadić, Ilija
collection PubMed
description With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing), but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can also be observed in healthy tissues and are not compulsorily associated with tumors. Therefore, it is important to keep in mind that even for the known variants of ALK fusion genes, the biological function is not known for all variants, and that no information is available on the homogeneity of ALK fusion variants within a single tumor. These facts, in concert with data for ALK mutation prevalence and therapy outcomes of a German cohort of NSCLC patients, support the hypothesis that, by using novel companion diagnostic tools in combination with therapy outcome predictions, massive cost savings could be possible in European Health Care systems without a loss of patient care.
format Online
Article
Text
id pubmed-5532624
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-55326242017-08-07 Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics Nenadić, Ilija Staber, Janine Dreier, Susanne Simons, Guus Schildgen, Verena Brockmann, Michael Schildgen, Oliver Cancers (Basel) Opinion With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing), but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can also be observed in healthy tissues and are not compulsorily associated with tumors. Therefore, it is important to keep in mind that even for the known variants of ALK fusion genes, the biological function is not known for all variants, and that no information is available on the homogeneity of ALK fusion variants within a single tumor. These facts, in concert with data for ALK mutation prevalence and therapy outcomes of a German cohort of NSCLC patients, support the hypothesis that, by using novel companion diagnostic tools in combination with therapy outcome predictions, massive cost savings could be possible in European Health Care systems without a loss of patient care. MDPI 2017-07-11 /pmc/articles/PMC5532624/ /pubmed/28696381 http://dx.doi.org/10.3390/cancers9070088 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Opinion
Nenadić, Ilija
Staber, Janine
Dreier, Susanne
Simons, Guus
Schildgen, Verena
Brockmann, Michael
Schildgen, Oliver
Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title_full Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title_fullStr Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title_full_unstemmed Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title_short Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
title_sort cost saving opportunities in nsclc therapy by optimized diagnostics
topic Opinion
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532624/
https://www.ncbi.nlm.nih.gov/pubmed/28696381
http://dx.doi.org/10.3390/cancers9070088
work_keys_str_mv AT nenadicilija costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT staberjanine costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT dreiersusanne costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT simonsguus costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT schildgenverena costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT brockmannmichael costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics
AT schildgenoliver costsavingopportunitiesinnsclctherapybyoptimizeddiagnostics