Next Article in Journal
Cancer Takes a Toll on Skeletal Muscle by Releasing Heat Shock Proteins—An Emerging Mechanism of Cancer-Induced Cachexia
Next Article in Special Issue
Unique Aberrations in Intimal Sarcoma Identified by Next-Generation Sequencing as Potential Therapy Targets
Previous Article in Journal
Skeletal Metastases of Unknown Primary: Biological Landscape and Clinical Overview
Previous Article in Special Issue
A Multi-Center Study of BRCA1 and BRCA2 Germline Mutations in Mexican-Mestizo Breast Cancer Families Reveals Mutations Unreported in Latin American Population
Open AccessArticle

In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients

1
Université Côte d’Azur, 06000 Nice, France
2
Team 4, Institute for Research on Cancer and Aging Nice (IRCAN), Institut de la Santé et de le Recherche Médicale (INSERM) U1081/CNRS 7284, 06107 Nice, France
3
Laboratory of Clinical and Experimental Pathology, Biobank BB-0033-00025, Centre Hospitalier Universitaire de Nice, 06000 Nice, France
4
FHU OncoAge, Pasteur Hospital, 06000 Nice, France
5
Department of Pulmonology and Thoracic Oncology, Centre Hospitalier Universitaire de Nice, 06000 Nice, France
6
Epione Team, Inria, Sophia Antipolis, 06902 Valbonne, France
7
Department of Oncology, Antoine Lacassagne Comprehensive Cancer Center, 06200 Nice, France
8
Department of Nuclear Medicine, Antoine Lacassagne Comprehensive Cancer Center, 06200 Nice, France
9
Department of Dermatology, Archet II Hospital, Centre Hospitalier Universitaire de Nice, 06000 Nice, France
10
Department of Radiology, Archet 2 Hospital, Centre Hospitalier Universitaire de Nice, 06000 Nice, France
11
Centre Méditerranéen de Médecine Moléculaire (C3M), Institut de la Santé et de le Recherche Médicale (INSERM) U1065, 06204 Nice, France
12
Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
13
Center for Personalized Oncology (DKFZ-HIPO), Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1271; https://doi.org/10.3390/cancers11091271
Received: 18 July 2019 / Revised: 13 August 2019 / Accepted: 28 August 2019 / Published: 29 August 2019
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R2 = 0.73) and melanoma (R2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC. View Full-Text
Keywords: tumor mutational burden; FoundationOne assay; Oncomine TML assay; lung cancer; melanoma; immunotherapy tumor mutational burden; FoundationOne assay; Oncomine TML assay; lung cancer; melanoma; immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Heeke, S.; Benzaquen, J.; Long-Mira, E.; Audelan, B.; Lespinet, V.; Bordone, O.; Lalvée, S.; Zahaf, K.; Poudenx, M.; Humbert, O.; Montaudié, H.; Dugourd, P.-M.; Chassang, M.; Passeron, T.; Delingette, H.; Marquette, C.-H.; Hofman, V.; Stenzinger, A.; Ilié, M.; Hofman, P. In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients. Cancers 2019, 11, 1271.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop