A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents.
Raman spectroscopy is a noninvasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR, or BRAF inhibitors, which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor. Our algorithm, based on partial least squares-discriminant analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events. For MEK and EGFR inhibitors, discriminative power was more than 90% in the viable epidermis skin layer; whereas for BRAF inhibitors, discriminative power was 71%. There was a 81.5% correlation between blood drug concentration and Raman signature of skin in the case of EGFR inhibitors and viable epidermis skin layer. Our results demonstrate the power of Raman spectroscopy to detect apparition of skin toxicity in patients treated with tyrosine kinase inhibitors at levels not detectable via dermatological inspection and histological evaluation. Cancer Res; 77(2); 557-65. ©2016 AACR.
UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France. antoine.azan@gustaveroussy.fr.
Antoine
A
Azan
Center for Optical Diagnostics & Therapy, Department of Dermatology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.|RiverD International B.V. Rotterdam, the Netherlands.
Peter J
PJ
Caspers
Center for Optical Diagnostics & Therapy, Department of Dermatology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.|RiverD International B.V. Rotterdam, the Netherlands.
Tom C
TC
Bakker Schut
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Séverine
S
Roy
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Céline
C
Boutros
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Christine
C
Mateus
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Emilie
E
Routier
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Benjamin
B
Besse
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
David
D
Planchard
Department of Pharmacology and Drug Analysis, Gustave Roussy, Villejuif, France.
Atmane
A
Seck
UMR 981, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
Nyam
N
Kamsu Kom
Department of Pathology, Gustave Roussy, Villejuif, France.
Gorana
G
Tomasic
Department of Pathology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.
Senada
S
Koljenović
Department of Pathology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.
Vincent
V
Noordhoek Hegt
UMR 1018, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
Matthieu
M
Texier
UMR 1018, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
Emilie
E
Lanoy
Department of Medical Oncology, Gustave Roussy, Villejuif, France.|Faculty of Medicine, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin Bicêtre, France.
Alexander M M
AM
Eggermont
UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.|Department of Pharmacology and Drug Analysis, Gustave Roussy, Villejuif, France.
Angelo
A
Paci
Department of Medical Oncology, Gustave Roussy, Villejuif, France.|UMR 981, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.|Faculty of Medicine, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin Bicêtre, France.
Caroline
C
Robert
Center for Optical Diagnostics & Therapy, Department of Dermatology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.|RiverD International B.V. Rotterdam, the Netherlands.
Gerwin J
GJ
Puppels
UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
Lluis M
LM
Mir
D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D003875:Drug Eruptions / Q000175:diagnosis*; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D007211:Indoles / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010091:Oximes / Q000009:adverse effects; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D011728:Pyridones / Q000009:adverse effects; D011744:Pyrimidinones / Q000009:adverse effects; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013449:Sulfonamides / Q000009:adverse effects; D000077484:Vemurafenib
D000970:Antineoplastic Agents; D015415:Biomarkers; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; D000069347:Erlotinib Hydrochloride; C561627:dabrafenib