ABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0116388.].
ABSTRACT
PURPOSE: Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called "precision medicine." However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kinases. Kinase activity profiling is therefore theorized to be more reflective of in vivo biology than many current molecular analysis techniques. As a result, this study seeks to prove the feasibility of combining a novel minimally invasive biopsy technique that expands the number of lesions amenable for biopsy with subsequent ex vivo kinase activity analysis. METHODS: Eight patients with lung lesions of varying location and size were biopsied using the novel electromagnetic navigational bronchoscopy (ENB) technique. Basal kinase activity (kinomic) profiles and ex vivo interrogation of samples in combination with tyrosine kinase inhibitors erlotinib, crizotinib, and lapatinib were performed by PamStation 12 microarray analysis. RESULTS: Kinomic profiling qualitatively identified patient specific kinase activity profiles as well as patient and drug specific changes in kinase activity profiles following exposure to inhibitor. Thus, the study has verified the feasibility of ENB as a method for obtaining tissue in adequate quantities for kinomic analysis and has demonstrated the possible use of this tissue acquisition and analysis technique as a method for future study of lung cancer biomarkers. CONCLUSIONS: We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients.
Subject(s)
Bronchoscopy/methods , Gene Expression Profiling/methods , Lung Neoplasms/pathology , Phosphotransferases/metabolism , Protein Kinase Inhibitors/pharmacology , Aged , Aged, 80 and over , Crizotinib , Electromagnetic Phenomena , Erlotinib Hydrochloride , Female , Gene Expression Profiling/instrumentation , Humans , Lapatinib , Lung Neoplasms/enzymology , Male , Middle Aged , Precision Medicine/methods , Pyrazoles/pharmacology , Pyridines/pharmacology , Quinazolines/pharmacologyABSTRACT
PURPOSE: To determine whether the method or extent of construction of the high-dose clinical target volume (CTV) and high-dose planning target volume (PTV) in intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are associated with an increased risk of locoregional failure. MATERIALS AND METHODS: Patients with nasopharyngeal, oropharyngeal, oral cavity, hypopharyngeal, or laryngeal squamous cell carcinomas treated definitively with IMRT were included. All patients without local relapse had a minimum follow-up of 12 months. Median follow-up for all patients was 24 months. Treatment plans of 85 available patients were reviewed, and the gross tumor volume (GTV) to PTV expansion method was estimated. RESULTS: The GTVs were expanded volumetrically in 71 of 85 patients, by a median of 15 mm (range, 4-25 mm). An anatomic component to the expansion of GTV was used in 14 of 85 patients. Eighteen patients failed locoregionally, for an actuarial locoregional control rate of 77.2% at 2 years. There was no significant difference in locoregional control between patients with GTVs expanded volumetrically vs. those with a component of anatomic expansion. In patients with GTVs expanded volumetrically, no increase in risk of local failure was seen in patients with a total GTV expansion of < or =15 mm. CONCLUSION: In this retrospective study, there was not an increased risk of local failure using smaller margins or expanding GTVs volumetrically when treating head-and-neck cancer patients definitively with IMRT.
