[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients.
PLoS ONE 12/2014; 9(12):e116388. DOI:10.1371/journal.pone.0116388 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Spatial accuracy is most crucial when small targets like the trigeminal nerve are treated. Although current quality assurance procedures typically verify that individual apparatus, like the MRI scanner, CT scanner, Gamma Knife, etc., are meeting specifications, the cumulative error of all equipment and procedures combined may exceed safe margins. This study uses an end-to-end approach to assess the overall targeting errors that may have occurred in individual patients previously treated for trigeminal neuralgia.
The trigeminal nerve is simulated by a 3 mm long, 3.175 mm (1/8 in.) diameter MRI-contrast filled cavity embedded within a PMMA plastic capsule. The capsule is positioned within the head frame such that the location of the cavity matches the Gamma Knife coordinates of an arbitrarily chosen, previously treated patient. Gafchromic EBT2 film is placed at the center of the cavity in coronal and sagittal orientations. The films are marked with a pinprick to identify the cavity center. Treatments are planned for radiation delivery with 4 mm collimators according to MRI and CT scans using the clinical localizer boxes and acquisition protocols. Shots are planned so that the 50% isodose surface encompasses the cavity. Following irradiation, the films are scanned and analyzed. Targeting errors are defined as the distance between the pinprick, which represents the intended target, and the centroid of the 50% isodose line, which is the center of the radiation field that was actually delivered.
Averaged over ten patient simulations, targeting errors along the x, y, and z coordinates (patient's left-to-right, posterior-to-anterior, and head-to-foot) were, respectively, -0.060 ± 0.363, -0.350 ± 0.253, and 0.348 ± 0.204 mm when MRI was used for treatment planning. Planning according to CT exhibited generally smaller errors, namely, 0.109 ± 0.167, -0.191 ± 0.144, and 0.211 ± 0.094 mm. The largest errors along individual axes in MRI- and CT-planned treatments were, respectively, -0.761 mm in the y-direction and 0.428 mm in the x-direction, well within safe limits.
The highly accurate dose delivery was possible because the Gamma Knife, MRI scanner, and other equipment performed within tight limits and scans were acquired using the thinnest slices and smallest pixel sizes available. Had the individual devices performed only near the limits of their specifications, the cumulative error could have left parts of the trigeminal nerve undertreated. The presented end-to-end test gives assurance that patients had received the expected high quality treatment. End-to-end tests should become part of clinical practice.
Medical Physics 11/2014; 41(11):111703. DOI:10.1118/1.4896819 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
International journal of radiation oncology, biology, physics 05/2009; 76(1):164-8. DOI:10.1016/j.ijrobp.2009.01.037 · 4.26 Impact Factor