Predictors of Survival for Patients with Non-small Cell Lung Cancer and Synchronous Brain Metastases with FDG-PET/CT Staging

Purpose: The clinical course of patients diagnosed with non-small cell lung cancer (NSCLC) with brain metastases (BM) at presentation is variable. Here we seek to identify predictors of survival in patients staged with FDG-PET/CT. American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, P

Decrease of Morbidity and Cost of Care with Prophylactic Cranial Irradiation for Non-small Cell Lung Cancer

Purpose: While several studies analyze the incidence of brain metastases in patients with non-small cell lung cancer (NSCLC) treated with prophylactic cranial irradiation (PCI), there is little data available on how this treatment can affect medical cost and morbidity. Our goal was to analyze those issues patients encounter secondary to brain metastases, often in the final months of their lives, and to support the hypothesis of economic benefit and cost effectiveness resulting from the use of PCI in this population. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Comparison of Online 6 Degree-of-Freedom Image Registration of Varian TrueBeam Cone-Beam CT and BrainLab ExacTrac X-Ray for Intracranial Radiosurgery.

PURPOSE: The study was aimed to compare online 6 degree-of-freedom image registrations of TrueBeam cone-beam computed tomography and BrainLab ExacTrac X-ray imaging systems for intracranial radiosurgery. METHODS: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (version 2.5), which is integrated with a BrainLab ExacTrac imaging system (version 6.1.1). The phantom study was based on a Rando head phantom and was designed to evaluate isocenter location dependence of the image registrations. Ten isocenters at various locations representing clinical treatment sites were selected in the phantom. Cone-beam computed tomography and ExacTrac X-ray images were taken when the phantom was located at each isocenter. The patient study included 34 patients. Cone-beam computed tomography and ExacTrac X-ray images were taken at each patient\u27s treatment position. The 6 degree-of-freedom image registrations were performed on cone-beam computed tomography and ExacTrac, and residual errors calculated from cone-beam computed tomography and ExacTrac were compared. RESULTS: In the phantom study, the average residual error differences (absolute values) between cone-beam computed tomography and ExacTrac image registrations were 0.17 ± 0.11 mm, 0.36 ± 0.20 mm, and 0.25 ± 0.11 mm in the vertical, longitudinal, and lateral directions, respectively. The average residual error differences in the rotation, roll, and pitch were 0.34° ± 0.08°, 0.13° ± 0.09°, and 0.12° ± 0.10°, respectively. In the patient study, the average residual error differences in the vertical, longitudinal, and lateral directions were 0.20 ± 0.16 mm, 0.30 ± 0.18 mm, 0.21 ± 0.18 mm, respectively. The average residual error differences in the rotation, roll, and pitch were 0.40°± 0.16°, 0.17° ± 0.13°, and 0.20° ± 0.14°, respectively. Overall, the average residual error differences wer

Phase i study of \u27dose-dense\u27 pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma.

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m2) q3 weeks × 2 -3 cycles. RESULTS: Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. CONCLUSIONS: Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC

Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the treatment delivery accuracy as well

Combination of Vorinostat with Whole-brain Radiotherapy in the Treatment of Brain Metastases

Background: A third of patients with solid malignancies develop brain metastases. Expected overall survival is 4-7 months depending on age, performance status, and extracranial disease. Standard treatment is controversial; however, the majority of patients receive wholebrain radiation therapy at some point. Vorinostat (suberoylanilide hydroxamic acid, SAHA), an FDA-approved HDAC inhibitor, has been demonstrated to radiosensitize tumor cells in vitro, as assessed by both radiation-induced DNA damage and clonogenic cell survival (Munshi et al. Molecular Cancer Therapeutics 5, 1967-1974, 2006). We have shown that vorinostat downregulates key genes involved in double-strand DNA repair (Rad50, Rad51, XRCC2, XRCC3, XRCC6), as assessed by quantitative PCR. This suggests that the drug’s mechanism of radiosensitization is epigenetic coordinated inhibition of the DNA repair process. We hypothesize that the combination of vorinostat with whole-brain radiation therapy will be both safe and efficacious. American Society of Clinical Oncology (ASCO) 46th Annual Meeting June 4-8, Chicago, IL

Reirradiation for Recurrent Meningioma

Purpose/Objective(s): Management options for meningioma include observation, surgical resection, and radiation therapy (RT). In cases of progressive or recurrent disease after RT, similar options exist. The control rate following a second course of RT is unknown. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Dosimetric Evaluation of Tumor Tracking in 4D Radiotherapy

Purpose: In some patients the tumors in lung, pancreas, liver, breast, and other organs move significantly during cardiac and breathing cycles. In this study we have investigated the dosimetric benefits of real-time tumor tracking for patients who were diagnosed with lung cancer. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database

Pathologic Correlation of PET-CT Based Auto Contouring for Radiation Planning in Lung Cancer

Purpose/Objective(s): Radiation therapy in lung cancer relies on CT and functional imaging (FDG-PET) to delineate tumor volumes. Semi-automatic contouring tools have been developed for PET to improve on the inter-observer bias of manual contouring and intrinsic differences in imaging equipment. A common method involves using a threshold at a given percentage of the max activity, which may be less accurate with smaller tumors and tumors with low source to background ratio. To overcome this deficiency, a gradient algorithm, which detects changes in image counts at the border of the tumor, has been developed. Few studies have correlated these methods to pathological specimens. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C