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

Lymphocytes sensitivity to Fas stimulation in healthy and asthmatic children.

The T cell hypothesis of asthma is based on the concept that the disease is driven and maintained by the persistence of a specialized subset of chronically activated T memory cells sensitized against an array of allergenic, occupational or viral antigens. Overreaction of CD4+ T cells in the peripheral blood and airway tissues is an invariant feature of asthma; therefore a potent mechanism for augmenting the number of activated T cells in this disease would be the resistance to the normally programmed pathway for cell death. The aim of the study was to evaluate the presence of apoptotic markers on peripheral blood lymphocytes from healthy and asthmatic children before and after stimulation with antiCD95 antibodies. The blood was collected from 21 children with atopic asthma suffering from allergic rhinitis because of house dust mite and/or grass pollen allergens and 8 healthy children matched for their age and sex. Blood was mixed with purified monoclonal antibody antiCD95 (Beckman Coulter), incubated for 24 hours and than stained with Annexin V andPI (Becton Dickinson). Prepared suspensions were analyzed with Cytomics FC 500 (Beckman Coulter) flow cytometer. Annexin V(+)/PI(-) cells were characterized as early apoptotic, Annexin V(+)/PI(+) as late apoptotic and Annexin V(-)/PI(+) as dead. In unstimulated sample from asthmatic children 21.09+/-11.20% cells were characterized as Annexin V positive/PI negative. After stimulation with antiCD95 Annexin V positive/PI negative cells constituted 18.72+/-9.42% of cells, p=0.1. In unstimulated sample from healthy children 11.69+/-6.70% cells were characterized as Annexin V positive/PI negative. In the sample stimulated with antiCD95 16.54+/-2.98% of cells were Annexin V positive/PI negative, p=0.02. There were no differences between results of late apoptotic and necrotic lymphocytes from healthy and asthmatic children. Performed research indicates that lymphocytes from asthmatic children are resistant to Fas mediated apoptosis

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

Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs. Gamma Knife.

OBJECTIVES: This study compares the dosimetry and efficiency of two modern radiosurgery [stereotactic radiosurgery (SRS)] modalities for multiple brain metastases [Gamma Knife (GK) and LINAC-based RapidArc/volumetric modulated arc therapy], with a special focus on the comparison of low-dose spread. METHODS: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 to 10.5 cc. SRS doses were prescribed according to the size of lesions. SRS plans were made using both Gamma Knife(®) Perfexion and a single-isocenter, multiple non-coplanar RapidArc(®). Dosimetric parameters analyzed included RTOG conformity index (CI), gradient index (GI), 12 Gy isodose volume (V 12Gy) for each target, and the dose spread (Dspread) for each plan. Dspread reflects SRS plan\u27s capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread), such that once dose decreases below Dspread (on total tissue dose-volume histogram), isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc/0.1 Gy dose decrease. RESULTS: RapidArc SRS has smaller CI (1.19 ± 0.14 vs. 1.50 ± 0.16, p \u3c 0.001) and larger GI (4.77 ± 1.49 vs. 3.65 ± 0.98, p \u3c 0.01). V 12Gy results were comparable (2.73 ± 1.38 vs. 3.06 ± 2.20 cc, p = 0.58). Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. GK plans achieved better very low-dose spread (≤3 Gy) and also had slightly smaller Dspread, 1.9 vs. 2.5 Gy. Total treatment time for GK is estimated between 60 and 100 min. GK treatments are between 3 and 5 times longer compared to RapidArc treatment techniques. CONCLUSION: Dosimetric parameters reflecting prescription dose conformality (CI), dose fall off (GI), radiation necrosis indicator (V 12Gy), and dose spread (Dspread) were compared between GK SRS and RapidArc SRS for multi-mets. RapidArc plans have smaller CI but larger GI. V 12Gy are comparable. GK appears better at reducing only very low-dose spread (\u3c3 \u3eGy). The treatment time of RapidArc SRS is significantly reduced compared to GK SRS

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m²with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00330044">NCT00330044</a></p

Increasing Tumor Volume Is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study In Patients With Inoperable Non-Small-Cell Lung Cancer

Purpose Patients with non–small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels.We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm3) vs. larger (\u3e45 cm3) tumors. Results The distribution of the GTV was as follows: ≤45 cm3 in 79 (49%) and \u3e45 cm3 in 82 (51%) of 161 patients. The median GTV was 47.3 cm3. N0 status and female gender were associated with better tumor responses. Patients with smaller (≤45 cm3) tumors achieved a longer MST and better PFS than did patients with larger (\u3e45 cm3) tumors (29.7 vs. 13.3 months, p \u3c 0.0001; and 15.8 vs. 8.3 months, p \u3c 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p \u3c 0.0001; and HR, 1.39, p \u3c 0.0001, respectively). Conclusions Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume. Int. J. Radiation Oncology Biol. Physics, Volume 70, No. 2, pp. 385-390, 200

Stereotactic image-guided lung radiotherapy (SBRT) for clinical early-stage NSCLC: a long-term report from a multi-institutional database of patients treated with or without a pathologic diagnosis

PURPOSE: Early stage lung cancer is treated with stereotactic body radiation therapy (SBRT) in patients who are unable or unwilling to undergo surgical resection. Some patients' comorbidities are so severe that they are unable to even undergo a biopsy. A clinical diagnosis without biopsy before SBRT has been used, but there are limited data on its efficacy. METHODS AND MATERIALS: Data on patients treated with SBRT for non-small cell lung cancer, with and without tissue confirmation, were collected from multiple institutions across Europe, Canada, and the United States. Patients with a minimum of 2 years of comprehensive follow up were selected for analysis. Treatment and patient characteristics were compared. Overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and rates of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) were calculated and analyzed. RESULTS: A total of 701 patients were identified, of which 67% had tissue confirmation of their tumors. The 3- and 5-year outcomes for OS, CSS, and DFS were 83.8%, 93.1%, 69%, and 60.6%, 86.7%, 45.5%, respectively. The rates for LR, RR, and DM at 3 and 5 years were 6.4%, 9.3%, 14.3%, and 10.5%, 14.3%, 19.7%, respectively. There were no statistically significant differences in survival outcomes or recurrences between the biopsy and no-biopsy cohorts. CONCLUSIONS: SBRT for clinically diagnosed lung cancers is efficacious in appropriately selected patients, with similar outcomes as those with a pathologic diagnosis. Thorough clinical and radiographic evaluations in a multidisciplinary setting are critical to the management of these patients