Hubert Y. Pan

Implementation and evaluation of various demons deformable image registration algorithms on a GPU

Online adaptive radiation therapy (ART) promises the ability to deliver an optimal treatment in response to daily patient anatomic variation. A major technical barrier for the clinical implementation of online ART is the requirement of rapid image segmentation. Deformable image registration (DIR) has been used as an automated segmentation method to transfer tumor/organ contours from the planning image to daily images. However, the current computational time of DIR is insufficient for online ART. In this work, this issue is addressed by using computer graphics processing units (GPUs). A gray-scale-based DIR algorithm called demons and five of its variants were implemented on GPUs using the compute unified device architecture (CUDA) programming environment. The spatial accuracy of these algorithms was evaluated over five sets of pulmonary 4D CT images with an average size of 256 x 256 x 100 and more than 1100 expert-determined landmark point pairs each. For all the testing scenarios presented in this paper, the GPU-based DIR computation required around 7 to 11 s to yield an average 3D error ranging from 1.5 to 1.8 mm. It is interesting to find out that the original passive force demons algorithms outperform subsequently proposed variants based on the combination of accuracy, efficiency and ease of implementation.

GPU-based ultra-fast dose calculation using a finite size pencil beam model

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity-modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation in the case of a water phantom and the case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200 to 400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27 GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a nine-field prostate IMRT plan with this new framework is less than 1 s. This indicates that the GPU-based FSPB algorithm is well suited for online re-planning for adaptive radiotherapy.

Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).

Importance Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. Objective To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non–small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA. Design, Setting, and Participants This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. Main Outcomes and Measures The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. Results The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-molGPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. Conclusions and Relevance In recent years, patient survival and physicians’ ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

Frameless, real-time, surface imaging-guided radiosurgery: clinical outcomes for brain metastases.

Frameless stereotactic radiosurgery (SRS) for intracranial brain metastases can provide more comfortable treatment setup than rigid frame-based immobilization with equivalent accuracy. The aim of this study is to report the UCSD SRS experience and update the clinical outcomes using a novel real-time, frameless, surface imaging-guided (SIG-RS) technique in the treatment of brain metastases. Data were retrospectively examined for 163 patients totaling 490 lesions and 45 post-operative cavities treated with SIG- RS in a median delivery of 1 fraction (range, 1-5 fraction) and to a median dose of 22 Gy (range, 12-30 Gy). Local control and overall survival were estimated by the Kaplan-Meier method. Median follow-up for all patients was 6.7 months (range, 0.5-45.1 months), with 119 of 163 (73%) deceased at the time of analysis. The 134 patients (82%) with follow-up imaging studies totaling 378 lesions and 39 post-operative cavities were evaluated for local control. The actuarial 6- and 12-month local control was 90% (95% confidence interval (CI), 84-94%) and 79% (95% CI, 71-86%), respectively. The actuarial 6- and 12-month overall survival was 80% (95% CI, 74-85%) and 56% (95% CI, 49-63%), respectively. There is no significant difference in local control between treatment to post-operative cavities or intact lesions. Consistent with our earlier report of 44 patients, SIG-RS for treatment of intracranial metastases can produce outcomes comparable to those with conventional frame-based and frameless SRS techniques while providing greater patient comfort with an open-faced mask and fast treatment time.

Clinical practice patterns of lung stereotactic body radiation therapy in the United States: a secondary analysis.

Objectives:Stereotactic body radiation therapy (SBRT) is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to ≥1 extracranial target(s). Although recent studies have shown that SBRT provides effective local tumor control in medically inoperable early-stage lung cancer patients, its implementation in clinical practice is unknown. Methods:A random sample of 1600 American radiation oncologists was surveyed regarding lung SBRT usage, including year adopted, most common prescription, respiratory motion management, and target localization. A biological equivalent dose (BED) was calculated using the linear quadratic model with &agr;/&bgr;=10. Spearman rank correlation coefficients (rs) were calculated to identify factors associated with BED. Results:Of 1373 contactable physicians, 551 responses (40%) were received. Of 510 evaluable responses, 275 physicians (54%) reported using lung SBRT, over half of whom adopted it in 2008 or later. The most commonly reported prescriptions were 20 Gy×3 (22%), 18 Gy×3 (21%), and 12 Gy×4 (17%). Three fraction regimens were most common (48%), with nearly all (89%) prescribing ≥18 Gy/fraction. The median BED was 132 Gy, with 95% of reported prescriptions having BED≥100 Gy. Factors associated with increased BED included use of fiducial markers (rs=0.26, P<0.001), use of planar imaging (rs=0.18, P<0.01), and years of experience with lung SBRT (rs=0.13, P=0.04). Conclusions:Lung SBRT has rapidly become a widely adopted treatment approach in the United States with a range of varying implementations. Further research and additional prospective trials are necessary to optimize this novel approach.

Supply and Demand for Radiation Oncology in the United States: Updated Projections for 2015 to 2025

PURPOSE Prior studies have forecasted demand for radiation therapy to grow 10 times faster than the supply between 2010 and 2020. We updated these projections for 2015 to 2025 to determine whether this imbalance persists and to assess the accuracy of prior projections. METHODS AND MATERIALS The demand for radiation therapy between 2015 and 2025 was estimated by combining current radiation utilization rates determined by the Surveillance, Epidemiology, and End Results data with population projections provided by the US Census Bureau. The supply of radiation oncologists was forecast by using workforce demographics and full-time equivalent (FTE) status provided by the American Society for Radiation Oncology (ASTRO), current resident class sizes, and expected survival per life tables from the US Centers for Disease Control. RESULTS Between 2015 and 2025, the annual total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 19%, from 490,000 to 580,000. Assuming a graduating resident class size of 200, the number of FTE physicians is expected to increase by 27%, from 3903 to 4965. In comparison with prior projections, the new projected demand for radiation therapy in 2020 dropped by 24,000 cases (a 4% relative decline). This decrease is attributable to an overall reduction in the use of radiation to treat cancer, from 28% of all newly diagnosed cancers in the prior projections down to 26% for the new projections. By contrast, the new projected supply of radiation oncologists in 2020 increased by 275 FTEs in comparison with the prior projection for 2020 (a 7% relative increase), attributable to rising residency class sizes. CONCLUSION The supply of radiation oncologists is expected to grow more quickly than the demand for radiation therapy from 2015 to 2025. Further research is needed to determine whether this is an appropriate correction or will result in excess capacity.

Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials.

OBJECTIVE The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS. METHODS Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS. RESULTS SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38-75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033) CONCLUSIONS SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.

Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

PURPOSE To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). METHODS AND MATERIALS In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. RESULTS Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). CONCLUSIONS Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT.

Prospective exploratory analysis of cardiac biomarkers and electrocardiogram abnormalities in patients receiving thoracic radiation therapy with high-dose heart exposure.

Introduction: Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods: Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received more than or equal to 45 Gy to the thorax, with pretreatment estimates of more than or equal to 20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results: The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median TnI or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (p = 0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion: Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.

Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials.

PURPOSE There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. METHODS AND MATERIALS Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥ 3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derived survival score. RESULTS Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P = .007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P < .001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P < .001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P < .05). CONCLUSIONS We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.