B. Keller

A Monte Carlo-based model of gold nanoparticle radiosensitization accounting for increased radiobiological effectiveness.

Radiosensitization using gold nanoparticles (AuNPs) has been shown to vary widely with cell line, irradiation energy, AuNP size, concentration and intracellular localization. We developed a Monte Carlo-based AuNP radiosensitization predictive model (ARP), which takes into account the detailed energy deposition at the nano-scale. This model was compared to experimental cell survival and macroscopic dose enhancement predictions. PC-3 prostate cancer cell survival was characterized after irradiation using a 300xa0kVp photon source with and without AuNPs present in the cell culture media. Detailed Monte Carlo simulations were conducted, producing individual tracks of photoelectric products escaping AuNPs and energy deposition was scored in nano-scale voxels in a model cell nucleus. Cell survival in our predictive model was calculated by integrating the radiation induced lethal event density over the nucleus volume. Experimental AuNP radiosensitization was observed with a sensitizer enhancement ratio (SER) of 1.21 ± 0.13. SERs estimated using the ARP model and the macroscopic enhancement model were 1.20 ± 0.12 and 1.07 ± 0.10 respectively. In the hypothetical case of AuNPs localized within the nucleus, the ARP model predicted a SER of 1.29 ± 0.13, demonstrating the influence of AuNP intracellular localization on radiosensitization.

Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Men With Intermediate-Risk Prostate Cancer: Analysis of Short- and Medium-Term Toxicity and Quality of Life

PURPOSEnTo determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15 Gy and hypofractionated external beam radiation therapy for prostate cancer.nnnMETHODS AND MATERIALSnEligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of <20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml. Patients received high-dose-rate brachytherapy as a single 15-Gy dose, followed by external beam radiation therapy at 37.5 Gy in 15 fractions, and were followed prospectively for toxicity (using Common Terminology Criteria for Adverse Events version 3.0), urinary symptoms (using the International Prostate Symptom Score [IPSS]), erectile function (with the International Index of Erectile Function [IIEF]), and health-related quality of life (with the Expanded Prostate Cancer Index Composite [EPIC]). Clinical examinations and PSA measurements were performed at every visit, and prostate biopsies were repeated at 2 years. The trial accrued 125 patients, with a median follow-up of 1.14 years.nnnRESULTSnAcute grade 2 and 3 genitourinary toxicity occurred in 62% and 1.6% of patients, respectively, and acute grade 2 gastrointestinal toxicity occurred in 6.5% of patients. No grade 3 late toxicity has occurred: 47% of patients had grade 2 genitourinary and 10% of patients had grade 2 gastrointestinal toxicity. Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months. Of the total number of patients who were initially potent (IIEF, >21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy.nnnCONCLUSIONSnTreatment is well tolerated in the short and medium term, with low toxicity and encouraging early indicators of disease control.

Influence of breast composition and interseed attenuation in dose calculations for post-implant assessment of permanent breast 103Pd seed implant.

The impact of tissue heterogeneity and interseed attenuation is studied in post-implant evaluation of five clinical permanent breast (103)Pd seed implants using the Monte Carlo (MC) dose calculation method. Dose metrics for the target (PTV) as well as an organ at risk (skin) are used to visualize the differences between a TG43-like MC method and more accurate MC methods capable of considering the breast tissue heterogeneity as well as the interseed attenuation. PTV dose is reduced when using a breast tissue model instead of water in MC calculations while the dose to the skin is increased. Furthermore, we investigate the effect of varying the glandular/adipose proportion of the breast tissue on dose distributions. The dose to the PTV (skin) decreases (increases) with the increasing adipose proportion inside the breast. In a complete geometry and compared to a TG43-like situation, the average PTV D(90) reduction varies from 3.9% in a glandular breast to 35.5% when the breast consists entirely of adipose. The skin D(10) increases by 28.2% in an entirely adipose breast. The results of this work show the importance of an accurate and patient-dependent breast tissue model to be used in the dosimetry for this kind of low energy implant.

Predictive Factors for Local Control in Primary and Metastatic Lung Tumours after Four to Five Fraction Stereotactic Ablative Body Radiotherapy: A Single Institution's Comprehensive Experience

AIMSnWe report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control.nnnMATERIALS AND METHODSnIn total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60xa0Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses.nnnRESULTSnOf the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control.nnnCONCLUSIONSnLung SABR of 48-60xa0Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.

Lung stereotactic body radiation therapy (SBRT) delivered over 4 or 11 days: A comparison of acute toxicity and quality of life

PURPOSEnThe optimal duration over which lung SBRT should be delivered is unknown. We conducted a randomized pilot study in patients treated with four fractions of lung SBRT delivered over 4 or over 11 days.nnnMETHODSnPatients with a peripheral solitary lung tumor (NSCLC or pulmonary metastasis) ≤ 5 cm were eligible. For NSCLC lung tumors ≤ 3 cm, a dose of 48 Gy in 4 fractions was used, otherwise 52 Gy in 4 fractions was delivered. Patients were randomized to receive treatment over 4 consecutive days or over 11 days. The primary end-point was acute grade ≥ 2 toxicity. Secondary end-points included quality of life (QOL) assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires.nnnRESULTSnFifty four patients were enrolled. More patients in the 11 day group had respiratory symptoms at baseline. 55.6% patients treated over 4 days and 33.3% of patients treated over 11 days experienced acute grade ≥ 2 toxicity (p=0.085). Dyspnea, fatigue and coughing domains were worse in the 11 day group at baseline. At 1 and 4 months, more patients in the 4 day group experienced a clinically meaningful worsening in the dyspnea QOL domain compared to the 11 day group (44.5% vs 15.4%, p=0.02; 38.5% vs 12.0%, p=0.03, respectively). However, raw QOL scores were not different at these time-points between treatment groups.nnnCONCLUSIONSnGrade 2 or higher acute toxicity was more common in the 4 day group, approaching statistical significance. More patients treated on 4 consecutive days reported a clinically meaningful increase in dyspnea, although interpretation of these results is challenging due to baseline imbalance between treatment groups. Larger studies are required to validate these results.

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy

AIMSnTo determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR).nnnMATERIALS AND METHODSnPatients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity.nnnRESULTSnThe median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture.nnnCONCLUSIONSnNone of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.

Consequences of dose heterogeneity on the biological efficiency of 103 Pd permanent breast seed implants

Brachytherapy is associated with highly heterogeneous spatial dose distributions. This heterogeneity is usually ignored when estimating the biological effective dose (BED). In addition, the heterogeneities of the medium including the tissue heterogeneity (TH) and the interseed attenuation (ISA) are also contributing to the heterogeneity of the dose distribution, but they are both ignored in Task Group 43 (TG43)-based protocols. This study investigates the effect of dose heterogeneity, TH and ISA on metrics that are commonly used to quantify biological efficiency in brachytherapy. The special case of 29 breast cancer patients treated with permanent (103)Pd seed implant is considered here. BED is compared to equivalent uniform BED (EUBED) capable of considering the spatial heterogeneity of the dose distribution. The effects of TH and ISA on biological efficiency of treatments are taken into account by comparing TG43 with Monte Carlo (MC) dose calculations for each patient. The effect of clonogenic repopulation is also considered. The analysis is performed for different sets of (α/β, α) ratios of (2, 0.3), (4, 0.27) and (10, 0.3) [Gy, Gy(-1)] covering the whole range of reported α/β values in the literature. BED is sometimes larger and sometimes smaller than EUBED(TG43) indicating that the effect of the dose heterogeneity is not similar among patients. The effect of the dose heterogeneity can be characterized by using the D(99)xa0dose metric. For each set of the radiobiological parameters considered, a D(99)xa0threshold is found over which dose heterogeneity will cause an overestimation of the biological efficiencies while the inverse happens for smaller D(99)xa0values. EUBED(MC) is always larger than EUBED(TG43) indicating that by neglecting TH and ISA in TG43-based dosimetry algorithms, the biological efficiencies may be underestimated by about 10 Gy. Overall, by going from BED to the more accurate EUBED(MC) there is a gain of about 9.6 to 13 Gy on the biological efficiency. The efficiency gain is about 10.8 to 14 Gy when the repopulation is considered. Dose heterogeneity does not have a constant impact on the biological efficiencies and may under- or overestimate the efficacy in different patients. However, the combined effect of neglecting dose heterogeneity, TH and ISA results in underestimation of the biological efficiencies in permanent breast seed implants.

Online Adaptive Radiation Therapy

The current paradigm of radiation therapy has the treatment planned on a snapshot dataset of the patients anatomy taken at the time of simulation. Throughout the course of treatment, this snapshot may vary from initial simulation. Although there is the ability to image patients within the treatment room with technologies such as cone beam computed tomography, the current state of the art is largely limited to rigid-body matching and not accounting for any geometric deformations in the patients anatomy. A plan that was once attuned to the initial simulation can become suboptimal as the treatment progresses unless improved technologies are brought to bear. Adaptive radiation therapy (ART) is an evolving paradigm that seeks to address this deficiency by accounting for ongoing changes in the patients anatomy and/or physiology during the course of treatment, affording an increasingly more accurate targeting of disease. ART relies on several components working in concert, namely in-room treatment image guidance, deformable image registration, automatic recontouring, plan evaluation and reoptimization, dose calculation, and quality assurance. Various studies have explored how a putative ART solution would improve the current state of the art of radiation therapy-some centers have even clinically implemented online adaptation. These explorations are reviewed here for a variety of sites.

Magnetic field dose effects on different radiation beam geometries for hypofractionated partial breast irradiation

Abstract Purpose Hypofractionated partial breast irradiation (HPBI) involves treatment to the breast tumor using high doses per fraction. Recent advances in MRI‐Linac solutions have potential in being applied to HPBI due to gains in the soft tissue contrast of MRI; however, there are potentially deleterious effects of the magnetic field on the dose distribution. The purpose of this work is to determine the effects of the magnetic field on the dose distribution for HPBI tumors using a tangential beam arrangement (TAN), 5‐beam intensity‐modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Methods Five patients who have received HPBI were selected with two patients having bilateral disease resulting in a total of two tumors in this study. Six planning configurations were created using a treatment planning system capable of modeling magnetic field dose effects: TAN, IMRT and VMAT beam geometries, each of these optimized with and without a transverse magnetic field of 1.5 T. Results The heart and lung doses were not statistically significant when comparing plan configurations. The magnetic field had a demonstrated effect on skin dose: for VMAT plans, the skin (defined to a depth of 3 mm) D1cc was elevated by +11% and the V30 by +146%; for IMRT plans, the skin D1cc was increased by +18% and the V30 by +149%. Increasing the number of beam angles (e.g., going from IMRT to VMAT) with the magnetic field on reduced the skin dose. Conclusion The impact of a magnetic field on HPBI dose distributions was analyzed. The heart and lung doses had clinically negligible effects caused by the magnetic field. The magnetic field increases the skin dose; however, this can be mitigated by increasing the number of beam angles.

SU-E-T-416: Experimental Evaluation of a Commercial GPU-Based Monte Carlo Dose Calculation Algorithm

Purpose: A new commercial GPU-based Monte Carlo dose calculation algorithm (GPUMCD) developed by the vendor Elekta™ to be used in the Monaco Treatment Planning System (TPS) is capable of modeling dose for both a standard linear accelerator and for an Elekta MRI-Linear accelerator (modeling magnetic field effects). We are evaluating this algorithm in two parts: commissioning the algorithm for an Elekta Agility linear accelerator (the focus of this work) and evaluating the algorithm’s ability to model magnetic field effects for an MRI-linear accelerator. Methods: A beam model was developed in the Monaco TPS (v.5.09.06) using the commissioned beam data for a 6MV Agility linac. A heterogeneous phantom representing tumor-in-lung, lung, bone-in-tissue, and prosthetic was designed/built. Dose calculations in Monaco were done using the current clinical algorithm (XVMC) and the new GPUMCD algorithm (1 mm3 voxel size, 0.5% statistical uncertainty) and in the Pinnacle TPS using the collapsed cone convolution (CCC) algorithm. These were compared with the measured doses using an ionization chamber (A1SL) and Gafchromic EBT3 films for 2×2 cm2, 5×5 cm2, and 10×10 cm2 field sizes. Results: The calculated central axis percentage depth doses (PDDs) in homogeneous solid water were within 2% compared to measurements for XVMC and GPUMCD. For tumor-in-lung and lung phantoms, doses calculated by all of the algorithms were within the experimental uncertainty of the measurements (±2% in the homogeneous phantom and ±3% for the tumor-in-lung or lung phantoms), except for 2×2 cm2 field size where only the CCC algorithm differs from film by 5% in the lung region. The analysis for bone-in-tissue and the prosthetic phantoms are ongoing. Conclusion: The new GPUMCD algorithm calculated dose comparable to both the XVMC algorithm and to measurements in both a homogeneous solid water medium and the heterogeneous phantom representing lung or tumor-in-lung for 2×2 cm2-10×10 cm2 field sizes. Funding support was obtained from Elekta.