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DOE OSTI2024

A preliminary investigation into the feasibility of laser ablation U–Pb isotope ratio measurement via all‐faraday cup detection with 10 11 ‐ and 10 13 ‐Ω amplifiers on the Neoma multicollector‐inductively coupled plasma‐mass spectrometer

Rationale Signal detection for uranium–lead (U–Pb) dating of zircon is typically performed via ion counters. Here, we develop a preliminary understanding of the strengths and limitations of faraday‐cup‐based detection. Methods A suite of zircon reference materials and the NIST‐610 glass were sampled using laser ablation followed by U–Pb isotope ratio measurement on a Neoma multicollector‐inductively coupled plasma‐mass spectrometer. Results We were able to produce geologically accurate 207 Pb/ 206 Pb, 206 Pb/ 238 U, and 207 Pb/ 235 U ratios for the NIST‐610 glass and the zircon standards, with ages ranging from ~2.5 Ga to ~337 Ma (TanBrown A, Oracle, 91550, Mud Tank, Temora, and Plešovice). Two of the younger zircon standards examined (94‐35, ~55.6 Ma, and Fish Canyon, 28.6 Ma) yielded accurate 206 Pb/ 238 U but not 207 Pb/ 235 U or 207 Pb/ 206 Pb ratios, whereas the youngest zircon standard (Penglai, ~4.4 Ma) failed for all three ratios of interest. The accuracy and precision of the all‐faraday method are directly tied to signal intensity, with reliable data capable of being produced even when both isotopes in a ratio have signals below ~0.001 V (equivalent to ~62 500 cps on an ion counter). Conclusion The all‐faraday cup multicollection method provides sufficient sensitivity to obtain geologically meaningful U–Pb data, with possible advantages being that laser pit depth‐dependent changes in the observed interelemental fractionation behavior may be easier to correct using a static collector configuration compared to when the ion beam is swept across a single detector while also removing the need for an interdetector‐type calibration. Further work is needed to refine the all‐faraday cup method (e.g., application of background subtraction and common Pb corrections, outlier removal, and interelement as well as down‐hole fractionation corrections), but our initial results demonstrate that the faraday detector method has sufficient sensitivity to warrant further study.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2019

Hemobilia after CT-guided radiofrequency ablation of liver tumors: frequency, risk factors, and clinical significance

Purpose: The purpose of the study is to evaluate the frequency, risk factors, and clinical significance of hemobilia after percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) of liver tumors. Materials and methods: From January 2013 to September 2016, 195 patients received 267 sessions of CT-guided RFA for liver tumors at our institution. The CT images during and immediately after the RFA were retrospectively reviewed. The frequency of hemobilia development and clinical outcome of patients with hemobilia were studied. Risk factors were identified by comparison between the hemobilia and non-hemobilia groups using univariate and multivariate analysis. The clinical courses of patients with hemobilia were also reviewed. Results: The frequency of CT detected hemobilia after RFA was 8.2% (22/267). The majority of the clinical courses were self-limited. Univariate analysis showed that the tumor numbers (p = 0.015), the central type puncture track (p < 0.001), the length of the puncture track (p = 0.033), and the platelet count (p = 0.026) were significantly associated with the development of hemobilia. Multivariate analysis demonstrated that the central type puncture track (p < 0.024) and the platelet count (p = 0.023) were significant independent risk factors. Conclusion: Detection of hemobilia on CT images immediately after percutaneous RFA for liver tumors was not rare. Low platelet count and central type puncture track are independent risk factors. In most cases, hemobilia presented as a minor complication with favorable prognosis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Combination therapy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma: comparison with TACE or RFA monotherapy

Purpose: To compare the safety and efficacy of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) with those of TACE or RFA monotherapy. Methods: This study included 34 combined TACE and RFA (TACE-RFA), 87 TACE, and 136 ultrasound-guided RFA, which were performed to treat HCC (≤ 3 cm, 3 or fewer) between March and August 2009. The safety (Child–Pugh score indicating hepatic functional reserve, patient discomfort requiring medication, duration of hospitalization, and complications) and efficacy (1-month, 6-month, and 1-year tumor responses) profiles of each treatment were evaluated and compared. Results: TACE-RFA group showed longer hospital stay and more frequent patient discomfort requiring medication than TACE or RFA group (P < 0.001). The frequency of overall complications after TACE-RFA was higher than TACE (P = 0.006) or RFA (P = 0.009). There were no statistical differences in major complication rates between the three groups (P = 0.094). Child–Pugh score at 1-month follow-up showed no significant difference between the three groups (P = 0.162). 1-month, 6-month, and 1-year tumor responses of TACE-RFA were similar to those of RFA and better than those of TACE. Conclusions: TACE-RFA appears to result in more frequent patient discomfort requiring medication, longer hospital stay, and more frequent complications than TACE or RFA monotherapy. Tumor response of TACE-RFA seems to be similar to that of RFA and better than TACE monotherapy. Thus, TACE-RFA for treating small HCC may be required for the selected patients, especially patients with small HCC ineligible for RFA monotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2013

Acute Cor Pulmonale and Right Heat Failure Complicating Ethanol Ablative Therapy: Anesthetic and Radiologic Considerations and Management

Ethanol is an effective ablative agent used for the treatment of certain solid organ tumors and vascular malformations (VMs). The egress of ethanol beyond the target tissue can be associated with significant changes to the cardiopulmonary system that can lead to cardiac arrest. This article reviews the contemporary role of ethanol in tumor and VM treatment and discusses the physiological mechanisms of acute pulmonary hypertension and cardiovascular collapse. The importance of periprocedural recognition of the hemodynamic changes that can occur with the use of ethanol and the treatment of this condition are discussed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Reiterative Radiofrequency Ablation in the Management of Pediatric Patients with Hepatoblastoma Metastases to the Lung, Liver, or Bone

Background and Purpose: Conventional treatments of systemic chemotherapy and surgical resection for recurrent or metastatic hepatoblastoma (HB) may be inhibitive for the pediatric patient and family who have already been through extensive therapies. This single-institution case series evaluates the safety and efficacy of percutaneous radiofrequency ablation (RFA) in the management of metastatic HB. Materials and Methods: Between March 2008 and February 2015, RFA was used as part of multidisciplinary management for HB recurrence or metastasis in 5 children (median 5.0 years old) in an attempt to provide locoregional control and preclude additional surgery. Combined local treatments of 38 metachronous metastases included surgical metastasectomy (14 lesions: 7 lung, 7 liver), percutaneous RFA (23 lesions: 21 lung, 1 liver, 1 bone), and stereotactic radiotherapy (1 liver lesion). Results: For lesions treated with RFA (median diameter 6 mm, range 3–15 mm), local control was achieved in 22/23 metastases (95.6%) with median follow-up of 30.1 months after RFA (range 18.9–65.7). Median hospitalization was 3 days (2–7), with major complications limited to 1 pneumothorax requiring temporary small-caliber chest tube. Four children remain in complete remission with median follow-up of 67 months (range 41.2–88.8) after primary tumor resection, with mean disease-free survival of 31.7 months after last local treatment. One child succumbed to rapidly progressive disease 12 months after RFA (23.9 months after primary tumor resection). Conclusion: RFA provides a safe and effective reiterative treatment option in the multidisciplinary management of children with metastatic HB.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2019

Radiofrequency Ablation of the Marginal Venous System in Patients with Venous Malformations

Purpose: To evaluate radiofrequency ablation (RFA) for closure of marginal veins in pediatric and adult patients with venous malformations. Materials and methods: Medical records, imaging and procedure details were retrospectively reviewed in patients who underwent RFA of the marginal vein in a 17-month period. Additional sclerotherapy (n = 19) and coil embolization of the marginal vein were performed (n = 2). Results: A total of 23 marginal veins were treated in 20 patients. Mean age at treatment was 16 years ± 9.4 (1–37 years). Pre-procedural magnetic resonance imaging revealed thoracoabdominal marginal veins in 3 patients. A type I marginal vein (draining in the great saphenous vein below the popliteal vein) was identified in 1 and type IIa/IIb (draining in a median/lateral accessory saphenous vein) in 2/8 cases. Type III (draining into the profunda femoral vein) was detected in 8, and type IV (draining into gluteal veins) in 1. Mean diameter of the marginal veins was 13.2 mm ± 4 (7–20 mm). Patency was found in 1 during follow-up (22 months ± 9.8). Complete or partial occlusion was achieved in 94.5% of the veins. One patient showed signs of thrombophlebitis after the procedure, and another incomplete paresis of the peroneal nerve. Conclusion: RFA is effective as minimally invasive treatment of the marginal venous system. These veins should be treated early in life. Marginal veins with large diameter, residual tributaries and the intrafascial courses usually require adjunct coil embolization and sclerotherapy. Level of Evidence: Case series, Level IV.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Effects of laser fluence on the Cd(OH){sub 2}/CdO nanostructures produced by pulsed laser ablation method

In this experimental study, Cd (OH){sub 2}/CdO nanostructures were produced by pulsed laser ablation method. The beam of a Q-switched Nd:YAG laser with wavelength of 1064 nm at different fluences was employed to irradiate the cadmium target in distilled water. The obtained products at different fluences of laser pulse were characterized by UV–Vis-NIR spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Results show that both morphology and chemical bonds of produced Cd nanostructures were changed by increasing the laser fluence. The absorption spectra shows that the Cd(OH){sub 2} nanostructures could be transformed into CdO nanostructures with increasing the laser fluence. XRD analysis showed the presence of crystalline γ-Cd(OH){sub 2}, Cd(OH){sub 2} and CdO phases, in the monoclinic, hexagonal and cubic structure, respectively. Results revealed that obtained nanostructures are particle in lowest fluence, while wire shaped nanostructures were formed with increasing the laser fluence. An increase of the laser fluence induced the synthesis of higher aspect ratio nanowires with a smaller tendency of adhesion.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

DOE OSTI2021

Defect Characterization Using Positron Annihilation Spectroscopy on Laser-Ablated Surfaces

In recent years, short, pulsed laser ablation has been gaining popularity for machining small-scale test geometries from bulk samples and for efficient serial sectioning. These laser-based techniques are being added to the toolbox in material science, which makes it necessary to understand the changes in the material that occur from the laser–material interaction. Positron annihilation spectroscopy is a unique, nondestructive technique to investigate small defects in materials difficult to investigate by other tools. In this work, Doppler broadening and positron lifetime annihilation spectroscopy are utilized to help quantify the damage in materials treated with short, pulsed lasers. Using a femtosecond laser on single crystal silicon, this manuscript shows that clusters of vacancy-like defects and small voids increase systematically with laser power. Lastly, the damage induced by the laser can also reach to micrometer depths.

36 MATERIALS SCIENCE↗

DOE OSTI2020

Calcium fluoride as a dominating matrix for quantitative analysis by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS): A feasibility study

Here, calcium fluoride formed by the reaction between ammonium bifluoride and calcium chloride was investigated as a dominating matrix for quantitative analysis by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Transformation from a solid sample to the calcium fluoride-based matrix permitted quantitative analysis based on calibration standards made from elemental standards. A low abundance stable calcium isotope, i.e. 44 Ca + , was monitored as the internal standard for quantitative analysis by LA-ICP-MS. Correlation coefficient factors for multiple elements were obtained with values over 0.999. The results for multiple elements in a certified reference material of soil (NIST SRM 2710a) agreed with the certified values in the range of expanded uncertainty, indicating the present method was valid for quantitation of elements in solid samples.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2018

Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors

Highlights: • A functional ghrelin receptor GHSR1a is dominantly found in DA neurons in the SNc. • GHSR1a is also located on GABAergic neurons in the SNr. • Activation of GHSRs on SNc-DA neurons improves motor deficits. • GHSRs located on non-DA cells are not associated with motor function. Ghrelin plays roles in a wide range of central functions by activating the growth hormone secretagogue receptor (GHSR). This receptor has recently been found in the substantia nigra (SN) to control dopamine (DA)-related physiological functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the consequent depletion of striatal DA are known to underlie the motor deficits observed in Parkinson's disease (PD). In the present study, we further investigated the role of the SN-ghrelin system in motor function under the stereotaxic injection of AAV-CMV-FLEX-diphtheria toxin A (DTA) into the SN of dopamine transporter (DAT)-Cre (DAT{sup SN}::DTA) mice to expunge DA neurons of the SNc. First, we confirmed the dominant expression of GHSR1a, which is a functional GHSR, in tyrosine hydroxylase (TH)-positive DA neurons in the SNc of control mice. In DAT{sup SN}::DTA mice, we clearly observed motor dysfunction using several behavioral tests. An immunohistochemical study revealed a dramatic loss of TH-positive DA neurons in the SNc and DAT-labeled axon terminals in the striatum, and an absence of mRNAs for TH and DAT in the SN of DAT{sup SN}::DTA mice. The mRNA level of GHSR1a was drastically decreased in the SN of these mice. In normal mice, we also found the mRNA expression of GHSR1a within GABAergic neurons in the SN pars reticulata (SNr). Under these conditions, a single injection of ghrelin into the SN failed to improve the motor deficits caused by ablation of the nigrostriatal DA network using DAT{sup SN}::DTA mice, whereas intra-SN injection of ghrelin suppressed the motor dysfunction caused by the administration of haloperidol, which is associated with the transient inhibition of DA transmission. These findings suggest that phasic activation of the SNc-ghrelin system could improve the dysregulation of nigrostriatal DA transmission related to the initial stage of PD, but not the motor deficits under the depletion of nigrostriatal DA. Although GHSRs are found in non-DA cells of the SNr, GHSRs on DA neurons in the SNc may play a crucial role in motor function.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Targeted cancer cell ablation in mice by an α-particle-emitting astatine-211-labeled antibody against major histocompatibility complex class I chain-related protein A and B

Highlights: • MICA/B is expressed in several human cancer cells. • We generated an α-particle-emitting {sup 211}At-labelled antibody targeting MICA/B. • {sup 211}At-labelled antibody specifically killed human cancer cells expressing MICA/B. • {sup 211}At-labelled antibody targeting MICA/B showed anti-tumor activity in vivo. Major histocompatibility complex class I chain-related protein A and B (MICA/B) are ligands of the immune receptor, natural-killer group 2 member D. MICA/B expression is often found in several types of cancer but is restricted in normal tissues. Here, we show that an α-particle emitting astatine-211 ({sup 211}At)-labeled antibody targeting MICA/B ({sup 211}At-anti MICA/B Ab) efficiently ablates cancer cells in vitro and in vivo. We generated {sup 211}At-anti MICA/B Ab, an anti-MICA/B antibody conjugated with a highly cytotoxic α-particle emitting radionuclide {sup 211}At. {sup 211}At-anti MICA/B Ab binds to human osteosarcoma SaOS2 and U2OS cells that exhibit high levels of MICA/B expression and efficiently kills those cells in vitro. Biodistribution analysis using xenograft mouse models of HCT116 p53{sup −/−} positive for MICA/B expression, showed increased {sup 211}At in the xenografts for up to 22 h after injection as time proceeded. A single dose of {sup 211}At-anti MICA/B Ab (1 MBq) showed significant reduction in the tumor growth rate of HCT116 p53{sup −/−} xenografts compared to {sup 211}At-labeled mouse IgG (1 MBq) at 21 days after injection. No body weight loss and erythrocytopenia was evident in mice that received {sup 211}At-anti MICA/B. Leukocytopenia and thrombocytopenia were observed within a week after {sup 211}At-anti MICA/B injection, but counts of red blood cells and platelets were recovered to control levels at about 3–4 weeks after injection. Taken together, these data strongly demonstrate that targeted α-particle therapy using {sup 211}At-anti-MICA/B Ab emitting highly cytotoxic α-particles is a potential new therapeutic option for several types of cancer.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Inkless, dry printing nanographene via in-Situ Coordinated laser ablation and sintering processes

Printing carbon, such as graphene and other carbon structures, for flexible and printed electronics currently relies on either ink-based printing, laser-induced forward transfer (LIFT), or laser-induced graphitization (LIG) to convert carbon-rich precursor materials, such as polymers, to graphene-like carbon structures. Liquid inks contain toxic solvents, surfactants, and stabilizing additives that degrade electrical conductivity and require high-temperature post-processing. On the other hand, LIG is limited by the substrate. Here, this study introduces an additive manufacturing method for dry-printing carbon nanomaterials, ranging from amorphous carbon to crystalline graphene-like structures, on various substrates. The system utilizes laser ablation of a solid graphite target to create pure carbon nanoparticles in situ and on demand. An inert gas carries the nanoparticles onto the substrate, where they can be deposited either as amorphous structures or laser-sintered in real time to form various graphitic structures. The study of laser processing parameters, specifically fluence and pulse repetition frequency, revealed three unique regimes of nanostructure evolution that influence the morphological and electrical properties of these printed structures. Raman spectroscopy confirmed graphitization with a resistivity slightly higher than that of the bulk graphite target. The conductivity/resistivity could be tuned as a function of sintering laser power. Scanning transmission electron microscopy (STEM) revealed that turbostratic nanographene formed with an interlayer spacing of 0.40 nm. Despite ink-based printing methods, such as screen printing, inkjet printing (IJP), and aerosol jet printing (AJP), this eco-friendly and green manufacturing technique could eliminate toxic chemicals, reduce environmental impact, and enable single-step fabrication of carbon-based devices for applications in wearable sensors, energy storage, flexible electronics, and Internet of Things (IoT) devices.

Additive nanomanufacturing↗

DOE OSTI2019

Early time dynamics of laser-ablated silicon using ultrafast grazing incidence X-ray scattering

Controlling the morphology of laser-derived nanomaterials is dependent on developing a better understanding of the particle nucleation dynamics in the ablation plume. Here in this paper, we utilize the femtosecond-length pulses from an x-ray free electron laser to perform time-resolved grazing incidence x-ray scattering measurements on a laser-produced silicon plasma plume. At 20 ps we observe a dramatic increase in the scattering amplitude at small scattering vectors, which we attribute to incipient formation of liquid silicon droplets. These results demonstrate the utility of XFELs as a tool for characterizing the formation dynamics of nanomaterials in laser-produced plasma plumes on ultrafast timescales.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2016

Impact of ablator thickness and laser drive duration on a platform for supersonic, shockwave-driven hydrodynamic instability experiments

Here, we discuss changes to a target design that improved the quality and consistency of data obtained through a novel experimental platform that enables the study of hydrodynamic instabilities in a compressible regime. The experiment uses a laser to drive steady, supersonic shockwave over well-characterized initial perturbations. Early experiments were adversely affected by inadequate experimental timescales and, potentially, an unintended secondary shockwave. These issues were addressed by extending the 4 x 10 13 W/cm 2 laser pulse from 19 ns to 28 ns, and increasing the ablator thickness from 185 µm to 500 µm. We present data demonstrating the performance of the platform.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2013

Clinical Implementation of Intrafraction Cone Beam Computed Tomography Imaging During Lung Tumor Stereotactic Ablative Radiation Therapy

Purpose: To develop and clinically evaluate a volumetric imaging technique for assessing intrafraction geometric and dosimetric accuracy of stereotactic ablative radiation therapy (SABR). Methods and Materials: Twenty patients received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At the beginning of each fraction, pretreatment cone beam computed tomography (CBCT) was used to align the soft-tissue tumor position with that in the planning CT. Concurrent with dose delivery, we acquired fluoroscopic radiograph projections during VMAT using the Varian on-board imaging system. Those kilovolt projections acquired during millivolt beam-on were automatically extracted, and intrafraction CBCT images were reconstructed using the filtered backprojection technique. We determined the time-averaged target shift during VMAT by calculating the center of mass of the tumor target in the intrafraction CBCT relative to the planning CT. To estimate the dosimetric impact of the target shift during treatment, we recalculated the dose to the GTV after shifting the entire patient anatomy according to the time-averaged target shift determined earlier. Results: The mean target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the 95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6, and 4.9 mm along the anterior-posterior, left-right, and superior-inferior directions. Thus, the time-averaged intrafraction gross tumor volume (GTV) position was always within the planning target volume. We observed some degree of target blurring in the intrafraction CBCT, indicating imperfect breath-hold reproducibility or residual motion of the GTV during treatment. By our estimated dose recalculation, the GTV was consistently covered by the prescription dose (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100% PD for 18 patients and >95% PD for all patients. Conclusions: Intrafraction CBCT during VMAT can provide geometric and dosimetric verification of SABR valuable for quality assurance and potentially for treatment adaptation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Threshold Doses for Focal Liver Reaction After Stereotactic Ablative Body Radiation Therapy for Small Hepatocellular Carcinoma Depend on Liver Function: Evaluation on Magnetic Resonance Imaging With Gd-EOB-DTPA

Purpose: Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). Methods and Materials: In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose–volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD. Results: A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively. Conclusion: The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Study of 201 Non-Small Cell Lung Cancer Patients Given Stereotactic Ablative Radiation Therapy Shows Local Control Dependence on Dose Calculation Algorithm

Purpose: Pencil beam (PB) and collapsed cone convolution (CCC) dose calculation algorithms differ significantly when used in the thorax. However, such differences have seldom been previously directly correlated with outcomes of lung stereotactic ablative body radiation (SABR). Methods and Materials: Data for 201 non-small cell lung cancer patients treated with SABR were analyzed retrospectively. All patients were treated with 50 Gy in 5 fractions of 10 Gy each. The radiation prescription mandated that 95% of the planning target volume (PTV) receive the prescribed dose. One hundred sixteen patients were planned with BrainLab treatment planning software (TPS) with the PB algorithm and treated on a Novalis unit. The other 85 were planned on the Pinnacle TPS with the CCC algorithm and treated on a Varian linac. Treatment planning objectives were numerically identical for both groups. The median follow-up times were 24 and 17 months for the PB and CCC groups, respectively. The primary endpoint was local/marginal control of the irradiated lesion. Gray's competing risk method was used to determine the statistical differences in local/marginal control rates between the PB and CCC groups. Results: Twenty-five patients planned with PB and 4 patients planned with the CCC algorithms to the same nominal doses experienced local recurrence. There was a statistically significant difference in recurrence rates between the PB and CCC groups (hazard ratio 3.4 [95% confidence interval: 1.18-9.83], Gray's test P=.019). The differences (Δ) between the 2 algorithms for target coverage were as follows: ΔD99{sub GITV} = 7.4 Gy, ΔD99{sub PTV} = 10.4 Gy, ΔV90{sub GITV} = 13.7%, ΔV90{sub PTV} = 37.6%, ΔD95{sub PTV} = 9.8 Gy, and ΔD{sub ISO} = 3.4 Gy. GITV = gross internal tumor volume. Conclusions: Local control in patients receiving who were planned to the same nominal dose with PB and CCC algorithms were statistically significantly different. Possible alternative explanations are described in the report, although they are not thought likely to explain the difference. We conclude that the difference is due to relative dosimetric underdosing of tumors with the PB algorithm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Stereotactic Ablative Radiation Therapy for Centrally Located Early Stage or Isolated Parenchymal Recurrences of Non-Small Cell Lung Cancer: How to Fly in a “No Fly Zone”

Purpose: We extended our previous experience with stereotactic ablative radiation therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen; and suggested modified dose-volume constraints. Methods and Materials: Four-dimensional computed tomography (4DCT)-based volumetric image-guided SABR was used for 100 patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal recurrence of NSCLC (n=19). All disease was staged with positron emission tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Endpoints were toxicity, overall survival (OS), local and regional control, and distant metastasis. Results: At a median follow-up time of 30.6 months, median OS time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative actuarial local, regional, and distant control rates were 96.5%, 87.9%, and 77.2%, respectively. The most common toxicities were chest-wall pain (18% grade 1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V{sub 20} >12%, or ipsilateral lung V{sub 30} >15% to independently predict radiation pneumonitis; and 3 of 9 patients with brachial plexus D{sub max} >35 Gy experienced brachial neuropathy versus none of 73 patients with brachial D{sub max} <35 Gy (P=.001). Other toxicities were analyzed and new dose-volume constraints are proposed. Conclusions: SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected.

62 RADIOLOGY AND NUCLEAR MEDICINE↗