Publications by authors named "Martina Descovich"

31 Publications

Stereotactic Body Radiation Therapy and High-Dose-Rate Brachytherapy Boost in Combination With Intensity Modulated Radiation Therapy for Localized Prostate Cancer: A Single-Institution Propensity Score Matched Analysis.

Int J Radiat Oncol Biol Phys 2021 Jun 30;110(2):429-437. Epub 2020 Dec 30.

Department of Radiation Oncology, University of California San Francisco, San Francisco, California. Electronic address:

Purpose: To perform a propensity-score matched analysis comparing stereotactic body radiation therapy (SBRT) boost and high-dose-rate (HDR) boost for localized prostate cancer.

Methods And Materials: A single-institution retrospective chart review was conducted of men treated with pelvic external beam radiation therapy (EBRT) and SBRT boost (21 Gy and 19 Gy in 2 fractions) to the prostate for prostate cancer. A cohort treated at the same institution with HDR brachytherapy boost (19 Gy in 2 fractions) was compared. Propensity-score (PS) matching and multivariable Cox regression were used for analysis. Outcomes were biochemical recurrence freedom (BCRF) and metastasis freedom (MF).

Results: One hundred thirty-one men were treated with SBRT boost and 101 with HDR boost with median follow-up of 73.4 and 186.0 months, respectively. In addition, 68.8% of men had high-risk and 26.0% had unfavorable-intermediate disease, and 94.3% received androgen deprivation therapy. Five- and 10-year unadjusted BCRF was 88.8% and 85.3% for SBRT and 91.8% and 74.6% for HDR boost (log-rank P = .3), and 5- and 10-year unadjusted MF was 91.7% and 84.3% for SBRT and 95.8% and 82.0% for HDR (log-rank P = .8). After adjusting for covariates, there was no statistically significant difference in BCRF (hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.37-1.79; P = .6) or MF (HR 1.07; 95% CI, 0.44-2.57; P = .9) between SBRT and HDR boost. Similarly, after PS matching, there was no statistically significant difference between SBRT and HDR (BCRF: HR 0.66, 0.27-1.62, P = .4; MF: HR 0.84, 0.31-2.26, P = .7). Grade 3+ genitourinary and gastrointestinal toxicity in the SBRT cohort were 4.6% and 1.5%, and 3.0% and 0.0% in the HDR cohorts (P = .4, Fisher exact test).

Conclusions: SBRT boost plus pelvic EBRT for prostate cancer resulted in similar BCRF and MF to HDR boost in this single institution, PS matched retrospective analysis. Toxicity was modest. Prospective evaluation of SBRT boost for the treatment of unfavorable-intermediate and high-risk prostate cancer is warranted.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.034DOI Listing
June 2021

Improved contrast and noise of megavoltage computed tomography (MVCT) through cycle-consistent generative machine learning.

Med Phys 2021 Feb 27;48(2):676-690. Epub 2020 Dec 27.

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.

Purpose: Megavoltage computed tomography (MVCT) has been implemented on many radiation therapy treatment machines as a tomographic imaging modality that allows for three-dimensional visualization and localization of patient anatomy. Yet MVCT images exhibit lower contrast and greater noise than its kilovoltage CT (kVCT) counterpart. In this work, we sought to improve these disadvantages of MVCT images through an image-to-image-based machine learning transformation of MVCT and kVCT images. We demonstrated that by learning the style of kVCT images, MVCT images can be converted into high-quality synthetic kVCT (skVCT) images with higher contrast and lower noise, when compared to the original MVCT.

Methods: Kilovoltage CT and MVCT images of 120 head and neck (H&N) cancer patients treated on an Accuray TomoHD system were retrospectively analyzed in this study. A cycle-consistent generative adversarial network (CycleGAN) machine learning, a variant of the generative adversarial network (GAN), was used to learn Hounsfield Unit (HU) transformations from MVCT to kVCT images, creating skVCT images. A formal mathematical proof is given describing the interplay between function sensitivity and input noise and how it applies to the error variance of a high-capacity function trained with noisy input data. Finally, we show how skVCT shares distributional similarity to kVCT for various macro-structures found in the body.

Results: Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were improved in skVCT images relative to the original MVCT images and were consistent with kVCT images. Specifically, skVCT CNR for muscle-fat, bone-fat, and bone-muscle improved to 14.8 ± 0.4, 122.7 ± 22.6, and 107.9 ± 22.4 compared with 1.6 ± 0.3, 7.6 ± 1.9, and 6.0 ± 1.7, respectively, in the original MVCT images and was more consistent with kVCT CNR values of 15.2 ± 0.8, 124.9 ± 27.0, and 109.7 ± 26.5, respectively. Noise was significantly reduced in skVCT images with SNR values improving by roughly an order of magnitude and consistent with kVCT SNR values. Axial slice mean (S-ME) and mean absolute error (S-MAE) agreement between kVCT and MVCT/skVCT improved, on average, from -16.0 and 109.1 HU to 8.4 and 76.9 HU, respectively.

Conclusions: A kVCT-like qualitative aid was generated from input MVCT data through a CycleGAN instance. This qualitative aid, skVCT, was robust toward embedded metallic material, dramatically improves HU alignment from MVCT, and appears perceptually similar to kVCT with SNR and CNR values equivalent to that of kVCT images.
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http://dx.doi.org/10.1002/mp.14616DOI Listing
February 2021

Technical Note: Performance of CyberKnife tracking using low-dose CT and kV imaging.

Med Phys 2020 Dec 28;47(12):6163-6170. Epub 2020 Oct 28.

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.

Purpose: To investigate the effects of CT protocol and in-room x-ray technique on CyberKnife (Accuray Inc.) tracking accuracy by evaluating end-to-end tests.

Methods: End-to-end (E2E) tests were performed for the different tracking methods (6D skull, fiducial, spine, and lung) using an anthropomorphic head phantom (Accuray Inc.) and thorax phantom (CIRS Inc.). Bolus was added to the thorax phantom to simulate a large patient and to evaluate the performance of lung tracking in a more realistic condition. The phantoms were scanned with a Siemens Sensation Open 24 slice CT at low dose (120 kV, 70 mAs, 1.5 mm slice thickness) and high dose (120 kV, 700 mAs, 1.5 mm slice thickness) to generate low-dose and high-dose digitally reconstructed radiographs (DRRs). The difference in initial phantom alignment, Δ(Align), and in total targeting accuracy, E2E, were obtained for all tracking methods with low- and high-dose DRRs. Additionally, Δ(Align) was determined for different in-room x-ray imaging techniques (0.5 to 50 mAs and 100 to 140 kV) using a low-dose lung tracking plan.

Results: Low-dose CT scans produced images with high noise; however, for these phantoms the targets could be easily delineated on all scans. End-to-end results were less than 0.95 mm for all tracking methods and all plans. The greatest difference in initial alignment Δ(Align) and E2E results between low- and high-dose CT protocols was 0.32 and 0.24 mm, respectively. Similar results were observed with a large thorax phantom. Tracking using different in-room x-ray imaging techniques (mAs) corresponding to low exposures (resulting in high image noise) or high exposure (resulting in image saturation) had alignment accuracy Δ(Align) greater than 1 mm.

Conclusions: End-to-end targeting accuracy within tolerance (<0.95 mm) was obtained for all tracking methods using low-dose CT protocols, suggesting that CT protocol should be set by target contouring needs. Additionally, high tracking accuracy was achieved for in-room x-ray imaging techniques that produce high-quality images.
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http://dx.doi.org/10.1002/mp.14537DOI Listing
December 2020

DoseGAN: a generative adversarial network for synthetic dose prediction using attention-gated discrimination and generation.

Sci Rep 2020 07 6;10(1):11073. Epub 2020 Jul 6.

Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA.

Deep learning algorithms have recently been developed that utilize patient anatomy and raw imaging information to predict radiation dose, as a means to increase treatment planning efficiency and improve radiotherapy plan quality. Current state-of-the-art techniques rely on convolutional neural networks (CNNs) that use pixel-to-pixel loss to update network parameters. However, stereotactic body radiotherapy (SBRT) dose is often heterogeneous, making it difficult to model using pixel-level loss. Generative adversarial networks (GANs) utilize adversarial learning that incorporates image-level loss and is better suited to learn from heterogeneous labels. However, GANs are difficult to train and rely on compromised architectures to facilitate convergence. This study suggests an attention-gated generative adversarial network (DoseGAN) to improve learning, increase model complexity, and reduce network redundancy by focusing on relevant anatomy. DoseGAN was compared to alternative state-of-the-art dose prediction algorithms using heterogeneity index, conformity index, and various dosimetric parameters. All algorithms were trained, validated, and tested using 141 prostate SBRT patients. DoseGAN was able to predict more realistic volumetric dosimetry compared to all other algorithms and achieved statistically significant improvement compared to all alternative algorithms for the V and V of the PTV, V of the rectum, and heterogeneity index.
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http://dx.doi.org/10.1038/s41598-020-68062-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338467PMC
July 2020

DoseNet: a volumetric dose prediction algorithm using 3D fully-convolutional neural networks.

Phys Med Biol 2018 12 4;63(23):235022. Epub 2018 Dec 4.

These two authors contributed equally.

The goal of this study is to demonstrate the feasibility of a novel fully-convolutional volumetric dose prediction neural network (DoseNet) and test its performance on a cohort of prostate stereotactic body radiotherapy (SBRT) patients. DoseNet is suggested as a superior alternative to U-Net and fully connected distance map-based neural networks for non-coplanar SBRT prostate dose prediction. DoseNet utilizes 3D convolutional downsampling with corresponding 3D deconvolutional upsampling to preserve memory while simultaneously increasing the receptive field of the network. DoseNet was implemented on 2 Nvidia 1080 Ti graphics processing units and utilizes a 3 phase learning protocol to help achieve convergence and improve generalization. DoseNet was trained, validated, and tested with 151 patients following Kaggle completion rules. The dosimetric quality of DoseNet was evaluated by comparing the predicted dose distribution with the clinically approved delivered dose distribution in terms of conformity index, heterogeneity index, and various clinically relevant dosimetric parameters. The results indicate that the DoseNet algorithm is a superior alternative to U-Net and fully connected methods for prostate SBRT patients. DoseNet required ~50.1 h to train, and ~0.83 s to make a prediction on a 128  ×  128  ×  64 voxel image. In conclusion, DoseNet is capable of making accurate volumetric dose predictions for non-coplanar SBRT prostate patients, while simultaneously preserving computational efficiency.
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http://dx.doi.org/10.1088/1361-6560/aaef74DOI Listing
December 2018

A continuous arc delivery optimization algorithm for CyberKnife m6.

Med Phys 2018 Jun 1. Epub 2018 Jun 1.

Department of Radiation Oncology, University of California, San Francisco, CA, USA.

Purpose: This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6).

Methods And Materials: CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives.

Results: Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans.

Conclusions: The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times.
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http://dx.doi.org/10.1002/mp.13022DOI Listing
June 2018

Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

J Appl Clin Med Phys 2018 Jul 26;19(4):48-57. Epub 2018 Apr 26.

Department of Radiation Oncology, University of California San, Francisco, CA, USA.

Purpose/objectives: For lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model.

Materials/method: 20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified.

Results: Prescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio.

Conclusions: The use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.
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http://dx.doi.org/10.1002/acm2.12338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036380PMC
July 2018

Respiration-Induced Intraorgan Deformation of the Liver: Implications for Treatment Planning in Patients Treated With Fiducial Tracking.

Technol Cancer Res Treat 2017 Dec 10;16(6):776-782. Epub 2017 Jan 10.

Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA.

Stereotactic body radiation therapy is a well-tolerated modality for the treatment of primary and metastatic liver lesions, and fiducials are often used as surrogates for tumor tracking during treatment. We evaluated respiratory-induced liver deformation by measuring the rigidity of the fiducial configuration during the breathing cycle. Seventeen patients, with 18 distinct treatment courses, were treated with stereotactic body radiosurgery using multiple fiducials. Liver deformation was empirically quantified by measuring the intrafiducial distances at different phases of respiration. Data points were collected at the 0%, 50%, and 100% inspiration points, and the distance between each pair of fiducials was measured at the 3 phases. The rigid body error was calculated as the maximum difference in the intrafiducial distances. Liver disease was calculated with Child-Pugh score using laboratory values within 3 months of initiation of treatment. A peripheral fiducial was defined as within 1.5 cm of the liver edge, and all other fiducials were classified as central. For 5 patients with only peripheral fiducials, the fiducial configuration had more deformation (average maximum rigid body error 7.11 mm, range: 1.89-11.35 mm) when compared to patients with both central and peripheral and central fiducials only (average maximum rigid body error 3.36 mm, range: 0.5-9.09 mm, = .037). The largest rigid body errors (11.3 and 10.6 mm) were in 2 patients with Child-Pugh class A liver disease and multiple peripheral fiducials. The liver experiences internal deformation, and the fiducial configuration should not be assumed to act as a static structure. We observed greater deformation at the periphery than at the center of the liver. In our small data set, we were not able to identify cirrhosis, which is associated with greater rigidity of the liver, as predictive for deformation. Treatment planning based only on fiducial localization must take potential intraorgan deformation into account.
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http://dx.doi.org/10.1177/1533034616687193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762032PMC
December 2017

Interfraction Anatomical Variability Can Lead to Significantly Increased Rectal Dose for Patients Undergoing Stereotactic Body Radiotherapy for Prostate Cancer.

Technol Cancer Res Treat 2017 04 8;16(2):178-187. Epub 2016 Jul 8.

1 Department of Radiation Oncology, University of California, San Francisco, CA, USA.

Stereotactic body radiotherapy for prostate cancer is rapidly growing in popularity. Stereotactic body radiotherapy plans mimic those of high-dose rate brachytherapy, with tight margins and inhomogeneous dose distributions. The impact of interfraction anatomical changes on the dose received by organs at risk under these conditions has not been well documented. To estimate anatomical variation during stereotactic body radiotherapy, 10 patients were identified who received a prostate boost using robotic stereotactic body radiotherapy after completing 25 fractions of pelvic radiotherapy with daily megavoltage computed tomography. Rectal and bladder volumes were delineated on each megavoltage computed tomography, and the stereotactic body radiotherapy boost plan was registered to each megavoltage computed tomography image using a point-based rigid registration with 3 fiducial markers placed in the prostate. The volume of rectum and bladder receiving 75% of the prescription dose (V75%) was measured for each megavoltage computed tomography. The rectal V75% from the daily megavoltage computed tomographies was significantly greater than the planned V75% (median increase of 0.93 cm, P < .001), whereas the bladder V75% on megavoltage computed tomography was not significantly changed (median decrease of -0.12 cm, P = .57). Although daily prostate rotation was significantly correlated with bladder V75% (Spearman ρ = .21, P = .023), there was no association between rotation and rectal V75% or between prostate deformation and either rectal or bladder V75%. Planning organ-at-risk volume-based replanning techniques using either a 6-mm isotropic expansion of the plan rectal contour or a 1-cm expansion from the planning target volume in the superior and posterior directions demonstrated significantly improved rectal V75% on daily megavoltage computed tomographies compared to the original stereotactic body radiotherapy plan, without compromising plan quality. Thus, despite tight margins and full translational and rotational corrections provided by robotic stereotactic body radiotherapy, we find that interfraction anatomical variations can lead to a substantial increase in delivered rectal doses during prostate stereotactic body radiotherapy. A planning organ-at-risk volume-based approach to treatment planning may help mitigate the impact of daily organ motion and reduce the risk of rectal toxicity.
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http://dx.doi.org/10.1177/1533034616649495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5616028PMC
April 2017

An Evaluation of Robotic and Conventional IMRT for Prostate Cancer: Potential for Dose Escalation.

Technol Cancer Res Treat 2017 06 31;16(3):267-275. Epub 2016 Mar 31.

1 Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

This study compares conventional and robotic intensity modulated radiation therapy (IMRT) plans for prostate boost treatments and provides clinical insight into the strengths and weaknesses of each. The potential for dose escalation with robotic IMRT is further investigated using the "critical volume tolerance" method proposed by Roach et al. Three clinically acceptable treatment plans were generated for 10 prostate boost patients: (1) a robotic IMRT plan using fixed cones, (2) a robotic IMRT plan using the Iris variable aperture collimator, and (3) a conventional linac based IMRT (c-IMRT) plan. Target coverage, critical structure doses, homogeneity, conformity, dose fall-off, and treatment time, were compared across plans. The average bladder and rectum V75 was 17.1%, 20.0%, and 21.4%, and 8.5%, 11.9%, and 14.1% for the Iris, fixed, and c-IMRT plans, respectively. On average the conformity index (nCI) was 1.20, 1.30, and 1.46 for the Iris, fixed, and c-IMRT plans. Differences between the Iris and the c-IMRT plans were statistically significant for the bladder V75 (P= .016), rectum V75 (P= .0013), and average nCI (P =.002). Dose to normal tissue in terms of R50 was 4.30, 5.87, and 8.37 for the Iris, fixed and c-IMRT plans, respectively, with statistically significant differences between the Iris and c-IMRT (P = .0013) and the fixed and c-IMRT (P = .001) plans. In general, the robotic IMRT plans generated using the Iris were significantly better compared to c-IMRT plans, and showed average dose gains of up to 34% for a critical rectal volume of 5%.
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http://dx.doi.org/10.1177/1533034616639729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5616040PMC
June 2017

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients.

J Appl Clin Med Phys 2015 09 8;16(5):284–295. Epub 2015 Sep 8.

University of California at San Francisco.

The purpose of this study was to evaluate the performance of a commercially avail-able CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK-MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK-MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%-3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25min for the whole pelvis plans and 19 min for the intracranial cases. The CK-MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while main-taining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (> 100 cm3) were generated that achieved high prescription isodose levels. The CK-MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments.
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http://dx.doi.org/10.1120/jacmp.v16i5.5502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690182PMC
September 2015

Dose-volume analysis and the temporal nature of toxicity with stereotactic body radiation therapy for prostate cancer.

Pract Radiat Oncol 2015 Sep-Oct;5(5):e465-e472. Epub 2015 Mar 18.

Department of Radiation Oncology, University of California at San Francisco, San Francisco, California.

Purpose: The purpose of this study was to evaluate the dose-volume relationships of genitourinary toxicity after stereotactic body radiation therapy (SBRT) monotherapy for prostate cancer.

Methods And Materials: Fifty-six patients diagnosed with low- to intermediate-risk prostate cancer treated with SBRT alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. Overall, acute, and late genitourinary toxicity were documented according to the Common Terminology Criteria for Adverse Events (version 4) and International Prostate Symptom Scores (IPSS).

Results: The median age at treatment was 68 years, and the median prostate volume was 45.5 mL, with a median baseline IPSS of 9.95. The median prescription isodose line was 68%. The median clinical follow-up was 35.49 months. Acute grade 1, 2, and 3 genitourinary toxicities occurred in 41.1%, 35.7%, and 0% of patients. All acute genitourinary toxicities resolved except 1 patient with grade 2 toxicity that progressed to grade 3 late toxicity. No dose-volume relationships were associated with acute genitourinary grade 2+ toxicity. Late grade 1, 2, and 3 genitourinary toxicity occurred in 19.6%, 19.6%, and 3.6% of cases, respectively. Of the cases with late toxicities, 16.7% were persistent. Late grade 2+ genitourinary toxicity was associated with prostate volume ≥50 mL, lower homogeneity index, and urethral maximum point dose ≥47 Gy. The overall risk of any grade 2+ genitourinary toxicity was associated with baseline IPSS >7, prostate volume ≥50 mL, urethral volume receiving 44 Gy, and bladder volume receiving 19 Gy.

Conclusions: SBRT for prostate cancer appears well tolerated, with mostly transient low-grade toxicity. Urethral sparing should be used with a maximum point dose <47 Gy, volume receiving 120 Gy <50% of the prostate, and bladder volume receiving 19 Gy <15 mL in 4 fraction treatments. Patients with prostate volumes ≥50 mL should be counseled regarding the increased risk of moderate-grade genitourinary toxicity.
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http://dx.doi.org/10.1016/j.prro.2015.02.001DOI Listing
June 2016

Comparison between target margins derived from 4DCT scans and real-time tumor motion tracking: insights from lung tumor patients treated with robotic radiosurgery.

Med Phys 2015 Mar;42(3):1280-7

UCSF Department of Radiation Oncology, San Francisco, California 94115.

Purpose: A unique capability of the CyberKnife system is dynamic target tracking. However, not all patients are eligible for this approach. Rather, their tumors are tracked statically using the vertebral column for alignment. When using static tracking, the internal target volume (ITV) is delineated on the four-dimensional (4D) CT scan and an additional margin is added to account for setup uncertainty [planning target volume (PTV)]. Treatment margins are difficult to estimate due to unpredictable variations in tumor motion and respiratory pattern during the course of treatment. The inability to track the target and detect changes in respiratory characteristics might result in geographic misses and local tumor recurrences. The purpose of this study is to develop a method to evaluate the adequacy of ITV-to-PTV margins for patients treated in this manner.

Methods: Data from 24 patients with lesions in the upper lobe (n = 12), middle lobe (n = 3), and lower lobe (n = 9) were included in this study. Each patient was treated with dynamic tracking and underwent 4DCT scanning at the time of simulation. Data including the 3D coordinates of the target over the course of treatment were extracted from the treatment log files and used to determine actual target motion in the superior-inferior (S-I), anterior-posterior (A-P), and left-right (L-R) directions. Different approaches were used to calculate anisotropic and isotropic margins, assuming that the tumor moves as a rigid body. Anisotropic margins were calculated by separating target motion in the three anatomical directions, and a uniform margin was calculated by shifting the gross tumor volume contours in the 3D space and by computing the percentage of overlap with the PTV. The analysis was validated by means of a theoretical formulation.

Results: The three methods provided consistent results. A uniform margin of 4.5 mm around the ITV was necessary to assure 95% target coverage for 95% of the fractions included in the analysis. In the case of anisotropic margins, the expansion required in the S-I direction was larger (8.1 mm) than those in the L-R (4.9 mm) and A-P (4.5 mm) directions. This margin accounts for variations of target position within the same treatment fraction.

Conclusions: The use of bony alignment for CyberKnife lung stereotactic body radiation therapy requires careful considerations, in terms of the potential for increased toxicity or local miss. Our method could be used by other centers to determine the adequacy of ITV-to-PTV margins for their patients.
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http://dx.doi.org/10.1118/1.4907956DOI Listing
March 2015

Evaluation of ray tracing and Monte Carlo algorithms in dose calculation and clinical outcomes for robotic stereotactic body radiotherapy of lung cancers.

J Radiosurg SBRT 2014 ;3(1):67-79

University of California, San Francisco, Department of Radiation Oncology, 1600 Divisadero St., Suite H1031, San Francisco, CA 94143, USA.

Purpose/objective: Dose calculation in treatment planning must account for tissue heterogeneity, especially for tumors within low-density lung tissues. While Monte Carlo (MC) calculation methods are the most accurate, Ray Tracing (RT) methods are also commonly employed. We evaluated dose calculation differences between the RT and MC algorithms in central and peripheral lung tumors treated with CyberKnife SBRT to determine which planning parameters may predict dose differences. We also examined clinical outcomes of local-regional control (LRC) and long-term treatment-related toxicity as a function of calculation method.

Materials/methods: A retrospective series of 70 patient plans (19 central and 51 peripheral lung lesions) treated between 2009 and 2011 were analyzed. Among those, 33 were primary lung cancer and 37 were metastatic lesions. Thirty-three treatment plans were developed with the RT method, and 37 plans used MC. Groups were recalculated with the reciprocal method for dose comparison. Parameters examined to quantify dose differences between the two algorithms included: dose delivered to 95% (D95) of the planning target volume (PTV), dose heterogeneity, and dose to organs at risk (OAR). Dose differences were analyzed as a function of target volume, distance to soft tissue, and fraction of target overlap with soft tissue. For the subset of primary lung tumors, LRC was assessed radiographically at a median follow-up of 19 months (mo) (range, 2 to 41 mo).

Results: Compared to MC, the RT algorithm largely overestimated the dose delivered to the PTV. The dose difference between RT and MC plans correlated to the volume of PTV overlapping with soft tissue; the smaller the overlap volume, the larger the dose differences between RT and MC. Compared to MC, the RT algorithm overestimated the dose delivered to 10% of the ipsilateral lung (D10%). Evidence of local progression was noted in only one of the 31 patients treated for primary lung malignancy. DFS and OS were not significantly different between RT and MC plans.

Conclusion: There is a significant range of discordance between MC and RT dose calculations for SBRT treated peripheral lung tumors. While variation is correlated to target size and proximity to soft tissue, no single parameter can reliably predict dose differences. Ultimately, local control and long-term toxicity appear independent of the dose calculation method.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725332PMC
January 2014

Analysis of dose distribution and risk of pneumonitis in stereotactic body radiation therapy for centrally located lung tumors: a comparison of robotic radiosurgery, helical tomotherapy and volumetric modulated arc therapy.

Technol Cancer Res Treat 2015 Feb 11;14(1):49-60. Epub 2014 Nov 11.

Department of Radiation Oncology, University of California, San Francisco

Stereotactic body radiation therapy (SBRT) to central lung tumors is associated with normal -tissue toxicity. Highly conformal technologies may reduce the risk of complications. This study compares physical dose characteristics and anticipated risks of radiation pneumonitis (RP) among three SBRT modalities: robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT). Nine patients with central lung tumors ≤5 cm were compared. RR, HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included target coverage, conformity index, heterogeneity index, gradient index, maximal dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk (OARs). Efficiency endpoints included total beam-on time and monitor units. RP risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The average GTV and PTV were 11.6 ± 7.86 cm(3) and 36.8 ± 18.1 cm(3). All techniques resulted in similar target coverage (p = 0.64) and dose conformity (p = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p = 0.02), HT and VMAT produced greater homogeneity (p < 0.001) and delivery efficiency (p = 0.001). RP risk predicted from whole or contralateral lung volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes. Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes, RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were able to provide clinically acceptable plans following the guidelines provided by RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV. VMAT and HT produced greater homogeneity, potentially desirable for a large PTV-OAR overlap. VMAT probably yields the lowest RP risk for a large PTV. Understanding subtle differences among these technologies may assist in situations where multiple choices of modality are available.
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http://dx.doi.org/10.7785/tcrt.2012.500394DOI Listing
February 2015

Improving plan quality and consistency by standardization of dose constraints in prostate cancer patients treated with CyberKnife.

J Appl Clin Med Phys 2013 Sep 6;14(5):162-72. Epub 2013 Sep 6.

University of California San Francisco.

Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal treatment plan has been achieved, and physicians rely on their personal experience to evaluate the plan's quality. In this study, we propose a method for determining rectal and bladder dose constraints achievable for a given patient's anatomy. We expect that this method will improve the overall plan quality and consistency, and facilitate comparison of clinical outcomes across different institutions. The 3D proximity of the organs at risk to the target is quantified by means of the expansion-intersection volume (EIV), which is defined as the intersection volume between the target and the organ at risk expanded by 5 mm. We determine a relationship between EIV and relevant dosimetric parameters, such as the volume of bladder and rectum receiving 75% of the prescription dose (V75%). This relationship can be used to establish institution-specific criteria to guide the treatment planning and evaluation process. A database of 25 prostate patients treated with CyberKnife SBRT is used to validate this approach. There is a linear correlation between EIV and V75% of bladder and rectum, confirming that the dose delivered to rectum and bladder increases with increasing extension and proximity of these organs to the target. This information can be used during the planning stage to facilitate the plan optimization process, and to standardize plan quality and consistency. We have developed a method for determining customized dose constraints for prostate patients treated with robotic SBRT. Although the results are technology specific and based on the experience of a single institution, we expect that the application of this method by other institutions will result in improved standardization of clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714582PMC
http://dx.doi.org/10.1120/jacmp.v14i5.4333DOI Listing
September 2013

Comparison between prone and supine patient setup for spine stereotactic body radiosurgery.

Technol Cancer Res Treat 2012 Jun;11(3):229-36

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

This paper investigates the dosimetric characteristics of stereotactic body radiotherapy (SBRT) treatment plans of spine patients in the prone position compared to the supine position. A feasibility study for treating spine patients in the prone position using a fiducial-less tracking method is presented. One patient with a multilevel spinal metastasis was simulated for SBRT treatment in both the supine and prone position. CT scans of the patient were acquired, and treatment plans were created using the CyberKnife® planning platform. The potential advantage of the prone setup as a function of lesion location and number of vertebral bodies involved was studied for targets extending over 1, 2 and 3 consecutive vertebral bodies in the thoracic and lumbar spine. The same process was repeated on an anthropomorphic phantom. A dose of 30 Gy in 5 fractions was prescribed to 95% of the tumor volume and the dose to the cord was limited to 25 Gy. To investigate the feasibility of a fiducial-less tracking method in the prone setup, the patient was positioned prone on the treatment table and the spine motion was monitored as a function of time. Patient movement with the respiratory cycle was reduced by means of a belly-board. Plans in the prone and supine position achieved similar tumor coverage and sparing of the critical structures immediately adjacent to the spine (such as cord and esophagus). However, the prone plans systematically resulted in a lower dose to the normal structures located in the anterior part of the body (such as heart for thoracic cases; stomach, lower gastrointestinal tract and liver for lumbar cases). In addition, prone plans resulted in a lower number of monitor units compared to supine plans.
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http://dx.doi.org/10.7785/tcrt.2012.500291DOI Listing
June 2012

Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy.

Phys Med Biol 2011 Dec 22;56(24):7767-75. Epub 2011 Nov 22.

Department of Radiation Oncology, University of California, San Francisco, CA, USA.

The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/β = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field 'dose-bathing' type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R² = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.
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http://dx.doi.org/10.1088/0031-9155/56/24/006DOI Listing
December 2011

Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases.

J Neurosurg 2011 Jun 4;114(6):1580-4. Epub 2011 Mar 4.

Department of Radiation Oncology, University of California, San Francisco, 94143, USA.

Object: Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent.

Methods: The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain.

Results: Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted.

Conclusions: The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.
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http://dx.doi.org/10.3171/2011.1.JNS101056DOI Listing
June 2011

A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia.

J Neurosurg 2010 Dec;113 Suppl:199-206

Department of Radiation Oncology, University of California, San Francisco, California, USA.

Object: The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radio surgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness. The goal of this study was to develop a method for planning a CyberKnife treatment for trigeminal neuralgia that would reproduce the dosimetric characteristics of a Gamma Knife plan. A comparison between Gamma Knife and CyberKnife treatment plans obtained with this method is presented.

Methods: Five patients treated using the Gamma Knife Perfexion Unit were selected for this study. All patients underwent CT cisternography to accurately identify the position of the trigeminal nerve. The Gamma Knife plans used either one 4-mm-diameter collimator or two coincident 4-mm collimators (one open and one with sector blocking) placed at identical isocenter coordinates. A maximum local dose of 80 Gy was prescribed. Critical structures and representative isodose lines were outlined in GammaPlan and exported to the CyberKnife treatment planning platform. CyberKnife treatments were developed using the 5-mm-diameter cone and the trigeminal node set, which provides an effective collimation diameter of 4 mm at the isocenter. The 60-Gy isodose volume imported from GammaPlan was used as the target in the CyberKnife plans. The CyberKnife treatments were optimized to achieve target dose and critical structure sparing similar to the Gamma Knife plans. Isocentric and nonisocentric delivery techniques were investigated. Treatment plans were compared in terms of dosimetric characteristics, delivery, and planning efficiency.

Results: CyberKnife treatments using the 5-mm cone and the trigeminal node set can closely reproduce the dose distribution of Gamma Knife plans. CyberKnife isocentric and nonisocentric plans provide comparable results. The average length of the trigeminal nerve receiving a dose of 60 Gy was 4.5, 4.5, and 4.4 mm for Gamma Knife, nonisocentric CyberKnife, and isocentric CyberKnife, respectively. However, minimizing the dose to the critical structures was more difficult with the CyberKnife and required the use of tuning structures. In addition, the dose fall off away from the target was steeper in Gamma Knife plans, probably due to the larger number of beams (192 beams for perfexion vs ~ 100 beams for cyberknife). While the treatment time with the cyberknife is generally shorter, the planning time is significantly longer.

Conclusions: CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe,and cranial nerves VII and VIII) and in steeper dose fall off away from the target. The clinical significance of these effects is unknown. (DOI: 10.3171/2010.8.GKS101002)
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December 2010

Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response.

Int J Radiat Oncol Biol Phys 2012 Jan 22;82(1):228-34. Epub 2010 Dec 22.

Department of Radiation Oncology, University of California San Francisco, San Francisco, California, USA.

Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation.

Patients And Methods: To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison.

Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3).

Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.
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http://dx.doi.org/10.1016/j.ijrobp.2010.10.026DOI Listing
January 2012

Equivalence in dose fall-off for isocentric and nonisocentric intracranial treatment modalities and its impact on dose fractionation schemes.

Int J Radiat Oncol Biol Phys 2010 Mar;76(3):943-8

Department of Radiation Oncology, University of California, San Francisco, CA 94143, USA.

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing.

Methods And Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities.

Results: The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5.

Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.
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http://dx.doi.org/10.1016/j.ijrobp.2009.07.1721DOI Listing
March 2010

Dose gradient near target-normal structure interface for nonisocentric CyberKnife and isocentric intensity-modulated body radiotherapy for prostate cancer.

Int J Radiat Oncol Biol Phys 2010 Sep 3;78(1):58-63. Epub 2010 Feb 3.

Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA 94143-1708, USA.

Purpose: The treatment planning quality between nonisocentric CyberKnife (CK) and isocentric intensity modulation treatment was studied for hypofractionated prostate body radiotherapy. In particular, the dose gradient across the target and the critical structures such as the rectum and bladder was characterized.

Methods And Materials: In the present study, patients treated with CK underwent repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT) using identical contour sets and dose-volume constraints. To calculate the dose falloff, the clinical target volume contours were expanded 30 mm anteriorly and posteriorly and 50 mm uniformly in other directions for all patients in the CK and IMRT plans.

Results: We found that all the plans satisfied the dose-volume constraints, with the CK plans showing significantly better conformity than the IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder volumes receiving a low dose were also lower for CK than for IMRT. The average conformity index, the ratio of the prescription isodose volume and clinical target volume, was 1.18 +/- 0.08 for the CK plans vs. 1.44 +/- 0.11 for the IMRT plans. The average homogeneity index, the ratio of the maximal dose and the prescribed dose to the clinical target volume, was 1.45 +/- 0.12 for the CK plans vs. 1.28 +/- 0.06 for the IMRT plans. The average percentage of dose falloff was 2.9% +/- 0.8%/mm for CK and 3.1% +/- 1.0%/mm for IMRT in the anterior direction, 3.8% +/- 1.6%/mm for CK and 3.2% +/- 1.9%/mm for IMRT in the posterior direction, and 3.6% +/- 0.4% for CK and 3.6% +/- 0.4% for IMRT in all directions.

Conclusion: Nonisocentric CK was as capable of producing equivalent fast dose falloff as high-number fixed-field IMRT delivery.
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http://dx.doi.org/10.1016/j.ijrobp.2009.07.1752DOI Listing
September 2010

Nonrandom intrafraction target motions and general strategy for correction of spine stereotactic body radiotherapy.

Int J Radiat Oncol Biol Phys 2009 Nov 3;75(4):1261-5. Epub 2009 Aug 3.

Department of Radiation Oncology, University of California, San Francisco, California 94143, USA.

Purpose: To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed.

Methods And Materials: Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case, time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions.

Results: Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1 degrees of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level).

Conclusions: A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions.
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http://dx.doi.org/10.1016/j.ijrobp.2009.04.027DOI Listing
November 2009

Physical performance and image optimization of megavoltage cone-beam CT.

Med Phys 2009 Apr;36(4):1421-32

Department of Radiation Oncology, Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.

Megavoltage cone-beam CT (MVCBCT) is the most recent addition to the in-room CT systems developed for image-guided radiation therapy. The first generation MVCBCT system consists of a 6 MV treatment x-ray beam produced by a conventional linear accelerator equipped with a flat panel amorphous silicon detector. The objective of this study was to evaluate the physical performance of MVCBCT in order to optimize the system acquisition and reconstruction parameters for image quality. MVCBCT acquisitions were performed with the clinical system but images were reconstructed and analyzed with a separate research workstation. The geometrical stability and the positioning accuracy of the system were evaluated by comparing geometrical calibrations routinely performed over a period of 12 months. The beam output and detector intensity stability during MVCBCT acquisition were also evaluated by analyzing in-air acquisitions acquired at different exposure levels. Several system parameters were varied to quantify their impact on image quality including the exposure (2.7, 4.5, 9.0, 18.0, and 54.0 MU), the craniocaudal imaging length (2, 5, 15, and 27.4 cm), the voxel size (0.5, 1, and 2 mm), the slice thickness (1, 3, and 5 mm), and the phantom size. For the reconstruction algorithm, the study investigated the effect of binning, averaging and diffusion filtering of raw projections as well as three different projection filters. A head-sized water cylinder was used to measure and improve the uniformity of MVCBCT images. Inserts of different electron densities were placed in a water cylinder to measure the contrast-to-noise ratio (CNR). The spatial resolution was obtained by measuring the point-spread function of the system using an iterative edge blurring technique. Our results showed that the geometric stability and accuracy of MVCBCT were better than 1 mm over a period of 12 months. Beam intensity variations per projection of up to 35.4% were observed for a 2.7 MU MVCBCT acquisition. These variations did not cause noticeable reduction in the image quality. The results on uniformity suggest that the cupping artifact occurring with MVCBCT is mostly due to off-axis response of the detector and not scattered radiation. Simple uniformity correction methods were developed to nearly eliminate this cupping artifact. The spatial resolution of the baseline MVCBCT reconstruction protocol was approximately 2 mm. An optimized reconstruction protocol was developed and showed an improvement of 75% in CNR with a penalty of only 8% in spatial resolution. Using this new reconstruction protocol, large adipose and muscular structures were differentiated at an exposure of 9 MU. A reduction of 36% in CNR was observed on a larger (pelvic-sized) phantom. This study demonstrates that soft-tissue visualization with MVCBCT can be substantially improved with proper system settings. Further improvement is expected from the next generation MVCBCT system with an optimized megavoltage imaging beamline.
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http://dx.doi.org/10.1118/1.3096706DOI Listing
April 2009

Comparison between hybrid direct aperture optimized intensity-modulated radiotherapy and forward planning intensity-modulated radiotherapy for whole breast irradiation.

Int J Radiat Oncol Biol Phys 2010 Jan;76(1):91-9

Department of Radiation Oncology, University of California San Francisco, School of Medicine, San Francisco, CA 94143-1708, USA.

Purpose: To investigate the planning efficiency and dosimetric characteristics of hybrid direct aperture optimized (hDAO) intensity-modulated radiotherapy (IMRT) compared with forward planning (FP)-IMRT for whole breast irradiation with two tangential beams.

Methods And Materials: A total of 15 patients with left-sided breast cancer, categorized with three different breast volumes, were selected for this study. All patients were treated with FP plans to 50 Gy in 25 fractions. The hDAO plans were created by combining two open fields with eight segments in two tangential beam directions and were inversely optimized.

Results: The FP and hDAO plans achieved similar breast coverage and sparing of critical organs. The volume of breast receiving 105% of the prescription dose was significantly smaller in the hDAO than in the FP plans: 25% vs. 63% (p = .008) for small, 22% vs. 57% (p = .005) for medium, and 28% vs. 53% (p = .005) for large breasts. Furthermore, the tumor cavity coverage was slightly better in the hDAO plans (92.4% vs. 90.9%).

Conclusion: Compared with FP-IMRT, hDAO-IMRT provided dosimetric advantages, significantly reducing the size of the hot spot and slightly improving the coverage of the tumor cavity. In addition, hDAO-IMRT required less planning time and was less dependent on the planner's ability.
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http://dx.doi.org/10.1016/j.ijrobp.2009.01.011DOI Listing
January 2010

Effect of composite sector collimation on average dose fall-off for Gamma Knife Perfexion.

J Neurosurg 2008 Dec;109 Suppl:15-20

Department of Radiation Oncology, University of California, San Francisco, California 94143, USA.

Object: The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model.

Methods: A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V(0)) = (D/D(0))(gamma), where V is the volume of the peripheral isodose line with the value of D, V(0) is the reference prescription isodose volume, D(0) is the prescription dose, and gamma is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean gamma values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution-from 100% of the prescription dose to 75, 50, and 25% of the prescription dose.

Results: The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R(2)> 0.99 for all the cases. The overall gamma values (mean +/- 2 standard deviations) were as follows: gamma = -1.74 +/- 0.47 (Model 4C) versus -1.77 +/- 0.40 (Perfexion) within 100-75% of the prescription dose; gamma = -1.57 +/- 0.26 (Model 4C) versus -1.58 +/- 0.25 (Perfexion) within 100-50% of the prescription dose; gamma = -1.47 +/- 0.18 (Model 4C) versus -1.50 +/- 0.16 (Perfexion) within 100-25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively.

Conclusions: The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.
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http://dx.doi.org/10.3171/JNS/2008/109/12/S4DOI Listing
December 2008

Whole-procedure clinical accuracy of gamma knife treatments of large lesions.

Med Phys 2008 Nov;35(11):5110-4

Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143, USA.

The mechanical accuracy of Gamma Knife radiosurgery based on single-isocenter measurement has been established to within 0.3 mm. However, the full delivery accuracy for Gamma Knife treatments of large lesions has only been estimated via the quadrature-sum analysis. In this study, the authors directly measured the whole-procedure accuracy for Gamma Knife treatments of large lesions to examine the validity of such estimation. The measurements were conducted on a head-phantom simulating the whole treatment procedure that included frame placement, computed tomography imaging, treatment planning, and treatment delivery. The results of the measurements were compared with the dose calculations from the treatment planning system. Average agreements of 0.1-1.6 mm for the isodose lines ranging from 25% to 90% of the maximum dose were found despite potentially large contributing uncertainties such as 3-mm imaging resolution, 2-mm dose grid size, 1-mm frame registration, multi-isocenter deliveries, etc. The results of our measurements were found to be significantly smaller (>50%) than the calculated value based on the quadrature-sum analysis. In conclusion, Gamma Knife treatments of large lesions can be delivered much more accurately than predicted from the quadrature-sum analysis of major sources of uncertainties from each step of the delivery chain.
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http://dx.doi.org/10.1118/1.2987669DOI Listing
November 2008

Patient dose considerations for routine megavoltage cone-beam CT imaging.

Med Phys 2007 May;34(5):1819-27

Comprehensive Cancer Center Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143, USA.

Megavoltage cone-beam CT (MVCBCT), the recent addition to the family of in-room CT imaging systems for image-guided radiation therapy (IGRT), uses a conventional treatment unit equipped with a flat panel detector to obtain a three-dimensional representation of the patient in treatment position. MVCBCT has been used for more than two years in our clinic for anatomy verification and to improve patient alignment prior to dose delivery. The objective of this research is to evaluate the image acquisition dose delivered to patients for MVCBCT and to develop a simple method to reduce the additional dose resulting from routine MVCBCT imaging. Conventional CT scans of phantoms and patients were imported into a commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc treatment mimicking the MVCBCT acquisition process was generated to compute the delivered acquisition dose. To validate the dose obtained from the TPS, a simple water-equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber was used to measure the MVCBCT image acquisition dose. Absolute dose distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU) on pelvis and head and neck patients, respectively. A compensation factor was introduced to generate composite plans of treatment and MVCBCT imaging dose. The article provides a simple equation to compute the compensation factor. The developed imaging compensation method was tested on routinely used clinical plans for prostate and head and neck patients. The quantitative comparison between the calculated dose by the TPS and measurement points on the cylindrical phantom were all within 3%. The dose percentage difference for the ion chamber placed in the center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to patients forms a small anterior-posterior gradient ranging from 0.6 to 1.2 cGy per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver slightly more dose than current portal imaging but render soft tissue information for positioning. Overall, the additional dose from daily 9 MU MVCBCTs of prostate patients is small compared to the treatment dose (<4%). Dose-volume histograms of compensated plans for pelvis and head and neck patients imaged daily with MVCBCT showed no additional dose to the target and small increases at low doses. The results indicate that the dose delivered for MVCBCT imaging can be precisely calculated in the TPS and therefore included in the treatment plan. This allows simple plan compensations, such as slightly reducing the treatment dose, to minimize the total dose received by critical structures from daily positioning with MVCBCT. The proposed compensation factor reduces the number of MU per treatment beam per fraction. Both the number of fractions and the beam arrangement are kept unchanged. Reducing the imaging volume in the cranio-caudal direction can further reduce the dose delivered for MVCBCT. This is a useful feature to eliminate the imaging dose to the eyes or to focus on a specific region of interest for alignment.
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http://dx.doi.org/10.1118/1.2722470DOI Listing
May 2007

Dose calculation using megavoltage cone-beam CT.

Int J Radiat Oncol Biol Phys 2007 Mar;67(4):1201-10

Comprehensive Cancer Center, Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.

Purpose: To demonstrate the feasibility of performing dose calculation on megavoltage cone-beam CT (MVCBCT) of head-and-neck patients in order to track the dosimetric errors produced by anatomic changes.

Methods And Materials: A simple geometric model was developed using a head-size water cylinder to correct an observed cupping artifact occurring with MVCBCT. The uniformity-corrected MVCBCT was calibrated for physical density. Beam arrangements and weights from the initial treatment plans defined using the conventional CT were applied to the MVCBCT image, and the dose distribution was recalculated. The dosimetric inaccuracies caused by the cupping artifact were evaluated on the water phantom images. An ideal test patient with no observable anatomic changes and a patient imaged with both CT and MVCBCT before and after considerable weight loss were used to clinically validate MVCBCT for dose calculation and to determine the dosimetric impact of large anatomic changes.

Results: The nonuniformity of a head-size water phantom ( approximately 30%) causes a dosimetric error of less than 5%. The uniformity correction method developed greatly reduces the cupping artifact, resulting in dosimetric inaccuracies of less than 1%. For the clinical cases, the agreement between the dose distributions calculated using MVCBCT and CT was better than 3% and 3 mm where all tissue was encompassed within the MVCBCT. Dose-volume histograms from the dose calculations on CT and MVCBCT were in excellent agreement.

Conclusion: MVCBCT can be used to estimate the dosimetric impact of changing anatomy on several structures in the head-and-neck region.
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Source
http://dx.doi.org/10.1016/j.ijrobp.2006.10.048DOI Listing
March 2007