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1.  Stereotactic Radiosurgery for Gynecologic Cancer 
Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, intricate treatment planning, on-board imaging, and reduced number of ablative radiation doses to cancer targets usually refractory to chemotherapy and conventional radiation. Steep SBRT radiation dose drop-off permits narrow 'pencil beam' treatment fields to be used for ablative radiation treatment condensed into 1 to 3 treatments.
Treating physicians must appreciate that SBRT comes at a bigger danger of normal tissue injury and chance of geographic tumor miss. Both must be tackled by immobilization of cancer targets and by high-precision treatment delivery. Cancer target immobilization has been achieved through use of indexed customized Styrofoam casts, evacuated bean bags, or body-fix molds with patient-independent abdominal compression.1-3 Intrafraction motion of cancer targets due to breathing now can be reduced by patient-responsive breath hold techniques,4 patient mouthpiece active breathing coordination,5 respiration-correlated computed tomography,6 or image-guided tracking of fiducials implanted within and around a moving tumor.7-9 The Cyberknife system (Accuray [Sunnyvale, CA]) utilizes a radiation linear accelerator mounted on a industrial robotic arm that accurately follows patient respiratory motion by a camera-tracked set of light-emitting diodes (LED) impregnated on a vest fitted to a patient.10 Substantial reductions in radiation therapy margins can be achieved by motion tracking, ultimately rendering a smaller planning target volumes that are irradiated with submillimeter accuracy.11-13
Cancer targets treated by SBRT are irradiated by converging, tightly collimated beams. Resultant radiation dose to cancer target volume histograms have a more pronounced radiation "shoulder" indicating high percentage target coverage and a small high-dose radiation "tail." Thus, increased target conformality comes at the expense of decreased dose uniformity in the SBRT cancer target. This may have implications for both subsequent tumor control in the SBRT target and normal tissue tolerance of organs at-risk. Due to the sharp dose falloff in SBRT, the possibility of occult disease escaping ablative radiation dose occurs when cancer targets are not fully recognized and inadequate SBRT dose margins are applied. Clinical target volume (CTV) expansion by 0.5 cm, resulting in a larger planning target volume (PTV), is associated with increased target control without undue normal tissue injury.7,8 Further reduction in the probability of geographic miss may be achieved by incorporation of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET).8 Use of 18F-FDG PET/CT in SBRT treatment planning is only the beginning of attempts to discover new imaging target molecular signatures for gynecologic cancers.
PMCID: PMC3466654  PMID: 22546879
Medicine;  Issue 62;  radiosurgery;  Cyberknife stereotactic radiosurgery;  radiation;  ovarian cancer;  cervix cancer
2.  Adequacy of inhale/exhale breathhold CT based ITV margins and image-guided registration for free-breathing pancreas and liver SBRT 
To evaluate use of breath-hold CTs and implanted fiducials for definition of the internal target volume (ITV) margin for upper abdominal stereotactic body radiation therapy (SBRT). To study the statistics of inter- and intra-fractional motion information.
Methods and materials
11 patients treated with SBRT for locally advanced pancreatic cancer (LAPC) or liver cancer were included in the study. Patients underwent fiducial implantation, free-breathing CT and breath-hold CTs at end inhalation/exhalation. All patients were planned and treated with SBRT using volumetric modulated arc therapy (VMAT). Two margin strategies were studied: Strategy I uses PTV = ITV + 3 mm; Strategy II uses PTV = GTV + 1.5 cm. Both CBCT and kV orthogonal images were taken and analyzed for setup before patient treatments. Tumor motion statistics based on skeletal registration and on fiducial registration were analyzed by fitting to Gaussian functions.
All 11 patients met SBRT planning dose constraints using strategy I. Average ITV margins for the 11 patients were 2 mm RL, 6 mm AP, and 6 mm SI. Skeletal registration resulted in high probability (RL = 69%, AP = 4.6%, SI = 39%) that part of the tumor will be outside the ITV. With the 3 mm ITV expansion (Strategy 1), the probability reduced to RL 32%, AP 0.3%, SI 20% for skeletal registration; and RL 1.2%, AP 0%, SI 7% for fiducial registration. All 7 pancreatic patients and 2 liver patients failed to meet SBRT dose constraints using strategy II. The liver dose was increased by 36% for the other 2 liver patients that met the SBRT dose constraints with strategy II.
Image guidance matching to skeletal anatomy is inadequate for SBRT positioning in the upper abdomen and usage of fiducials is highly recommended. Even with fiducial implantation and definition of an ITV, a minimal 3 mm planning margin around the ITV is needed to accommodate intra-fractional uncertainties.
PMCID: PMC3896695  PMID: 24401365
SBRT; Pancreas; Liver; Fiducial; Radiotherapy; Stereotactic body radiation therapy
3.  Reconstitution of internal target volumes by combining four-dimensional computed tomography and a modified slow computed tomography scan in stereotactic body radiotherapy planning for lung cancer 
To evaluate the volumetric and geometric differences in the ITVs generated by four-dimensional (4D) computed tomography (CT), a modified slow CT scan, and a combination of these CT methods in lung cancer patients treated with stereotactic body radiotherapy (SBRT).
Both 4D CT and modified slow CT using a multi-slice CT scanner were performed for SBRT planning in 14 patients with 15 pulmonary targets. Volumetric and geometric analyses were performed for (1) ITVall, generated by combining the gross tumor volumes (GTVs) from all 8 phases of the 4D CT; (2) ITV2, generated by combining the GTVs from 2 extreme phases of the 4D CT; (3) ITVslow, derived from the GTV on the modified slow CT scan; (4) ITVall+slow, generated by combining ITVall and ITVslow; and (5) ITV2+slow, generated by combining ITV2 and ITVslow. Three SBRT plans were performed using 3 ITVs to assess the dosimetric effects on normal lung caused by the various target volumes.
ITVall (11.8 ± 8.3 cm3) was significantly smaller than ITVall+slow (12.5 ± 8.9 cm3), with mean values of 5.8% for the percentage volume difference, and a mean of 7.5% of ITVslow was not encompassed in ITVall. The geometric coverages of ITV2 and ITVslow for ITVall were 84.7 ± 6.6% and 76.2 ± 9.3%, respectively, but the coverage for ITVall increased to 90.9 ± 5.9% by using the composite of these two ITVs. There were statistically significant increases in the lung-dose parameters of the plans based on ITVall+slow compared to the plans based on ITVall or ITV2+slow. However, the magnitudes of these differences were relatively small, with a value of less than 3% in all dosimetric parameters.
Due to its ability to provides additional motion information, the combination of 4D CT and a modified slow CT scan in SBRT planning for lung cancer can be used to reduce possible errors in true target delineation caused by breathing pattern variations.
PMCID: PMC4018979  PMID: 24885768
4D CT; Slow CT; Internal target volume; Lung cancer; Stereotactic body radiotherapy
4.  Geographic miss of lung tumours due to respiratory motion: a comparison of 3D vs 4D PET/CT defined target volumes 
PET/CT scans acquired in the radiotherapy treatment position are typically performed without compensating for respiratory motion. The purpose of this study was to investigate geographic miss of lung tumours due to respiratory motion for target volumes defined on a standard 3D-PET/CT.
29 patients staged for pulmonary malignancy who completed both a 3D-PET/CT and 4D-PET/CT were included. A 3D-Gross Tumour Volume (GTV) was defined on the standard whole body PET/CT scan. Subsequently a 4D-GTV was defined on a 4D-PET/CT MIP. A 5 mm, 10 mm, 15 mm symmetrical and 15×10 mm asymmetrical Planning Target Volume (PTV) was created by expanding the 3D-GTV and 4D-GTV’s. A 3D conformal plan was generated and calculated to cover the 3D-PTV. The 3D plan was transferred to the 4D-PTV and analysed for geographic miss. Three types of miss were measured. Type 1: any part of the 4D-GTV outside the 3D-PTV. Type 2: any part of the 4D-PTV outside the 3D-PTV. Type 3: any part of the 4D-PTV receiving less than 95% of the prescribed dose. The lesion motion was measured to look at the association between lesion motion and geographic miss.
When a standard 15 mm or asymmetrical PTV margin was used there were 1/29 (3%) Type 1 misses. This increased 7/29 (24%) for the 10 mm margin and 23/29 (79%) for a 5 mm margin. All patients for all margins had a Type 2 geographic miss. There was a Type 3 miss in 25 out of 29 cases in the 5, 10, and 15 mm PTV margin groups. The asymmetrical margin had one additional Type 3 miss. Pearson analysis showed a correlation (p < 0.01) between lesion motion and the severity of the different types of geographic miss.
Without any form of motion suppression, the current standard of a 3D- PET/CT and 15 mm PTV margin employed for lung lesions has an increasing risk of significant geographic miss when tumour motion increases. Use of smaller asymmetric margins in the cranio-caudal direction does not comprise tumour coverage. Reducing PTV margins for volumes defined on 3D-PET/CT will greatly increase the chance and severity of a geometric miss due to respiratory motion. 4D-imaging reduces the risk of geographic miss across the population of tumour sizes and magnitude of motion investigated in the study.
PMCID: PMC4278238  PMID: 25511904
4D-PET/CT; Geographic miss; Lung cancer; Margins; Radiotherapy
5.  Incorporating breath holding and image guidance in the adjuvant gastric cancer radiotherapy: a dosimetric study 
The respiratory related target motion and setup error will lead to a large margin in the gastric radiotherapy. The purpose of this study is to investigate the dosimetric benefit and the possibility of incorporating the breath-hold (BH) technique with online image-guided radiotherapy in the adjuvant gastric cancer radiotherapy.
Setup errors and target motions of 22 post-operative gastric cancer patients with surgical clips were analyzed. Clips movement was recorded using the digital fluoroscopics and the probability distribution functions (pdf) of the target motions were created for both the free breathing (FB) and BH treatment. For dosimetric comparisons, two intensity-modulated radiotherapy (IMRT) treatment plans, i.e. the free breathing treatment plan (IMRTFB) and the image-guided BH treatment plan (IMRTIGBH) using the same beam parameters were performed among 6 randomly selected patients. Different margins for FB and BH plans were derived. The plan dose map was convoluted with various pdfs of the setup errors and the target motions. Target coverage and dose to organs at risk were compared and the dose-escalation probability was assessed.
The mean setup errors were 1.2 mm in the superior-inferior (SI), 0.0 mm in the left-right (LR), and 1.4 mm in the anterior-posterior (AP) directions. The mean target motion for the free breathing (vs. BH) was 11.1 mm (vs. 2.2 mm), 1.9 mm (vs. 1.1 mm), and 5.5 mm (vs. 1.7 mm) in the SI, LR, and AP direction, respectively. The target coverage was comparable for all the original plans. IMRTIGBH showed lower dose to the liver compared with IMRTFB (p = 0.01) but no significant difference in the kidneys. Convolved IMRTIGBH showed better sparing in kidneys (p < 0.01) and similar in liver (p = 0.08).
Combining BH technique with online image guided IMRT can minimize the organ motion and improve the setup accuracy. The dosimetric comparison showed the dose could be escalated to 54 Gy without increasing the critical organs toxicities, although further clinical data is needed.
PMCID: PMC3439279  PMID: 22716276
Gastric cancer; Intensity-modulated radiotherapy; Breath holding; Image-guided radiotherapy; Dose convolution
6.  Dosimetric impact of motion in free-breathing and gated lung radiotherapy: A 4D Monte Carlo study of intrafraction and interfraction effects 
Medical physics  2008;35(1):356-366.
The purpose of this study was to investigate if interfraction and intrafraction motion in free-breathing and gated lung IMRT can lead to systematic dose differences between 3DCT and 4DCT. Dosimetric effects were studied considering the breathing pattern of three patients monitored during the course of their treatment and an in-house developed 4D Monte Carlo framework. Imaging data were taken in free-breathing and in cine mode for both 3D and 4D acquisition. Treatment planning for IMRT delivery was done based on the free-breathing data with the corvus (North American Scientific, Chatsworth, CA) planning system. The dose distributions as a function of phase in the breathing cycle were combined using deformable image registration. The study focused on (a) assessing the accuracy of the corvus pencil beam algorithm with Monte Carlo dose calculation in the lung, (b) evaluating the dosimetric effect of motion on the individual breathing phases of the respiratory cycle, and (c) assessing intrafraction and interfraction motion effects during free-breathing or gated radiotherapy. The comparison between (a) the planning system and the Monte Carlo system shows that the pencil beam algorithm underestimates the dose in low-density regions, such as lung tissue, and overestimates the dose in high-density regions, such as bone, by 5% or more of the prescribed dose (corresponding to approximately 3–5 Gy for the cases considered). For the patients studied this could have a significant impact on the dose volume histograms for the target structures depending on the margin added to the clinical target volume (CTV) to produce either the planning target (PTV) or internal target volume (ITV). The dose differences between (b) phases in the breathing cycle and the free-breathing case were shown to be negligible for all phases except for the inhale phase, where an underdosage of the tumor by as much as 9.3 Gy relative to the free-breathing was observed. The large difference was due to breathing-induced motion/deformation affecting the soft/lung tissue density and motion of the bone structures (such as the rib cage) in and out of the beam. Intrafraction and interfraction dosimetric differences between (c) free-breathing and gated delivery were found to be small. However, more significant dosimetric differences, of the order of 3%–5%, were observed between the dose calculations based on static CT (3DCT) and the ones based on time-resolved CT (4DCT). These differences are a consequence of the larger contribution of the inhale phase in the 3DCT data than in the 4DCT.
PMCID: PMC2268084  PMID: 18293590
organ motion; IGRT; Monte Carlo; 4DCT; motion average dose
7.  Effects of organ motion on IMRT treatments with segments of few monitor units 
Medical physics  2007;34(3):923-934.
Interplay between organ (breathing) motion and leaf motion has been shown in the literature to have a small dosimetric impact for clinical conditions (over a 30 fraction treatment). However, previous studies did not consider the case of treatment beams made up of many few-monitor-unit (MU) segments, where the segment delivery time (1–2 s) is of the order of the breathing period (3–5 s). In this study we assess if breathing compromises the radiotherapy treatment with IMRT segments of low number of MUs. We assess (i) how delivered dose varies, from patient to patient, with the number of MU per segment, (ii) if this delivered dose is identical to the average dose calculated without motion over the path of the motion, and (iii) the impact of the daily variation of the delivered dose as a function of MU per segment. The organ motion was studied along two orthogonal directions, representing the left-right and cranial-caudal directions of organ movement for a patient setup in the supine position. Breathing motion was modeled as sin(x), sin4(x), and sin6(x), based on functions used in the literature to represent organ motion. Measurements were performed with an ionization chamber and films. For a systematic study of motion effects, a MATLAB simulation was written to model organ movement and dose delivery. In the case of a single beam made up of one single segment, the dose delivered to point in a moving target over 30 fractions can vary up to 20% and 10% for segments of 10 MU and 20 MU, respectively. This dose error occurs because the tumor spends most of the time near the edges of the radiation beam. In the case of a single beam made of multiple segments with low MU, we observed 2.4%, 3.3%, and 4.3% differences, respectively, for sin(x), sin4(x), and sin6(x) motion, between delivered dose and motion-averaged dose for points in the penumbra region of the beam and over 30 fractions. In approximately 5–10% of the cases, differences between the motion-averaged dose and the delivered 30-fraction dose could reach 6%, 8% and 10–12%, respectively for sin(x), sin4(x), and sin6(x) motion. To analyze a clinical IMRT beam, two patient plans were randomly selected. For one of the patients, the beams showed a likelihood of up to 25.6% that the delivered dose would deviate from the motion-averaged dose by more than 1%. For the second patient, there was a likelihood of up to 62.8% of delivering a dose that differs by more than 1% from the motion-averaged dose and a likelihood of up to ~30% for a 2% dose error. For the entire five-beam IMRT plan, statistical averaging over the beams reduces the overall dose error between the delivered dose and the motion-averaged dose. For both patients there was a likelihood of up to 7.0% and 33.9% that the dose error was greater than 1%, respectively. For one of the patients, there was a 12.6% likelihood of a 2% dose error. Daily intrafraction variation of the delivered dose of more than 10% is non-negligible and can potentially lead to biological effects. We observed [for sin(x), sin4(x), and sin6(x)] that below 10–15 MU leads to large daily variations of the order of 15–35%. Therefore, for small MU segments, non-negligible biological effects can be incurred. We conclude that for most clinical cases the effects may be small because of the use of many beams, it is desirable to avoid low-MU segments when treating moving targets. In addition, dose averaging may not work well for hypo-fractionation, where fewer fractions are used. For hypo-fractionation, PDF modeling of the tumor motion in IMRT optimization may not be adequate.
PMCID: PMC2034283  PMID: 17441238
organ motion; IGRT; motion average-dose; small MU segments; hypo-fractionation
8.  Approach to dose definition to the gross tumor volume for lung cancer with respiratory tumor motion 
Journal of Radiation Research  2012;54(1):140-145.
The purpose of this study was to validate the dose prescription defined to the gross tumor volume (GTV) 3D and 4D dose distributions of stereotactic radiotherapy for lung cancer. Treatment plans for 94 patients were generated based on computed tomography (CT) under free breathing. A uniform margin of 8 mm was added to the internal target volume (ITV) to generate the planning target volume (PTV). A leaf margin of 2 mm was added to the PTV. The prescription dose was defined such that 99% of the GTV should receive 100% of the dose using the Monte Carlo calculation (iPlan RT DoseTM) for 6-MV photon beams. The 3D dose distribution was determined using CT under free breathing. The 4D dose distribution plan was recalculated to investigate the effect of tumor motion using the same monitor units as those used for the 3D dose distribution plan. D99 (99% of the GTV) in the 4D plan was defined as the average D99 in each of the four breathing phases (0%, 25%, 50% and 75%). The dose difference between maximum and minimum at D99 of the GTV in 4D calculations was 0.6 ± 1.0% (range 0.2–4.6%). The average D99 of the GTV from 4D calculations in most patients was almost 100% (99.8 ± 1.0%). No significant difference was found in dose to the GTV between 3D and 4D dose calculations (P = 0.67). This study supports the clinical acceptability of treatment planning based on the dose prescription defined to the GTV.
PMCID: PMC3534263  PMID: 22951318
four-dimensional computed tomography; gross tumor volume; Monte Carlo calculation; stereotactic body radiotherapy; lung cancer
9.  Breathing Synchronized Delivery (BSD): A Potential Four Dimensional Tomotherapy Treatment Technique 
To introduce a four dimensional tomotherapy treatment technique with improved motion control and patient tolerance.
Material and Methods
CT images at ten breathing phases were acquired for treatment planning. The full exhalation phase was chosen as planning phase and the CT images at this phase were used as treatment planning images. ROI delineation was the same as traditional treatment planning except that no breathing motion margin was used in CTV-PTV expansion. The correlation between delivery and breathing phases was set assuming a constant gantry speed and a fixed breathing period. Deformable image registration yielded the deformation fields at each phase relative to the planning phase. With the delivery/breathing phase correlation and voxel displacements at each breathing phase, a 4D tomotherapy plan was obtained by incorporating the motion into inverse treatment plan optimization. A combined laser/spirometer breathing tracking system has been developed to monitor patient’s breathing. This system is able to produce stable and reproducible breathing signals representing tidal volume.
We compared 4D tomotherapy treatment planning method to conventional tomotherapy on static target. The results showed that 4D tomotherapy can achieve similar dose distributions on a moving target as conventional delivery on a stationary target. Regular breathing motion is fully compensated by motion-incorporated BSD planning. 4D tomotherapy also has close to 100% duty cycle and does not prolong treatment time.
Breathing synchronized delivery is a feasible 4D tomotherapy treatment technique with improved motion control and patient tolerance.
PMCID: PMC2074875  PMID: 17570608
Tomotherapy; breathing motion; respiratory gating; deformable image registration; treatment plan optimization
10.  Volume Modulated Arc Therapy (VMAT) for pulmonary Stereotactic Body Radiotherapy (SBRT) in patients with lesions in close approximation to the chest wall 
Purpose: Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall.
Materials and Methods: Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis.
Results: In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20).
Conclusions: VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.
PMCID: PMC3579242  PMID: 23440876
Volume Modulated Arc Therapy; radiation therapy; intrathoracic lesions; stereotactic body radiotherapy; chest wall
11.  Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy: A Dosimetric and Radiobiological Analysis 
We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V20; (b) Radiobiologically by calculating the biological effective uniform dose (D̿) for the target and organs at risk (OAR) and the complication free tumor control probability (P+). As a reference for the comparative study, we included a 4D Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V20 and MLD were respectively (13.1±6.9) % and (11.4±5.6) % for the MPP modality, whereas for the SPP modality they were (9.4±6.2) % and (7.2±4.7) %. On the other hand, the CGI was observed to improve by 15.3±13.2 and 9.6±10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P+ improved on average by (6.7±4.9) % and (4.1±3.6) % for the MPP and SPP modalities, respectively while the D̿ computed for the OAR decreased on average by (6.2±3.6) % and (3.8±3.5) % for the MPP and SPP tracking modalities, respectively. The D̿ calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.
PMCID: PMC2864553  PMID: 20218742
4D planning; Tracking radiotherapy; Deformable image registration; Radiobiological analysis
12.  Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors 
To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors.
Materials and methods
Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results.
Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm ± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm ± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs.
Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability.
PMCID: PMC3484063  PMID: 22682767
Lung cancer; Image-guidance; Cone-beam CT; Inter-observer variability; Respiration correlated imaging
13.  The Effects of Respiratory Motion on Passively Scattered Proton Therapy vs. IMRT for Stage III Lung Cancer - Are Proton Plans More Sensitive to Breathing Motion? 
International journal of radiation oncology, biology, physics  2013;87(3):10.1016/j.ijrobp.2013.07.007.
(1) To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans. (2) To establish the relationship between the magnitude of tumor motion and the respiratory induced dose difference for both modalities.
Methods and Materials
In a randomized clinical trial comparing PSPT and IMRT, radiotherapy plans have been designed following common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging 3-17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dose-volume histogram (DVH) differences (4D-3D) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion.
The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19/20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the two modalities were not statistically significant (p <0.05) for all DVH indices (mean ± SD) except the lung V5 (PSPT: +1.1±0.9%, IMRT: +0.4±1.2%) and maximum cord dose (PSPT: +1.5±2.9 Gy, IMRT: 0.0±0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only two indices: Dose to 95% PTV, and heterogeneity index.
With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2/11 of 4D-3D indices (Lung V5 and spinal cord max) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Due to the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.
PMCID: PMC3825187  PMID: 24074932
IMRT; Proton Therapy; Lung Radiation Therapy; 4D Dose Calculation; Respiratory Motion
14.  A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer 
Head & Neck Oncology  2012;4:12.
Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure.
We retrospectively reviewed 96 patients with rSCCHN treated with SBRT. Seven patients (7%) were treated after surgical resection of rSCCHN and 89 patients (93%) were treated definitively. PET-CT treatment planning was used for 45 patients whereas non-PET-CT planning was used for 51 patients. Categories of failure were assigned by comparing recurrences on post-treatment scans to the planning target volume (PTV) from planning scans using the deformable registration function of VelocityAI™. Failures were defined: In-field (>75% inside PTV), Overlap (20-75% inside PTV), Marginal (<20% inside PTV but closest edge within 1cm of PTV), or Regional/Distant (more than 1cm from PTV).
Median follow-up was 7.4 months (range, 2.6–52 months). Of 96 patients, 47 (49%) developed post-SBRT failure. Failure distribution was: In-field–12.3%, Overlap–24.6%, Marginal–36.8%, Regional/Distant–26.3%. There was a significant improvement in overall failure-free survival (log rank p = 0.037) and combined Overlap/Marginal failure-free survival (log rank p = 0.037) for those receiving PET-CT planning vs. non-PET-CT planning in the overall cohort (n = 96). Analysis of the definitive SBRT subgroup (n = 89) increased the significance of these findings (overall failure: p = 0.008, Overlap/Marginal failure: p = 0.009). There were no significant differences in age, gender, time from prior radiation, dose, use of cetuximab with SBRT, tumor differentiation, and tumor volume between the PET-CT and non-PET-CT groups.
Most failures after SBRT treatment for rSCCHN were near misses, i.e. Overlap/Marginal failures (61.4%), suggesting an opportunity to improve outcomes with more sensitive imaging. PET-CT treatment planning showed the lowest rate of overall and near miss failures and is beneficial for SBRT treatment planning.
PMCID: PMC3414786  PMID: 22515371
Stereotactic body radiotherapy; Recurrent head & neck cancer; Salvage; PET-CT; Patterns of failure
15.  Integrating respiratory-gated PET-based target volume delineation in liver SBRT planning, a pilot study 
To assess the feasibility and benefit of integrating four-dimensional (4D) Positron Emission Tomography (PET) – computed tomography (CT) for liver stereotactic body radiation therapy (SBRT) planning.
8 patients with 14 metastases were accrued in the study. They all underwent a non-gated PET and a 4D PET centered on the liver. The same CT scan was used for attenuation correction, registration, and considered the planning CT for SBRT planning. Six PET phases were reconstructed for each 4D PET. By applying an individualized threshold to the 4D PET, a Biological Internal Target Volume (BITV) was generated for each lesion. A gated Planning Target Volume (PTVg) was created by adding 3 mm to account for set-up margins. This volume was compared to a manual Planning Target Volume (PTV) delineated with the help of a semi-automatic Biological Target Volume (BTV) obtained from the non-gated exam. A 5 mm radial and a 10 mm craniocaudal margins were applied to account for tumor motion and set-up margins to create the PTV.
One undiagnosed liver metastasis was discovered thanks to the 4D PET. The semi-automatic BTV were significantly smaller than the BITV (p = 0.0031). However, after applying adapted margins, 4D PET allowed a statistically significant decrease in the PTVg as compared to the PTV (p = 0.0052).
In comparison to non-gated PET, 4D PET may better define the respiratory movements of liver targets and improve SBRT planning for liver metastases. Furthermore, non respiratory-gated PET exams can both misdiagnose liver metastases and underestimate the real internal target volumes.
PMCID: PMC4050417  PMID: 24885897
Respiratory-gated PET; Liver metastases; SBRT; Radiotherapy planning; 4D PET
16.  Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies 
Journal of Thoracic Disease  2014;6(4):303-318.
In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation.
PMCID: PMC3968554  PMID: 24688775
Lung cancer; motion management; dose calculation; treatment planning
17.  Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: a dosimetric comparison with 3D technique 
Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion. However dose distributions can be quite different from standard 3D therapy. This study quantifies those differences, with focus on VMAT plans using unflattened photon beams.
A total of 15 lung cancer patients previously treated with 3D or VMAT SBRT were randomly selected. For each patient, non-coplanar 3D, coplanar and non-coplanar VMAT and flattening filter free VMAT (FFF-VMAT) plans were generated to meet the same objectives with 50 Gy covering 95% of the PTV. Two dynamic arcs were used in each VMAT plan. The couch was set at ± 5° to the 0° straight position for the two non-coplanar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, Fitchburg WI) treatment planning system with VMAT capabilities was used. We analyzed the conformity index (CI), which is the ratio of the total volume receiving at least the prescription dose to the target volume receiving at least the prescription dose; the conformity number (CN) which is the ratio of the target coverage to CI; and the gradient index (GI) which is the ratio of the volume of 50% of the prescription isodose to the volume of the prescription isodose; as well as the V20, V5, and mean lung dose (MLD). Paired non-parametric analysis of variance tests with post-tests were performed to examine the statistical significance of the differences of the dosimetric indices.
Dosimetric indices CI, CN and MLD all show statistically significant improvement for all studied VMAT techniques compared with 3D plans (p < 0.05). V5 and V20 show statistically significant improvement for the FFF-VMAT plans compared with 3D (p < 0.001). GI is improved for the FFF-VMAT and the non-coplanar VMAT plans (p < 0.01 and p < 0.05 respectively) while the coplanar VMAT plans do not show significant difference compared to 3D plans. Dose to the target is typically more homogeneous in FFF-VMAT plans. FFF-VMAT plans require more monitor units than 3D or non-coplanar VMAT ones.
Besides the advantage of faster delivery times, VMAT plans demonstrated better conformity to target, sharper dose fall-off in normal tissues and lower dose to normal lung than the 3D plans for lung SBRT. More monitor units are often required for FFF-VMAT plans.
PMCID: PMC3354344  PMID: 22070866
18.  Improving Radiation Conformality in the Treatment of Non–Small Cell Lung Cancer 
Seminars in radiation oncology  2010;20(3):171-177.
One of the many challenges of lung cancer radiotherapy is conforming the radiation dose to the target due to tumor/organ motion and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4-D) image-based motion management, daily on-board imaging and adaptive radiotherapy, have enabled us to improve the therapeutic index of radiation therapy for lung cancer by permitting the design of personalized treatments that deliver adequate doses conforming to the target while sparing the surrounding critical normal tissues. Four-dimensional computed tomography (CT) image-based motion management provides an opportunity to individualize target motion margins and reduce the risk of a geographical target miss. Daily on-board imaging and adaptive radiotherapy reduce set-up and motion/anatomy uncertainties over the course of radiotherapy. These achievements in image guidance have permitted the implementation in lung cancer patients of highly conformal treatment delivery techniques that are exquisitely sensitive to organ motion and anatomic change such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy. More clinical studies are needed to further optimize conformal radiotherapy using individualized treatment adaptations based on changes in anatomy and tumor motion during the course of radiotherapy and using functional and biological imaging to selectively escalate doses to radioresistant subregions within the tumor.
PMCID: PMC2905742  PMID: 20652085
19.  To study tumor motion and planning target volume margins using four dimensional computed tomography for cancer of the thorax and abdomen regions 
In this study, four dimensional computed tomography (4DCT) scanning was performed during free breathing on a 16-slice Positron emission tomography PET /computed tomography (CT) for abdomen and thoracic patients. Images were sorted into 10 phases based on the temporal correlation between surface motion and data acquisition with an Advantage Workstation. Gross tumor volume gross tumor volume (GTV) s were manually contoured on all 10 phases of the 4DCT scan. GTVs in the multiple CT phases were called GTV4D. GTV4D plus an isotropic margin of 1.0 cm was called CTV4D. Two sets of planning target volume (PTV) 4D (PTV4D) were derived from the CTV4D, i.e. PTV4D2cm = CTV4D plus 1 cm setup margin (SM) and 1 cm internal margin (IM) and PTV4D1.5cm = CTV4D plus 1 cm SM and 0.5cm IM. PTV3D was derived from a CTV3D of the helical CT scan plus conventional margins of 2 cm. PTVgated was generated only selecting three CT phases, with a total margin of 1.5 cm. All four volumes were compared. To quantify the extent of the motion, we selected the two phases where the tumor exhibited the greatest range of motion. We also studied the effect of different PTV volumes on dose to the surrounding critical structures. Volume of CTV4D was greater than that of CTV3D. We found, on an average, a reduction of 14% volume of PTV4D1.5cm as compared with PTV3D and reduction of 10% volume of PTVgated as compared with PTV4D1.5cm. We found that 2 cm of margin was inadequate if true motion of tumor was not known. We observed greater sparing of critical structures for PTVs drawn taking into account the tumor motion.
PMCID: PMC3048953  PMID: 21430857
four dimensional computed tomography; tumor motion and PTV margin reduction for thoracic and abdomen tumor
20.  Evaluation of the dose variation for prostate heavy charged particle therapy using four-dimensional computed tomography 
Journal of Radiation Research  2012;54(2):357-366.
We quantified dose variation effects due to respiratory-induced intrafractional motion in conventional carbon-ion prostate treatment by using four-dimensional computed tomography (4DCT). 4DCT scans of 20 patients were acquired under free-breathing conditions using a 256 multi-slice CT scanner. The clinical target volume (CTV) was defined as the prostate and the seminal vesicle. Two types of planning target volumes (PTVs) were defined to minimize excessive dose to the rectum. The first PTV (= PTV1) was calculated by adding a 3D uniform margin to the CTV. The second PTV (= PTV2) was cut in a straight line from the top surface of the rectum from PTV1. Compensating boli were designed for the respective PTVs at the peak-exhalation phase, and carbon-ion dose distributions for a single respiratory cycle were calculated using these boli. Dose conformation to prostate, CTV, PTV1 and PTV2 were unchanged for all respiratory phases. The dose for >95% volume irradiation (D95) was 97.7% for prostate, 92.5% for CTV, 74.1% for PTV1 and 96.1% for PTV2 averaged over all patients. The rectum volume at inhalation phase receiving ≤50% of the prescribed dose was smaller than the planning dose due to the abdominal thickness variation. The target dose is not affected by intrafractional respiration in carbon-ion prostate treatment. Small dose variations, however, were observed due to respiratory-induced abdominal thickness variation; therefore the geometrical changes should be considered for prostate particle therapy.
PMCID: PMC3589943  PMID: 23263729
charged particle therapy; 4DCT; intrafractional motion; prostate
21.  An evaluation of planning techniques for stereotactic body radiation therapy in lung tumors 
To evaluate four planning techniques for stereotactic body radiation therapy (SBRT) in lung tumors.
Methods and Materials
Four SBRT plans were performed for 12 patients with stage I/II non-small-cell lung cancer under the following conditions: (1) conventional margins on free-breathing CT (plan 1), (2) generation of an internal target volume (ITV) using 4DCT with beam delivery under free-breathing conditions (plan 2), (3) gating at end-exhale (plan 3), and (4) gating at end-inhale (plan 4). Planning was performed following the RTOG 0236 protocol with a prescription dose of 54Gy (3 fractions). For each plan 4D dose was calculated using deformable image registration.
There was no significant difference in tumor dose delivered by the 4 plans. However, compared with plan 1, plans 2-4 reduced total lung BED by 1.9±1.2Gy, 3.1±1.6Gy and 3.5±2.1Gy, reduced mean lung dose by 0.8±0.5Gy, 1.5±0.8Gy, and 1.6±1.0Gy, reduced V20 by 1.5±1.0%, 2.7±1.4%, and 2.8±1.8% respectively with p<0.01. Compared with plan 2, plans 3-4 reduced lung BED by 1.2±1.0Gy and 1.6±1.5Gy, reduced mean lung dose by 0.6±0.5Gy and 0.8±0.7Gy, reduced V20 by 1.2±1.1% and 1.3±1.5% respectively with p<0.01. The differences in lung BED, mean dose and V20 of plan 4 compared with plan 3 are insignificant.
Tumor dose coverage was statistically insignificant between all plans. However, compared with plan 1, plans 2-4 significantly reduced lung doses. Compared with plan 2, plan 3-4 also reduced lung toxicity. The difference in lung doses between plan 3 and plan 4 was not significant.
PMCID: PMC2706126  PMID: 18359529
image registration; 4D dose; SBRT; lung tumor
22.  Dynamic simulation of motion effects in IMAT lung SBRT 
Intensity modulated arc therapy (IMAT) has been widely adopted for Stereotactic Body Radiotherapy (SBRT) for lung cancer. While treatment dose is optimized and calculated on a static Computed Tomography (CT) image, the effect of the interplay between the target and linac multi-leaf collimator (MLC) motion is not well described and may result in deviations between delivered and planned dose. In this study, we investigated the dosimetric consequences of the inter-play effect on target and organs at risk (OAR) by simulating dynamic dose delivery using dynamic CT datasets.
Fifteen stage I non-small cell lung cancer (NSCLC) patients with greater than 10 mm tumor motion treated with SBRT in 4 fractions to a dose of 50 Gy were retrospectively analyzed for this study. Each IMAT plan was initially optimized using two arcs. Simulated dynamic delivery was performed by associating the MLC leaf position, gantry angle and delivered beam monitor units (MUs) for each control point with different respiratory phases of the 4D-CT using machine delivery log files containing time stamps of the control points. Dose maps associated with each phase of the 4D-CT dose were calculated in the treatment planning system and accumulated using deformable image registration onto the exhale phase of the 4D-CT. The original IMAT plans were recalculated on the exhale phase of the CT for comparison with the dynamic simulation.
The dose coverage of the PTV showed negligible variation between the static and dynamic simulation. There was less than 1.5% difference in PTV V95% and V90%. The average inter-fraction and cumulative dosimetric effects among all the patients were less than 0.5% for PTV V95% and V90% coverage and 0.8 Gy for the OARs. However, in patients where target is close to the organs, large variations were observed on great vessels and bronchus for as much as 4.9 Gy and 7.8 Gy.
Limited variation in target dose coverage and OAR constraints were seen for each SBRT fraction as well as over all four fractions. Large dose variations were observed on critical organs in patients where these organs were closer to the target.
PMCID: PMC4243813  PMID: 25365935
SBRT; Lung motion; Interplay; IMAT
23.  Utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer and atelectasis 
To investigate the utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer (NSCLC) and atelectasis.
Thirty NSCLC patients who underwent radical radiotherapy from August 2010 to March 2012 were included in this study. All patients were pathologically confirmed to have atelectasis by imaging examination. PET-CT scanning was performed in these patients. According to the PET-CT scan results, the gross tumor volume (GTV) and organs at risk (OARs, including the lungs, heart, esophagus and spinal cord) were delineated separately both on CT and PET-CT images. The clinical target volume (CTV) was defined as the GTV plus a margin of 6-8 mm, and the planning target volume (PTV) as the GTV plus a margin of 10-15mm. An experienced physician was responsible for designing treatment plans PlanCT and PlanPET-CT on CT image sets. 95% of the PTV was encompassed by the 90% isodose curve, and the two treatment plans kept the same beam direction, beam number, gantry angle, and position of the multi-leaf collimator as much as possible. The GTV was compared using a target delineation system, and doses distributions to OARs were compared on the basis of dose-volume histogram (DVH) parameters.
The GTVCT and GTVPET-CT had varying degrees of change in all 30 patients, and the changes in the GTVCT and GTVPET-CT exceeded 25% in 12 (40%) patients. The GTVPET-CT decreased in varying degrees compared to the GTVCT in 22 patients. Their median GTVPET-CT and median GTVPET-CT were 111.4 cm3 (range, 37.8 cm3-188.7 cm3) and 155.1 cm3 (range, 76.2 cm3-301.0 cm3), respectively, and the former was 43.7 cm3 (28.2%) less than the latter. The GTVPET-CT increased in varying degrees compared to the GTVCT in 8 patients. Their median GTVPET-CT and median GTVPET-CT were 144.7 cm3 (range, 125.4 cm3-178.7 cm3) and 125.8 cm3 (range, 105.6 cm3-153.5 cm3), respectively, and the former was 18.9 cm3 (15.0%) greater than the latter. Compared to PlanCT parameters, PlanPET-CT parameters showed varying degrees of changes. The changes in lung V20, V30, esophageal V50 and V55 were statistically significant (Ps< 0.05 for all), while the differences in mean lung dose, lung V5, V10, V15, heart V30, mean esophageal dose, esophagus Dmax, and spinal cord Dmax were not significant (Ps> 0.05 for all).
PET-CT allows a better distinction between the collapsed lung tissue and tumor tissue, improving the accuracy of radiotherapy target delineation, and reducing radiation damage to the surrounding OARs in NSCLC patients with atelectasis.
PMCID: PMC3608960  PMID: 23506629
Atelectasis; PET-CT; Non-small cell lung cancer; Target volume; Three-dimensional conformal radiotherapy
24.  Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations 
Frontiers in Oncology  2014;4:321.
Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients.
Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution.
Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years.
Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.
PMCID: PMC4241836  PMID: 25505732
CyberKnife; prostate cancer; dosimetry; HDR; brachytherapy; image guided; stereotactic body radiotherapy
25.  Markerless EPID image guided dynamic multi-leaf collimator tracking for lung tumors 
Physics in medicine and biology  2013;58(12):4195-4204.
Compensation of target motion during the delivery of radiotherapy has the potential to improve treatment accuracy, dose conformity and sparing of healthy tissue. We implement an online image guided therapy system based on soft tissue localization (STiL) of the target from electronic portal images and treatment aperture adaptation with a dynamic multi-leaf collimator (DMLC). The treatment aperture is moved synchronously and in real-time with the tumor during the entire breathing cycle.
The system is implemented and tested on a Varian TX clinical linear accelerator featuring an AS-1000 electronic portal imaging device (EPID) acquiring images at a frame rate of 12.86 Hz throughout the treatment. A position update cycle for the treatment aperture consists of 4 steps: in the first step at time t = t0 a frame is grabbed, in the second step the frame is processed with the STiL algorithm to get the tumor position at t = t0, in a third step the tumor position at t = t + δt is predicted to overcome system latencies and in the fourth step, the DMLC control software calculates the required leaf motions and applies them at time t = t + δt. The prediction model is trained before the start of the treatment with data representing the tumor motion. We analyze the system latency with a dynamic chest phantom (4D motion phantom, Washington University). We estimate the average planar position deviation between target and treatment aperture in a clinical setting by driving the phantom with several lung tumor trajectories (recorded from fiducial tracking during radiotherapy delivery to the lung).
DMLC tracking for lung SBRT without fiducial markers was successfully demonstrated. The inherent system latency is found to be δt = (230 ± 11) ms for a MV portal image acquisition frame rate of 12.86 Hz. The root mean square deviation between tumor and aperture position is smaller than 1 mm.
We demonstrate the feasibility of real-time markerless DMLC tracking with a standard LINAC-mounted (EPID).
PMCID: PMC4182919  PMID: 23715431
lung; markerless; real-time; DMLC; motion estimation; tracking; EPID; portal image; SBRT; beams-eye-view; radiotherapy

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