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.
four-dimensional computed tomography; gross tumor volume; Monte Carlo calculation; stereotactic body radiotherapy; lung cancer
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.
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.
image registration; 4D dose; SBRT; lung tumor
To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic-body radiotherapy (SBRT), and investigate their geometric causes.
Methods and Materials
Thirty previously treated liver cancer patients were retrospectively evaluated. SBRT was planned on the static exhale CT for 27 – 60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT (CBCT) guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning 4DCT (predicted breathing dose), and also over each fraction’s respiratory-correlated CBCT (accumulated treatment dose). The contribution of different geometric errors on changes between the accumulated and predicted breathing dose were quantified.
Twenty one patients (70%) had accumulated dose deviations relative to the planned static prescription dose greater than 5%, ranging from −15 to 5% in tumors and −42 to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4DCT-predicted dose, which were similar in magnitude. Thirty two tissues in these 16 patients had deviations > 5% relative to the 4DCT-predicted dose, and residual setup errors (n=17) were most often the largest cause of the deviations, followed by deformations (n=8) and breathing variations (n=7).
The majority of patients had accumulated dose deviations greater than 5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in over half the patients, commonly due to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose-escalation, adaptive SBRT, and aid in correlation with clinical outcomes.
Deformable registration; Dose accumulation; Image-guided radiotherapy; Stereotactic-body radiotherapy; Liver cancer
The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the
need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed.
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.
Medicine; Issue 62; radiosurgery; Cyberknife stereotactic radiosurgery; radiation; ovarian cancer; cervix cancer
The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/β = 10Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76Gy10). Total NTIDs for both techniques was calculated considering α/β = 3Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.
stereotactic body radiation therapy; integral dose; linear-quadratic model; biologically effective dose; BED; radio-induced secondary malignancies
Heterogeneity correction algorithms can have a large impact on the dose distributions of stereotactic body radiation therapy (SBRT) for lung tumors. Treatment plans of 20 patients who underwent SBRT for lung tumors with the prescribed dose of 48 Gy in four fractions at the isocenter were reviewed retrospectively and recalculated with different heterogeneity correction algorithms: the pencil beam convolution algorithm with a Batho power-law correction (BPL) in Eclipse, the radiological path length algorithm (RPL), and the X-ray Voxel Monte Carlo algorithm (XVMC) in iPlan. The doses at the periphery (minimum dose and D95) of the planning target volume (PTV) were compared using the same monitor units among the three heterogeneity correction algorithms, and the monitor units were compared between two methods of dose prescription, that is, an isocenter dose prescription (IC prescription) and dose–volume based prescription (D95 prescription). Mean values of the dose at the periphery of the PTV were significantly lower with XVMC than with BPL using the same monitor units (P < 0.001). In addition, under IC prescription using BPL, RPL and XVMC, the ratios of mean values of monitor units were 1, 0.959 and 0.986, respectively. Under D95 prescription, they were 1, 0.937 and 1.088, respectively. These observations indicated that the application of XVMC under D95 prescription results in an increase in the actually delivered dose by 8.8% on average compared with the application of BPL. The appropriateness of switching heterogeneity correction algorithms and dose prescription methods should be carefully validated from a clinical viewpoint.
heterogeneity correction; lung tumor; Monte Carlo dose calculation; stereotactic body radiation therapy
The overall treatment time of stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer is usually 3 to over 10 days. If it is longer than 7 days, tumor volume expansion during SBRT may jeopardize the target dose coverage. In this study, volume change of stage I NSCLC during SBRT was investigated.
Fifty patients undergoing 4-fraction SBRT with a total dose of 48 Gy (n = 36) or 52 Gy (n = 14) were analyzed. CT was taken for registration at the first and third SBRT sessions with an interval of 7 days in all patients. Patient age was 29–87 years (median, 77), and 39 were men. Histology was adenocarcinoma in 28, squamous cell carcinoma in 17, and others in 5. According to the UICC 7th classification, T-stage was T1a in 9 patients, T1b in 27, and T2a in 14. Tumor volumes on the first and 8th days were determined on CT images taken during the exhalation phase, by importing the data into the Dr. View/LINAX image analysis system. After determining the optimal threshold for distinguishing tumor from pulmonary parenchyma, the region above -250 HU was automatically extracted and the tumor volumes were calculated.
The median tumor volume was 7.3 ml (range, 0.5-35.7) on day 1 and 7.5 ml (range, 0.5-35.7) on day 8. Volume increase of over 10% was observed in 16 cases (32%); increases by >10 to ≤20%, >20 to ≤30%, and >30% were observed in 9, 5, and 2 cases, respectively. The increase in the estimated tumor diameter was over 2 mm in 3 cases and 1–2 mm in 6. A decrease of 10% or more was seen in 3 cases. Among the 16 tumors showing a volume increase of over 10%, T-stage was T1a in 2 patients, T1b in 9, and T2a in 5. Histology was adenocarcinoma in 10 patients, squamous cell carcinoma in 5, and others in 1.
Volume expansion >10% was observed in 32% of the tumors during the first week of SBRT, possibly due to edema or sustained tumor progression. When planning SBRT, this phenomenon should be taken into account.
To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions.
Methods and Materials
Thirty-two patients with 33 spinal lesions underwent computed tomography–based simulation while free breathing. Gross/clinical target volumes included involved portions of the vertebral body and paravertebral/epidural tumor. Planning target volume (PTV) expansion was 6 mm axially and 3 mm radially; the cord was excluded from the PTV. Biologic equivalent dose was calculated using the linear quadratic model with α/β = 3 Gy. Treatment was linear accelerator based with on-board imaging; dose was adjusted to maintain cord dose within tolerance. Survival, local control, pain, and neurologic status were monitored.
Twenty-one patients are alive at 1 year (median survival, 14 months). Median follow-up is 6 months for all patients (7 months for survivors). Mean previous radiotherapy dose to 22 patients was 35 Gy, and median interval was 17 months. Renal (31%), breast, and lung (19% each) were the most common histologic sites. Three SBRT fractions (range, one to four fractions) of 7 Gy (range, 5–16 Gy) were delivered. Median cord and target biologic equivalent doses were 70 Gy3 and 34.3 Gy10, respectively. Thirteen patients reported complete and 17 patients reported partial pain relief at 1 month. There were four failures (mean, 5.8 months) with magnetic resonance imaging evidence of in-field progression. No dosimetric parameters predictive of failure were identified. No treatment-related toxicity was seen.
Spinal SBRT is effective in the palliative/re-treatment setting. Volume expansion must ensure optimal PTV coverage while avoiding spinal cord toxicity. The long-term safety of spinal SBRT and the applicability of the linear-quadratic model in this setting remain to be determined, particularly the time-adjusted impact of prior radiotherapy.
Spinal cord; Spine radiosurgery; Stereotactic body radiotherapy; Normal tissue tolerance
To quantify the dosimetric effect and required margins to account for prostate intrafractional translation and residual setup error in a CBCT guided hypofractionated radiotherapy protocol.
Methods and Materials
Prostate position after online correction was measured during dose delivery using simultaneous kV fluoroscopy and post-treatment CBCT for 572 fractions from 30 patients. We reconstructed the dose distribution to the Clinical Tumor Volume (CTV) using a convolution of the static dose with a Probability Density Function (PDF) based on the kV fluoroscopy, and we calculated the minimum dose received by 99% of the CTV (D99). We compared reconstructed dose when the convolution was performed per beam, per patient, and when the PDF was created using post-treatment CBCT. We determined the minimum axis specific margins to limit CTV D99 reduction to 1%.
For 3mm margins, D99 reduction was ≤5% for 29/30 patients. Using post-CBCT rather than localizations at treatment delivery exaggerated dosimetric effects by ~47%, while there was no such bias between dose convolved with a beam specific and patient specific PDF. After 8 fractions, final cumulative D99 could be predicted with RMS error <1%. For 90% of patients, the required margins were ≤2, 4, and 3mm, with 70%, 40%, and 33% of patients requiring no RL, AP, and SI margins, respectively.
For protocols with CBCT guidance, RL, AP, and SI margins of 2, 4, and 3mm are sufficient to account for translational errors, however the large variation in patient specific margins suggests that adaptive management may be beneficial.
Prostate; Hypofractionation; Intrafraction Motion; Margin; Dosimetric
To clarify the clinical outcomes of two dose schedule of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using a real-time tumor-tracking radiation therapy (RTRT) system in single institution.
Using a superposition algorithm, we administered 48 Gy in 4 fractions at the isocenter in 2005–2006 and 40 Gy in 4 fractions to the 95% volume of PTV in 2007–2010 with a treatment period of 4 to 7 days. Target volume margins were fixed irrespective of the tumor amplitude.
In total, 109 patients (79 T1N0M0 and 30 T2N0M0). With a median follow-up period of 25 months (range, 4 to 72 months), the 5-year local control rate (LC) was 78% and the 5-year overall survival rate (OS) was 64%. Grade 2, 3, 4, and 5 radiation pneumonitis (RP) was experienced by 15 (13.8%), 3 (2.8%), 0, and 0 patients, respectively. The mean lung dose (MLD) and the volume of lung receiving 20 Gy (V20) were significantly higher in patients with RP Grade 2/3 than in those with RP Grade 0/1 (MLD p = 0.002, V20 p = 0.003). There was no correlation between larger maximum amplitude of marker movement and larger PTV (r = 0.137), MLD (r = 0.046), or V20 (r = 0.158).
SBRT using the RTRT system achieved LC and OS comparable to other SBRT studies with very low incidence of RP, which was consistent with the small MLD and V20 irrespective of tumor amplitude. For stage I NSCLC, SBRT using RTRT was suggested to be reliable and effective, especially for patients with large amplitude of tumor movement.
Stereotactic body radiotherapy; Radiation pneumonitis; Non-small cell lung cancer; Real-time tumor-tracking; Tumor motion; Gated radiotherapy
The aim of this study was to report the long-term clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer.
Materials and methods
Between March 2004 and July 2007, 26 patients with locally advanced, medically inoperable head and neck cancer or gross residual tumors in close proximity to critical structures following head and neck surgery were treated with SBRT as a boost treatment. All patients were initially treated with standard external beam radiotherapy (EBRT). SBRT boost was prescribed to the median 80% isodose line with a median dose of 21 (range 10–25) Gy in 2–5 (median, 5) fractions.
The median follow-up after SBRT was 56 (range 27.6 − 80.2) months. The distribution of treatment sites in 26 patients was as follows: the nasopharynx, including the base of the skull in 10 (38.5%); nasal cavity or paranasal sinus in 8 (30.8%); periorbit in 4 (15.4%); tongue in 3 (11.5%); and oropharyngeal wall in 1 (3.8%). The median EBRT dose before SBRT was 50.4 Gy (range 39.6 − 70.2). The major response rate was 100% with 21 (80.8%) complete responses (CR). Severe (grade ≥ 3) late toxicities developed in 9 (34.6%) patients, and SBRT boost volume was a significant parameter predicting severe late complication.
The present study demonstrates that a modern SBRT boost is a highly efficient tool for local tumor control. However, we observed a high frequency of serious late complications. More optimized dose fractionation schedule and patient selection are required to achieve excellent local control without significant late morbidities in head and neck boost treatment.
Boost; Head and neck cancer; Hypofractionation; Stereotactic body radiotherapy
Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.
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.
SBRT; Pancreas; Liver; Fiducial; Radiotherapy; Stereotactic body radiation therapy
Robotic Stereotactic Body Radiation Therapy with real-time tumor tracking has shown encouraging results for hepatic tumors with good efficacy and low toxicity. We studied the factors associated with local control of primary or secondary hepatic lesions post-SBRT.
Methods and materials
Since 2007, 153 stereotactic liver treatments were administered to 120 patients using the CyberKnife® System. Ninety-nine liver metastases (72 patients), 48 hepatocellular carcinomas (42 patients), and six cholangiocarcinomas were treated. On average, three to four sessions were delivered over 12 days. Twenty-seven to 45 Gy was prescribed to the 80% isodose line. Margins consisted of 5 to 10 mm for clinical target volume (CTV) and 3 mm for planning target volume (PTV).
Median size was 33 mm (range, 5–112 mm). Median gross tumor volume (GTV) was 32.38 cm3 (range, 0.2–499.5 cm3). Median total dose was 45 Gy in three fractions. Median minimum dose was 27 Gy in three fractions. With a median follow-up of 15.0 months, local control rates at one and two years were 84% and 74.6%, respectively. The factors associated with better local control were lesion size < 50 mm (p = 0.019), GTV volume (p < 0.05), PTV volume (p < 0.01) and two treatment factors: a total dose of 45 Gy and a dose–per-fraction of 15 Gy (p = 0.019).
Dose, tumor diameter and volume are prognostic factors for local control when a stereotactic radiation therapy for hepatic lesions is considered. These results should be considered in order to obtain a maximum therapeutic efficacy.
Hepatocellular carcinoma; Liver metastases; SBRT; Local control; Prognostic fractors
Advances in imaging and biological targeting have led to the development of stereotactic body radiation therapy (SBRT) as an alternative treatment of extracranial oligometastases. New radiobiological concepts, such as ceramide-induced endothelial apoptosis after hypofractionated high-dose SBRT, and the identification of patients with oligometastatic disease by microRNA expression may yet lead to further developments. Key factors in SBRT are delivery of a high dose per fraction, proper patient positioning, target localisation, and management of breathing–related motion. Our review addresses the radiation doses and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland oligometastases and treatment outcomes. Reported local control (LC) rates for liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 -100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are rare. SBRT of adrenal gland oligometastases shows promising results in the case of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe and effective treatment option for abdominal oligometastases.
Cancer; Gastrointestinal; Liver; Radiotherapy; Radiation biology; Surgery
To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC).
Materials and methods
Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30–48 Gy) in six fractions during two weeks.
The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy.
VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.
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.
Volume Modulated Arc Therapy; radiation therapy; intrathoracic lesions; stereotactic body radiotherapy; chest wall
In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system.
Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days.
By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients.
Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.
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.
Gastric cancer; Intensity-modulated radiotherapy; Breath holding; Image-guided radiotherapy; Dose convolution
To evaluate the impact of rotational setup errors on dose distribution in spinal stereotactic body radiotherapy (SBRT).
Methods and Materials
39 Cone Beam CT (CBCT) scans from 16 SBRT treatment courses were analyzed. Alignment (including rotation) to the treatment planning CT was performed, followed by translational alignment that reproduced the actual positioning. The planned fluence was then applied to determine the delivered dose to the targets and organs at risk.
The mean PTV volume was 71.01 mL (SD ± 60.05, range 22.62 – 250.65 mL). Prescribed dose (to the 62 – 82% isodose) was 14 – 30 Gy in one to six fractions. The average rotational displacements were 0.38 ± 1.21, 1.12 ± 1.82 and −0.51 ± 2.0 degrees with maximal rotations of −4.29, 5.76 and −6.64 degrees along the x (pitch), y (yaw), and z (roll) axes, respectively.
PTV coverage changed by an average of −0.07 Gy (SD ± 0.20 Gy) between the rotated and the original plan, representing 0.92% of prescription dose (SD ± 2.65%).
For the spinal cord, planned with 2 mm expansion to create a planning organ at risk volume (PRV), the difference in minimum dose to the upper 10% of the PRV volume was 0.03 ± 0.3 Gy (maximum 0.9 Gy). Other organs at risk saw insignificant changes in dose.
PRV expansion generally assures safe treatment delivery in the face of typically encountered rotations. Given the variability of delivered dose within this expansion for certain cases, caution should be taken to properly interpret doses to the cord when considering clinical dose limits.
SBRT; CBCT; IGRT; Rotation
This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.
Organs at risk; Survival; Toxicity; Patient positioning; Quality assurance; Risikoorgane; Überleben; Toxizität; Patientenpositionierung; Qualitätssicherung
To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration.
Method and Materials
Twenty one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale CT for 27 – 60 Gy in 6 fractions, were included. A biomechanical model-based deformable image registration algorithm, retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified.
Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was −1 (−14, 8) to minimum tumor, −4 (−15, 0) to max bowel, −4 (−25, 1) to max duodenum, 2 (−1, 9) to max esophagus, −2 (−13, 4) to max stomach, 0 (−3, 4) to mean liver, and −1 (−5, 1) and −2 (−7, 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues.
Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases due to breathing motion. These changes may not be accurately accounted for with rigid motion.
Deformable image registration; respiratory motion; 4D dose calculations; stereotactic body radiotherapy; liver cancer
The purpose of this study was to assess stereotactic body radiation therapy (SBRT) results and toxicity for stage I non-small cell lung cancer patients with low performance status and severe comorbidity.
Patients and Methods
From September 2008 to April 2010, 36 patients with 38 lesions were treated with hypofractionated SBRT. All except one were medically inoperable, had low performance status and/or severe cardiovascular and/or cardiopulmonary comorbidity. The patients were immobilized in an Elekta stereotactic body frame to improve setup accuracy, and four-dimensional CT scans were used for target delineation. Fractions of 15 Gy were prescribed to cover the planning target volume, giving a total dose of 45 Gy, with 1 fraction every second day. Cone beam CT was applied at each fraction to correct for setup errors. The patients were followed with toxicity evaluation and radiographic follow-up.
Median follow-up time was 13.8 months (0–21 months). The local tumor control after 12 months was 100%. Four patients developed regional relapse about 12 months after SBRT. The 1-year disease-free survival was 83%. The median tumor shrinkage at 1 year was 22 mm. Three patients experienced systemic relapse after 13 months. One patient developed grade 3 chest pain toxicity and 16 patients reported temporary grade 1 chest pain toxicity. Two patients reported temporary increased dyspnea. No patient experienced a reduction of the performance status after SBRT.
SBRT is an effective and safe treatment modality for elderly patients with early-stage non-small cell lung cancer, having low performance status and severe comorbidity. It is possible to achieve high local control rates with good tolerance.
Early-stage non-small cell lung cancer; Stereotactic body radiation therapy; Low performance status; Severe comorbidity