R Popple

Feasibility of Single-Isocenter Volumetric Modulated Arc Radiosurgery for Treatment of Multiple Brain Metastases

PURPOSE To evaluate the relative plan quality of single-isocenter vs. multi-isocenter volumetric modulated arc therapy (VMAT) for radiosurgical treatment of multiple central nervous system metastases. METHODS AND MATERIALS VMAT plans were created using RapidArc technology for treatment of simulated patients with three brain metastases. The plans consisted of single-arc/single-isocenter, triple-arc (noncoplanar)/single-isocenter, and triple-arc (coplanar)/triple-isocenter configurations. All VMAT plans were normalized to deliver 100% of the 20-Gy prescription dose to all lesions. The plans were evaluated by calculation of Paddick and Radiation Therapy Oncology Group conformity index scores, Paddick gradient index scores, and 12-Gy isodose volumes. RESULTS All plans were judged clinically acceptable, but differences were observed in the dosimetric parameters, with the use of multiple noncoplanar arcs showing small improvements in the conformity indexes compared with the single-arc/single-isocenter and triple-arc (coplanar)/triple-isocenter plans. Multiple arc plans (triple-arc [noncoplanar]/single-isocenter and triple-arc [coplanar]/triple-isocenter) showed smaller 12-Gy isodose volumes in scenarios involving three metastases spaced closely together, with only small differences noted among all plans involving lesions spaced further apart. CONCLUSION Our initial results suggest that single-isocenter VMAT plans can be used to deliver conformity equivalent to that of multiple isocenter VMAT techniques. For targets that are closely spaced, multiple noncoplanar single-isocenter arcs might be required. VMAT radiosurgery for multiple targets using a single isocenter can be efficiently delivered, requiring less than one-half the beam time required for multiple isocenter set ups. VMAT radiosurgery will likely replace multi-isocenter techniques for linear accelerator-based treatment of multiple targets.

Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma

Retroperitoneal sarcomas (RPSs) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates. Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue expander to limit exposure of small bowel to higher radiation doses.

TUMOR CONTROL PROBABILITY FOR SELECTIVE BOOSTING OF HYPOXIC SUBVOLUMES, INCLUDING THE EFFECT OF REOXYGENATION

PURPOSE To study the effect on tumor control probability of selectively boosting the dose to hypoxic subvolumes. METHODS AND MATERIALS A Monte Carlo model was developed that separates the tumor into two compartments, one of which receives a primary dose, and one of which receives a higher boost dose. During radiation delivery, each compartment consists of three clonogen subpopulations: those that are well oxygenated, those that are temporarily hypoxic (geometrically transient hypoxia), and those that are permanently hypoxic (geometrically stable hypoxia). The spatial location of temporary hypoxia within the tumor volume varies over time, whereas, the spatial location of permanent hypoxia does not. The effect of reoxygenation was included. Clonogen proliferation was not included in the model. RESULTS A modest boost dose (120%-150% of the primary dose) increases tumor control probability to that found in the absence of permanent hypoxia. The entire hypoxic subvolume need not be included to obtain a significant benefit. However, only tumors with a geometrically stable hypoxic volume will have an improved control rate. CONCLUSIONS Tumors with an identifiable geometrically stable hypoxic volume will have an improved control rate if the dose to the hypoxic volume is escalated. Further work is required to determine the spatiotemporal evolution of the hypoxic volumes before and during the course of radiotherapy.

Effect of multileaf collimator leaf width on physical dose distributions in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy.

The purpose of this work is to examine physical radiation dose differences between two multileaf collimator (MLC) leaf widths (5 and 10 mm) in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy (IMRT). Three clinical patients with CNS tumors were planned with two different MLC leaf sizes, 5 and 10 mm, representing Varian-120 and Varian-80 Millennium multileaf collimators, respectively. Two sets of IMRT treatment plans were developed. The goal of the first set was radiation dose conformality in three dimensions. The goal for the second set was organ avoidance of a nearby critical structure while maintaining adequate coverage of the target volume. Treatment planning utilized the CadPlan/Helios system (Varian Medical Systems, Milpitas CA) for dynamic MLC treatment delivery. All beam parameters and optimization (cost function) parameters were identical for the 5 and 10 mm plans. For all cases the number of beams, gantry positions, and table positions were taken from clinically treated three-dimensional conformal radiotherapy plans. Conformality was measured by the ratio of the planning isodose volume to the target volume. Organ avoidance was measured by the volume of the critical structure receiving greater than 90% of the prescription dose (V(90)). For three patients with squamous cell carcinoma of the head and neck (T2-T4 N0-N2c M0) 5 and 10 mm leaf widths were compared for parotid preservation utilizing nine coplanar equally spaced beams delivering a simultaneous integrated boost. Because modest differences in physical dose to the parotid were detected, a NTCP model based upon the clinical parameters of Eisbruch et al. was then used for comparisons. The conformality improved in all three CNS cases for the 5 mm plans compared to the 10 mm plans. For the organ avoidance plans, V(90) also improved in two of the three cases when the 5 mm leaf width was utilized for IMRT treatment delivery. In the third case, both the 5 and 10 mm plans were able to spare the critical structure with none of the structure receiving more than 90% of the prescription dose, but in the moderate dose range, less dose was delivered to the critical structure with the 5 mm plan. For the head and neck cases both the 5 and 10 x 2.5 mm beamlets dMLC sliding window techniques spared the contralateral parotid gland while maintaining target volume coverage. The mean parotid dose was modestly lower with the smaller beamlet size (21.04 Gy v 22.36 Gy). The resulting average NTCP values were 13.72% for 10 mm dMLC and 8.24% for 5 mm dMLC. In conclusion, five mm leaf width results in an improvement in physical dose distribution over 10 mm leaf width that may be clinically relevant in some cases. These differences may be most pronounced for single fraction radiosurgery or in cases where the tolerance of the sensitive organ is less than or close to the target volume prescription.

Comparison of Plan Quality and Delivery Time between Volumetric Arc Therapy (RapidArc) and Gamma Knife Radiosurgery for Multiple Cranial Metastases

BACKGROUND Volumetric modulated arc therapy (VMAT) has been shown to be feasible for radiosurgical treatment of multiple cranial lesions with a single isocenter. OBJECTIVE To investigate whether equivalent radiosurgical plan quality and reduced delivery time could be achieved in VMAT for patients with multiple intracranial targets previously treated with Gamma Knife (GK) radiosurgery. METHODS We identified 28 GK treatments of multiple metastases. These were replanned for multiarc and single-arc, single-isocenter VMAT (RapidArc) in Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan was normalized for 100% prescription dose to 99% to 100% of target volume. Plan quality was analyzed by target conformity (Radiation Therapy Oncology Group and Paddick conformity indices [CIs]), dose falloff (area under the dose-volume histogram curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other end points included beam-on and treatment time. RESULTS Compared with GK, multiarc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; P < .001) with no significant difference in median dose falloff (P = .269), 12 Gy isodose volume (P = .500), or low isodose spill (P = .49). Multiarc VMAT plans were associated with markedly reduced treatment time. A predictive model of the 12 Gy isodose volume as a function of tumor number and volume was also developed. CONCLUSION For multiple target stereotactic radiosurgery, 4-arc VMAT produced clinically equivalent conformity, dose falloff, 12 Gy isodose volume, and low isodose spill, and reduced treatment time compared with GK. Because of its similar plan quality and increased delivery efficiency, single-isocenter VMAT radiosurgery may constitute an attractive alternative to multi-isocenter radiosurgery for some patients.

Image guided radiation therapy (IGRT) technologies for radiation therapy localization and delivery.

Image Guided Radiation Therapy (IGRT) Technologies for Radiation Therapy Localization and Delivery Jennifer De Los Santos, MD,* Richard Popple, PhD,* Nzhde Agazaryan, PhD,y John E. Bayouth, PhD,z Jean-Pierre Bissonnette, PhD,x Mary Kara Bucci, MD,k Sonja Dieterich, PhD,{ Lei Dong, PhD, Kenneth M. Forster, PhD,** Daniel Indelicato, MD,yy Katja Langen, PhD,zz Joerg Lehmann, PhD,{ Nina Mayr, MD,xx Ishmael Parsai, PhD,{{ William Salter, PhD, Michael Tomblyn, MD, MS,*** William T.C. Yuh, MD, MSEE,kk and Indrin J. Chetty, PhDyyy *Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama; yDepartment of Radiation Oncology, University of California Los Angeles, Los Angeles, California; zDepartment of Radiation Oncology, University of Iowa, Iowa City, Iowa; xDepartment of Radiation Physics, Princess Margaret Hospital, Toronto, Ontario, Canada; kAnchorage Radiation Therapy Center, Anchorage, Alaska; {Department of Radiation Oncology, University of California Davis, Sacramento, California; Scripps Proton Therapy Center, San Diego, California; **Department of Radiation Oncology, University of South Alabama, Mobile, Alabama; yyDepartment of Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida; zzDepartment of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, Florida; Departments of xxRadiation Oncology and kkRadiology, Ohio State University, Columbus, Ohio; {{Department of Radiation Oncology, University of Toledo College of Medicine, Toledo, Ohio; Department of Radiation Oncology, Huntsman Cancer Hospital, Salt Lake City, Utah; ***Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; and yyyDepartment of Radiation Oncology, Henry Ford Hospital and Health Centers, Detroit, Michigan

Dosimetric and radiobiological impact of dose fractionation on respiratory motion induced IMRT delivery errors: A volumetric dose measurement study

Respiratory motion can introduce substantial dose errors during IMRT delivery. These errors are difficult to predict because of the nonsynchronous interplay between radiation beams and tissues. The present study investigates the impact of dose fractionation on respiratory motion induced dosimetric errors during IMRT delivery and their radiobiological implications by using measured 3D dose. We focused on IMRT delivery with dynamic multileaf collimation (DMLC-IMRT). IMRT plans using several beam arrangements were optimized for and delivered to a polystyrene phantom containing a simulated target and critical organs. The phantom was set in linear sinusoidal motion at a frequency of 15 cycles/min (0.25 Hz). The amplitude of the motion was +/- 0.75 cm in the longitudinal direction and +/- 0.25 cm in the lateral direction. Absolute doses were measured with a 0.125 cc ionization chamber while dose distributions were measured with transverse films spaced 6 mm apart. Measurements were performed for varying number of fractions with motion, with respiratory-gated motion, and without motion. A tumor control probability (TCP) model for an inhomogeneously irradiated tumor was used to calculate and compare TCPs for the measurements and the treatment plans. Equivalent uniform doses (EUD) were also computed. For individual fields, point measurements using an ionization chamber showed substantial dose deviations (-11.7% to 47.8%) for the moving phantom as compared to the stationary phantom. However, much smaller deviations (-1.7% to 3.5%) were observed for the composite dose of all fields. The dose distributions and DVHs of stationary and gated deliveries were in good agreement with those of treatment plans, while those of the nongated moving phantom showed substantial differences. Compared to the stationary phantom, the largest differences observed for the minimum and maximum target doses were -18.8% and +19.7%, respectively. Due to their random nature, these dose errors tended to average out over fractionated treatments. The results of five-fraction measurements showed significantly improved agreement between the moving and stationary phantom. The changes in TCP were less than 4.3% for a single fraction, and less than 2.3% for two or more fractions. Variation of average EUD per fraction was small (< 3.1 cGy for a fraction size of 200 cGy), even when the DVHs were noticeably different from that of the stationary tumor. In conclusion, IMRT treatment of sites affected by respiratory motion can introduce significant dose errors in individual field doses; however, these errors tend to cancel out between fields and average out over dose fractionation. 3D dose distributions, DVHs, TCPs, and EUDs for stationary and moving cases showed good agreement after two or more fractions, suggesting that tumors affected by respiration motion may be treated using IMRT without significant dosimetric and biological consequences.

Validation of target volume and position in respiratory gated CT planning and treatment

The capability of a commercial respiratory gating system based on video tracking of reflective markers to reduce motion-induced CT planning and treatment errors was evaluated. Spherical plastic shells (2.8-82 cm3), simulating the gross target volume (GTV), were placed in a water-filled body phantom that was moved sinusoidally along the longitudinal axis of the CT scanner and the accelerator for +/- 1 cm at 15-30 cycle/min. During gated CT imaging, the x-ray exposure was initiated by the gating system shortly before the end of expiration (so that the imaging time would be centered at the end of expiration); it was terminated by the scanner after completion of each slice. In nongated CT images, the target appeared distorted and often broken up. GTVs volume errors ranged 16%-110% in axial scans, and 7%-36% in spiral scans. In gated CT images, the spheres appeared 3 and 5 mm longer than their actual diameters (volume errors 2%-16%), at the respective respiration rates of 15 and 20 cycles/min. At 30 cycles/min the target appeared 1 cm longer, and volume error ranged 25%-53%. During treatment, gating kept the beam on for a duration equal to the CT acquisition time of 1 s/slice. The difference in positional errors between gated CT and portal films was 1 mm, regardless the size of residual motion errors. Because of the potential of suboptimal placement of the gating window between CT imaging and treatment, an extra 1.5-2.5 mm safety margin can be added regardless of the size of residual motion error. For respiratory rates > or = 30 cycles/min, the effectiveness of gating is limited by large residual motion in the 1 s CT acquisition time.

Plan quality and treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy

PURPOSE To demonstrate plan quality and provide a practical, systematic approach to the treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy (VMAT; RapidArc, Varian Medical systems, Palo Alto, CA). METHODS AND MATERIALS Fifteen patients with 1 or more brain metastases underwent single isocenter VMAT radiosurgery. All plans were normalized to deliver 100% of the prescription dose to 99%-100% of the target volume. All targets per plan were treated to the same dose. Plans were created with dose control tuning structures surrounding targets to maximize conformity and dose gradient. Plan quality was evaluated by calculation of conformity index (CI = 100% isodose volume/target volume) and homogeneity index (HI = maximum dose/prescription dose) scores for each target and a Paddick gradient index (GI = 50% isodose volume/100% isodose volume) score for each plan. RESULTS The median number of targets per patient was 2 (range, 1-5). The median number of non-coplanar arcs utilized per plan was 2 (range, 1- 4). Single target plans were created with 1 or 2 non-coplanar arcs while multitarget plans utilized 2 to 4 non-coplanar arcs. Prescription doses ranged from 5-16 Gy in 1-5 fractions. The mean conformity index was 1.12 (± SD, 0.13) and the mean HI was 1.44 (± SD, 0.11) for all targets. The mean GI per plan was 3.34 (± SD, 0.42). CONCLUSIONS We have outlined a practical approach to cranial radiosurgery treatment planning using the single isocenter VMAT platform. One or 2 arc single isocenter plans are often adequate for treatment of single targets, while 2-4 arcs may be more advantageous for multiple targets. Given the high plan quality and extreme clinical efficiency, this single isocenter VMAT approach will continue to become more prevalent for linac-based radiosurgical treatment of 1 or more intracranial targets and will likely replace multiple isocenter techniques.

Evaluation of the interplay effect when using RapidArc to treat targets moving in the craniocaudal or right-left direction

PURPOSE We have investigated the dosimetric errors caused by the interplay between the motions of the LINAC and the tumor during the delivery of a volume modulated arc therapy treatment. This includes the development of an IMRT QA technique, applied here to evaluate RapidArc plans of varying complexity. METHODS An IMRT QA technique was developed, which involves taking a movie of the delivered dose (0.2 s frames) using a 2D ion chamber array. Each frame of the movie is then moved according to a respiratory trace and the cumulative dose calculated. The advantage of this approach is that the impact of turning the beam on at different points in the respiratory trace, and of different types of motion, can be evaluated using data from a single irradiation. We evaluated this technique by comparing with the results when we actually moved the phantom during irradiation. RapidArc plans were created to treat a 62 cc spherical tumor in a lung phantom (16 plans) and a 454 cc irregular tumor in an actual patient (five plans). The complexity of each field was controlled by adjusting the MU (312-966 MU). Each plan was delivered to a phantom, and a movie of the delivered dose taken using a 2D ion chamber array. Patient motion was modeled by shifting each dose frame according to a respiratory trace, starting the motion at different phases. The expected dose distribution was calculated by blurring the static dose distribution with the target motion. The dose error due to the interplay effect was then calculated by comparing the delivered dose with the expected dose distribution. Peak-to-peak motion of 0.5, 1.0, and 2.0 cm in the craniocaudal and right-left directions, with target periods of 3 and 5 s, were evaluated for each plan (252 different target motion/plan combinations). RESULTS The daily dose error due to the interplay effect was less than 10% for 98.4% of all pixels in the target for all plans investigated. The percentage of pixels for which the daily dose error could be larger than 5% increased with increasing plan complexity (field MU), but was less than 15% for all plans if the motion was 1 cm or less. For 2 cm motion, the dose error could be larger than 5% for 40% of pixels, but was less than 5% for more than 80% of pixels for MU < 550, and was less than 10% for 99% of all pixels. The interplay effect was smaller for 3 s periods than for 5 s periods. CONCLUSIONS The interplay between the motions of the LINAC and the target can result in an error in the delivered dose. This effect increases with plan complexity, and with target magnitude and period. It may average out after many fractions.