Michael Lovelock

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

International spine radiosurgery consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery

PURPOSE Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery. METHODS AND MATERIALS Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines. RESULTS Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space. CONCLUSIONS This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.

Intensity-modulated Stereotactic Radiotherapy of Paraspinal Tumors: A Preliminary Report

OBJECTIVERadioresistant paraspinal tumors may benefit from conformal treatment techniques such as intensity-modulated radiotherapy (IMRT). Local tumor control and long-term palliation for both primary and metastatic tumors may be achieved with IMRT while reducing the risk of spinal cord toxicity associated with conventional radiotherapy techniques. In this article, we report our initial clinical experience in treating 16 paraspinal tumors with IMRT in which the planning target volume was 2 mm or greater from the spinal cord. METHODSIMRT was administered by using a linear accelerator mounted with a multileaf collimator. Two immobilization body frames developed at Memorial Sloan-Kettering Cancer Center were used for patients with and without spinal implants. During a 30-month period, 16 patients underwent IMRT for metastatic and primary tumors. Eleven patients were treated for symptomatic recurrences after undergoing surgery and prior external beam radiotherapy, and one patient was treated after undergoing radiotherapy for a metastatic pancreatic gastrinoma with overlapping ports to the spine. Four patients with primary tumors were treated after primary resection that resulted in positive histological margins. Twelve patients were symptomatic with pain, functional radiculopathy, or both. Tumoral doses were determined on the basis of the relative radiosensitivity of tumors. Patients with metastatic tumors were administered a median tumoral dose of 20 Gy in four to five fractions and a spinal cord maximum dose of 6.0 Gy in addition to the full tolerance dose administered in previous radiation treatments. The primary tumors were delivered a median dose of 70 Gy in 33 to 37 fractions and a spinal cord maximum dose of 16 Gy. The median tumoral volume was 7.8 cm3. RESULTSOf the 15 patients who underwent radiographic follow-up, 13 demonstrated either no interval growth or a reduction in tumor size in a median follow-up period of 12 months (range, 2–23 mo). Two patients, one with a thoracic chondrosarcoma and one with a chordoma, showed tumor progression 1 year after undergoing IMRT. Pain symptoms improved in 11 of 11 patients, and 4 of 4 patients had significant improvement in their functionally significant radiculopathy and/or plexopathy. Pain relief was durable in all patients except the two with tumor progression. No patient showed signs or symptoms of radiation-induced myelopathy, radiculopathy, or plexopathy, including 12 patients with a median follow-up of 18 months. CONCLUSIONIMRT was effective for treating pain and improving functional radiculopathy in patients with metastatic and primary tumors. Although long-term tumor control is not established in this study, high-dose tumoral irradiation can be performed without causing radiation myelopathy in more than 1 year of follow-up.

A patient-specific Monte Carlo dose-calculation method for photon beams.

A patient-specific, CT-based, Monte Carlo dose-calculation method for photon beams has been developed to correctly account for inhomogeneity in the patient. The method employs the EGS4 system to sample the interaction of radiation in the medium. CT images are used to describe the patient geometry and to determine the density and atomic number in each voxel. The user code (MCPAT) provides the data describing the incident beams, and performs geometry checking and energy scoring in patient CT images. Several variance reduction techniques have been implemented to improve the computation efficiency. The method was verified with measured data and other calculations, both in homogeneous and inhomogeneous media. The method was also applied to a lung treatment, where significant differences in dose distributions, especially in the low-density region, were observed when compared with the results using an equivalent pathlength method. Comparison of the DVHs showed that the Monte Carlo calculated plan predicted an underdose of nearly 20% to the target, while the maximum doses to the cord and the heart were increased by 25% and 33%, respectively. These results suggested that the Monte Carlo method may have an impact on treatment designs, and also that it can be used as a benchmark to assess the accuracy of other dose calculation algorithms. The computation time for the lung case employing five 15-MV wedged beams, with an approximate field size of 13 X 13 cm and the dose grid size of 0.375 cm, was less than 14 h on a 175-MHz computer with a standard deviation of 1.5% in the high-dose region.

Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases from renal cell carcinoma.

PURPOSE To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. PATIENTS AND METHODS Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). RESULTS The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). CONCLUSION High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

PURPOSE To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. METHODS AND MATERIALS A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. RESULTS The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses (≤22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). CONCLUSION High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

Impact of Dose on Local Failure Rates After Image-Guided Reirradiation of Recurrent Paraspinal Metastases

PURPOSE To examine the impact of dose on local failure (LF) rates in the re-treatment of recurrent paraspinal metastases with image-guided intensity-modulated radiotherapy (IG-IMRT). METHODS AND MATERIALS The records of patients with in-field recurrence after previous spine radiation (median dose, 30 Gy) who received salvage IG-IMRT with either five 4-Gy (20-Gy group, n = 42) or five 6-Gy (30-Gy group, n = 55) daily fractions between January 2003 and August 2008 were reviewed. Institutional practice was 20 Gy before April 2006, when it changed to 30 Gy. A total of 47 cases (48%) were treated adjuvantly, after surgery to decompress epidural disease. LF after IG-IMRT was defined radiographically. RESULTS The median follow-up was 12.1 months (range, 0.2-63.6 months). The 1-year cumulative incidences of LF after 20 Gy and 30 Gy IG-IMRT were 45% and 26%, respectively (p = 0.04). Of all treatment characteristics examined (20-Gy vs. 30-Gy dose group, dose to 95% of the planned and gross target volume, tumor size, histology, receipt of surgery, and interval between first and second radiation), only dose group had a significant impact on actuarial LF incidence (p = 0.04; unadjusted HR, 0.51; 95% CI, 0.27-0.96). There was no incidence of myelopathy. CONCLUSIONS A significant decrease in LF after IG-IMRT with five 6-Gy fractions compared with five 4-Gy fractions was observed without increased risk of myelopathy. Until prospective data comparing stereotactic hypofractionated and single-fraction regimens become available, when reirradiating recurrent paraspinal metastases with IG-IMRT, administration of five 6-Gy daily fractions is reasonable.

Motion monitoring for cranial frameless stereotactic radiosurgery using video-based three-dimensional optical surface imaging

PURPOSE To establish a new clinical procedure in frameless stereotactic radiosurgery (SRS) for patient setup verification at treatment couch angles as well as for head-motion monitoring during treatment using video-based optical surface imaging (OSI). METHODS A video-based three-dimensional (3D) OSI system with three ceiling-mounted camera pods was employed to verify setup at treatment couch angles as well as to monitor head motion during treatment. A noninvasive head immobilization device was utilized, which includes an alpha head mold and a dental mouthpiece with vacuum suction; both were locked to the treatment couch. Cone beam computed tomography (CBCT) was used as the standard for image-guided setup. Orthogonal 2D-kV imaging was applied for setup verification before treatment, between couch rotations, and after treatment at zero couch angle. At various treatment couch angles, OSI setup verification was performed, relative to initial OSI setup verification at zero couch angle after CBCT setup through a coordinate transformation. For motion monitoring, the setup uncertainty was decoupled by taking an on-site surface image as new reference to detect motion-induced misalignment in near real-time (1-2 frames per second). Initial thermal instability baseline of the real-time monitoring was corrected. An anthropomorphous head phantom and a 1D positioning platform were used to assess the OSI accuracy in motion detection in longitudinal and lateral directions. Two hypofractionated (9 Gy × 3 and 6 Gy × 5) frameless stereotactic radiotherapy (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS patients were treated using this frameless procedure. For comparison, 11 conventional frame-based SRS patients were monitored using the OSI to serve as clinical standards. Multiple noncoplanar conformal beams were used for planning both frameless and frame-based SRS with a micromultileaf collimator. RESULTS The accuracy of the OSI in 1D motion detection was found to be 0.1 mm with uncertainty of ±0.1 mm using the head phantom. The OSI registration against simulation computed tomography (CT) external contour was found to be dependent on the CT skin definition with ∼0.4 mm variation. For frame-based SRS patients, head-motion magnitude was detected to be <1.0 mm (0.3 ± 0.2 mm) and <1.0° (0.2° ± 0.2°) for 98% of treatment time, with exception of one patient with head rotation <1.5° for 98% of the time. For frameless SRT/SRS patients, similar motion magnitudes were observed with an average of 0.3 ± 0.2 mm and 0.2° ± 0.1° in ten treatments. For 98% of the time, the motion magnitude was <1.1 mm and 1.0°. Complex head-motion patterns within 1.0 mm were observed for frameless SRT/SRS patients. The OSI setup verification at treatment couch angles was found to be within 1.0 mm. CONCLUSIONS The OSI system is capable of detecting 0.1 ± 0.1 mm 1D spatial displacement of a phantom in near real time and useful in head-motion monitoring. This new frameless SRS procedure using the mask-less head-fixation system provides immobilization similar to that of conventional frame-based SRS. Head-motion monitoring using near-real-time surface imaging provides adequate accuracy and is necessary for frameless SRS in case of unexpected head motion that exceeds a set tolerance.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumors histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

Exponential Increase in Relative Biological Effectiveness Along Distal Edge of a Proton Bragg Peak as Measured by Deoxyribonucleic Acid Double-Strand Breaks

PURPOSE To quantify the relative biological effectiveness (RBE) of the distal edge of the proton Bragg peak, using an in vitro assay of DNA double-strand breaks (DSBs). METHODS AND MATERIALS U2OS cells were irradiated within the plateau of a spread-out Bragg peak and at each millimeter position along the distal edge using a custom slide holder, allowing for simultaneous measurement of physical dose. A reference radiation signal was generated using photons. The DNA DSBs at 3 hours (to assess for early damage) and at 24 hours (to assess for residual damage and repair) after irradiation were measured using the γH2AX assay and quantified via flow cytometry. Results were confirmed with clonogenic survival assays. A detailed map of the RBE as a function of depth along the Bragg peak was generated using γH2AX measurements as a biological endpoint. RESULTS At 3 hours after irradiation, DNA DSBs were higher with protons at every point along the distal edge compared with samples irradiated with photons to similar doses. This effect was even more pronounced after 24 hours, indicating that the impact of DNA repair is less after proton irradiation relative to photons. The RBE demonstrated an exponential increase as a function of depth and was measured to be as high as 4.0 after 3 hours and as high as 6.0 after 24 hours. When the RBE-corrected dose was plotted as a function of depth, the peak effective dose was extended 2-3 mm beyond what would be expected with physical measurement. CONCLUSIONS We generated a highly comprehensive map of the RBE of the distal edge of the Bragg peak, using a direct assay of DNA DSBs in vitro. Our data show that the RBE of the distal edge increases with depth and is significantly higher than previously reported estimates.