Kamil M. Yenice

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.

Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease.

A subset of patients with metastatic cancer in limited organs may benefit from metastasis‐directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis‐directed radiotherapy.

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.

Hypofractionated Stereotactic Radiotherapy Using Intensity-Modulated Radiotherapy in Patients with One or Two Brain Metastases

Purpose: A small fraction of patients with 1–2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. Methods: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. Results: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. Conclusions: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients.

An Initial Report of a Radiation Dose-Escalation Trial in Patients with One to Five Sites of Metastatic Disease

Purpose: Previous investigations have suggested that a subset of patients with metastatic cancer in a limited number of organs may benefit from local treatment. We investigated whether cancer patients with limited sites of metastatic disease (oligometastasis) who failed standard therapies could be identified and safely treated at one to five known sites of low-volume disease with radiotherapy. Experimental Design: Patients with one to five sites of metastatic cancer with a life expectancy of >3 months and good performance status received escalating doses of radiation to all known sites of cancer with hypofractionated radiation therapy. Patients were followed radiographically with computed tomography scans of the chest, abdomen, and pelvis and metabolically with [18F]fluorodeoxyglucose-positron emission tomography 1 month following treatment and then every 3 months. Acute toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system. Results: Twenty-nine patients with 56 metastatic lesions were enrolled from November 2004 to March 2007, with a median follow-up of 14.9 months. Two patients experienced acute (radiation pneumonitis and nausea) and one experienced chronic (gastrointestinal hemorrhage) grade ≥3 toxicity. Fifty-nine percent of patients responded to protocol therapy. Twenty-one percent of patients have not progressed following protocol treatment. Fifty-seven percent of treated lesions have not progressed at last follow-up. Progression was amenable to further local therapy in 48% of patients. Conclusions: Patients with low-volume metastatic cancer can be identified, safely treated, and may benefit from radiotherapy.

Accuracy and feasibility of cone‐beam computed tomography for stereotactic radiosurgery setup

Image fusion, target localization, and setup accuracy of cone-beam computed tomography (CBCT) for stereotactic radiosurgery (SRS) were investigated in this study. A Rando head phantom rigidly attached to a stereotactic Brown-Roberts-Wells (BRW) frame was utilized to study the geometric accuracy of CBCT. Measurements of distances and angular separations between selected pairs of multiple radio-opaque targets embedded in the head phantom from a conventional simulation CT provided comparative data for geometric accuracy analysis. Localization accuracy of the CBCT scan was investigated from an analysis of BRW localization of four cylindrical objects (9 mm in diameter and 25 mm in length) independently computed from CBCT and conventional CT scans. Image fusion accuracy was quantitatively evaluated from BRW localization of multiple simulated targets from the CBCT and conventional CT scan. Finally, a CBCT setup procedure for stereotactic radiosurgery treatments was proposed and its accuracy was assessed using orthogonal target verification imaging. Our study showed that CBCT did not present any significant geometric distortions. Stereotactic coordinates of the four cylindrical objects as determined from the CBCT differed from those determined from the conventional CT on average by 0.30 mm with a standard deviation (SD) of 0.09 mm. The mean image registration accuracy of CBCT with conventional CT was 0.28 mm (SD = 0.10 mm). Setup uncertainty of our proposed CBCT setup procedure was on the same order as the conventional framed-based stereotactic systems reported in the literature (mean = 1.34 mm, SD = 0.33 mm). In conclusion, CBCT can be used to guide SRS treatment setup with accuracy comparable to the currently used frame-based stereotactic radiosurgery systems provided that intra-treatment patient motion is prevented.

Accurate setup of paraspinal patients using a noninvasive patient immobilization cradle and portal imaging

Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager.

The utility of FDG-PET for assessing outcomes in oligometastatic cancer patients treated with stereotactic body radiotherapy: a cohort study

BackgroundStudies suggest that patients with metastases limited in number and destination organ benefit from metastasis-directed therapy. Stereotactic body radiotherapy (SBRT) is commonly used for metastasis directed therapy in this group. However, the characterization of PET response following SBRT is unknown in this population. We analyzed our cohort of patients to describe the PET response following SBRT.MethodsPatients enrolled on a prospective dose escalation trial of SBRT to all known sites of metastatic disease were reviewed to select patients with pre- and post-therapy PET scans. Response to SBRT was characterized on PET imaging based on standard PET response criteria and compared to CT based RECIST criteria for each treated lesion.Results31 patients had PET and CT data available before and after treatment for analysis in this study. In total, 58 lesions were treated (19 lung, 11 osseous, 11 nodal, 9 liver, 6 adrenal and 2 soft tissue metastases). Median follow-up was 14 months (range: 3–41). Median time to first post-therapy PET was 1.2 months (range; 0.5-4.1). On initial post-therapy PET evaluation, 96% (56/58) of treated metastases responded to therapy. 60% (35/58) had a complete response (CR) on PET and 36% (21/58) had a partial response (PR). Of 22 patients with stable disease (SD) on initial CT scan, 13 had CR on PET, 8 had PR, and one had SD. Of 21 metastases with PET PR, 38% became CR, 52% remained PR, and 10% had progressive disease on follow-up PET. 10/35 lesions (29%) with an initial PET CR progressed on follow-up PET scan with median time to progression of 4.11 months (range: 2.75-9.56). Higher radiation dose correlated with long-term PET response.ConclusionsPET response to SBRT enables characterization of metastatic response in tumors non-measurable by CT. Increasing radiation dose is associated with prolonged complete response on PET.

Image-guided radiotherapy using surgical clips as fiducial markers after prostatectomy: a report of total setup error, required PTV expansion, and dosimetric implications.

PURPOSE To determine the total setup error and the required planning target volume (PTV) margin for prostate bed without image guided radiotherapy (IGRT), and to demonstrate the feasibility and dosimetric benefit of IGRT post prostatectomy using surgical clips. MATERIALS AND METHODS Seventeen patients were treated with intensity modulated radiotherapy (IMRT) to the prostate bed with a 1cm PTV margin. Three-dimensional shifts of the surgical clips inside the prostate bed were measured with respect to the isocenter from 364 orthogonal kV image pairs, and the total setup error was calculated to determine the required PTV margin. Alternative IMRT plans using 5mm or 1cm PTV expansion were generated and compared for rectal and bladder sparing. RESULTS Surgical clips were reproducibly and reliably identified. The mean (standard deviation) shifts in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP), axes were: -0.1 mm (1.7 mm), 0.6 mm (2.4 mm), and -2.1 mm (2.6 mm), respectively. The required PTV margins were calculated to be 6, 8, and 9 mm in the LR, AP, and SI axis, respectively. A PTV expansion of 5mm, compared to 1cm, significantly reduced V65 Gy to the rectum by 10%. CONCLUSIONS In the absence of IGRT, a non-uniform PTV margin of 6mm LR, 8mm AP, and 9 mm SI should be considered. Use of clips as fiducial markers can decrease the total setup error, enable a smaller PTV margin, and improve rectal sparing.

Development of a frameless stereotactic radiosurgery system based on real-time 6D position monitoring and adaptive head motion compensation

Stereotactic radiosurgery delivers radiation with great spatial accuracy. To achieve sub-millimeter accuracy for intracranial SRS, a head ring is rigidly fixated to the skull to create a fixed reference. For some patients, the invasiveness of the ring can be highly uncomfortable and not well tolerated. In addition, placing and removing the ring requires special expertise from a neurosurgeon, and patient setup time for SRS can often be long. To reduce the invasiveness, hardware limitations and setup time, we are developing a system for performing accurate head positioning without the use of a head ring. The proposed method uses real-time 6D optical position feedback for turning on and off the treatment beam (gating) and guiding a motor-controlled 3D head motion compensation stage. The setup consists of a central control computer, an optical patient motion tracking system and a 3D motion compensation stage attached to the front of the LINAC couch. A styrofoam head cast was custom-built for patient support and was mounted on the compensation stage. The motion feedback of the markers was processed by the control computer, and the resulting motion of the target was calculated using a rigid body model. If the target deviated beyond a preset position of 0.2 mm, an automatic position correction was performed with stepper motors to adjust the head position via the couch mount motion platform. In the event the target deviated more than 1 mm, a safety relay switch was activated and the treatment beam was turned off. The feasibility of the concept was tested using five healthy volunteers. Head motion data were acquired with and without the use of motion compensation over treatment times of 15 min. On average, test subjects exceeded the 0.5 mm tolerance 86% of the time and the 1.0 mm tolerance 45% of the time without motion correction. With correction, this percentage was reduced to 5% and 2% for the 0.5 mm and 1.0 mm tolerances, respectively.