D. Michael Lovelock

High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

PURPOSE To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

ACUTE SKIN TOXICITY FOLLOWING STEREOTACTIC BODY RADIATION THERAPY FOR STAGE I NON-SMALL-CELL LUNG CANCER: WHO'S AT RISK?

PURPOSE We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. METHODS From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fishers exact test. RESULTS After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). CONCLUSIONS SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

Quality assurance for image-guided radiation therapy utilizing CT-based technologies: A report of the AAPM TG-179

PURPOSE Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. METHODS The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. RESULTS This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances. CONCLUSION A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

Segmenting the prostate and rectum in CT imagery using anatomical constraints

The automatic segmentation of the prostate and rectum from 3D computed tomography (CT) images is still a challenging problem, and is critical for image-guided therapy applications. We present a new, automatic segmentation algorithm based on deformable organ models built from previously segmented training data. The major contributions of this work are a new segmentation cost function based on a Bayesian framework that incorporates anatomical constraints from surrounding bones and a new appearance model that learns a nonparametric distribution of the intensity histograms inside and outside organ contours. We report segmentation results on 185 datasets of the prostate site, demonstrating improved performance over previous models.

A review of image-guided intensity-modulated radiotherapy for spinal tumors.

OBJECTIVE A new paradigm for the radiotherapeutic management of paraspinal tumors has emerged. Intensity-modulated radiotherapy (IMRT) has gained wide acceptance as a way of delivering highly conformal radiation to tumors. IMRT is capable of sparing sensitive structures such as the spinal cord of high-dose radiation even if only several millimeters away from the tumor. Image-guided treatment tools such as cone beam computed tomography coupled with IMRT have reduced treatment errors associated with traditional radiotherapy, making highly accurate and conformal treatment feasible. METHODS This review discusses the physics of image-guided radiotherapy, including immobilization, the radiobiological implications of hypofractionation, as well as outcomes. Image-guided technology has improved the accuracy of IMRT to within 2 mm of error. Thus, the marriage of image guidance with IMRT (IG IMRT) has allowed the safe treatment of spinal tumors to a high dose without increasing the risk of radiation-related toxicity. With the use of near real-time image-guided verification, very-high-dose radiation has been given for tumors in standard fractionation, hypofractionated, and single fraction schedules to doses beyond levels traditionally believed safe in terms of spinal cord tolerance. RESULTS Clinical results, in terms of treatment-related toxicity and tumor control, have been very favorable. With follow-up periods extending beyond 30 months, tumor control rates with single fraction IG IMRT (1800–2400 cGy) are in excess of 90%, regardless of histology, and without serious sequelae such as radiation myelopathy. Patients also report correspondingly high rates of palliation. Excellent results, both in terms of tumor control and minimal toxicity, have been consistently reported in the literature. CONCLUSION IG IMRT represents a significant technological advance. Paraspinal IG IMRT is proof of principle, making it possible to give very-high-dose radiation within close proximity to the spinal cord. By reducing treatment-related uncertainties, margins around tumors can be shortened, thereby reducing the volume of normal tissue that must be irradiated to tumoricidal doses, reducing the likelihood of toxicity. Similarly, higher doses of radiation can be administered safely, improving the likelihood of eradication. Dose escalation can be done to increase the likelihood of tumor cell kill without increasing the dose given to nearby sensitive structures.

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.

Development of a semi-automatic alignment tool for accelerated localization of the prostate

PURPOSE Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment. Therefore, the radiation can be accurately delivered to the target. Once the prostate position is determined with high confidence, planning target volume (PTV) safety margin might be reduced for further reduction of rectal toxicity. A rapid computed tomography (CT)-based online prostate localization method is presented for this purpose. METHODS AND MATERIALS Immediately before each treatment session, the patient is immobilized and undergoes a CT scan in the treatment position using a CT scanner situated in the treatment room. At the CT console, posterior, anterior, left, and right extents of the prostate are manually identified on each axial slice. The translational prostate displacements relative to the planned position are estimated by simultaneously fitting these identified extents from this CT scan to a template created from the finely sliced planning CT scan. A total of 106 serial CT scans from 8 prostate cancer patients were performed immediately before treatments and used to retrospectively evaluate the precision of this daily prostate targeting method. The three-dimensional displacement of the prostate with respect to its planned position was estimated. RESULTS Five axial slices from each treatment CT scan were sufficient to produce a reliable correction when compared with prostate center of gravity (CoG) displacements calculated from physician-drawn contours. The differences (mean +/- SD) between these two correction schemes in the right-left (R/L), posterior-anterior (P/A), and superior-inferior (S/I) directions are 0.0 +/- 0.4 mm, 0.0 +/- 0.7 mm, and -0.4 +/- 1.9 mm, respectively. With daily CT extent-fitting correction, 97% of the scans showed that the entire posterior prostate gland was covered by PTV given a margin of 6 mm at the rectum-prostate interface and 10 mm elsewhere. In comparison, only 74% and 65% could be achieved by the corrections based on daily and weekly bony matching on portal images, respectively. CONCLUSIONS Results show that daily CT extent fitting provides a precise correction of prostate position in terms of CoG. Identifying prostate extents on five axial CT slices at the CT console is less time-consuming compared with daily contouring of the prostate on many slices. Taking advantage of the prostate curvature in the longitudinal direction, this method also eliminates the necessity of identifying prostate base and apex. Therefore, it is clinically feasible and should provide an accelerated localization of the prostate immediately before daily treatment.

Correlation of local failure with measures of dose insufficiency in the high-dose single-fraction treatment of bony metastases.

PURPOSE In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. METHODS AND MATERIALS The minimum doses received by the hottest 100%, 98%, and 95% (D(min), D(98), and D(95)) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. RESULTS With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D(min), D(98), and D(95) for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D(min), D(98), and D(95) were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. CONCLUSIONS The results indicate that D(min), D(98), and D(95) may be important risk factors for local failure. No local failures in any histology were observed when D(min) was >15 Gy, suggesting that this metric may be an important predictor of local control.

Evaluation of respiration‐correlated digital tomosynthesis in lunga)

Digital tomosynthesis (DTS) with a linear accelerator-mounted imaging system provides a means of reconstructing tomographic images from radiographic projections over a limited gantry arc, thus requiring only a few seconds to acquire. Its application in the thorax, however, often results in blurred images from respiration-induced motion. This work evaluates the feasibility of respiration-correlated (RC) DTS for soft-tissue visualization and patient positioning. Image data acquired with a gantry-mounted kilovoltage imaging system while recording respiration were retrospectively analyzed from patients receiving radiotherapy for non-small-cell lung carcinoma. Projection images spanning an approximately 30 degrees gantry arc were sorted into four respiration phase bins prior to DTS reconstruction, which uses a backprojection, followed by a procedure to suppress structures above and below the reconstruction plane of interest. The DTS images were reconstructed in planes at different depths through the patient and normal to a user-selected angle close to the center of the arc. The localization accuracy of RC-DTS was assessed via a comparison with CBCT. Evaluation of RC-DTS in eight tumors shows visible reduction in image blur caused by the respiratory motion. It also allows the visualization of tumor motion extent. The best image quality is achieved at the end-exhalation phase of the respiratory motion. Comparison of RC-DTS with respiration-correlated cone-beam CT in determining tumor position, motion extent and displacement between treatment sessions shows agreement in most cases within 2-3 mm, comparable in magnitude to the intraobserver repeatability of the measurement. These results suggest the methods applicability for soft-tissue image guidance in lung, but must be confirmed with further studies in larger numbers of patients.

Clinical outcomes after reirradiation of paraspinal tumors

Objective:We present our experience with reirradiation of locally recurrent paraspinal tumors using image-guided intensity modulated radiotherapy (IG-IMRT). Methods:We performed a retrospective review of 37 patients who were reirradiated using IG-IMRT for recurrent paraspinal tumors between 2000 and 2005. We evaluated radiation dose to the spinal cord or cauda equina in first and second radiation treatments, time to first recurrence, and clinical outcomes after reirradiation including second recurrence, survival, pain, functional status, and toxicity. Results:Median time to local failure after first radiation was 13 months. All patients underwent salvage reirradiation, postoperatively or with IG-IMRT alone. Median radiation dose to the planning target volume (PTV) was 2000 cGy; median spinal cord or cauda equina dose was 990 cGy. Median cumulative spinal cord or cauda equina dose was 4198 cGy. Local control probability at a median follow-up of 8 months was 60%; median interval to second failure was 13 months. Survival probability at a median follow up of 12 months was 72%; median survival was 18 months. Thirty-four patients (91%) reported stable or improved pain after second radiation, and 26 (70%) had a stable or improved functional status. Mild acute toxicity occurred in 3 patients (8%). No long-term toxicity has been identified. Conclusions:Reirradiation using IG-IMRT is safe and achieves a meaningful interval of local control with improved symptoms. Further studies with more patients and longer follow up are needed to evaluate toxicity, predictors of failure, and timing of radiation after surgical salvage.