David Lockman

An off-line strategy for constructing a patient-specific planning target volume in adaptive treatment process for prostate cancer

PURPOSE To improve the efficacy of dose delivery and dose escalation for external beam radiotherapy of prostate cancer, an off-line strategy for constructing a patient-specific planning target volume is developed in the adaptive radiotherapy process using image feedback of target location and patient setup position. MATERIALS AND METHODS We hypothesize that a patient-specific confidence-limited planning target volume (cl-PTV), constructed using an initial sequence of daily measurements of internal target motion and patient setup error, exists and ensures that the clinical target volume (CTV) in the prostate cancer patient receives the prescribed dose within a predefined dose tolerance. A patient-specific bounding volume to correct for target location and compensate for target random motion was first constructed using the convex hull of the first k days of CT measurements. The bounding volume and the initial days of CT measurements were minimized based on a predefined dosimetric criterion. The hypothesis was tested using multiple daily CT images by mimicking the actual treatment of both conventional 4-field-box and intensity-modulated radiotherapy (IMRT) on each of 30 patients with prostate cancer. For each patient, a patient-specific setup margin was also applied to the bounding volume to form the final cl-PTV. This margin was determined using the random setup error predicted from the initial days of portal imaging measurements and the residuals after correcting for the systematic setup error. RESULTS The bounding volume constructed using daily CT measurements in the first week of treatment are adequate for the conventional beam delivery to achieve maximum dose reduction in the CTV of 2% or less of the prescription dose, for at least 80% of patients (p = 0.08), and 4.5% or less for 95% of patients (p = 0.1). However, for IMRT delivery, 2 weeks of daily CT measurements are required to achieve a similar level of the dosimetric criterion, otherwise the maximum dose reduction of 7%, on average, in the CTV is expected. Furthermore, the patient-specific setup margin required for the IMRT treatment is at least twice larger than that for the conventional treatment, to maintain the same dosimetric criterion. As compared to the conventional PTV, the volume of cl-PTV is significantly reduced, while maintaining the same dosimetric criterion. CONCLUSION The cl-PTV for prostate treatment can be constructed within the first week of treatment using the feedback of imaging measurements. The cl-PTV has the capability to exclude the systematic variation and compensate for the patient-specific random variation on target location and patient setup position. This implies that in the current off-line image feedback adaptive treatment process, a single plan modification can be performed within the second week of treatment to improve the efficacy of dose delivery and dose escalation for external beam therapy of prostate cancer.

Improvement in dose escalation using the process of adaptive radiotherapy combined with three-dimensional conformal or intensity-modulated beams for prostate cancer☆

PURPOSE Advances in technology allow the creation of complex treatment plans with tightly conforming doses. However, variations in positioning of the organ/patient with respect to treatment beams necessitate the use of an appreciable margin, potentially limiting dose escalation in many patients. To (1) reduce this margin and (2) test the hypothesis that the achievable level of dose escalation is patient dependent, a patient-specific, confidence-limited planning target volume (cl-PTV) was constructed using an adaptive radiotherapy (ART) process for prostate cancer treatment developed in-house. The potential dose escalation achievable with this ART process is quantified for both conformal radiotherapy (CRT) delivery and intensity-modulated radiotherapy (IMRT) delivery. MATERIAL AND METHODS Patients with organ confined prostate cancer were entered prospectively into an ART process developed in-house. This ART process has been designed to improve accuracy and precision of dose delivery, consequently enhancing dose escalation. In this process, a cl-PTV is constructed for each patient in the second week of treatment based upon on-line portal and CT images acquired during the first week of treatment. The treatment prescription dose, defined as the minimum dose to the cl-PTV, is selected based on predefined dose-volume constraints for rectum/bladder and derived from the pretreatment planning CT image. In addition, the treatment modality (CRT or IMRT) is determined based on the level of dose escalation achievable and the risk of inaccurate targeting. The potential for both dose escalation and the application of IMRT was evaluated by comparing the prescription doses delivered using the ART process, with the cl-PTV, to those in the traditional treatment process, with a conventional generic PTV. In addition, the distributions of potential geometric target underdosing and normal tissue overdosing were also calculated to evaluate the quality of the conventional treatment plans. RESULTS One hundred and fifty patients have been treated with the ART process. When compared to the treatment dose delivered with the conventional treatment process (generic PTV), an average 5% (2.5--10%) more dose could be delivered using the ART process with CRT, and 7.5% (2.5--15%) more dose could be delivered with IMRT. Of the 150 patients, 70% were treated to a minimum cl-PTV dose > or = 77.4 Gy (81.3 Gy ICRU isocenter dose). Dosimetric analysis revealed that 81 Gy to the cl-PTV (or 86.7 Gy ICRU) could be prescribed to at least 50% of patients if IMRT was applied using the ART process. In contrast, IMRT did not yield an obvious dose escalation gain if patients were treated using the generic PTV. Our results also demonstrate that the cl-PTV is significantly smaller than the conventional generic PTV for most patients, with a mean volume reduction of 24% (range, 5--43%). CONCLUSION These results support our hypothesis that the achievable level of dose escalation using ART is patient dependent. By using the ART process to develop a cl-PTV, one can (1) optimize the dose level, (2) increase the applicability of IMRT, and (3) improve the quality of dose delivery. The ART process provides the foundation to identify a suitable option (CRT or IMRT) for the delivery of a safe treatment and dose escalation. It is now our standard of practice for prostate cancer treatment.

SETUP ERROR IN RADIOTHERAPY: ON-LINE CORRECTION USING ELECTRONIC KILOVOLTAGE AND MEGAVOLTAGE RADIOGRAPHS

PURPOSE We hypothesize that the difference in image quality between the traditional kilovoltage (kV) prescription radiographs and megavoltage (MV) treatment radiographs is a major factor hindering our ability to accurately measure, thus correct, setup error in radiation therapy. The objective of this work is to study the accuracy of on-line correction of setup errors achievable using either kV- or MV-localization (i.e., open-field) radiographs. METHODS AND MATERIALS Using a gantry mounted kV and MV dual-beam imaging system, the accuracy of on-line measurement and correction of setup error using electronic kV- and MV-localization images was examined based on anthropomorphic phantom and patient imaging studies. For the phantom study, the users ability to accurately detect known translational shifts was analyzed. The clinical study included 14 patients with disease in the head and neck, thoracic, and pelvic regions. For each patient, 4 orthogonal kV radiographs acquired during treatment simulation from the right lateral, anterior-to-posterior, left lateral, and posterior-to-anterior directions were employed as reference prescription images. Two-dimensional (2D) anatomic templates were defined on each of the 4 reference images. On each treatment day, after positioning the patient for treatment, 4 orthogonal electronic localization images were acquired with both kV and 6-MV photon beams. On alternate weeks, setup errors were determined from either the kV- or MV-localization images but not both. Setup error was determined by aligning each 2D template with the anatomic information on the corresponding localization image, ignoring rotational and nonrigid variations. For each set of 4 orthogonal images, the results from template alignments were averaged. Based on the results from the phantom study and a parallel study of the inter- and intraobserver template alignment variability, a threshold for minimum correction was set at 2 mm in any direction. Setup correction was applied by translating the treatment couch in the lateral, superior-to-inferior and vertical directions only. During treatment, kV open-field images were acquired for off-line treatment verification and analysis. Each patient study spanned 2-6 weeks. The 14 patient studies were completed with 8248 electronic images acquired and analyzed. RESULTS Results from the phantom studies showed that the users were able to detect the applied translational shift to better than 2 mm, and mostly to within 1 mm. The intraobserver variability of template alignment was on the order of 1 mm using a sample of either MV or kV patient images. The difference between using MV or kV images was significant for only a few cases. However in most cases, interobserver alignment variability was larger when using MV images than kV. For on-line setup correction, the study procedure added 10 min. to conventional treatment time. Setup variation measured with either kV- or MV-localization images was similar. The initial magnitude of setup error was appreciable, with a mean displacement of about 6.6 +/- 2.4 mm for the 14 patients. On-line correction using either kV- or MV-localization images improved setup accuracy. Over all study patients, setup errors occurred with standard deviations greater than 2 mm in any direction with a frequency of 48% before correction, and were reduced to 16% after correction. On average, kV image-based correction reduced radial setup variation to 2.6 +/- 1.6 mm compared to the 3.3 +/- 1.8 mm attained using MV images. The difference detected between the kV and MV data was not statistically significant when averaged over all patients. However, for on-line corrections in the neck and thoracic regions, using kV-localization images reduced setup error significantly more than using MV images. CONCLUSIONS In our anatomic template alignment study, interobserver variability was smaller using kV images than MV images. Intraobserver variability was smaller for alignments on kV images

Organ/patient geometric variation in external beam radiotherapy and its effects

Treatment variation in positioning of the organ/patient with respect to the radiation beams causes a temporal dose variation in critical normal tissues adjacent to the treatment target. This temporal variation induces uncertainties in understanding the normal tissue dose response, thereby limiting reliable treatment evaluation and optimization. The aim of this study is to model and analyze the temporal variation of organ dose distribution, and its effect on the biological effective dose. The study mainly focuses on the temporal dose variation caused by intertreatment organ motion/ deformation and daily setup error. Sensitivity of the biological effective dose to organ/patient geometric variation, dose distribution, and treatment fractionation will be investigated. Significant deviation of the biological effective dose could be expected in a critical normal structure, even if the cumulative dose deviation in this structure is negligible. Patients with similar geometric variation characteristics can experience significantly different biological effective dose, and the differences are sensitive to the dose distribution and the total number of treatment fractions.

The influence of interpatient and intrapatient rectum variation on external beam treatment of prostate cancer.

PURPOSE The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions. METHODS AND MATERIALS Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined. RESULTS Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least +/- 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2. CONCLUSIONS Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

Estimating the dose variation in a volume of interest with explicit consideration of patient geometric variation.

A method to measure the effects of internal organ motion and deformation and patient setup error on cumulative dose variation in a volume of interest is proposed. The method uses multiple CT scans and electronic portal images of a single patient to numerically simulate dose-volume effects over the entire course of the patients external beam treatment. The results are expressed in the form of a novel dose-volume histogram, called an expected dose-volume histogram (EDVH).

Effect of the first day correction on systematic setup error reduction.

Treatment simulation is usually performed with a conventional simulator using kV X-rays or with a computed tomography (CT) simulator before the treatment course begins. The purpose is to verify patient setup under the same conditions as for treatment planning. Systematic (preparation) setup errors can be introduced by this process. The purpose of this study is to characterize the setup errors using electronic portal image (EPI) analyses and to propose a method to reduce the systematic component by performing simulation and patient preparation on the treatment machine. In this study, the first four or five days EPIs were analyzed from a total of 533 prostate cancer patients who were simulated on conventional simulators. We characterized setup errors using four parameters: {M(microi), Sigma (microi), RMS(microi), sigma (sigmai)}, where microi and sigmai are individual patient mean and standard deviation, M, Sigma, and RMS are the mean, standard deviation, and root-mean-square of underlying variables (microi and sigmai). We have performed a simulation of removing systematic components by correcting the first day setup error. As a comparison, we also carried out a similar analyses for patients simulated on a CT simulator and patients treated on a linac with an on-board kV CT imaging system, although a limited number of patients were available in these two samples. We found that Sigma (/ui)=(2.6,3.4,2.4) mm, and RMS(sigmai)=(1.5,1.9,1.0) mm in lateral, anterior/posterior, and cranial/caudal directions, indicating that systematic errors are much larger than random errors. Strong correlations were found between measurement on the first day and microi, implying the first days measurement is a good predictor for microi. The same parameters were also computed for days 2-4, with and without the first day correction. Without correction, M(microi)2-4=(0.7,1.6,-1.0) mm, and Sigma(microi)2-4=(2.6,3.5,2.4) mm. With correction, M(microi)2-4=(0.0,0.4,0.4) mm, much closer to zero, and Sigma(microi)2-4=(1.8,2.2, 1.2) mm, also much smaller. While the use of a CT simulator can reduce the systematic errors, the benefits of first day correction can still be observed, although at a smaller magnitude. Therefore, the systematic setup error can be significantly reduced if the patient is marked and fields are verified on the treatment machine on the first fraction, preferably with an on-board kV imaging system.

Evaluating target margins achieved by different portal image feedback strategies: a retrospective examination for external beam prostate cancer radiotherapy

Materials/Methods: From August 1999 to March 2002, 330 prostate cancer patients were treated on our clinic’s adaptive radiotherapy (ART) protocol. This protocol demands analysis of each patient’s setup error, discerned by way of electronic portal images (EPIs) acquired for each treatment field. Therefore, for the i patient in this population we have available both the systematic error i,k and standard deviation i,k of the random error, where the index k 1,2,3 indicates the coordinate direction. The estimate i,k includes a residual i,k, which is an upper bound on the uncorrected systematic error–due either to lack of statistical confidence, or to the uncertainty induced by out-of-plane rotations. A minimal k(N) exists and satisfies i,k Mk(N) for at least N% of our population. Define k(N) and k(N) similarly for the residuals and standard deviations, respectively.

External Beam Adaptive Radiation Therapy (ART) on a Conventional Medical Accelerator

Theadvent of inverseplanning and IMRThas allowed thedeliveryof radiationdose that conforms tightly to the target butwhich falls off sharply tominimize irradiation of surrounding structures. The exquisite dose distributions, however, have their misgivings as they often lure the clinicians into prescribing a smaller treatment margin which may not be valid. Treatment margins, or more specifically, planning target volume (PTV) and clinical target volume (CTV) are our acknowledgements that there are uncertainties associated with the patient treatment setup and disease extension, respectively. They are prescribed to minimize the risk of geometric misses. The conventional approach in radiation therapy is to employ a generic margin for the patient population, which will vary depending on anatomic site. The generic margin is based on the clinical experience and is meant to accommodate the patient population. Often overlooked, however, is that this generic margin is institution-specific, as the nature of treatment variation depends verymuch on the treatment techniqueandpersonnel.Oneneeds tobevigilant in validating the efficacy of a published margin if it were to be adopted for a new treatment method, such as IMRT. 7.2 Stratification of Treatment Strategies Based on Adaptive Radiation Therapy for Prostate Cancer