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Biomedical subjects

Randall K Ten Haken

Publications and source records attributed to Randall K Ten Haken.

At least 19 recordsLinked to original sources
PubMed2006

The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy.

PURPOSE: A common side effect experienced by head and neck cancer patients after radiation therapy (RT) is impairment of the parotid glands' ability to produce saliva. Our purpose is to investigate the relationship between radiation dose and saliva changes in the 2 years after treatment. METHODS AND MATERIALS: The study population includes 142 patients treated with conformal or intensity-modulated radiotherapy. Saliva flow rates from 266 parotid glands are measured before and 1, 3, 6, 12, 18, and 24 months after treatment. Measurements are collected separately from each gland under both stimulated and unstimulated conditions. Bayesian nonlinear hierarchical models were developed and fit to the data. RESULTS: Parotids receiving higher radiation produce less saliva. The largest reduction is at 1-3 months after RT followed by gradual recovery. When mean doses are lower (e.g., <25 Gy), the model-predicted average stimulated saliva recovers to pretreatment levels at 12 months and exceeds it at 18 and 24 months. For higher doses (e.g., >30 Gy), the stimulated saliva does not return to original levels after 2 years. Without stimulation, at 24 months, the predicted saliva is 86% of pretreatment levels for 25 Gy and <31% for >40 Gy. We do not find evidence to support that the overproduction of stimulated saliva at 18 and 24 months after low dose in 1 parotid gland is the result of low saliva production from the other parotid gland. CONCLUSIONS: Saliva production is affected significantly by radiation, but with doses <25-30 Gy, recovery is substantial and returns to pretreatment levels 2 years after RT.

Adult↗
PubMed2006

Ideal spatial radiotherapy dose distributions subject to positional uncertainties.

In radiotherapy a common method used to compensate for patient setup error and organ motion is to enlarge the clinical target volume (CTV) by a 'margin' to produce a 'planning target volume' (PTV). Using weighted power loss functions as a measure of performance for a treatment plan, a simple method can be developed to calculate the ideal spatial dose distribution (one that minimizes expected loss) when there is uncertainty. The spatial dose distribution is assumed to be invariant to the displacement of the internal structures and the whole patient. The results provide qualitative insights into the suitability of using a margin at all, and (if one is to be used) how to select a 'good' margin size. The common practice of raising the power parameters in the treatment loss function, in order to enforce target dose requirements, is shown to be potentially counter-productive. These results offer insights into desirable dose distributions and could be used, in conjunction with well-established inverse radiotherapy planning techniques, to produce dose distributions that are robust against uncertainties.

Algorithms↗
PubMed2006

Reporting and analyzing statistical uncertainties in Monte Carlo-based treatment planning.

PURPOSE: To investigate methods of reporting and analyzing statistical uncertainties in doses to targets and normal tissues in Monte Carlo (MC)-based treatment planning. METHODS AND MATERIALS: Methods for quantifying statistical uncertainties in dose, such as uncertainty specification to specific dose points, or to volume-based regions, were analyzed in MC-based treatment planning for 5 lung cancer patients. The effect of statistical uncertainties on target and normal tissue dose indices was evaluated. The concept of uncertainty volume histograms for targets and organs at risk was examined, along with its utility, in conjunction with dose volume histograms, in assessing the acceptability of the statistical precision in dose distributions. The uncertainty evaluation tools were extended to four-dimensional planning for application on multiple instances of the patient geometry. All calculations were performed using the Dose Planning Method MC code. RESULTS: For targets, generalized equivalent uniform doses and mean target doses converged at 150 million simulated histories, corresponding to relative uncertainties of less than 2% in the mean target doses. For the normal lung tissue (a volume-effect organ), mean lung dose and normal tissue complication probability converged at 150 million histories despite the large range in the relative organ uncertainty volume histograms. For "serial" normal tissues such as the spinal cord, large fluctuations exist in point dose relative uncertainties. CONCLUSIONS: The tools presented here provide useful means for evaluating statistical precision in MC-based dose distributions. Tradeoffs between uncertainties in doses to targets, volume-effect organs, and "serial" normal tissues must be considered carefully in determining acceptable levels of statistical precision in MC-computed dose distributions.

Esophagus↗
PubMed2006

Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): predictors for radiation pneumonitis and fibrosis.

PURPOSE: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. METHODS AND MATERIALS: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. RESULTS: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p<0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. CONCLUSIONS: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.

Adult↗
PubMed2006

Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors.

PURPOSE: To evaluate whether increasing numbers of intensity-modulated radiation therapy (IMRT) fields enhance lung-tumor dose without additional predicted toxicity for difficult planning geometries. METHODS AND MATERIALS: Data from 8 previous three dimensional conformal radiation therapy (3D-CRT) patients with tumors located in various regions of each lung, but with planning target volumes (PTVs) overlapping part of the esophagus, were used as input. Four optimized-beamlet IMRT plans (1 plan that used the 3D-CRT beam arrangement and 3 plans with 3, 5, or 7 axial, but predominantly one-sided, fields) were compared. For IMRT, the equivalent uniform dose (EUD) in the whole PTV was optimized simultaneously with that in a reduced PTV exclusive of the esophagus. Normal-tissue complication probability-based costlets were used for the esophagus, heart, and lung. RESULTS: Overall, IMRT plans (optimized by use of EUD to judiciously allow relaxed PTV dose homogeneity) result in better minimum PTV isodose surface coverage and better average EUD values than does conformal planning; dose generally increases with the number of fields. Even 7-field plans do not significantly alter normal-lung mean-dose values or lung volumes that receive more than 13, 20, or 30 Gy. CONCLUSION: Optimized many-field IMRT plans can lead to escalated lung-tumor dose in the special case of esophagus overlapping PTV, without unacceptable alteration in the dose distribution to normal lung.

Esophagus↗
PubMed2006

The clinical application of intensity-modulated radiation therapy.

Intensity-modulated radiation therapy is a delivery system that, when coupled with a treatment-planning optimization system, presents the opportunity to conform the dose to the target better than 3-dimensional conformal therapy, particularly in the case of concave targets. Appropriate clinical applications of this technology to challenging patient treatment scenarios requires careful consideration of issues related to target volume-dose heterogeneity and the influence of patient setup uncertainties. These issues are reviewed and illustrated. To date, clinical reports of these treatments for prostate and head and neck cancers have the most mature data. Those results are summarized here. Future applications of this technology can be expected to take careful, considered advantage of this technology to further rearrange dose distributions across target volumes to produce an integrated overall gain in treatment objectives. However, these innovative applications need to be approached with caution, preferably in prospective clinical trials that would help determine if the hypothetical clinical benefits are in fact realizable.

Humans↗
PubMed2006

A practical approach for quantitative estimates of voxel-by-voxel liver perfusion using DCE imaging and a compartmental model.

Voxel-by-voxel estimation of liver perfusion using nonlinear least-squares fits of dynamic contrast enhanced computed tomography or magnetic resonance imaging data to a compartmental model is a computational expensive process. In this report, a "linear" least-squares method for estimation of liver perfusion is described. Simulated data and the data from an example case of a patient with intrahepatic cancer are presented. Compared to the nonlinear method, the new method can improve computational speed by a factor of approximately 400, which makes it practical for use in clinical trials.

Algorithms↗
PubMed2005

Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies.

PURPOSE: A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies. PATIENTS AND METHODS: Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level. RESULTS: The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The total dose was the only significant predictor of survival. Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases. Overall toxicity was acceptable, with 27 patients (21%) and 11 patients (9%) developing grade 3 and 4 toxicity, respectively, and one treatment-related death. CONCLUSION: The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors. This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer.

Adult↗
PubMed2005

Monte Carlo-based lung cancer treatment planning incorporating PET-defined target volumes.

Despite the well-known benefits of positron emission tomography (PET) imaging in lung cancer diagnosis and staging, the poor spatial resolution of PET has limited its use in radiotherapy planning. Methods used for segmenting tumor from normal tissue, such as threshold boundaries using a fraction of the standardized uptake value (SUV), are subject to uncertainties. The issue of respiratory motion in the thorax confounds the problem of accurate target definition. In this work, we evaluate how changing the PET-defined target volume by varying the threshold value in the segmentation process impacts target and normal lung tissue doses. For each of eight lung cancer patients we retrospectively generated multiple PET-target volumes; each target volume corresponds to those voxels with intensities above a given threshold level, defined by a percentage of the maximum voxel intensity. PET-defined targets were compared to those from CT; CT targets comprise a composite volume generated from breath-hold inhale and exhale datasets; the CT dataset therefore also includes the extents of tumor motion. Treatment plans using Monte Carlo dose calculation were generated for all targets; the dose uniformity was approximately 100+/-5% within the internal target volume (ITV) (formed by a uniform 8-mm expansion of the composite gross target volume (GTV)). In all cases differences were observed in the generalized equivalent uniform doses (gEUDs) to the targets and in the mean lung doses (MLDs) and normal tissue complication probabilities (NTCPs) to the normal lung tissues. The magnitudes of the dose differences were found to depend on the target volume, location, and amount of irradiated normal lung tissue, and in many instances were clinically meaningful (greater than a single 2 Gy fraction). For those patients studied, results indicate that accurate dosimetry using PET volumes is highly dependent on accurate target segmentation. Further study with correlation to clinical outcome will be helpful in determining how to apply these various PET and CT volumes in treatment planning, to potentially improve local tumor control and reduce normal tissue toxicities.

Algorithms↗
PubMed2005

Normal tissue complication probability modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer.

PURPOSE: To evaluate the ability of a well-known normal tissue complication probability (NTCP) model to predict radiation esophagitis by determining updated model parameters and then comparing these results with the predictive value of other dosimetric parameters. MATERIAL AND METHODS: Clinical and dosimetric data regarding esophagitis were analyzed in 101 inoperable/unresectable non-small-cell lung cancer patients treated by external beam irradiation. Grade 2 or higher esophagitis counted as events. Parameters (TD50, n, and m) of the Lyman normal tissue complication probability (NTCP) model were determined using maximum likelihood analysis, and compared to other dose/volume threshold values including: percentage of esophagus receiving > 40 Gy (V40) to > 75 Gy (V75), and maximum esophageal doses. RESULTS: Sixteen patients developed grade 2-3 acute esophagitis (no G4 or 5). The maximum likelihood analysis produced new Lyman model parameters of: TD50 = 51 Gy, n = 0.44 and m = 0.32. The mean NTCP value is significantly lower (P < 0.001) in the group of patients without esophagitis (13.5%) than with esophagitis (27.2%). The rates of esophagitis are 2.5, 7, 9 and 13.4%, respectively, when the NTCP values are <10%, <15%, <20% and <25%. A significant association is found between esophagitis and dose/volume parameters V40 (P = 0.001) to V70 (P = 0.024). CONCLUSIONS: New values of TD50, n and m offer a good description of the esophagitis distribution in our population. Compared to the use of this model with previously published parameters (associated with late toxicity) predictions of the model for acute esophagitis using the new parameters would indicate that, for a population of patients, the distribution of events as a function of uniform dose would occur with a lower mean uniform dose value (smaller TD50), over a wider range of uniform doses (larger m), while also exhibiting a bigger volume effect (larger n). These new parameter values are supported in essence by the correlations found for the dose/volume threshold parameters.

Acute Disease↗
PubMed2005

High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: long-term results of a radiation dose escalation study.

PURPOSE: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes > or =1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. RESULTS: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. CONCLUSIONS: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy.

Adult↗
PubMed2005

Evaluating the influence of setup uncertainties on treatment planning for focal liver tumors.

PURPOSE: A mechanism has been developed to evaluate the influence of random setup variations on dose during treatment planning. The information available for studying these factors shifts from population-based models toward patient-specific data as treatment progresses and setup measurements for an individual patient become available. This study evaluates the influence of population as well as patient-specific setup distributions on treatment plans for focal liver tumors. METHODS AND MATERIALS: Eight patients with focal liver tumors were treated on a protocol that involved online setup measurement and adjustment, as well as ventilatory immobilization. Summary statistics from these three-dimensional conformal treatments yielded individual and population distributions of position at initial setup for each fraction. A convolution model for evaluation of the influence of random setup variation on calculated dose distributions has been previously described and investigated for application to focal liver radiotherapy by our department. Individual patient doses based on initial setup positions were calculated by convolving the calculated dose distribution with an anisotropic probability distribution function representing the individual patient's random variations. A separate convolution using population-averaged random variations was performed. Individual beam apertures were then adjusted to provide plans that ensured proper dose to the clinical target volume following convolution with population distributions, as well as individual patient position uncertainty models. RESULTS: Individual patient setup distributions for the course of treatment had random setup variations (sigma) that ranged from 2.5 to 5.7 mm (left-right), 2.1 to 8.3 mm (anterior-posterior), and 4.1 to 10.8 mm (cranial-caudal). The population random components were 4.2 mm (left-right), 4.1 mm (anterior-posterior), and 7.0 mm (cranial-caudal) at initial setup. The initial static planned dose distribution overestimated the volume of liver irradiated to high doses, because inclusion of setup uncertainties generally blurred the resulting doses, shifting the higher-dose region of normal liver dose-volume histograms to lower doses. Furthermore, the population-based dose convolution tended to predict a higher risk of radiation damage to the liver (based on an in-house parameterization of the Lyman normal tissue complication probability model) than the individual patient calculations. For an individual plan, application of different individual random variations yielded change in effective volume differences with a 3% range. Plan adjustment to account for random setup variations generally resulted in a lower change in effective volume than initial planning using a planning target volume followed by calculation of delivered dose based on random offsets. CONCLUSION: This study hints at the factors that most strongly influence planning of liver treatments taking into account geometric variations. Given a setup verification methodology that rapidly reduces systematic offsets, the importance of realistic incorporation of geometric variations as an initial step in treatment planning, as well as possible plan refinement, is demonstrated.

Feasibility Studies↗
PubMed2005

Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

PURPOSE: To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. RESULTS: The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. CONCLUSIONS: Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

Aged↗
PubMed2005

CT-based definition of thoracic lymph node stations: an atlas from the University of Michigan.

PURPOSE: Accurate delineation of the mediastinal and hilar lymph node regions is essential for a reproducible definition of target volumes used in conformal irradiation of non-small-cell lung cancer. The goal of this work was to generate a consensus to delineate these nodal regions based on definitions from the American Joint Committee on Cancer. METHODS AND MATERIALS: A dedicated thoracic radiologist, thoracic surgeon, medical physicist, and three radiation oncologists were gathered to generate a three-dimensional radiologic description for the mediastinal and hilar nodal regions on axial CT scans. This paper proposes an atlas of most of the lymph node stations described by Mountain and Dresler. RESULTS: The CT boundaries of lymph node stations 1-2, 3, 4, 5, 6, 7, 8, 10-11 were defined on axial CT, along with image illustrations. CONCLUSION: These CT-based illustrative definitions will provide guidelines for clinical practice and studies evaluating incidental radiation in radiotherapy. Studies are ongoing at the University of Michigan to measure quantitatively the incidental nodal radiation received by patients with non-small-cell lung cancer.

Humans↗
PubMed2005

Esophagus sparing with IMRT in lung tumor irradiation: an EUD-based optimization technique.

PURPOSE: The aim of this study was to evaluate (1) the use of generalized equivalent uniform dose (gEUD) to optimize dose escalation of lung tumors when the esophagus overlaps the planning target volume (PTV) and (2) the potential benefit of further dose escalation in only the part of the PTV that does not overlap the esophagus. METHODS AND MATERIALS: The treatment-planning computed tomography (CT) scans of patients with primary lung tumors located in different regions of the left and right lung were used for the optimization of beamlet intensity modulated radiation therapy (IMRT) plans. In all cases, the PTV overlapped part of the esophagus. The dose in the PTV was maximized according to 7 different primary cost functions: 2 plans that made use of mean dose (MD) (the reference plan, in which the 95% isodose surface covered the PTV and a second plan that had no constraint on the minimum isodose), 3 plans based on maximizing gEUD for the whole PTV with ever increasing assumptions for tumor aggressiveness, and 2 plans that used different gEUD values in 2 simultaneous, overlapping target volumes (the whole PTV and the PTV minus esophagus). Beam arrangements and NTCP-based costlets for the organs at risk (OARs) were kept identical to the original conformal plan for each case. Regardless of optimization method, the relative ranking of the resulting plans was evaluated in terms of the absence of cold spots within the PTV and the final gEUD computed for the whole PTV. RESULTS: Because the MD-optimized plans lacked a constraint on minimum PTV coverage, they resulted in cold spots that affected approximately 5% of the PTV volume. When optimizing over the whole PTV volume, gEUD-optimized plans resulted in higher equivalent uniform PTV doses than did the reference plan while still maintaining normal-tissue constraints. However, only under the assumption of extremely aggressive tumors could cold spots in the PTV be avoided. Generally, high-level overall results are obtained when optimization in the whole PTV is also associated with a second simultaneous optimization in the PTV minus overlapping portions of the esophagus. CONCLUSIONS: Intensity modulated radiation therapy optimizations that utilize gEUD-based cost functions for the PTV and NTCP-based constraints for the OARs result in increased doses to large portions of the PTV in cases where the PTV overlaps the esophagus, while still maintaining (and confining to the overlap region) minimum dose coverage equivalent to the homogeneous PTV optimization cases.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Retrospective analysis of prostate cancer patients with implanted gold markers using off-line and adaptive therapy protocols.

PURPOSE: To determine the efficacy of applying adaptive and off-line setup correction models to bony anatomy and gold fiducial markers implanted in the prostate, relative to daily alignment to skin tattoos and daily on-line corrections of the implanted gold markers. METHODS AND MATERIALS: Ten prostate cancer patients with implanted gold fiducial markers were treated using a daily on-line setup correction protocol. The patients' positions were aligned to skin tattoos and two orthogonal diagnostic digital radiographs were obtained before treatment each day. These radiographs were compared with digitally reconstructed radiographs to obtain the translational setup errors of the bony anatomy and gold markers. The adaptive, no-action-level and shrinking-action-level off-line protocols were retrospectively applied to the bony anatomy to determine the change in the setup errors of the gold markers. The protocols were also applied to the gold markers directly to determine the residual setup errors. RESULTS: The percentage of remaining fractions that the gold markers fell within the adaptive margins constructed with 1.5sigma' (estimated random variation) after 5, 10, and 15 measurement fractions was 74%, 88%, and 93% for the prone patients and 55%, 77%, and 93% for the supine patients, respectively. Using 2sigma', the percentage after 5, 10, and 15 measurements was 85%, 95%, and 97% for the prone patients and 68%, 87%, and 99% for the supine patients, respectively. The average initial three-dimensional (3D) setup error of the gold markers was 0.92 cm for the prone patients and 0.70 cm for the supine patients. Application of the no-action-level protocol to bony anatomy with N(m) = 3 days resulted in significant benefit to 4 of 10 patients, but 3 were significantly worse. The residual average 3D setup error of the gold markers was 1.14 cm and 0.51 cm for the prone and supine patients, respectively. When applied directly to the gold markers with N(m) = 3 days, 5 patients benefited and 3 were significantly worse. The residual 3D error of the gold markers was 1.14 cm and 0.76 cm for the prone and supine patients, respectively. Application of the shrinking-action-level protocol to bony anatomy with an initial action level of 1.0 cm and N(max) = 5 days decreased the residual systematic offset of the gold markers in 2 of 10 patients. The residual average 3D setup error of the gold markers was 1.2 cm and 1.0 cm for the prone and supine patients, respectively. When applied directly to the gold markers with N(max) = 5 days, the residual systematic offset of the gold markers decreased in 6 of 10 patients (0.84 cm and 0.67 cm for the prone and supine patients, respectively). In general, between 3 and 5 of the 10 patients showed significant decreases in setup errors with the application of these off-line protocols, and the remaining patients showed no significant improvement or showed significantly larger setup errors, as determined by the residual error of the gold markers. CONCLUSION: Changes in a prostate cancer patient's systematic and random setup characteristics during the course of therapy often violate the gaussian assumptions of adaptive and off-line correction models. Thus, off-line setup correction procedures, especially those directed at prostate localization using markers, will result in limited benefit to a minority of patients. The relative benefit of on-line localization is still potentially significant if the intrafraction motion is relatively small.

Gold↗
PubMed2005

An application of Bayesian statistical methods to adaptive radiotherapy.

In adaptive radiotherapy, measured patient-specific setup variations are used to modify the patient setup and treatment plan, potentially many times during the treatment course. To estimate the setup adjustments and re-plan the treatment, the measured data are usually processed using Kalman filtering or by computing running averages. We propose, as an alternative, the use of Bayesian statistical methods, which combine a population (prior) distribution of systematic and random setup errors with the measurements to determine a patient-specific (posterior) probability distribution. The posterior distribution can either be used directly in the re-planning of the treatment or in the generation of statistics needed for adjustments. Based on the assumption that day-to-day setup variations are independent and identically distributed Normal distributions, we can efficiently compute parameters of the posterior distribution from parameters of the prior distribution and statistics of the measurements. We illustrate a simple procedure to apply the method in practice to adaptive radiotherapy, allowing for multiple adjustments of treatment parameters during the course of treatment.

Algorithms↗