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Title: An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer

Abstract

Purpose: To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation. Methods and Materials: Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the 'best' rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment. Results: For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 {+-} 1.6more » Gy, which was better than the pCT rectum (2.1 {+-} 3.0 Gy) and the alternative average rectums (1.0 {+-} 2.6 Gy and 1.4 {+-} 3.2 Gy). Conclusions: Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [3]
  1. Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  2. (Netherlands)
  3. Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands). E-mail: j.lebesque@nki.nl
Publication Date:
OSTI Identifier:
20951604
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2006.12.010; PII: S0360-3016(06)03645-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; COMPUTERIZED TOMOGRAPHY; PATIENTS; PLANNING; PROSTATE; RADIATION DOSE DISTRIBUTIONS; RADIATION DOSES; RADIOTHERAPY; RECTUM

Citation Formats

Nuver, Tonnis T., Hoogeman, Mischa S., Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, Remeijer, Peter, Herk, Marcel van, and Lebesque, Joos V.. An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.010.
Nuver, Tonnis T., Hoogeman, Mischa S., Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, Remeijer, Peter, Herk, Marcel van, & Lebesque, Joos V.. An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer. United States. doi:10.1016/j.ijrobp.2006.12.010.
Nuver, Tonnis T., Hoogeman, Mischa S., Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, Remeijer, Peter, Herk, Marcel van, and Lebesque, Joos V.. Sun . "An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer". United States. doi:10.1016/j.ijrobp.2006.12.010.
@article{osti_20951604,
title = {An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer},
author = {Nuver, Tonnis T. and Hoogeman, Mischa S. and Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam and Remeijer, Peter and Herk, Marcel van and Lebesque, Joos V.},
abstractNote = {Purpose: To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation. Methods and Materials: Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the 'best' rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment. Results: For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 {+-} 1.6 Gy, which was better than the pCT rectum (2.1 {+-} 3.0 Gy) and the alternative average rectums (1.0 {+-} 2.6 Gy and 1.4 {+-} 3.2 Gy). Conclusions: Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans.},
doi = {10.1016/j.ijrobp.2006.12.010},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 67,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}
  • 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 andmore » 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 1.5{sigma}' (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 2{sigma}', 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{sub 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{sub 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{sub 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{sub 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.« less
  • Purpose: Radiation doses delivered to patients with head and neck cancer (HN) may deviate from the planned doses because of variations in patient setup and anatomy. This study was to evaluate whether off-line Adaptive Radiotherapy (ART) is sufficient. Methods: Ten HN patients, who received IMRT under daily imaging guidance using CT-on-rail/KV-CBCT, were randomly selected for this study. For each patient, the daily treatment setup was corrected with translational only directions. Sixty weekly verification CTs were retrospectively analyzed. On these weekly verification CTs, the tumor volumes and OAR contours were manually delineated by a physician. With the treatment iso-center placed onmore » the verification CTs, according to the recorded clinical shifts, the treatment beams from the original IMRT plans were then applied to these CTs to calculate the delivered doses. The electron density of the planning CTs and weekly CTs were overridden to 1 g/cm3. Results: Among 60 fractions, D99 of the CTVs in 4 fractions decreased more than 5% of the planned doses. The maximum dose of the spinal cord exceeded 10% of the planned values in 2 fractions. A close examination indicated that the dose discrepancy in these 6 fractions was due to patient rotations, especially shoulder rotations. After registering these 6 CTs with the planning CT allowing six degree of freedoms, the maximum rotations around 3 axes were > 1.5┬░ for these fractions. With rotation setup errors removed, 4 out of 10 patients still required off-line ART to accommodate anatomical changes. Conclusion: A significant shoulder rotations were observed in 10% fractions, requiring patient re-setup. Off-line ART alone is not sufficient to correct for random variations of patient position, although ART is effective to adapt to patients' gradual anatomic changes. Re-setup or on-line ART may be considered for patients with large deviations detected early by daily IGRT images. The study is supported in part by Siemens Medical Solutions.« less
  • Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignmentmore » and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. Methods and materials: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a {chi}{sup 2} analysis and were removed from the data set before further analysis. Results: Comparing gray value registration to contour registration, we found a success rate of 91%. The accuracy for rotations around the left-right, cranial-caudal, and anterior-posterior axis was 2.4 degrees, 1.6 degrees, and 1.3 degrees (1 SD), respectively, and for translations along these axes 0.7, 1.3, and 1.2 mm (1 SD), respectively. A large part of the error is attributed to uncertainty in the reference contour set. Automatic prostate localization takes about 45 seconds on a 1.7 GHz Pentium IV personal computer. Conclusions: This newly developed method localizes the prostate quickly, accurately, and with a good success rate, although visual inspection is still needed to detect outliers. With this approach, it will be possible to correct on-line or off-line for prostate movement. Combined with the conformity of intensity-modulated dose distributions, this method might permit dose escalation beyond that of current conformal approaches, because margins can be safely reduced.« less
  • Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portalmore » images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage {<=} T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035). Conclusions: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.« less
  • Purpose: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. Methods and Materials: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. Results: The 3-year rates of Grade {>=}2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planningmore » target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving {>=}30 Gy (V30) and {>=}82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade {>=}2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade {>=}2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade {>=}2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade {>=}2 and Grade 3 chronic urinary toxicity. Conclusions: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm{sup 3} and the V82 to <7 cm{sup 3} when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.« less