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Title: Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer

Abstract

Purpose: Online image guidance (IG) has been used to effectively correct the setup error and inter-fraction rigid organ motion for prostate cancer. However, planning margins are still necessary to account for uncertainties such as deformation and intra-fraction motion. The purpose of this study is to investigate the effectiveness of an adaptive planning technique incorporating offline dose feedback to manage inter-fraction motion and residuals from online correction. Methods: Repeated helical CT scans from 28 patients were included in the study. The contours of prostate and organs-at-risk (OARs) were delineated on each CT, and online IG was simulated by matching center-of-mass of prostate between treatment CTs and planning CT. A seven beam intensity modulated radiation therapy (IMRT) plan was designed for each patient on planning CT for a total of 15 fractions. Dose distribution at each fraction was evaluated based on actual contours of the target and OARs from that fraction. Cumulative dose up to each fraction was calculated by tracking each voxel based on a deformable registration algorithm. The cumulative dose was compared with the dose from initial plan. If the deviation exceeded the pre-defined threshold, such as 2% of the D{sub 99} to the prostate, an adaptive planning technique calledmore » dose compensation was invoked, in which the cumulative dose distribution was fed back to the treatment planning system and the dose deficit was made up through boost radiation in future treatment fractions. The dose compensation was achieved by IMRT inverse planning. Two weekly compensation delivery strategies were simulated: one intended to deliver the boost dose in all future fractions (schedule A) and the other in the following week only (schedule B). The D{sub 99} to prostate and generalized equivalent uniform dose (gEUD) to rectal wall and bladder were computed and compared with those without the dose compensation. Results: If only 2% underdose is allowed at the end of the treatment course, then 11 patients fail. If the same criteria is assessed at the end of each week (every five fractions), then 14 patients fail, with three patients failing the 1st or 2nd week but passing at the end. The average dose deficit from these 14 patients was 4.4%. They improved to 2% after the weekly compensation. Out of these 14 patients who needed dose compensation, ten passed the dose criterion after weekly dose compensation, three patients failed marginally, and one patient still failed the criterion significantly (10% deficit), representing 3.6% of the patient population. A more aggressive compensation frequency (every three fractions) could successfully reduce the dose deficit to the acceptable level for this patient. The average number of required dose compensation re-planning per patient was 0.82 (0.79) per patient for schedule A (B) delivery strategy. The doses to OARs were not significantly different from the online IG only plans without dose compensation. Conclusions: We have demonstrated the effectiveness of offline dose compensation technique in image-guided radiotherapy for prostate cancer. It can effectively account for residual uncertainties which cannot be corrected through online IG. Dose compensation allows further margin reduction and critical organs sparing.« less

Authors:
;  [1]
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)
Publication Date:
OSTI Identifier:
22098684
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 38; Journal Issue: 12; Other Information: (c) 2011 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 61 RADIATION PROTECTION AND DOSIMETRY; ALGORITHMS; BEAMS; CAT SCANNING; CENTER-OF-MASS SYSTEM; CORRECTIONS; CRITICAL ORGANS; DEFORMATION; DOSIMETRY; IMAGE PROCESSING; NEOPLASMS; PATIENTS; PLANNING; PROSTATE; RADIATION DOSE DISTRIBUTIONS; RADIATION DOSES; RADIOTHERAPY; RECTUM

Citation Formats

Liu Han, and Wu Qiuwen. Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer. United States: N. p., 2011. Web. doi:10.1118/1.3658567.
Liu Han, & Wu Qiuwen. Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer. United States. doi:10.1118/1.3658567.
Liu Han, and Wu Qiuwen. 2011. "Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer". United States. doi:10.1118/1.3658567.
@article{osti_22098684,
title = {Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer},
author = {Liu Han and Wu Qiuwen},
abstractNote = {Purpose: Online image guidance (IG) has been used to effectively correct the setup error and inter-fraction rigid organ motion for prostate cancer. However, planning margins are still necessary to account for uncertainties such as deformation and intra-fraction motion. The purpose of this study is to investigate the effectiveness of an adaptive planning technique incorporating offline dose feedback to manage inter-fraction motion and residuals from online correction. Methods: Repeated helical CT scans from 28 patients were included in the study. The contours of prostate and organs-at-risk (OARs) were delineated on each CT, and online IG was simulated by matching center-of-mass of prostate between treatment CTs and planning CT. A seven beam intensity modulated radiation therapy (IMRT) plan was designed for each patient on planning CT for a total of 15 fractions. Dose distribution at each fraction was evaluated based on actual contours of the target and OARs from that fraction. Cumulative dose up to each fraction was calculated by tracking each voxel based on a deformable registration algorithm. The cumulative dose was compared with the dose from initial plan. If the deviation exceeded the pre-defined threshold, such as 2% of the D{sub 99} to the prostate, an adaptive planning technique called dose compensation was invoked, in which the cumulative dose distribution was fed back to the treatment planning system and the dose deficit was made up through boost radiation in future treatment fractions. The dose compensation was achieved by IMRT inverse planning. Two weekly compensation delivery strategies were simulated: one intended to deliver the boost dose in all future fractions (schedule A) and the other in the following week only (schedule B). The D{sub 99} to prostate and generalized equivalent uniform dose (gEUD) to rectal wall and bladder were computed and compared with those without the dose compensation. Results: If only 2% underdose is allowed at the end of the treatment course, then 11 patients fail. If the same criteria is assessed at the end of each week (every five fractions), then 14 patients fail, with three patients failing the 1st or 2nd week but passing at the end. The average dose deficit from these 14 patients was 4.4%. They improved to 2% after the weekly compensation. Out of these 14 patients who needed dose compensation, ten passed the dose criterion after weekly dose compensation, three patients failed marginally, and one patient still failed the criterion significantly (10% deficit), representing 3.6% of the patient population. A more aggressive compensation frequency (every three fractions) could successfully reduce the dose deficit to the acceptable level for this patient. The average number of required dose compensation re-planning per patient was 0.82 (0.79) per patient for schedule A (B) delivery strategy. The doses to OARs were not significantly different from the online IG only plans without dose compensation. Conclusions: We have demonstrated the effectiveness of offline dose compensation technique in image-guided radiotherapy for prostate cancer. It can effectively account for residual uncertainties which cannot be corrected through online IG. Dose compensation allows further margin reduction and critical organs sparing.},
doi = {10.1118/1.3658567},
journal = {Medical Physics},
number = 12,
volume = 38,
place = {United States},
year = 2011,
month =
}
  • 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: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error.more » Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades {>=}2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm{sup 3}, 5.6 cm{sup 2}, and 53.3 cm{sup 3}, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades {>=}2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is independent of rectal volume/distension while maintaining very low rates of chronic GI toxicity.« less
  • Purpose: To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer. Methods and Materials: Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data. Results: The 10-year likelihood of SM development was 25% after EBRT andmore » 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population. Conclusions: Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased, number of skin cancers in the EBRT patients compared with that of the general population.« less
  • Purpose: To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Methods and materials: Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and onlinemore » IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. Results: With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of bladder wall and rectal wall for conventional IMRT vs. online IG-IMRT were 70.1% vs. 47.3%, and 79.4% vs. 72.2%, respectively. On average, a target dose increase of 13% (SD = 9.7%) can be achieved with online IG-IMRT based on rectal wall EUDs and 53.3% (SD = 15.3%) based on bladder wall EUDs. However, the variation (SD = 9.7%) is fairly large among patients; 27% of patients had only minimal benefit (<5% of dose increment) from online IG-IMRT, and 32% had significant benefit (>15%-41% of dose increment). Conclusions: The ideal maximum dose increment achievable with online IG-IMRT is, on average, 13% with respect to the dose-limiting organ of rectum. However, there is a large interpatient variation, ranging <5%-41%. The results can be applied to calibrate other practical online image-guided techniques for prostate cancer radiotherapy, when intratreatment organ motion/deformation and machine delivery accuracy are considered.« less
  • Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladdermore » walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.« less