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Title: Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis

Abstract

Purpose: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. Methods and Materials: Five prostate cancer patients with {approx}16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. Results: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). Conclusions: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.

Authors:
 [1];  [2];  [3];  [1];  [2];  [1];  [2];  [2];  [4]
  1. Radiation Treatment Program, London Regional Cancer Program, London Health Sciences Centre, London, Ontario (Canada)
  2. (Canada)
  3. Department of Medical Physics, Toronto Sunnybrook Cancer Centre, Sunnybrook and Women's Health Sciences Centre, Toronto, Ontario (Canada)
  4. Radiation Treatment Program, London Regional Cancer Program, London Health Sciences Centre, London, Ontario (Canada) and Department of Medical Biophysics, University of Western Ontario, London, Ontario (Canada) and Department of Oncology, University of Western Ontario, London, Ontario (Canada). E-mail: jake.vandyk@lhsc.on.ca
Publication Date:
OSTI Identifier:
20788297
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2005.08.037; PII: S0360-3016(05)02582-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The 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; EVALUATION; IMAGES; MATERIALS; PATIENTS; PROSTATE; RADIOTHERAPY

Citation Formats

Song, William Y., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Schaly, Bryan, Bauman, Glenn, Department of Oncology, University of Western Ontario, London, Ontario, Battista, Jerry J., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Department of Oncology, University of Western Ontario, London, Ontario, and Van Dyk, Jake. Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Song, William Y., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Schaly, Bryan, Bauman, Glenn, Department of Oncology, University of Western Ontario, London, Ontario, Battista, Jerry J., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Department of Oncology, University of Western Ontario, London, Ontario, & Van Dyk, Jake. Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis. United States. doi:10.1016/J.IJROBP.2005.0.
Song, William Y., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Schaly, Bryan, Bauman, Glenn, Department of Oncology, University of Western Ontario, London, Ontario, Battista, Jerry J., Department of Medical Biophysics, University of Western Ontario, London, Ontario, Department of Oncology, University of Western Ontario, London, Ontario, and Van Dyk, Jake. Sun . "Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20788297,
title = {Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: A radiobiologic analysis},
author = {Song, William Y. and Department of Medical Biophysics, University of Western Ontario, London, Ontario and Schaly, Bryan and Bauman, Glenn and Department of Oncology, University of Western Ontario, London, Ontario and Battista, Jerry J. and Department of Medical Biophysics, University of Western Ontario, London, Ontario and Department of Oncology, University of Western Ontario, London, Ontario and Van Dyk, Jake},
abstractNote = {Purpose: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. Methods and Materials: Five prostate cancer patients with {approx}16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. Results: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). Conclusions: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 64,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
  • The purpose of this study is to evaluate a geometric image guidance strategy that simultaneously correct for various inter-fractional rigid and nonrigid geometric uncertainties in an on-line environment, using field shape corrections (called the 'MU-MLC' technique). The effectiveness of this strategy was compared with two other simpler on-line image guidance strategies that are more commonly used in the clinic. To this end, five prostate cancer patients, with at least 15 treatment CT studies each, were analyzed. The prescription dose was set to the maximum dose that did not violate the rectum and bladder dose-volume constraints, and hence, was unique tomore » each patient. Deformable image registration and dose-tracking was performed on each CT image to obtain the cumulative treatment dose distributions. From this, maximum, minimum, and mean dose, as well as generalized equivalent uniform dose (gEUD) were calculated for each image guidance strategy. As expected, some dosimetric differences in the clinical target volume (CTV) were observed between the three image guidance strategies investigated. For example, up to {+-}2% discrepancy in prostate minimum dose were observed among the techniques. Of them, only the 'MU-MLC' technique did not reduce the prostate minimum dose for all patients (i.e., {>=}100%). However, the differences were clinically not significant to indicate the preference of one strategy over another, when using a uniform 5 mm margin size. For the organ-at-risks (OARs), the large rectum sparing effect ({<=}5.7 Gy, gEUD) and bladder overdosing effect ({<=}16 Gy, gEUD) were observed. This was likely due to the use of bladder contrast during CT simulation studies which was not done during the treatment CT studies. Therefore, ultimately, strategies to maintain relatively constant rectum and bladder volumes, throughout the treatment course, are required to minimize this effect. In conclusion, the results here suggest that simple translational corrections based on three-dimensional (3D) images is adequate to maintain target coverage, for margin sizes at least as large as 5 mm. In addition, due to large fluctuations in OAR volumes, innovative image guidance strategies are needed to minimize dose and maintain consistent sparing during the whole course of radiation therapy.« less
  • Purpose: Setup errors and prostate intrafraction motion are main sources of localization uncertainty in prostate cancer radiation therapy. This study evaluates four different imaging modalities 3D ultrasound (US), kV planar images, cone-beam computed tomography (CBCT), and implanted electromagnetic transponders (Calypso/Varian) to assess inter- and intrafraction localization errors during intensity-modulated radiation therapy based treatment of prostate cancer. Methods: Twenty-seven prostate cancer patients were enrolled in a prospective IRB-approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall, 1100 fractions were evaluated. For each fraction, treatment targets were localized using US, kV planar images, and CBCT in amore » sequence defined to determine setup offsets relative to the patient skin tattoos, intermodality differences, and residual errors for each patient and patient cohort. Planning margins, following van Herk's formalism, were estimated based on error distributions. Calypso-based localization was not available for the first eight patients, therefore centroid positions of implanted gold-seed markers imaged prior to and immediately following treatment were used as a motion surrogate during treatment. For the remaining 19 patients, Calypso transponders were used to assess prostate intrafraction motion. Results: The means ({mu}), and standard deviations (SD) of the systematic ({Sigma}) and random errors ({sigma}) of interfraction prostate shifts (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and US, averaged over all patients and fractions, were: [{mu}{sub CBCT}= (-1.2, 0.2, 1.1) mm, {Sigma}{sub CBCT}= (3.0, 1.4, 2.4) mm, {sigma}{sub CBCT}= (3.2, 2.2, 2.5) mm], [{mu}{sub kV}= (-2.9, -0.4, 0.5) mm, {Sigma}{sub kV}= (3.4, 3.1, 2.6) mm, {sigma}{sub kV}= (2.9, 2.0, 2.4) mm], and [{mu}{sub US}= (-3.6, -1.4, 0.0) mm, {Sigma}{sub US}= (3.3, 3.5, 2.8) mm, {sigma}{sub US}= (4.1, 3.8, 3.6) mm], in the anterior-posterior (A/P), superior-inferior (S/I), and the left-right (L/R) directions, respectively. In the treatment protocol, adjustment of couch was guided by US images. Residual setup errors as assessed by kV images were found to be: {mu}{sub residual}= (-0.4, 0.2, 0.2) mm, {Sigma}{sub residual}= (1.0, 1.0,0.7) mm, and {sigma}{sub residual}= (2.5, 2.3, 1.8) mm. Intrafraction prostate motion, evaluated using electromagnetic transponders, was: {mu}{sub intrafxn}= (0.0, 0.0, 0.0) mm, {Sigma}{sub intrafxn}= (1.3, 1.5, 0.6) mm, and {sigma}{sub intrafxn}= (2.6, 2.4, 1.4) mm. Shifts between pre- and post-treatment kV images were: {mu}{sub kV(post-pre)}= (-0.3, 0.8, -0.2), {Sigma}{sub kV(post-pre)}= (2.4, 2.7, 2.1) mm, and {sigma}{sub kV(post-pre)}= (2.7, 3.2, 3.1) mm. Relative to skin tattoos, planning margins for setup error were within 10-11 mm for all image-based modalities. The use of image guidance was shown to reduce these margins to less than 5 mm. Margins to compensate for both residual setup (interfraction) errors as well as intrafraction motion were 6.6, 6.8, and 3.9 mm in the A/P, S/I, and L/R directions, respectively. Conclusions: Analysis of interfraction setup errors, performed with US, CBCT, planar kV images, and electromagnetic transponders, from a large dataset revealed intermodality shifts were comparable (within 3-4 mm). Interfraction planning margins, relative to setup based on skin marks, were generally within the 10 mm prostate-to-planning target volume margin used in our clinic. With image guidance, interfraction residual planning margins were reduced to approximately less than 4 mm. These findings are potentially important for dose escalation studies using smaller margins to better protect normal tissues.« less
  • Purpose and Objectives: We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials: Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 monthsmore » using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion: Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.« less
  • Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities weremore » scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). Conclusions: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.« less
  • Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers inmore » place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning may represent the preferred mode of external-beam radiotherapy delivery for the treatment of prostate cancer.« less