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ABSTRACT: Prior studies have derived low values of alpha-beta ratio (a/ß) for prostate cancer of approximately 1-2 Gy. These studies used poorly matched groups, differing definitions of biochemical failure, and insufficient follow-up.
National Comprehensive Cancer Network low- or low-intermediate risk prostate cancer patients, treated with external beam radiotherapy or permanent prostate brachytherapy, were matched for prostate-specific antigen, Gleason score, T-stage, percentage of positive cores, androgen deprivation therapy, and era, yielding 118 patient pairs. The Phoenix definition of biochemical failure was used. The best-fitting value for a/ß was found for up to 90-month follow-up using maximum likelihood analysis, and the 95% confidence interval using the profile likelihood method. Linear quadratic formalism was applied with the radiobiological parameters of relative biological effectiveness = 1.0, potential doubling time = 45 days, and repair half-time = 1 hour. Bootstrap analysis was performed to estimate uncertainties in outcomes, and hence in a/ß. Sensitivity analysis was performed by varying the values of the radiobiological parameters to extreme values.
The value of a/ß best fitting the outcomes data was >30 Gy, with lower 95% confidence limit of 5.2 Gy. This was confirmed on bootstrap analysis. Varying parameters to extreme values still yielded best-fit a/ß of >30 Gy, although the lower 95% confidence interval limit was reduced to 0.6 Gy.
Using carefully matched groups, long follow-up, the Phoenix definition of biochemical failure, and well-established statistical methods, the best estimate of a/ß for low and low-tier intermediate-risk prostate cancer is likely to be higher than that of normal tissues, although a low value cannot be excluded.
International journal of radiation oncology, biology, physics 03/2011; 79(4):1029-36. · 4.59 Impact Factor
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ABSTRACT: This planning study compared RapidArc, fixed-field IMRT (cIMRT), 3D conformal radiotherapy (3D-CRT), and a parallel-opposed pair (POP) for children with retroperitoneal tumors.
Plans were generated in eight patients to treat the PTV (dose range 19.8-45 Gy) while limiting kidney and liver doses. In selected patients, vertebral body (VB) dose heterogeneity was minimized. Cumulative DVH parameters, monitor units (MU), and treatment times were compared for the four techniques using the Wilcoxon matched pairs test.
RapidArc and cIMRT covered target volumes more conformally than 3D-CRT and POP (P = 0.012). There was no difference in the ability to meet kidney dose constraints. A significantly lower volume of the liver received 12 Gy with cIMRT or RapidArc compared with 3D-CRT (P = 0.028). Where VB was included in PTV, VB dose homogeneity was generally within 94-104% of the prescription dose. Time to deliver a single fraction with RapidArc, POP, 3D-CRT, and cIMRT was 1.25 ± 0.01, 1.38 ± 0.10, 2.6 ± 0.45, and 4.02 ± 1.12 min, respectively (P = 0.012). Monitor units for a single fraction with POP, 3D-CRT, RapidArc, and cIMRT were 203 ± 26, 235 ± 32, 325 ± 71, and 665 ± 215, respectively (P < 0.05).
POP resulted in favorable MU, treatment time and dosimetry but had poor conformality. 3D-CRT was more conformal but had higher MU and treatment time. RapidArc and cIMRT were generally no better dosimetrically than conformal techniques. RapidArc was dosimetrically very similar to cIMRT, but resulted in a major reduction in time and MU used to deliver the radiation.
Pediatric Blood & Cancer 01/2011; 56(1):16-23. · 1.89 Impact Factor
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Richard Shaffer FRCR,
Emily Vollans MSc,
Rosie Vellani RTT,
Margaret Welsh RTT,
Vitali Moiseenko PhD,
Karen Goddard FRCPC, Richard Shaffer,
Emily Vollans,
Rosie Vellani,
Margaret Welsh,
Vitali Moiseenko,
Karen Goddard
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ABSTRACT: Background
This planning study compared RapidArc, fixed-field IMRT (cIMRT), 3D conformal radiotherapy (3D-CRT), and a parallel-opposed pair (POP) for children with retroperitoneal tumors.ProcedurePlans were generated in eight patients to treat the PTV (dose range 19.8–45 Gy) while limiting kidney and liver doses. In selected patients, vertebral body (VB) dose heterogeneity was minimized. Cumulative DVH parameters, monitor units (MU), and treatment times were compared for the four techniques using the Wilcoxon matched pairs test.ResultsRapidArc and cIMRT covered target volumes more conformally than 3D-CRT and POP (P = 0.012). There was no difference in the ability to meet kidney dose constraints. A significantly lower volume of the liver received 12 Gy with cIMRT or RapidArc compared with 3D-CRT (P = 0.028). Where VB was included in PTV, VB dose homogeneity was generally within 94–104% of the prescription dose. Time to deliver a single fraction with RapidArc, POP, 3D-CRT, and cIMRT was 1.25 ± 0.01, 1.38 ± 0.10, 2.6 ± 0.45, and 4.02 ± 1.12 min, respectively (P = 0.012). Monitor units for a single fraction with POP, 3D-CRT, RapidArc, and cIMRT were 203 ± 26, 235 ± 32, 325 ± 71, and 665 ± 215, respectively (P < 0.05).ConclusionsPOP resulted in favorable MU, treatment time and dosimetry but had poor conformality. 3D-CRT was more conformal but had higher MU and treatment time. RapidArc and cIMRT were generally no better dosimetrically than conformal techniques. RapidArc was dosimetrically very similar to cIMRT, but resulted in a major reduction in time and MU used to deliver the radiation. Pediatr Blood Cancer. 2010;56:16–23. © 2010 Wiley-Liss, Inc.
Pediatric Blood & Cancer 12/2010; 56(1):16 - 23. · 1.89 Impact Factor
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ABSTRACT: Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (cIMRT), in which an optimized three-dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to RapidArc (Varian Medical System). This study compared VMAT with cIMRT and with conventional modified wide-tangent (MWT) techniques for locoregional radiotherapy for left-sided breast cancer, including internal mammary nodes.
Therapy for 5 patients previously treated with 50 Gy/25 fractions using nine-field cIMRT was replanned with VMAT and MWT. Comparative endpoints were planning target volume (PTV) dose homogeneity, doses to surrounding structures, number of monitor units, and treatment delivery time.
For VMAT, two 190 degrees arcs with 2-cm overlapping jaws were required to optimize over the large treatment volumes. Treatment plans generated using VMAT optimization resulted in PTV homogeneity similar to that of cIMRT and MWT. The average heart volumes receiving >30 Gy for VMAT, cIMRT, and MWT were 2.6% +/- 0.7%, 3.5% +/- 0.8%, and 16.4% +/- 4.3%, respectively, and the average ipsilateral lung volumes receiving >20 Gy were 16.9% +/- 1.1%, 17.3% +/- 0.9%, and 37.3% +/- 7.2%, respectively. The average mean dose to the contralateral medial breast was 3.2 +/- 0.6 Gy for VMAT, 4.3 +/- 0.4 Gy for cIMRT, and 4.4 +/- 4.7 Gy for MWT. The healthy tissue volume percentages receiving 5 Gy were significantly larger with VMAT (33.1% +/- 2.1%) and IMRT (45.3% +/- 3.1%) than with MWT (19.4% +/- 3.7%). VMAT reduced the number of monitor units by 30% and the treatment time by 55% compared with cIMRT.
VMAT achieved similar PTV coverage and sparing of organs at risk, with fewer monitor units and shorter delivery time than cIMRT.
International journal of radiation oncology, biology, physics 09/2009; 76(1):287-95. · 4.59 Impact Factor
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ABSTRACT: Volumetric modulated arc therapy (VMAT), the predecessor to Varian's RapidArc, is a novel extension of intensity-modulated radiotherapy (IMRT) wherein the dose is delivered in a single gantry rotation while the multileaf collimator leaves are in motion. Leaf positions and the weights of field samples along the arc are directly optimized, and a variable dose rate is used. This planning study compared seven-field coplanar IMRT (cIMRT) with VMAT for high-grade gliomas that had planning target volumes (PTVs) overlapping organs at risk (OARs).
10 previously treated patients were replanned to 60 Gy in 30 fractions with cIMRT and VMAT using the following planning objectives: 98% of PTV covered by 95% isodose without violating OAR and hotspot dose constraints. Mean OAR doses were maximally decreased without reducing PTV coverage or violating hotspot constraints. We compared dose-volume histogram data, monitor units, and treatment times.
There was equivalent PTV coverage, homogeneity, and conformality. VMAT significantly reduced maximum and mean retinal, lens, and contralateral optic nerve doses compared with IMRT (p < 0.05). Brainstem, chiasm, and ipsilateral optic nerve doses were similar. For 2-Gy fractions, mean monitor units were as follows: cIMRT = 789 +/- 112 and VMAT = 363 +/- 45 (relative reduction 54%, p = 0.002), and mean treatment times (min) were as follows: cIMRT = 5.1 +/- 0.4 and VMAT = 1.8 +/- 0.1 (relative reduction 65%, p = 0.002).
Compared with cIMRT, VMAT achieved equal or better PTV coverage and OAR sparing while using fewer monitor units and less time to treat high-grade gliomas.
International journal of radiation oncology, biology, physics 07/2009; 76(4):1177-84. · 4.59 Impact Factor
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Radiotherapy and Oncology 05/2009; · 5.58 Impact Factor
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ABSTRACT: To examine the acute cardiotoxicity of internal mammary chain (IMC) irradiation with concurrent trastuzumab.
Clinical and cardiac function data were collected on 59 patients with early breast cancer who were treated with adjuvant trastuzumab and chemotherapy with or without radiotherapy (often including IMC) at BC Cancer Agency in 2005.
Forty-four of fifty-nine patients received adjuvant radiotherapy (RT). Thirteen had left-sided IMC RT. For left-sided RT, IMC inclusion increased the mean percentage dose to 5% of the heart, but the mean doses to 50% and 90% of the heart were similar. Median baseline left ventricular ejection fraction (LVEF) was 62% and similar in all groups. Median absolute decrease in LVEF after RT was 4%, which was not significantly different according to side or inclusion of IMCs. Trastuzumab was stopped in 11 of 59 patients (18.6%) due to decrease in LVEF. After median follow up of 15 months, three patients developed clinical congestive heart failure, none of whom received left-sided IMC RT.
There was no excess acute cardiotoxicity observed with the combination of left-sided IMC irradiation and concurrent trastuzumab.
Radiotherapy and Oncology 11/2008; 90(1):122-6. · 5.58 Impact Factor
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ABSTRACT: Volumetric modulated arc therapy (VMAT) is a novel form of intensity-modulated radiotherapy (IMRT) optimization that allows the radiation dose to be delivered in a single gantry rotation of up to 360 degrees , using either a constant dose rate (cdr-VMAT) or variable dose rate (vdr-VMAT) during rotation. The goal of this study was to compare VMAT prostate RT plans with three-dimensional conformal RT (3D-CRT) and IMRT plans.
The 3D-CRT, five-field IMRT, cdr-VMAT, and vdr-VMAT RT plans were created for 10 computed tomography data sets from patients undergoing RT for prostate cancer. The parameters evaluated included the doses to organs at risk, equivalent uniform doses, dose homogeneity and conformality, and monitor units required for delivery of a 2-Gy fraction.
The IMRT and both VMAT techniques resulted in lower doses to normal critical structures than 3D-CRT plans for nearly all dosimetric endpoints analyzed. The lowest doses to organs at risk and most favorable equivalent uniform doses were achieved with vdr-VMAT, which was significantly better than IMRT for the rectal and femoral head dosimetric endpoints (p < 0.05) and significantly better than cdr-VMAT for most bladder and rectal endpoints (p < 0.05). The vdr-VMAT and cdr-VMAT plans required fewer monitor units than did the IMRT plans (relative reduction of 42% and 38%, respectively; p = 0.005) but more than for the 3D-CRT plans (p = 0.005).
The IMRT and VMAT techniques achieved highly conformal treatment plans. The vdr-VMAT technique resulted in more favorable dose distributions than the IMRT or cdr-VMAT techniques, and reduced the monitor units required compared with IMRT.
International journal of radiation oncology, biology, physics 05/2008; 72(4):996-1001. · 4.59 Impact Factor
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ABSTRACT: To evaluate region-specific dose metrics as predictors of biochemical relapse in prostate brachytherapy patients.
In a cohort of 1006 low-risk and "low-tier" intermediate-risk prostate brachytherapy patients treated to a planned dose of 144 Gy mPD (minimal peripheral dose), 30 of 32 with biochemical relapse (nadir+2 ng/mL definition) had postimplant CT scans available for retrospective analysis. These were matched to nonrelapsing controls from the same era. Three copies of each CT were created and, after randomization and deletion of identifiers and original contours, were re-contoured by three radiation oncologists. Prostate contours were then divided into quadrants: Anterior-Superior (ASQ), Posterior-Superior (PSQ), Anterior-Inferior (AIQ), and Posterior-Inferior (PIQ), and dosimetric parameters calculated. Results were analyzed using mixed-effects linear regression and multivariate logistic regression.
Whole prostate volume of the prostate receiving at least 100% of the prescribed dose (V(100)) and minimum dose, as a percentage of the prescribed dose, received by 90% of the prostate volume (D(90)) were similar for relapses and controls (p=0.40 and 0.48, respectively). Among the quadrants, the largest differences between relapses and controls were seen for the AIQ. Mean AIQ V(100)s were 91.2% (relapses) and 95.5% (controls) (p=0.096), and D(90)s were 112.8% (relapses) and 119.3% (controls) (p=0.145). Overall, the lowest doses were in the ASQ, but were not very different for relapses and controls (V(100)=76.5% and 78.5%, respectively) (p=0.54). On multivariate analysis along with various clinical parameters, AIQ metrics approached significance at the p ≤ 0.05 level in models that also included initial prostate-specific antigen, androgen suppression, and risk group.
Although whole prostate dose metrics did not predict for biochemical relapse in our data set, dose to the AIQ was predictive in multivariate analysis.
Brachytherapy 10(2):87-97. · 1.47 Impact Factor
