Accurate Calculation of Biological Equivalent Dose from Six Dosimetric Quality Indicators in a Randomized Trial for Intermediate-Risk Prostate Patients

Accurate Calculation of Biological Equivalent Dose from Six Dosimetric Quality Indicators in a Randomized Trial for Intermediate-Risk Prostate Patients

Abstracts / Brachytherapy 12 (2013) S11eS77 respectively), this difference was not statistically significant (HR 1.02, 95% CI 0.20-5.12, p50.98). Pri...

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Abstracts / Brachytherapy 12 (2013) S11eS77 respectively), this difference was not statistically significant (HR 1.02, 95% CI 0.20-5.12, p50.98).

Primary Histology

Median OS

95% Confidence Interval

All Metastases (n5104) Colorectal mets (n550) All neuroendocrine mets (n536) Non-neuroendocrine mets (n568) Pancreatic neuroendocrine mets (n512) Non-pancreatic neuroendocrine mets (n524)

14.8 months 8.2 months 29.2 months

2.0-27.6 4.3-12.0 17.0-41.3

8.7 months 41.9 months

5.7-11.6 15.8-68.1

24.6 months

10.9-38.4

Conclusions: Radioembolization with Yttrium-90 microspheres has been shown in previous studies to be a safe and effective treatment for metastases to the liver with some demonstrating a survival benefit over other treatment modalities. Our data confirm the utility of this treatment method in multiple histologies, particularly neuroendocrine primary lesions. Additional prospective dosimetric studies are needed to determine how to optimally escalate Yttrium-90 microspheres in an attempt to further improve survival of these patients.

OR17 Presentation Time: 2:36 PM Incidence and Treatment of Toxicity following 125I Episcleral Plaque Brachytherapy for Uveal Melanoma Shahed N. Badiyan, MD1, Rajesh C. Rao, MD2, Anthony J. Apicelli, MD, PhD1, Sahaja Acharya, MD1, Vivek Verma, BS1, Adam A. Garsa, MD1, Todd DeWees, PhD1, Christina K. Speirs, MD, PhD1, Jose GarciaRamirez, MS1, Perry W. Grigsby, MD, MS1, James W. Harbour, MD3. 1 Radiation Oncology, Siteman Cancer Center, Washington University Medical Center, Saint Louis, MO; 2Opthalmology and Visual Sciences, Washington University Medical Center, Saint Louis, MO; 3Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL. Purpose: To determine the incidence and treatment of ocular toxicity following 125I episcleral plaque brachytherapy. Materials and Methods: Medical records were reviewed for 469 patients treated with COMS style 125I plaque brachytherapy for uveal melanoma from 1996 to 2011. Ophthalmologic followup records were analyzed to assess the incidence of ocular toxicities after therapy. Rates of toxicities were determined using the Kaplan-Meier method. Fischer’s exact test was performed to determine association between date of plaque brachytherapy and need for enucleation due to toxicity. Results: Mean tumor thickness and long basal diameter were 5.0 mm and 12.1 mm, respectively. The median plaque size was 18 mm. One hundred fourteen plaques (24.3%) required a notch due to proximity to the optic nerve. The median followup was 47 months (range 6-175 months). The median visual acuity in the effected eye prior to treatment was 20/40 and on most recent followup was 20/150. The 3-year rates of radiation retinopathy, radiation papillopathy, and exudative retinal detachment were 45% (n5162), 14% (n547), and 10% (n541), respectively. The 3-year rates of cystoid macular edema, vitreous hemorrhage, and enucleation due to radiation toxicity were 17% (n561), 12% (n547), and 4% (n514), respectively. The 3-year rates of cataract formation, neovascularization of the iris and neovascular glaucoma were 29% (n5115), 6% (n524), and 4% (n516), respectively. Twenty-nine patients (6.2%) received intravitreal triamcinolone acetonide for treatment of cystoid macular edema, and thirty two patients (6.8%) received subtenons triamcinolone acetonide injections for treatment of cystoid macular edema or radiation retinopathy. Beginning in 2005 patients began receiving intravitreal bevacizumab for treatment of cystoid macular edema, neovascularization of the iris, or neovascular glaucoma. Seventy-one patients (15.1%) received intravitreal bevacizumab. Patients undergoing plaque brachytherapy after 2005 were significantly less

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likely to require an enucleation due to radiation toxicity than patients undergoing plaque brachytherapy prior to 2005 (p 5 0.01). Conclusions: Radiation retinopathy and cataract formation are common toxicities three years following 125I plaque brachytherapy for uveal melanoma. Patients treated after 2005 were significantly less likely to require an enucleation due to toxicity than patients treated prior to 2005, possibly due to the use of bevacizumab. OR18 Presentation Time: 2:45 PM HDR-IORT for Locally Advanced or Recurrent Rectal Cancers: Technique and the Peter Mac Experience Sarat Chander, MD, FRANZCR1, Jennifer Tan, FRANZCR1, Alexander Heriot, MD, MBA, FRCS, FRACS2, John Mackay, FRACS, FRCS2, Craig Lynch, MBBS, MMedSci, FRAC2, Sylvia van Dyk, DAppSc1, Mathias AB. Bressel, MSc3, Trevor Leong, MD, FRANZCR1, Sam Ngan, MBBS, FRCSEd, FRANZCR1. 1Radiation Oncology; 2Surgical Oncology; 3 Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Purpose: Our technique and experience in delivering high-dose-rate intraoperative radiotherapy (HDR-IORT) for locally advanced primary or recurrent rectal cancer using a custom-made brachytherapy applicator is described. Materials and Methods: Patients selected are those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high-risk of positive resection margins, without evidence of metastasis. Chemoradiation is followed by radical surgery. The tumor is excised and the boundaries of the tumor bed are marked with surgical clips. A customized applicator is fashioned using layers of self-adhesive skin dressing (StomahesiveÒ) and flexible catheters, which can be molded to the shape of the tumor bed. Ten gray (Gy) is delivered to tumor bed via a customized IORT applicator at time of surgery. Results: Twenty-seven patients were treated between Feb 2004 and June 2007. There were 15% primary and 85% recurrent cancers. Seventy-one percent received preoperative chemoradiation to 45-50.4 Gy. R0, R1 and R2 resection were 70%, 22% and 7%, respectively. Irradiated sites included tumor beds (18), nodal regions (2) and wider pelvic areas (12). Ten patients [37% (95% CI519-58)] experienced grade 3 or 4 toxicities (3 wound, 4 abscesses, 3 soft tissue, 3 bowel obstructions, 3 ureteric obstructions, 2 sensory neuropathies). Local recurrence-free, failure free and overall survival rates at 2.5 years were 68% (95% CI552-89), 37% (95% CI523-61) and 82% (95% CI568-98), respectively. Conclusions: The addition of IORT, via a customized applicator at the time of surgery appears to be safe and may be beneficial for local control.

PHYSICS ORAL Thursday, April 18, 2013 3:30 PMe5:00 PM OR19 Presentation Time: 3:30 PM Accurate Calculation of Biological Equivalent Dose from Six Dosimetric Quality Indicators in a Randomized Trial for Intermediate-Risk Prostate Patients Wayne M. Butler, PhD, Gregory S. Merrick, MD. Schiffler Cancer Center, Wheeling Hospital, Wheeling, WV. Purpose: To calculate the biologically equivalent dose (BED) using 6 brachytherapy dosimetric quality indicators and compare BEDs between two arms of a randomized trial. Materials and Methods: All 246 intermediate-risk patients randomized to either a conventional dose of 44 Gy external beam radiotherapy (EBRT) or a reduced EBRT dose of 20 Gy followed by a scaled brachytherapy boost had complete data on 6 dosimetric quality indicators. The trial, closed in June 2004, added 90 Gy 103Pd to 44 Gy EBRT versus 115 Gy 103Pd added to 20 Gy EBRT. Six dosimetric quality indicators, D100, D90, V90, V100, V150, and V200, help define the shape of the brachytherapy dose volume histogram (DVH). Using the radiobiological methodology of AAPM

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Abstracts / Brachytherapy 12 (2013) S11eS77

Comparison of dosimetry and calculated radiobiologic parameters between the two arms of the 20 Gy vs. 44 Gy EBRT plus brachytherapy trial 20Gy XRT þ 115Gy103Pd

Overall n 5 246

n 5 119

44Gy XRT þ 90Gy103Pd n 5 127

Day 0 Quality Indicator or Radiobiological Parameter

Mean

SD

Mean

 SD

Mean

 SD

py

D100 (% mPD) V90 (% vol) V100 (% vol) D90 (% mPD) V150 (% vol) V200 (% vol) Brachytherapy BED (Gy) Total BED: BTx þ EBRT (Gy) Tumor control probability BED from D90 alone (Gy) Total BED D90 þ EBRT (Gy)

73.2 99.4 98.2 126.6 76.0 45.6 103.8 152.9 .9972 118.4 167.5

11.1 0.8 1.7 11.3 7.3 8.3 11.5{ 12.2{ .0076 13.6{ 13.2{

70.5 99.2 97.8 123.4 74.0 43.3 112.8 143.1 .9944 128.1 158.4

9.4 0.8 1.8 10.0 6.6 7.6 8.5{ 8.5{ .0102{ 10.5{ 10.6{

75.8 99.6 98.7 129.5 77.9 47.7 95.5 162.1 .9997 109.3 176.0

12.0 0.7 1.5 11.7 7.4 8.4 6.7{ 6.7{ .0008{ 9.3{ 9.3{

!0.001 0.001 !0.001 !0.001 !0.001 !0.001 !0.001 !0.001 !0.001 !0.001 !0.001

y

Independent samples t-test Matched pair t-tests between 6-component radiobiological values and those calculated from D90 have p!0.001

{

TG-137, BED and tumor control probability (TCP) were calculated for each patient by applying an appropriate volume increment to each quality indicator. The validity of this approach was verified by comparing 33 patients with accurate BEDs and TCPs calculated from the full DVH. Results: Paired sample t-tests showed no significant differences between BEDs calculated by the 6-indicator or detailed DVH approaches in the 33patient calibration group. However, there were significant differences between the protocol cohorts for the whole population. Because of the smaller prescribed 103Pd dose in the 44 Gy arm, the brachytherapy BED was 96  7 Gy compared to 113  8 Gy for the 20 Gy arm. Including EBRT in the radiobiological calculation gave total mean BEDs of 162  7 Gy and 143  8 Gy for the 44 Gy and 20 Gy arms, respectively (p ! 0.001). Differences in the mean TCP also had p ! 0.001, with mean TCP of 1.000  0.001 in the 44 Gy arm vs. 0.994  0.010 in the 20 Gy arm. Conclusions: BEDs and TCPs calculated from 6 brachytherapy dosimetric quality indicators were nearly the same as those derived from detailed DVH analysis. Applying the 6-indicator approach to radiobiological calculations for patients in a randomized trial indicated significant differences in BED between the arms. Despite the clinically large difference of 19 Gy in total BED between arms, the difference in total TCP was small, 0.005. This finding is consistent with a published analysis of this trial showing no significant difference between the arms at any post-treatment time point, with the 10-year biochemical progression-free survival at 93.4% and 93.1% for the 44 Gy and 20 Gy arms, respectively.

diameters (4plaque), and used to determine the radiation dose distribution diameter (4Rx) at the eye surface for each plaque as a function of prescription depth (dRx) to assess adequacy of the 2e3mm margin for various GTV basal diameters (4GTV). Four sets of ellipsoidal tumors (5mm#4GTV#14mm) with a range of apical heights (2mm#dGTV#8mm) were contoured in a reference CT environment, with plaque placement uncertainties quantified as circumferential displacements (D) at the outer scleral surface. Tumor DVHs were generated and compared for all D with D90 and D95 used to evaluate tumor margin adequacy. Results: Physical and clinical dosimetric implications of COMS plaque size selection are shown in Figure 1. Dashed curves correspond to 125I data (indistinguishable within 0.4mm from 131Cs) and solid curves are 103Pd data. Legend values follow the curve vertical order at dRx55mm, with 4Rx on the left vertical axis as a function of dRx. For example, 125I plaques with 4plaque510, 12, 14, and 16mm prescribed to 5mm depth have 4Rx512.0, 13.0, 13.8, and 14.6mm, respectively. Using these plaques to treat 4GTV512mm and dGTV55mm while assuming D50mm results in tumor basal radiation margins of 0.0, 0.5, 0.9, and 1.3 mm, respectively. For equivalent 4plaque and dRx, 4Rx values were typically 0.4e0.8mm less for 103Pd than for 125I or 131Cs.

OR20 Presentation Time: 3:39 PM Dosimetric Analysis of the 2003 American Brachytherapy Society Report Tumor Margin Recommendations for COMS Eye Plaque Brachytherapy Nolan L. Gagne, PhD, Mark J. Rivard, PhD. Radiation Oncology, Tufts Medical Center, Boston, MA. Purpose: The 2003 ABS-recommended 2e3 mm tumor margin contributes in part to the excellent local control rates typical of COMS plaque brachytherapy treatments. However, the report acknowledges that ‘‘the optimal margin required around the tumor base is unknown.’’ These margins cause irradiation of adjacent uninvolved healthy retina and may contribute to ocular toxicities and visual complications sometimes present at post-implant followup. Therefore, this study quantifies the dosimetric adequacy of the ABS recommended 2e3 mm margin for plaque size selection with respect to both basal and volumetric radiation coverage, accounting for clinical plaque placement uncertainties. Subsequent GTV and CTV expansions are investigated for choroidal melanoma. Materials and Methods: Plaque heterogeneity-corrected dose distributions were generated for the range of available radionuclides and COMS plaque

For the tumor sizes (4GTV, dGTV) and radionuclides investigated, normalized D90 and D95 values were as low as 68% and 64%, respectively, using 4plaque and D in accordance with the 2003 ABS report recommendations. These values tended to increase with dGTV, 4plaque, and decreasing D. For example, selecting a 4plaque that instead provided a 4e5mm tumor margin resulted in D90 improvements up to 19% and D95 improvements up to 20% compared to a 2e3mm tumor margin assuming D53 mm. 103Pd plaque