Beverly Steffey

Acute urinary toxicity following transperineal prostate brachytherapy using a modified quimby loading method

PURPOSE To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity. METHODS AND MATERIALS One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) < or = 6, Gleason score (GS) < or = 6, clinical stage < T2b, and prostate volumes generally less than 40 cc. Patients with larger prostate volumes were given neoadjuvant antiandrogen therapy. Those with GS > 6, PSA > 6, or Stage > T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale. RESULTS Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p = 0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p = 0.002), and those with more seeds implanted (p < 0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p = 0.01), with larger prostate volumes (p = 0.01), and those with more seeds implanted (p < 0.001). CONCLUSION Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest incidence of significant toxicity.

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

PURPOSE To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. METHODS AND MATERIALS A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. RESULTS The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). CONCLUSIONS Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

PURPOSE To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. METHODS AND MATERIALS A retrospective review was performed to evaluate patients treated for uveal melanoma with (125)I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpoint variables. RESULTS One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). CONCLUSIONS Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis-free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.

RENAL SHIELDING AND DOSIMETRY FOR PATIENTS WITH SEVERE SYSTEMIC SCLEROSIS RECEIVING IMMUNOABLATION WITH TOTAL BODY IRRADIATION IN THE SCLERODERMA: CYCLOPHOSPHAMIDE OR TRANSPLANTATION TRIAL

PURPOSE To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry.

PURPOSE To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. METHODS For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 10(9) photon histories from a (137)Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for (137)Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE(®) dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)(3) isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. RESULTS The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D γ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D(2cc) to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. CONCLUSIONS Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.PURPOSE To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. METHODS For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 109 photon histories from a 137 Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for 137 Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE® dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)3 isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. RESULTS The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3Dγ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D2cc to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. CONCLUSIONS Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.

Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy

PURPOSE To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. METHODS AND MATERIALS In this institutional review board-approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance-guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. RESULTS A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. CONCLUSIONS Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted.

On the Feasibility of Verification of 3D Dosimetry Near Brachytherapy Sources Using PRESAGE/Optical-CT.

PURPOSE: The feasibility of using the PRESAGE/Optical-CT system for 3D dosimetry verification around a brachytherapy source is investigated. METHOD AND MATERIALS: Brachytherapy dose distributions were obtained by irradiation of cylindrical PRESAGE volumes 6cm in diameter by 8cm height with a GammaMed 12i Ir-192 HDR unit (Varian Medical Systems). A narrow channel on the central axis was created by setting a steel catheter in the Presage during manufacture, enabling measurements close to the source (~3mm). RESULTS: Comparison of dose line profiles shows good agreement between PRESAGE and verified calculated dose calculation, in both high and low dose regions. CONCLUSION: The PRESAGE/Optical-CT shows good potential in verification of 3D dose distributions around brachytherapy sources.

Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies

OBJECTIVE To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. METHODS Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. RESULTS All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. CONCLUSION Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity.

Commissioning of Varian ring & tandem HDR applicators: reproducibility and interobserver variability of dwell position offsets

Studies have shown that source dwells within Varians HDR CT/MR compatible ring applicators can deviate from intended positions by several millimeters. Quantifying this offset is an important part of commissioning. The aims of this study were to: 1) determine the reproducibility of the offset, 2) study the interobserver variation in the offsets measurement, and 3) quantify the dosimetric impact of the offset. Offsets were measured for four ring applicators: two 30°, one 45°, and one 60°. Dwell positions were measured five times for each ring to determine the reproducibility of source positioning. Experiments were done to compare two separate source wires, as well as different time points within a single source wires lifecycle. Data were analyzed by three independent observers. To quantify the dosimetric impact of the offset, a treatment plan was generated using BrachyVision. The dose to point A, and the D2cc metric for rectum and bladder were calculated with and without the offset. For the 45° and 60° rings, measured offsets were 3.0 mm and 3.6 mm, respectively. The 30° ring showed substantial variation in distal dwell positions (maximum difference between the five experiments of 2.9 mm). Subsequent testing of a replacement ring showed an offset of 2.4 mm that was more reproducible. Offsets varied less than 1 mm between different source wires, and changed less than 1 mm over the course of a source wires lifecycle. When comparing observers, the average range in a measurement of a dwell position was 0. 5mm (σ = 0.2 mm, max 1.3 mm). The offset resulted in dose variations to point A, bladder, and rectum of less than 1%, 2%, and 5%, respectively. Results indicate that Varian rings can show systematic and random offsets of more than 3 mm. Some can be considered defective and should be replaced. Each applicator should be individually commissioned and reproducibility should be confirmed with multiple tests. PACS number: 87.56.‐v, 87.53.Jw

SU‐E‐J‐88: Dose Summation Between Multimodality Treatments for Cervical Cancer

Purpose: 1) To explore the feasibility of volumetric dose summation between external beam radiation (EBRT) and high dose rate (HDR) brachytherapy treatments for cervical cancer, and 2) to investigate the differences between two deformable registration platforms: MIM Software (M) and VelocityAI (V). Methods: Five patients treated with combined EBRT (45 Gy) and HDR (5 x 5.5 Gy/FX, T&R) were selected in this study. The doses were converted to EQD2 (α/β of 10 for early and 3 for late effects). The HDR CT sets were registered using rigid (r), based on applicator, and deformable (d) registration. To quantify geometrical similarities between the deformed secondary and the original primary structures, the Dice Similarity Coefficient (DSC) was calculated for HRCTV (for HDR sums only), bladder, and rectum. Each HDR fractional dose was resampled to a primary set. The registration between EBRT and HDR was performed using the HDR primary CT. The metrics HRCTV D90, and bladder/rectum D2cc were extracted from total dose DVHs and compared to the current clinical point dose summation protocol. Results: The average DSC for HRCTV, bladder and rectum was 0.72, 0.71, and 0.56 for MIM and 0.71, 0.70, and 0.51 for Velocity. Volumetric dose summation between the two modalities lead to differences from the point summation of 2.1±1.6% (r, M), 3.2±2.0% (r, V), 2.6±1.9% (d, M), and 3.9±1.5% (d, V) for HRCTV D90, 8.9±6.7% (r, M), 9.9±6.5% (r, V), 10.2± 6.2 (d, M), and 9.4± 4.5% (d, V) for bladder, and 5.2±3.4% (r, M), 5.0± 1.1%(r, V), 5.2± 3.3% (d, M), and 5.3± 3.8% (d, V) for rectum. Conclusion: The two algorithms produced similar results, with expected better DSC for HRCTV and bladder than for rectum. With understanding of the limitations of current deformable registration algorithms, 3D dose summation can be accomplished and composite dose estimates can be improved.