Jeffrey Demanes

High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer.

Purpose:The radiobiology of prostate cancer appears to favor large fractions. Accelerated hypofractionation treatments may therefore be used to improve the therapeutic ratio, particularly when the doses to rectum and bladder are kept below the prostate dose. The 5-year experience at William Beaumont Hospital (WBH) and the California Endocurietherapy Center (CET) with accelerated-hypofractionated high-dose-rate (HDR) monotherapy in favorable prostate cancer is presented. Materials and Methods:Between 1993 and 2004, 454 patients were treated with brachytherapy of which 248 treated with HDR and 206 patients treated with low-dose-rate Palladium (LDR-Pd103). The WBH-HDR dose was 38 Gy, in 4 fractions, twice a day. The CET-HDR dose was 42 Gy in 6 fractions in 2 separate implants 1 week apart. The WBH-LDR dose was 120 Gy. Results:Median follow-up was 4.8 years. The 5-year Phoenix biochemical control (BC) was 89%, 91%, and 88% for WBH-LDR, WBH- HDR, and CET-HDR, respectively. The majority of complications were grade 1. HDR was associated with less acute grade 1 to 3 dysuria 60% versus 39%, (P < 0.001), urinary frequency/urgency 90% to58% (P < 0.001), and rectal pain 17% to 6.5% (P < 0.001). Long-term urinary frequency/urgency 54% versus 43%, (P = 0.03) and dysuria 22% versus 15% were less with HDR. The 5-year actuarial impotence rate was 30% for LDR and 20% for HDR (P = 0.23). Conclusions:Although the same 5-year BC rates were achieved with HDR (248 patients) and LDR (206 patients) monotherapy, HDR brachytherapy was associated with less acute and chronic genitourinary and gastrointestinal toxicities. As another accepted standard of care, accelerated hypofractionated HDR monotherapy is target specific and efficient radiobiologically than EBRT which has many smaller doses per fraction. It could be considered today as the best option in accelerated hypofractionated prostate cancer treatment.

Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer.

PURPOSE To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. METHODS AND MATERIALS Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). RESULTS A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). CONCLUSIONS A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

Matched-pair Analysis of Prostate Cancer Patients With a High Risk of Positive Pelvic Lymph Nodes Treated With and Without Pelvic Rt and High-dose Radiation Using High Dose Rate Brachytherapy

Objective:Adding pelvic radiation to high-dose prostate radiation for prostate cancer patients with a >15% risk of positive lymph nodes (LN) is controversial. We performed a matched-pair analysis of patients treated at 2 institutions to assess the impact of pelvic radiotherapy (P-RT). Methods:From January 1993 to March 2003, 2 institutions treated 1432 prostate cancer patients with combined external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy. Those receiving EBRT were treated either to the prostate and seminal vesicles alone or to the entire pelvis (46 Gy). In all cases, prostate dose (EBRT and HDR) resulted in an average BED >100 Gy (α/β = 1.2). There were 755 cases identified as having a pelvic LN risk >15% using the Roach formula. Of these, 255 cases were treated without pelvic RT and randomly matched by Gleason score, T stage, and pretreatment PSA to 500 cases treated with pelvic RT, resulting in 250 pairs (1:1). Results:Median follow-up was 4.0 years (P = 0.7). The 4-year prostate biochemical failure (22% versus 14%, P = 0.12), distant metastasis (9% versus 4%, P = 0.6), event-free survival (72% versus 78%, P = 0.3), prostate cancer death rate (4% versus 2%, P = 0.9), and overall survival (89% versus 88%, P = 0.7) were not significantly different for patients treated with and without P-RT. Analysis with and without androgen deprivation therapy showed similar results. Conclusion:Improved biochemical, clinical, or survival outcomes were not observed for prostate cancer patients at risk for positive pelvic LN >15% when treated with high-dose EBRT and HDR brachytherapy to the prostate with or without pelvic radiation.

SU-G-201-14: Is Maximum Skin Dose a Reliable Metric for Accelerated Partial Breast Irradiation with Brachytherapy?

PURPOSE To evaluate the reliability of the maximum point dose (Dmax) to the skin surface as a dosimetric constraint, we investigated the correlation between Dmax at the skin surface and dose metrics at various definitions of skin thickness. METHODS 42 patients treated with APBI using a Strut Adjusted Volume Implant (SAVI) applicator between 2010 and 2014 were retrospectively reviewed. Target (PTV_EVAL) and organs at risk (OARs: skin, lung, and ribs) were delineated on a CT following NSABP B-39 guidelines. Six skin structures were contoured: a rind 3cm external to the body surface and 1, 2, 3, 4, and 5mm thick rinds deep to the body surface. Inverse planning simulated annealing optimization was used to deliver 32-34Gy in 8-10 fractions to the target while minimizing OAR doses. Dmax, D0.1cc, D1.0cc, and D2.0cc to the various skin structures were calculated. Linear regressions between the metrics were evaluated using the coefficient of determination (R2 ). RESULTS The average±SD PTV_EVAL volume and cavity-to-skin distances were 71.1±28.5cc and 6.9±5.0mm. The target V90 and V95 were 97.3±2.3% and 95.1±3.2%. The Dmax to the skin structures were 78.7±10.2% (skin surface), 82.2±10.7% (skin-1mm), 89.4±12.6% (skin-2mm), 97.9±15.4% (skin-3mm), 114.1±32.5% (skin-4mm), and 157.0±85.3% (skin-5mm). Linear regression analysis showed D1.0cc and D2.0cc to the skin 1mm and Dmax to the skin-4mm and 5mm were poorly correlated with other metrics (R2 =0.413±0.204). Dmax to the skin surface was well correlated (R2 =0.910±0.047) and D1.0cc to the skin-3mm was strongly correlated with all subsurface skin layers (R2 =0.935±0.050). CONCLUSION Dmax to the skin surface is a relevant metric for breast skin dose. Contouring discontinuities in the skin with a 1mm subsurface rind and the active dwells in the skin 4 and 5mm introduced significant variations in skin DVH. D0.1cc, D1.0cc, and D2.0cc to a 3mm skin rind are more robust metrics in breast brachytherapy.

SU-E-T-232: Custom High-Dose-Rate Brachytherapy Surface Mold Applicators: The Importance Source to Skin Distance.

Purpose: Surface mold applicators can be customized to fit irregular skin surfaces that are difficult to treat with other radiation therapy techniques. Optimal design of customized HDR skin brachytherapy is not well-established. We evaluated the impact of applicator thickness (source to skin distance) on target dosimetry. Methods: 27 patients had 34 treated sites: scalp 4, face 13, extremity 13, and torso 4. Custom applicators were constructed from 5–15 mm thick thermoplastic bolus molded over the skin lesion. A planar array of plastic brachytherapy catheters spaced 5–10 mm apart was affixed to the bolus. CT simulation was used to contour the target volume and to determine the prescription depth. Inverse planning simulated annealing followed by graphical optimization was used to plan and deliver 40–56 Gy in 8–16 fractions. Target coverage parameters (D90, Dmean, and V100) and dose uniformity (V110–200, D0.1cc, D1cc, and D2cc) were studied according to target depth (<5mm vs. ≥5mm) and applicator thickness (5–10mm vs. ≥10mm). Results: The average prescription depth was 4.2±1.5mm. The average bolus thickness was 9.2±2.4mm. The median CTV volume was 10.0 cc (0.2–212.4 cc). Similar target coverage was achieved with prescription depths of <5mm and ≥5mm (Dmean = 113.8% vs. 112.4% and D90 = 100.2% vs. 98.3%). The <5mm prescription depth plans were more uniform (D0.1cc = 131.8% vs. 151.8%). Bolus thickness <10mm vs. ≥10mm plans also had similar target coverage (Dmean = 118.2% vs. 110.7% and D90 = 100.1% vs. 99.0%). Applicators ≥10mm thick, however, provide more uniform target dosimetry (D0.1cc = 146.9% vs. 139.5%). Conclusion: Prescription depth is based upon the thickness of the lesion and upon the clinical needs of the patient. Applicators ≥10mm thick provide more dose uniformity than 5–10mm thick applicators. Applicator thickness is an important variable that should be considered during treatment planning to achieve optimal dose uniformity.

SU‐E‐T‐383: Can Stereotactic Body Radiotherapy Mimic the Dose Distribution of High‐Dose‐Rate Tandem and Ovoids/ring Brachytherapy?

PURPOSE To investigate whether stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) can mimic the dosimetry of tandem and ovoids/ring brachytherapy. METHODS We selected 5 patients treated with 3D-CT based high-dose rate (HDR) brachytherapy using 4 tandem and ovoid and 1 tandem and ring case. Manual optimization based on the Manchester system followed by graphical optimization (Nucletron Oncentra MasterPlan or Varian BrachyVision) was performed to deliver 6.0 Gy per fraction to a high-risk CTV while maintaining dose to organs at risk (OAR) below the ABS recommendations. For theoretical SBRT plans, CT images and OAR contours from the HDR plans were imported into Eclipse (Varian). The SBRT plan was created to mimic the heterogeneity of HDR plans by using a simultaneous integrated boost technique to match the V100, V150, and V200 isodose volumes from HDR. The OAR Dmax from HDR was used to define the OAR dose constraints for SBRT. Target coverage, dose spill-out, and OAR doses (D0.1cc, D1cc, and D2cc) between the HDR and SBRT plans were compared for significance using a two-tail paired ttest. RESULTS The mean isodose volumes for HDR vs. SBRT were 29.4 cc vs. 29.0 cc (V200, p = 0.674), 49.2 cc vs. 56.3 cc (V150, p = 0.017), 95.4 cc vs. 127.7 cc (V100, p = 0.001), and 271.9 cc vs. 581.6 cc (V50, p = 0.001). The D2cc to OAR for HDR vs. SBRT was 71.6% vs. 96.2% (bladder, p = 0.002), 69.2% vs. 101.7% (rectum, p = 0.0003), and 56.9% vs. 68.6% (sigmoid, p = 0.004). CONCLUSION SBRT with VMAT can provide similar dose target coverage (V200), but dose spill-out and doses to OAR were statistically significantly higher than HDR. This study clearly demonstrated that brachytherapy can not be substituted with SBRT in gynecologic cervical cancer treatment.

SU-E-T-322: A Dosimetric Comparison of PBI Brachytherapy Techniques: SAVI, Contura, and Tube and Button Applicators

PURPOSE To evaluate the dosimetry of partial breast irradiation brachytherapy techniques using the Strut Adjusted Volume Implant (SAVI), Contura, and Tube and Button (T&B) applicators. METHODS A total of 51 breast-cancer patients (23 SAVI, 6 Contura, and 22 T&B) were treated. The target was delineated following NSABP B-39 guidelines. 3D plans were optimized using the Inverse Planning Simulated Annealing algorithm to deliver 3.4 Gy per fraction to the target and minimize dose to organs at risk (OARs). Graphical optimization was then used to fine tune the final dose distribution. The minimum cavity-to-skin distance was measured. Target coverage (V90 and V95) and maximum dose (D0.1cc) to the OARs were evaluated. Dose homogeneity index (DHI = 1-V150/V100) was calculated. RESULTS The average cavity-to-skin distances were 4.1 mm (0.5-9.6 mm, SAVI) and 11.7 mm (7.1-15.4 mm, Contura). The target-to-skin distance for the T&B cases was 8.7 mm (5.0-13.7 mm). The average V90 and V95 to the target were 96.8% and 94.5% (SAVI), 97.0% and 93.0% (Contura), 98.6% and 97.3% (T&B). The mean D0.1cc to the skin, ribs, and lung was 91.5%, 58.8%, 44.5% (SAVI), 93.1%, 51.3%, 40.5% (Contura), 69.1%, 41.5%, and 31.9% (T&B). The average V150 and V200 to the normal breast tissue were 30.4 cc and 14.9 cc (SAVI), 29.5 cc and 7.3 cc (Contura), 18.3 cc and 7.1 cc (T&B). The average DHI for the SAVI, Contura, and T&B cases was 0.55 (0.50-0.60), 0.70 (0.63-0.78), and 0.76 (0.74-0.79). CONCLUSIONS All techniques provided clinically acceptable target coverage and dose to the OARs. The SAVI device provided a lower skin dose at close cavity-to-skin distances while providing excellent target coverage. However, the T&B and Contura applicators produced more homogeneous dose distribution (higher DHI) in the target than the SAVI. The correlations between dosimetric properties and follow-up mammogram results are under investigation.

SU‐D‐213AB‐02: Optimal Design of Multichannel Vaginal Cylinder Applicators for High Dose Rate Brachytherapy

PURPOSE To determine the optimal location of catheters in multichannel vaginal applicators to appropriately cover the vaginal cuff target and minimize dose to the organs at risk (OARs) and hot spots in the target. METHODS A new multichannel vaginal applicator with a diameter of 30 mmconsists of a single central catheter and an outer array of eight catheters. A total of 20 plans were generated from 5 patients by using different outer catheter locations at r = 4, 8, and 12 mm. The target was defined as a 5 mmcircumferential shell extending 4 cm in length around the applicator, excluding the bladder, rectum, and bowel. An inverse planning simulated annealing algorithm and graphical optimization was applied to ensure the prescription dose (7.0 Gy per fraction) covered >97% of the target and minimized dose to the OARs. Target coverage (D90 and V100), hot spots (V150 and V200), and OAR doses (D0.1cc, D1cc, and D2cc) from the various catheter placements were compared to single catheter plans. RESULTS By study design all plans had the same target coverage D90 (105.0- 108.3%) and V100 (97.1-97.2%). The V150 and V200 were 16.1% and 3.4% (r=0mm), 17.3% and 4.2% (r=4mm), 20.1% and 2.2% (r=8mm), and 30.1% and 6.0% (r=12mm). The DO.1cc to the OARs from the various catheter placements at r = 4, 8, and 12 mm was reduced by 4.0%, 8.6%, 11.9% (bladder), 7.4%, 13.2%, and 17.4% (rectum), when compared to the central catheter plans. CONCLUSIONS Multichannel vaginal applicators provide better dosimetry than single channel applicator. The catheter array located closest to the applicator surface most significantly reduces dose tothe OARs at the expense of larger hot spots in the target. The array in the middle of the applicator radius provides significantly decreased dose to the OARs and gave relatively smaller hot spots.

TU‐E‐BRA‐07: Post‐Operative Eye Plaque Imaging Using Tomotherapy MVCT

PURPOSE Intra-operative ultrasound is used to verify the positioning of episcleral eye plaques used to treat ocular melanoma. Ultrasound can be ambiguous because of image artifacts, and plaques may shift position after surgery. Ultrasound verification is particularly challenging for anterior tumors. Post-operative imaging could be used to trigger interventions that would prevent local treatment failure. We investigated if, and under what conditions, the Tomotherapy megavoltage computed tomography (MVCT) system could be used to perform post-implantation verification of eye plaque positioning. METHODS Plaques were placed on a preserved cows eye, and imaged with the megavoltage CT of a Tomotherapy linear accelerator (Accuray, Sunnyvale, CA). The images were visually and quantitatively assessed to determine if they were of sufficient quality to verify tumor coverage and plaque tilt with respect to the sclera. We used the visibility of the lens as a proxy for visibility of a tumor. To test the utility of hypothetical higher beam current Tomotherapy images, we averaged sequential images of the same setup. RESULTS The plaque, the lens of the eye, and the globe are visible in the images. The CNR of the lens with respect to the vitreous was 5.6 for a single image. For 10 images averaged, the CNR was 9.2. Estimated dose from a single image was 1.3 cGy (body CTDIvol); even 10 times this dose would be an acceptable image-guidance dose for radiotherapy patients. One limitation of the imaging procedure is the long scan time (up to 240 seconds), during which time any significant patient motion would lead to image artifacts. Human trials on eye plaque patients are planned. CONCLUSIONS Tomotherapy MVCT imaging could be used to verify tumor coverage and plaque tilt after episcleral plaque implantation. Tumors should be visible in standard Tomotherapy images but higher beam current images would be preferred if available.