D.J. Demanes

Clinical Outcomes for Patients with Gleason Score 9–10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis

BACKGROUND The long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons. OBJECTIVE To compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP. DESIGN, SETTING, PARTICIPANTS Retrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS The median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p<0.0001). Five-yr and 10-yr distant metastasis-free survival rates were significantly higher with EBRT+BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p=0.0005) or RP (79.1% and 61.5%, p<0.0001). The 5-yr and 10-yr CSS and OS rates were similar across all three cohorts. CONCLUSIONS Radiotherapy and RP provide equivalent CSS and OS. Extremely dose-escalated radiotherapy with ADT in particular offers improved systemic control when compared with either EBRT or RP. These data suggest that extremely dose-escalated radiotherapy with ADT might be the optimal upfront treatment for patients with biopsy GS 9-10 CaP. PATIENT SUMMARY While some prostate cancers are slow-growing requiring many years, sometimes decades, of follow-up in order to compare between radiation and surgery, high-risk and very aggressive cancers follow a much shorter time course allowing such comparisons to be made and updated as treatments, especially radiation, rapidly evolve. We showed that radiation-based treatments and surgery, with contemporary standards, offer equivalent survival for patients with very aggressive cancers (defined as Gleason score 9-10). Extremely-dose escalated radiotherapy with short-course androgen deprivation therapy offered the least risk of developing metastases, and equivalent long term survival.

A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy.

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. Materials and Methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel &khgr;2 metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ⩽3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

Predictors of distant metastasis after combined HDR brachytherapy and external beam radiation for prostate cancer

Purpose To determine predictors of distant metastases (DM) in prostate cancer patients treated with high dose rate brachytherapy boost (HDR-B) and external beam radiation therapy (EBRT). Material and methods From 1991 to 2002, 768 men with localized prostate cancer were treated with HDR-B and EBRT. The mean EBRT dose was 37.5 Gy (range: 30.6-45 Gy), and the HDR-B was 22 or 24 Gy delivered in 4 fractions. Univariate and multivariate analyses using a Cox proportional hazards model including age at diagnosis, T stage, Gleason score (GS), pretreatment PSA, biologically equivalent dose (BED), and use of androgen deprivation therapy (ADT) was used to determine predictors of developing distant metastases. Results The median follow-up time for the entire patient population was 4.2 years (range: 1-11.2 years). Distant metastases were identified in 22/768 (3%) of patients at a median of 4.1 years. PSA failure according to the Phoenix definition developed in 3%, 5%, and 14% of men with low, intermediate, and high risk disease with a median time to failure of 3.8 years. Prostate cancer specific mortality was observed in 2% of cases. T stage, GS, and use of ADT were significantly associated with developing DM on univariate analysis. GS, and use of ADT were the only factors significantly associated with developing DM on multivariate analysis (p < 0.01). Patients who received ADT had significantly higher risk features suggesting patient selection bias for higher DM in this group of patients rather than a negative interaction between HDR-B and EBRT. Conclusions In men treated with HDR-B and EBRT, GS is a significant factor on multivariate analysis for developing distant metastasis.

Comparison of patient‐reported acute urinary and sexual toxicity scores in a 6‐ versus 2‐fraction course of high‐dose‐rate prostate brachytherapy monotherapy

To identify differences in acute urinary and sexual toxicity between a 6‐fraction and 2‐fraction high‐dose‐rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short‐term toxicity.

SU‐E‐T‐380: Evaluation of Interfraction Motion of the Strut‐Adjusted Volume Implant (SAVI) Using 3D Reconstruction from CT Scout Images

Purpose: The Strut‐Adjusted Volume Implant (SAVI) is a partial breast irradiation applicator. We developed a method to reconstruct the 3D device location using scout images to provide applicator position and proper expansion verification. We also used this technique to evaluate interfraction motion. Methods: The SAVI device was implanted in a lumpectomy cavity. The patient was aligned by CT lasers and skin tattoos to ensure reproducible setup. A post‐operative CT scan was performed for treatment planning. The patient was treated in 10 fractions over the course of 5 days. Daily CT scans and anterior and lateral scout scans were acquired prior to each fraction. Radio‐opaque markers located on three of the struts were localized using a peak detection filter. The location of each marker on the 2D scout image was backprojected towards the CT x‐ray source. Each 3D marker position was reconstructed at the backprojection intersection. The 3D marker position was compared to the location in the 3D CTimage. The interfractional displacement of the device was assessed from the reconstructed marker locations. Results: The average distance (standard deviation) between the marker positions reconstructed using the scout images and the CTimages was 0.76 (0.28) mm. Using the scout image data, the average interfractional device movement (standard deviation) in the SI, AP, and LR directions, and 3D was 0.51 (0.46) mm, 0.95 (0.81) mm, 0.73 (0.61) mm, and 1.56 (0.68) mm. Conclusion: SAVI interfraction motion can be accurately measured using scout images. The patient setup for partial breast brachytherapy can be improved by correcting the applicator displacement. This proposed technique eliminates the need for CT verifications, and therefore additional dose to the patient, while still accurately identifying applicator displacement.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

Objectives: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. Materials and Methods: From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. Results: The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Conclusions: Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.

SU‐E‐T‐343: Dosimetric Analysis of Catheter Displacement in High Dose Rate Prostate Brachytherapy

PURPOSE To evaluate the dosimetric effect of catheter displacement on target coverage and doses to organs at risks (OARs) in high dose rate prostate brachytherapy. METHODS CT simulations from 21 prostate cancer patients treated with HDR monotherapy (7.25 Gy × 6 fractions) were used. The prostate CTV and OARs were contoured on the 3D-CT. Treatment plans were optimized using an inverse planning simulated annealing algorithm and graphical optimization to ensure dosimetry objectives: target coverage (CTV D90=100-115%, V100 >97%, and V150 <35%) and OAR dose constraints (D0.1cc <85% (rectum), 80&-95% (bladder), and <110% (urethra)). Craniocaudal catheter movements from 1 to 10 mm in 1 mm increments were simulated by simultaneously shifting all active dwell positions in the initial treatment plan using catheter offset in the Oncentra MasterPlan (Nucletron). Target coverage (D90 and V100) and OAR doses (D0.1cc and D1cc) were evaluated and compared to no displacement plans. RESULTS The mean prostate CTV volume was 74.7±22.8 cc (range: 24.8-113.7 cc). Initial treatment plans provided target D90 = 107.7±2.0% (103.0-111.2%) and V100 = 98.5±0.8% (97.1-99.5%). The D0.1cc to OARs was 77.3±2.3% (rectum), 84.2±2.0% (bladder), and 106.8±1.6% (urethra). The mean target coverage was not significantly different for 1-2 mm shifts. Shifts between 3 and 6 mm still met most dosimetry objectives, but provided progressively less good target coverage and doses to OARs. Displacements of greater than or equal to 7 mm resulted in dosimetry that did not meet our dosimetry objectives. CONCLUSION Small changes in catheter position Result in significant alterations in dosimetry and treatment delivery. The target coverage (D90 and V100) and bladder dose are reduced and the rectal and urethra doses are higher in direct proportion to the degree of displacement. It is essential to check and correct interstitial catheter positions before each HDR fraction to accurately deliver the planned radiation dose.