ASTRO Criteria Research Articles

Thursday, July 11, 20244:00 PM - 5:30 PM BP01 Presentation Time: 4:00 PM: Accelerated Partial Breast Irradiation Using Sole Interstitial Multicatheter Brachytherapy - GEC-ESTRO Phase 3 Trial: 10-year Results in Context of Current ASTRO and GEC-ESTRO Patient Selection Criteria

Thursday, July 11, 20244:00 PM - 5:30 PM BP01 Presentation Time: 4:00 PM: Accelerated Partial Breast Irradiation Using Sole Interstitial Multicatheter Brachytherapy - GEC-ESTRO Phase 3 Trial: 10-year Results in Context of Current ASTRO and GEC-ESTRO Patient Selection Criteria

MP73-06 OUTCOMES OF SALVAGE CRYOTHERAPY FOR BIOCHEMICAL RECURRENCE FOLLOWING PRIMARY RADIOTHERAPY IN THE MANAGEMENT OF PROSTATE CANCER - 14-YEARS SINGLE INSTITUTION EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023MP73-06 OUTCOMES OF SALVAGE CRYOTHERAPY FOR BIOCHEMICAL RECURRENCE FOLLOWING PRIMARY RADIOTHERAPY IN THE MANAGEMENT OF PROSTATE CANCER - 14-YEARS SINGLE INSTITUTION EXPERIENCE Gregory Mansour, Andrew Wang, and Robert Given Gregory MansourGregory Mansour More articles by this author , Andrew WangAndrew Wang More articles by this author , and Robert GivenRobert Given More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Salvage cryotherapy of the prostate remains a treatment option for biochemical recurrence (BCR) following either radiotherapy or other local ablative therapies of prostate cancer. Previous studies have assessed long-term oncologic results to include overall disease survival in addition to freedom from starting ADT. We aim to assess oncologic outcomes in addition to de novo stricture, fistula, urinary incontinence, and erectile dysfunction rates. METHODS: We retrospectively reviewed all men who underwent salvage cryotherapy following external beam radiation therapy (EBRT), proton beam therapy, primary cryotherapy, and brachytherapy at our institution from 2005 through 2019. Functional and oncologic outcomes were assessed. Biochemical recurrence-free survival was defined based on a combination of the Phoenix and Astro criteria and analyzed using Kaplan-Meier statistics. RESULTS: Of the total 85 patients included, 71 had primary EBRT, 9 had brachytherapy, 3 had combined EBRT and brachytherapy, and 2 had proton beam therapy. All patients had negative staging workups prior to salvage therapy. Recto-urethral fistulas occurred in 2 patients (2.3%), 21 patients (24.4%) developed urethral strictures, and 23 patients (26.7%) reported de novo incontinence requiring pads. 5- year overall biochemical free survival was 49%. A total of 53% of subjects had biochemical recurrence with a mean time of 39 months after salvage treatment. Overall cancer specific survival was 86% and metastasis free survival was 77.9%. There was not a statistically significant correlation identified between pretreatment PSA and timing to BCR R2=0.05 p=0.129. One patient did not have a PSA response after salvage cryotherapy and went on to develop metastatic disease. CONCLUSIONS: Salvage cryotherapy remains one of the few potentially curative interventions following primary radiotherapy for prostate cancer. This study highlights the necessity for patient counseling given the side effect profile. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1036 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gregory Mansour More articles by this author Andrew Wang More articles by this author Robert Given More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract PS15-11: Intraoperative radiation therapy (IORT) for1200 early breast tumors

Abstract Introduction: Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative with a low-risk of local recurrence compared to whole breast radiation therapy following breast conserving surgery for selected low-risk patients. We report the first 1200 tumors treated with this modality at our facility.Methods: 1200 distinct breast cancers in 1169 patients (31 bilateral) were treated with breast conserving surgery and X-ray IORT, using the Xoft Accent System from June 2010 to November 2018. Patients were enrolled in an IORT registry trial and data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. The primary endpoint was local recurrence.Results: To date, there have been 61 events in 54 patients: 50 ipsilateral local recurrences (14 DCIS and 36 invasive), 7 regional nodal recurrences and 4 distant recurrences. Of local recurrences, 9 were within the IORT field, 21 outside of the IORT field but within the same quadrant as the index cancer, and 20 were new cancers in different quadrants. There has been no breast cancer related deaths and 27 non-breast cancer deaths. Currently, with a median follow-up of 52 months, Kaplan Meier analysis projects 5.2 % local recurrence rate at 5 years. In the table below, the five-year probability of local recurrence is analyzed by quadrant and/or type of recurrence (all recurrences or just invasive). Using the 2017, ASTRO Categories, 520 patients (43%) were suitable for IORT, 415 (35%) were cautionary, and 265 (22%) were unsuitable for IORT after final histopathology was evaluated.Conclusion: IORT is profoundly convenient. When used as the only adjuvant breast irradiation, it eliminates approximately 15-35 outpatient visits. This has become increasingly important during the current COVID-19 pandemic. In the group of patients described here, more that 100,000 patient-hours were saved. The local, regional, and distant recurrence rates observed in this trial were slightly higher than those of the prospective randomized TARGIT-A and ELIOT Trials. This may be explained by 22% of our patients being considered unsuitable for IORT by ASTRO Criteria. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer. Citation Format: Melinda Epstein, Melvin Silverstein, Peter Chen, Kevin Lin, Brian Kim, Sadia Khan, Lincoln Snyder, Lisa E. Guerra, Colleen Coleman. Intraoperative radiation therapy (IORT) for1200 early breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-11.

Abstract PS14-24: Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results

Abstract Purpose: To report on the technique of intra-operative electronic brachytherapy, local control, side effects and complications after a single fraction of 2000 cGy at the time of partial mastectomy. Material & Methods: 1200 patients with early stage invasive ductal carcinoma and carcinoma in situ were enrolled in the Multi-Center Trial. 246 (20.5%) patients among these 1200 patients had carcinoma in situ and were treated by a single fraction of 2000 cGy dose by intra-operative irradiation to the lumpectomy cavity using Xoft system of electronic brachytherapy at the time of partial mastectomy. 80% of the patients were Caucasian, 7% African American, 7% Hispanic and 6% others. Estrogen receptor was positive in 211 patients, negative in 28 patients and unknown/not assessed in 7 patients. Progesterone receptor was positive in 190 patients, negative in 45 patients and unknown/not assessed in 11 patients. All patients were BRCA negative. 34 (14%) patients had low grade tumors, 109 (44%) intermediate grade tumors, and 103 (42%) high grade tumors. Seroma occurred in 9.8%, induration in 7.6%, and significant fibrosis in 3.5% of the patients. 2/246 (1%) developed ipsilateral recurrence and one patient developed a gastrointestinal cancer. 118 (48%) patients had characteristics of ASTRO criteria being suitable, 108 (44%) cautionary and 20 (8%) unsuitable. Conclusion: The relatively early 2.3 year results of a single fraction of 2000 cGy by IORT to the lumpectomy cavity at the time of partial mastectomy using Xoft Axxent electronic brachytherapy in the treatment of carcinoma in situ of the breast is safe and associated with low morbidity and local recurrence with good to excellent cosmesis in 80% of the patients. Citation Format: Alam M.Nisar Syed. Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-24.

The actual benefit of intraoperative radiation therapy using 50kV x-rays in early breast cancer: A retrospective study of 676 patients.

This French study reports the 5-year results of partial-breast irradiation using intraoperative radiation therapy (IORT) with 50kV x-rays, in select early breast cancer patients. We report a retrospective analysis of 676 consecutive early breast cancer patients treated between November 2011 and December 2015 by partial-breast irradiation using the INTRABEAM® system. Patients were highly selected based on the ASTRO and GEC-ESTRO criteria and underwent breast-conservative surgery and IORT, completed with additional whole-breast irradiation (WBI) when unexpected unfavorable prognostic factors were found at the final pathology report. Patients' outcomes relative to local and distant control, overall and breast cancer-specific survival, and toxicity are presented, as well as rates of additional WBI. Additional WBI was mandatory in one third of patients (31%), mainly due to lymph node involvement and extensive intraductal component. With a median follow-up time of 54months, the 5-year local recurrence rate was 1.7% [95%CI: 0.9-3.3]; the median time to local recurrence was 23months; ipsilateral breast recurrences mainly occurred in the same quadrant (7/11); in the restricted population, meeting all predefined criteria and treated with IORT alone (406 patients), the local recurrence rate was 1.5% [95%CI: 0.6-3.6]. Five-year distant tumor control was 98.6% [95%CI: 97.2-99.3], and the median time to distant recurrence was 22months. Five-year overall survival was 96.5% [95%CI: 94.2-97.8], and 5-year breast cancer-specific survival was 98.9% [95%CI: 97.6-99.7]. In patients treated with IORT alone, there was no grade 3 toxicity, only four grade 3 (mainly fibrosis) affected patients treated with IORT and WBI. Grade 1-2 toxicity rates were 14% and 34.4% in patients treated with IORT alone and IORT plus WBI, respectively. Partial-breast irradiation using IORT by a 50 kV photon device is safe and well-tolerated in select patients with early breast cancer and is a valuable option in patients reluctant for adjuvant WBI.

PSA Characteristics Post-Heterogeneous SBRT: Results From a Multi-institutional Phase 2 Trial

Following radiotherapy, PSA nadir is correlated with disease-free survival- lower nadir predicting higher long-term biochemical disease-free rates; however, temporary PSA rise (“bounce”) may confound this prediction. We present mature results from a prospective Phase II SBRT trial correlating PSA response kinetics with relapse, with detailed analysis of patients with any post-SBRT PSA rise. 17 institutions treated 259 low- and intermediate-risk patients with SBRT (38Gy/4 fx) with median and maximum post-SBRT follow-up of 5 and 8 years. “Heterogeneous” dosimetry was required: Dmax >150% of prescribed (Rx isodose 50-67%), with strict “HDR-like” urethra, bladder and rectal dose limitation. Androgen deprivation therapy was not used. Patients were considered biochemically relapsed if either Phoenix or ASTRO criteria were met. Median PSA levels measured 5.12 ng/mL pre-SBRT and 0.9, 0.2, 0.1 and 0.055 ng/mL at 1, 3, 5 and 7 years post-SBRT, respectively. Although 93.2% of patients remained disease-free at 5- and 7-years (100% low risk, 88.5% int. risk; nadir + 2), only 35% (90/259) had continuously decreasing PSA values post-SBRT, while 65% (169/259) had at least one rise (median 0.2 ng/mL; range 0.1-4.2 ng/mL). Of patients with any post-SBRT PSA rise, only 15/169 (8.9%) developed confirmed biochemical relapse (CBR), while 154/169 (91.1%) remained disease-free. Among patients with any PSA rise, those with CBR had a higher median PSA nadir (2.2 vs 1.2 ng/mL for non-relapsers, p=0.046), and shorter median time to 1strise (16 vs 23 months for non-relapsers, p=0.03). Median magnitude of first PSA rise was similar: 0.2 ng/mL for both. Among patients with any PSA rise, additional factors associated with relapse are in the Table.Abstract 2560; TableNo. relapse / No. with PSA risep-value (Univariate)Entire Series (n = 259)15/169 (8.9%)Age (<=60 v 61-70 v >70 yrs)1/34 (3%)6/81 (8%)8/54 (15%)0.002 (continuous variable)Risk Gp. (Low v favorable Intermediate v unfavorable Intermediate)0/72 (0%)10/73 (14%)5/24 (21%)0.0013Gleason score (3+3 v 3+4 v 4+3)5/106 (5%)6/49 (12%)4/14 (29%)0.01PSA <4 v 4.01-10 v > 10 ng/mL2/56 (4%)11/104 (11%)2/9 (22%)0.043 (continuous variable)Prostate VolumeNSPSA densityNS Open table in a new tab After heterogeneous SBRT, median PSA decreases through 7 years of follow-up, reaching <0.1 ng/mL after year 6. Nearly 2/3rds of patients experienced at least one post-SBRT PSA rise, with over 90% remaining disease-free thereafter. PSA rise associated with biochemical relapse tended to occur sooner and have a higher pre-bounce nadir level and was also more commonly seen in older patients and those with non-low-risk disease. These results may help physicians to better sort patients whose post-SBRT PSA rise is unlikely to portend relapse versus those who may require more intensive monitoring.

Lack of Consensus Guideline Driven Approach for Utilization of Accelerated Partial Breast Irradiation in the ASTRO “Cautionary” Group: A National Cancer Database Analysis

Development of accelerated partial breast radiotherapy (APBI) consensus guidelines arose in response to an increasing utilization of APBI, despite a lack of phase III data at the time. In 2009, ASTRO published their initial guidelines distinguishing three cohorts: suitable, cautionary, and unsuitable. These definitions differed, however, in comparison to those of other guidelines. Therefore, given the conflicting definition of “cautionary” among these guidelines, our intent was to evaluate utilization trends and factors influencing APBI use in patients defined as cautionary by the 2009 ASTRO guidelines. We retrospectively analyzed breast cancer patients who underwent breast conserving surgery and adjuvant radiation in the National Cancer Database from 2004-2013 and met the initial ASTRO criteria for “cautionary” use of APBI (i.e. Age >50, negative margins, pTis-pT2 (<3cm), pN0i-/N0i+, invasive lobular or ductal, ER+/-, no neoadjuvant chemo). We compared utilization of APBI to whole breast irradiation for this cohort, and completed a logistic regression analysis to identify independent predictors of APBI utilization (Odds ratio [OR]). From 2004-2013, the “cautionary” group included 163,344 women, of which 10.6% received APBI. On multivariate analysis, factors most associated with increased utilization of APBI in the “cautionary” group were living >50 miles from center (OR:2.2), south region (OR:1.7) and urban setting (OR:1.5), all p<0.0001. Factors associated with decreased odds were being at academic center, Her2-Neu positive, use of non-neoadjuvant chemo, and being pN0i+ (all p<0.002). Of note, the ASTRO “cautionary” factors of age 50 - 59, ER status, tumor size, and histology did not impact odds of receiving APBI. From 2004-2013, the 2009 ASTRO “cautionary” factors had little impact on APBI utilization in comparison to other more strongly associated factors, including treatment location (south region and academic center), patient convenience (distance to center) and signs of aggressive malignancies, including pN0i+, Her2Neu status and receipt of non-neoadjuvant chemotherapy. This demonstrates the lack of a guideline driven approach in the utilization of APBI, and necessiates further evaluation of the limitations present in adhering to guidelines.

MP18-16 PROPENSITY SCORE MATCHED COMPARISON OF PARTIAL TO WHOLE GLAND CRYOTHERAPY FOR INTERMEDIATE-RISK PROSTATE CANCER: AN ANALYSIS OF THE COLD REGISTRY DATA

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy1 Apr 2016MP18-16 PROPENSITY SCORE MATCHED COMPARISON OF PARTIAL TO WHOLE GLAND CRYOTHERAPY FOR INTERMEDIATE-RISK PROSTATE CANCER: AN ANALYSIS OF THE COLD REGISTRY DATA Kae Jack Tay, Thomas Polascik, Ahmed Elshafei, Efrat Tsivian, and J. Stephen Jones Kae Jack TayKae Jack Tay More articles by this author , Thomas PolascikThomas Polascik More articles by this author , Ahmed ElshafeiAhmed Elshafei More articles by this author , Efrat TsivianEfrat Tsivian More articles by this author , and J. Stephen JonesJ. Stephen Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2717AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with intermediate-risk prostate cancer constitute a unique group of patients in whom cure may be both necessary and possible. While there has been increasing interest in partial gland therapies to reduce the morbidity of treatment, randomized comparisons to whole gland therapies have been lacking. We aim to compare the oncological and functional outcomes of partial versus whole gland cryotherapy for intermediate-risk prostate cancer. METHODS Men with D'Amico intermediate-risk prostate cancer treated with primary prostate cryotherapy were selected from the Cryo On-Line Data Registry. Men treated with partial prostate ablation (targeted ablation, unilateral/ bilateral nerve-sparing ablations) were matched 1:1 to controls who had undergone whole gland cryotherapy using a propensity score approach. The propensity score was based on age, pre-biopsy serum prostate specific antigen level, biopsy Gleason score, clinical stage, prostate volume, use of neoadjuvant androgen deprivation and year of surgery. The outcomes analysed were biochemical progression free survival (BPFS) using the ASTRO and Phoenix criteria, the 12 month continence rate (defined as being pad-free) and sexual function at 12 months (defined as the ability to have sexual intercourse. RESULTS A total of 1,749 men were identified, of whom 1,488 had undergone whole gland and 288 partial prostate cryotherapy. 200 pairs of men with complete outcome data at a mean follow-up of 30 months were analysed. The 2 and 5 year BPFS rate was 71.6% and 63.5% for whole gland vs. 81.0% and 74.6% for partial prostate ablation using the ASTRO criteria (p=0.0275) and 89.6% and 79.1% for whole gland vs. 79.8% and 68.5% for partial prostate ablation using the Phoenix criteria (p=0.0588). Of 198 pairs of men, the 12- month continence rate was identical at 95%. Of 154 pairs of men, the 12-month rate of successful intercourse was 26.6% for whole gland and 45.5% for partial prostate ablation (p=0.001). The rate of rectal fistula was 0.37% in the partial ablation group. CONCLUSIONS Biochemical progression free survival after partial prostate ablation is not significantly inferior to whole gland cryotherapy in the short to medium term and may result in better sexual function at 12 months. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e199 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kae Jack Tay More articles by this author Thomas Polascik More articles by this author Ahmed Elshafei More articles by this author Efrat Tsivian More articles by this author J. Stephen Jones More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Accelerated partial breast irradiation in the elderly: 5-year results of high-dose rate multi-catheter brachytherapy.

ObjectiveTo evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT).Methods and materialsBetween 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported.ResultsWith a median follow-up of 60.9 months [4.6 – 90.1], median age was 80.7 years [62 – 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 – 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 – 210], median D90 EQD2 was 43.3 Gy [35 – 72.6] and median DHI was 0.54 [0.19 – 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%).ConclusionAPBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks.

Biochemical outcomes for patients with intermediate risk prostate cancer treated with I-125 interstitial brachytherapy monotherapy

Background and purposeRoutine use of I-125 interstitial brachytherapy (BT) alone in intermediate risk (IR) prostate cancer is controversial. It is often combined with external beam radiotherapy (EBRT). The biochemical outcome of a large cohort of only IR disease treated with BT monotherapy is reported. Materials and methodsBetween 2003 and 2007, 615 patients with Memorial Sloan-Kettering Cancer Centre (MSKCC) defined IR disease (one risk factor only-T2b, or Gleason score (GS) 7, or raised initial PSA (iPSA) 10.1–20ng/ml) were treated with BT monotherapy. ASTRO (3 consecutive rises) and Phoenix (nadir plus 2) criteria defined biochemical failure. Potential prognostic factors (pre- and post-implant dosimetric indices, GS 3+4 versus 4+3, androgen deprivation therapy (ADT)) were analysed. ResultsMedian follow-up was 5.0years. Forty-three patients had stage T2b, 180 had raised iPSA, 392 had GS 7 disease. ADT was received by 108 patients. The 5-year biochemical no evidence of disease (bNED) rates are 87.3% (by ASTRO), 88.6% (by Phoenix). Stratification by risk factor (T2b, GS7, raised iPSA) demonstrated raised iPSA to have poorer outcome only by Phoenix criteria (p=0.0002). Other potential prognostic variables were non-significant. ConclusionGood rates of biochemical control can be achieved in the medium term with BT monotherapy in IR disease. Raised iPSA correlated with a poorer outcome.

Effect of germ-line BRCA mutations in biochemical relapse and survival after treatment for localized prostate cancer.

29 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter cause-specific survival (CSS). Germline BRCA mutations are associated with worse PrCa outcomes. In this study, we analyzed biochemical-progression free survival (bPFS) after conventional treatments for localized PCa in a cohort of BRCA patients from the UK. Currently, BRCA1/2 carriers are treated with the same protocols used for non-carriers. Methods: In this retrospective case-control study, each BRCA carrier (10 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by: age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment (RT or RP), androgen-deprivation therapy (ADT) and year of treatment (±5yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 176 patients (pts) were included. Median follow-up was 97 months (ms). Median age at diagnosis was 58.5 yrs (43-75). 80 pts received RT (16 BRCA2, 4 BRCA1, 60 NC) and 85% also received ADT≥6 ms. 96pts underwent RP (18 BRCA2, 6 BRCA1 and 72 NC). Following RT treatment, 5yrs-CSS was 96% in NC and 47% in BRCA carriers (p=2x10-5), whilst no difference was seen after RP (5yrs-CSS was 98.5% in NC vs 93.3% in BRCA). Five-years bFPFS after RT was 74% in NC and 24% in BRCA (p=0.002). No difference was observed in 5yrs-bPFS between BRCA carriers and NC treated with RP (52% vs 66% , p=0.346). The adjusted MVA (including tumour stage, local treatment, ADT and BRCA status) confirmed the independent prognostic value of BRCA status for bPFS and CSS. Among BRCA carriers, the independent risk was greater when the analysis was limited to BRCA2 pts . Conclusions: Our results suggest that BRCA carriers have worse local disease control than NC when conventionally treated with RT. No differences in bPFS were observed in pts treated with RP after &gt;8 yrs median follow-up. These results may have implications for tailoring clinical management in these patients.

Biochemical control of prostate cancer with iodine-125 brachytherapy alone: experience from a single institution

Brachytherapy is an adequate option as monotherapy for localised prostate cancer. The objective of this study was to evaluate and compare biochemical failure free survival (BFFS) after low-dose-rate brachytherapy (LDRB) alone for patients with prostate cancer using ASTRO and Phoenix criteria, and detect prognostic factors. Data on 220 patients treated between 1998 and 2002 with LDRB were retrospectively analysed. Neoadjuvant hormone therapy was used in 74 (33.6%) patients. Median follow-up was 53.5 months (24-116). Five year BFFS was 83.0% and 83.7% using, respectively, the ASTRO and Phoenix criteria. Low -and intermediate- risk patients presented, respectively, 86.7% and 77.8% 5-year BFFS using the ASTRO definition (p=0.069), and 88.5% and 78.6% considering the Phoenix criteria (p=0.016). Bounce was observed in 66 (30%) patients. Multivariate analysis detected PSA at diagnosis <10 ng/ml and less than 50% positive biopsy fragments as favourable prognostic factors, regarding BF using both criteria. For the Phoenix criteria, also Gleason score <7 and low-risk group were identified as independent favourable prognostic factors. LDRB alone should be considered mostly for low-risk patients. PSA level was a strong independent prognostic factor. We support the use of the Phoenix criteria for detection of BF in patients submitted to LDRB alone.

Biochemical outcomes for patients with intermediate-risk, organ-confined prostate cancer treated with I-125 interstitial brachytherapy monotherapy.

192 Background: Treatment with low dose rate brachytherapy (LDR-BT) monotherapy is well established for low risk prostate cancer. The routine use of LDR-BT in intermediate risk (IR) is more controversial and is often combined with additional external beam radiotherapy (EBXRT). We report the biochemical outcome of a large cohort of patients with IR disease treated with LDR-BT monotherapy. Methods: A multi-institutional prospective database identified 615 patients with IR prostate cancer treated with I-125 interstitial BT between 2003–2007. IR was defined using Memorial Sloan-Kettering Cancer Centre (MSKCC) definition of either T2b, or Gleason score (GS) 7 or raised initial PSA (iPSA) 10.1-20ng/ml. Patients receiving additional EBXRT were excluded. Biochemical failure was defined by both ASTRO (3 rises past nadir) and Phoenix criteria (nadir plus 2). Kaplan-Meier methods were used to estimate biochemical no evidence of disease rates (bNED) and univariate analyses used to identify potential prognostic factors. Results: The median age was 64 years (range 49–82). Forty-three patients had stage T2b, 180 had iPSA 10.1-20 and 392 had GS 7 disease. Only 108 received androgen deprivation therapy (ADT) prior to implant. Median follow up was 5.0 years. The 5-year bNED rates (95% confidence interval) by ASTRO are 85.5% (82.0–88.3%) and for Phoenix 83.7% (80.0–86.7%). Use of ADT, GS 3+4 versus 4+3, and dosimetric indices were not significant prognostic variables. When stratified by risk factor (T2b, GS7 or raised iPSA) raised iPSA correlated to poorer outcome only by Phoenix criteria (by Phoenix p=0.001, by ASTRO p=0.311). Conclusions: We have demonstrated good biochemical control for IR patients treated with LDR-BT alone. No additional benefit was seen with the use of ADT. We believe LDR-BT alone is an effective treatment option in selected IR prostate cancer patients with comparable outcome to other treatment modalities such as surgery or EBXRT.

The relationship between radiotherapy efficacy and statin (St) use in prostate cancer (PC): A retrospective study.

e15100 Background: Preclinical antiproliferative, proapoptotic, and radiosensitizing St properties have been previously described. In addition, St use has been associated with a lower risk of PC incidence, low prostate-specific antigen (PSA) at diagnosis and longer freedom from biochemical recurrence (FFBR). The aim of this study was to correlate pre-radiotherapy St use with the risk of biochemical relapse in PC patients (pts) treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: Medical reports of 204 pts diagnosed with PC between 2000 and 2005 were reviewed, with a median follow-up of 54 months. Univariate and multivariate analysis were performed. Variables included were PSA at diagnosis, St treatment, clinical T stage (T1-2a vs T2b-c vs T3-4) and Gleason Score (GS). According to NCCN guidelines, risk category was defined as low (T1-T2a and PSA≤10 and GS ≤ 6), intermediate (T2b or 10<PSA<20 or GS=7) or high risk (≥T2c or PSA≤20 or GS 8-10). ASTRO criteria were used for biochemical progression. Results: Median (M) age was 71 y (range 47-84) and M radiation dose was 74 Gy. Twelve (6%), 41 pts (20%) and 149 pts (74%) were classified as low, medium and high risk respectively. Forty-six pts (23%) were taking St at diagnosis. No statistical differences were found between treatment groups regarding M age, risk category, clinical T stage, GS or M radiation dose. However, pts treated with St had a lower M PSA at diagnosis (7.95 vs 12.95) (p=0,197). At the time of analysis, only 32 pts (15.7%) had biochemical relapse (4 low risk, 6 intermediate, and 21 high risk). St use was not significantly associated with improved FFBR (p=0.641), regardless of risk group. In the multivariate analysis, none of the previous items was associated with FFBR. Conclusions: In our cohort, St use was not associated with a significant improvement in FFBR, in either risk group. Although there could be a bias due to the proportion of pts with high risk features with low rate of biochemical relapses. Our findings warrant further investigation.

Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer

Background and purposeTo evaluate biochemical control and treatment related toxicity of patients with localized adenocarcinoma of the prostate treated with high dose-rate brachytherapy (HDRB) combined with conventional 2D or 3D-conformal external beam irradiation (EBI). Material and methodsFour-hundred and three patients treated between December 2000 and March 2004. HDRB was delivered with three fractions of 5.5–7Gy with a single implant, followed by 45Gy delivered with 2D or 3D conformal EBI. ResultsThe median follow-up was 48.4months. Biochemical failure (BF) occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. Mean time to relapse was 13 and 26months, respectively. The 5-year BF free survival using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively; using Phoenix criteria, 92.4%, 88.0% and 85.3%, respectively. The only predictive factor of BF in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules detected by digital palpation, and patients younger than 60years presented a higher chance of failure using Phoenix criteria only. ConclusionsTreatment scheme is feasible and safe with good efficacy.

9097 Conformal radiotherapy in radical treatment of stage III non-small cell lung cancer (nsclc)

Objective: We evaluated the safety and efficacy of high dose rate (HDR) brachytherapy using Iridium-192 (Ir 192) and 3D conformal external beam radiotherapy in patients with localized prostate cancer.Methods: A total of 444 patients with localized prostate cancer underwent combined radiotherapy with interstitial Ir 192 and 3D conformal external beam radiotherapy between December 1992 and March 2001. The 230 patients, treated between December 1992 and December 1997 were analyzed. All patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Ir 192 was delivered twice with a 1-week interval in HDR remote control technique. The interstitial dose from December 1992 to December 1993 was 10 Gy, after December 1993 the dose was reduced to 9 Gy per treatment session. The interstitial application was followed by external beam radiation of 45 Gy for cT1–cT2 and 50.4 Gy for cT3 tumor (40 Gy from December 1992 to December 1993). Progression was defined as biochemical failure according to ASTRO criteria, e.g. three consecutive PSA rises following the PSA nadir.Results: The median PSA value decreased from 12.8 to 0.93 ng/ml 12 months after treatment. Median PSA value was 0.47 after 24 months, 0.30 ng/ml after 36 months and 0.18 ng/ml after 60 months. 68% of the biopsies were negative 24 months after therapy. Progression-free rate was 100% for cT1 tumors, 75% for cT2 and 60% for stage-cT3 on 5-year follow-up. Five-year overall survival was 93%, 5-year disease-specific survival was 98%. Initial PSA value <10 ng/ml, low stage and low grade were significantly related to 5-year progression-free survival.Conclusions: Combined HDR brachytherapy with Ir 192 is an alternative treatment option especially for patients with cT3 prostate cancer. Initial PSA value, stage and grade, are important prognostic factors.

Biochemical failure after radiation therapy for prostate cancer: Racial differences

e16071 Background: Many guidelines for prostate cancer treatment are based on clinical trials with predominantly white patient (pt) populations. The generalizability of these results assumes similar tumor biology among all races. We set out to examine biochemical failure (PSA failure) rates in a cohort of pts after definitive external beam radiation (EBRT) in the racially diverse population at our institution. Methods: We conducted an IRB-approved retrospective review of pts treated with definitive EBRT from January 2000 to April 2008. We excluded from analysis pts who received brachytherapy, salvage, adjuvant or palliative radiation. Race, country of origin, diagnostic data, pre- and post-treatment PSA, Gleason score (GS), clinical stage (CS), and treatment history were reviewed. CS was based on the original clinician's assessment at time of diagnosis. PSA failures were defined using 1996 ASTRO criteria. Two cohorts were grouped by race: white and nonwhite. Statistical analysis was performed using Fisher's Exact test. Results: One hundred seventy-four pts were treated with definitive EBRT. Forty-four pts were white and 130 were nonwhite. Both cohorts demonstrated similar distributions in GS and CS (see Table ). The white cohort had a high proportion of pts with a pretreatment PSA &lt;10 ng/ml (66%) as compared to the nonwhite cohort (46%). Distribution of race/region of origin is: White 44 (25%), Black-American 78 (45%), Black-Caribbean 28 (16%), Black-African 2 (1%), Hispanic 21 (12%), Asian 1 (1%). Just under 50% of each group received neoadjuvant androgen deprivation therapy. PSA failure rate was 7% for the white cohort and 13% for nonwhite (p = 0.41). Conclusions: In this retrospective analysis, there was no statistical difference among races with regard to PSA failure rates. The PSA and Gleason trends in each cohort were consistent with published data on this topic. Dedicated evaluation of the prognostic value of traditional risk stratification in nonwhite pt populations in a prospective trial is warranted. [Table: see text] No significant financial relationships to disclose.

Oncologic control provided by HIFU therapy as single treatment in men with clinically localized prostate cancer

To assess the long term oncologic results of high-intensity focused ultrasound therapy (HIFU) as a primary and single treatment for clinically localized prostate cancer. A total of 119 patients with clinically localized prostate cancer underwent HIFU (Ablatherm((R)), EDAP, France) as first-line treatment and were retrospectively reviewed. They were stratified according to risk groups proposed by D'Amico. No patient had undergone previous hormonal therapy. PSA level was monitored at 3, 6, 12, 18, 24 months and then yearly. According to the latest ASTRO criteria, failure was defined by a PSA rise of 2 ng/ml or more above the PSA nadir. The biochemical-free survival rate (BFSR) was calculated. Mean patient age was 68 +/- 7.8 years (46-83). Mean follow-up was 3.9 years (1-6.8). Overall 52 patients (43.7%) experienced a biochemical recurrence which included 26, 23 and 3 patients in the low, intermediate and high-risk groups, respectively. In univariate and multivariate analyses, there was a statistical association between preoperative PSA value > 10, a nadir PSA value > 1 and the risk of biochemical recurrence (P < 0.05). The 5-year BFSR rate was 30% with no statistical difference between low- and intermediate-risk patients. None of the 119 patients died of prostate cancer. High-intensity focused ultrasound therapy provides efficient oncologic control only in patients with low-risk prostate cancer. However, our data could be used to improve the selection of patients who are potential candidates for HIFU therapy.

PSA Nadir Is a Significant Predictor of Treatment Failure after High-Intensity Focussed Ultrasound (HIFU) Treatment of Localised Prostate Cancer

ObjectivesTo assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. MethodsOne hundred three patients after HIFU treatment (Ablatherm®, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA ≥2ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, ≤0.2ng/ml; group 2, 0.21–1ng/ml; group 3, >1ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. ResultsThe median follow–up was 4.9 (3–8.6) yr. Mean time to PSA nadir was 6.4±5.1 mo. A PSA nadir of ≤0.2ng/ml, 0.21–1ng/ml, and >1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). ConclusionsThe PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of ≤0.2ng/ml is reached.

Immunological and clinical effects of a multiple peptide vaccine and low-dose cyclophosphamide in prostate carcinoma patients

13502 Background: Despite effective therapeutic strategies for the treatment of prostate cancer (PC), patients still recur and progress in a significant percentage. Here we describe the preliminary clinical and immunological data of a peptide-based strategy of vaccination in biochemical relapsed PC patients. Methods: We planned to enroll 30 HLA-A*0201 patients with biochemical failure after surgery, radiation or androgen deprivation therapy (ADT), according to the ASTRO criteria. On entering the study, patients discontinue ADT. No selections were made based on PSA levels at diagnosis, Gleason pattern score or other pathological features. Vaccination includes three peptides derived from proteins highly expressed in PC, PSMA (PSMA-P14–12 and PSMA-P2711–719) and Survivin (SVV96- 104/97M). Peptides, emulsified in Montanide ISA 51, are administered subcutaneously (8 injections) at two-weeks intervals. Vaccine is preceded by systemic administration of low dose cyclophosphamide (300 mg/m2/four weeks), aimed at selectively down- modulating regulatory T cells (Treg). Immunological monitoring includes evaluation of peptide and tumor-specific CD8+T cells in peripheral blood (IFN?-Elispot and HLA/multimer staining) and analysis of the frequency and suppressive activity of CD4+CD25+Foxp3+Treg. Results: So far, ten patients have been enrolled. Treatment is well tolerated, with mild cutaneous toxicity due to Montanide injection. A significant increase in the frequency of antigen-specific CD8+ T cells was observed in 8/10 patients. Treg, only marginally expanded in these patients, do not seem to decrease by cyclophosphamide treatment, although studies on the potential modulation of their suppressive activity are in progress. After a follow-up of 6–12 months, PSA stabilization was observed in 7 patients, 2 of which entered the trial after maximal androgen blockade discontinuation. Interestingly, PSA stabilization appears to directly correlate with the induction of antigen-specific T cell responses. Conclusions: Our vaccination strategy proved to be safe, non toxic and well tolerated. Initial monitoring data show an expansion of antigen specific T cells, with an apparent correlation between immunological and biochemical responses. No significant financial relationships to disclose.