Patients Received Salvage Radiation Therapy Research Articles

Outcomes of Bridging and Salvage Radiotherapy in Relapsed or Refractory Mantle Cell Lymphoma Patients Undergoing CD19-Targeted CAR T-Cell Therapy.

We sought to describe our early experience of using bridging and salvage radiation therapy (RT) in patients with relapsed/refractory mantle cell lymphoma (MCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. A retrospective study was conducted for consecutive MCL patients who were treated with commercially available CD19-targeted CAR T-cell therapy between 2020 and 2022 at a single institution. Patients who received RT pre-and post-CAR T-cell therapy were identified and analyzed using descriptive and statistical analysis. Overall survival (OS) from the date of CAR T infusion was estimated with the Kaplan-Meier method. The duration of local control (LC) was defined as the time between the start date of RT and the date of in-field progression/relapse. Response to RT was analyzed based on the total number of irradiated sites. A total of 21 patients with MCL who received CD19-targeted CAR T-cell therapy were identified (17 brexu cel, 3 tisa-cel, and 1 liso-cel) with a median follow-up of 15.3 months (24 days-36.2 months). The median age was 65 years at time of apheresis (43-83 years). The median OS for the entire cohort following CAR T-cell therapy was 17 months (95% CI: 14.2 months-not reached). Of the 21 patients, 1 patient received bridging RT prior to CAR T infusion, 1 patient received RT pre-and post-CAR T, and 5 patients received salvage RT post-CAR T with a total of 23 irradiated sites. Sites of RT include: extremities (10), central nervous system (3), pelvis/groin (3), head and neck (3), chest (2), abdomen (1), and multiple sites (1). The median dose/fractionation were 16.5 Gy (range, 3.6-45 Gy) and 5.5 fractions (range, 2-16 fractions)- radiation data was incomplete only for 1 patient who received RT at an outside institution. The in-field responses of the 21 evaluable sites were as follows: complete response (CR) (n = 18, 86%) and partial response (PR) (n = 3, 14%), translating into an LC rate of 100%; the remaining 2 sites were not evaluable since the patient died shortly after receiving RT due to progressive lymphoma. Notably, there was no correlation between RT dose and LC; 9 sites received low-dose RT (3.6-6 Gy) with responses as follows: CR (n = 6, 67%) and PR (n = 3, 33%). Only 1 patient experienced grade 3-4 RT-related toxicities. At the time of the last follow-up, 4 patients remained alive, and 3 patients succumbed to progressive lymphoma. As no studies exclusively focusing on CAR T-cell therapy and bridging or salvage RT have been published among relapsed/refractory MCL patients, our early experience underlines that using RT as a bridging and salvage approach is associated with excellent in-field control and limited toxicity in the peri-CAR T setting. Low-dose RT for MCL appears to be very effective in this highly refractory population and warrants further investigation.

Radiation therapy as a bridging and salvage strategy in patients with relapsed or refractory multiple myeloma undergoing BCMA-targeted CAR T-cell therapy

Radiation therapy (RT) may play an important role prior to and following BCMA-targeted CAR T-cell therapy in multiple myeloma (MM). We report a series of 13 patients: 5 patients received bridging RT pre-CAR T, 4 patients received salvage RT post-CAR T failure, and 4 patients received both. There was no worsening of CAR-T- or RT-related toxicities. The RT in-field local control rate was 100%, with a median follow-up after each RT course of 7.3 months. RT as a bridging and salvage strategy is safe, feasible, and offers excellent local control in MM patients treated with CAR T-cell therapy.

RADIATION THERAPY AS A BRIDGING AND SALVAGE STRATEGY IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA UNDERGOING BCMA‐TARGETED CAR T‐CELL THERAPY

Introduction: Radiation therapy (RT) may be a useful bridging and/or salvage approach prior to and following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory multiple myeloma (MM). Thus, we sought to report our early experience evaluating the potential role of RT in bridging and salvage settings in MM patients undergoing CAR T-cell therapy. Methods: A multi-institutional retrospective study was conducted for consecutive MM patients who received CAR T-cell therapy between 2018 and 2022. Patients who were administered bridging RT pre-CAR T and salvage RT post-CAR T failure were identified and analyzed using descriptive and statistical analysis. Results: We retrospectively reviewed 13 patients who have been treated with RT pre- and/or post-CAR T-cell therapy infusion at two tertiary care centers [5 patients received bridging RT pre-CAR T, 4 patients received salvage RT post-CAR T failure, and 4 patients received both bridging and salvage RT]. A total of 17 sites were treated with bridging-RT with a median dose of 20 Gy (range, 4–24 Gy) and a median of 5 fractions (range, 1–12 fractions). Twelve sites were treated with salvage RT with a median dose/fractionation of 20 Gy (range, 4–30 Gy) and 5 fractions (range, 1–12 fractions). No worsening in CAR T-related toxicities occurred among the patients who were treated with bridging RT, and no significant RT-related toxicities were observed post-bridging or salvage RT. For the entire cohort, the median overall survival was 16.2 months (95% CI: 8.6 months-not reached), and the median progression-free survival was 4.1 months (95% CI: 1.07 months-not reached). The local control rate for patients receiving bridging RT and/or salvage RT was 100%, with a median follow-up after each RT course of 7.3 months. Conclusion: Our findings suggest that using RT as a bridging and salvage strategy is safe and feasible, and offers excellent local control among relapsed/refractory MM patients treated with CAR T-cell therapy infusion. Future larger studies with translational correlatives are required to assess the optimal role of RT in these settings. Keywords: Cellular therapies, Multiple Myeloma No conflicts of interests pertinent to the abstract.

Reappraisal of multimodality imaging for improved Radiation Therapy (RT) target volume determination of recurrent Oral Squamous Cell Carcinoma (OSCC): An original article

Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most frequent cancer sites around the globe. Within the heterogeneous group of HNSCC, Oral Squamous Cell Carcinoma (OSCC) deserves the utmost attention as an important subsite. Despite multimodality management, recurrence of OSCC is not uncommon. RT may play an integral role as part of initial management or as adjunctive therapy, or for treatment of recurrent disease. In this study, we evaluate multimodality imaging-based RT treatment volume definition for irradiation of recurrent OSCC. Materials and methods: Multimodality imaging-based RT treatment volume definition for radiotherapeutic management of recurrent OSCC was assessed. RT target volume determination by incorporation of Magnetic Resonance Imaging (MRI) or by Computed Tomography (CT)-simulation images only has been evaluated and comparative analysis has been performed for patients receiving salvage RT for recurrent OSCC. Results: Ground truth target volume has been found to be identical with treatment volume definition by CT-MR fusion-based imaging. Conclusion: Incorporation of MRI in target and treatment volume definition may improve target and treatment volume definition for recurrent OSCC.

Defining the Most Informative Intermediate Clinical Endpoints for Patients Treated with Salvage Radiotherapy for Prostate-specific Antigen Rise After Radical Prostatectomy

Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell’s c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0–8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44–11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. Patient summaryClinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials.

Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial

Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death. The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC. Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65). Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.

Impact of timing of radiation therapy on outcomes in atypical meningioma: A clinical audit

BackgroundThe role of early adjuvant radiation therapy (RT) in patients with atypical meningioma remains controversial. The goal of this work was to report the impact of timing of RT on outcomes in atypical meningioma. Methods and materialsPatients of atypical meningioma were identified through electronic search of institutional database. Following surgery, RT was delivered either in upfront adjuvant setting (early adjuvant RT) or after recurrence/progression (salvage RT). ResultsThere were 51 patients in the early adjuvant RT group and 30 patients in the salvage RT group. Six of 51 (12%) patients in the early adjuvant RT group recurred/progressed compared with 34 of 35 (97%) patients kept on observation after initial surgery. Thirty of these 34 patients received salvage RT, mostly after reexcision. Twelve of 30 (40%) patients recurred/progressed after salvage RT, compared with 6 of 51 (12%) patients after early adjuvant RT (P = .003). Post-RT 5-year progression-free survival was significantly better for early adjuvant RT compared to salvage RT (69% vs 28%, log-rank P < .001). ConclusionsWithin the limitations of any retrospective analysis, upfront early adjuvant RT can significantly reduce the risk of local recurrence/progression in atypical meningiomas compared with initial observation. A sizeable proportion of patients who are observed initially recur/progress over time necessitating salvage therapy; however, reexcision followed by salvage RT may not be as effective as early adjuvant RT.

Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain.

To define usual clinical management of prostate cancer (PCa) patients following postoperative radiation therapy (RT) (adjuvant or salvage) and its evolution over time in radiation oncology (RO) departments in Spain. An epidemiological, cross-sectional, multicentre study was conducted. 567 PCa patients that had undergone radical prostatectomy (RP) and received postoperative RT between February and December of both 2006 and 2011 participated in the study. In patients from 2006, health-related quality of life (HRQoL) was assessed using the EPIC questionnaire. Investigators completed a specific survey on two clinical cases of adjuvant and salvage RT. 70.6% of patients received salvage RT versus 29.4% who received adjuvant RT; no significant differences were found in terms of frequency for each procedure between both the years. Regarding the survey, a positive surgical margin was the main criteria used in adjuvant RT decision making. In terms of salvage RT scenario, 85.7% of the investigators stated that adjuvant RT should have been offered instead, 81.4% of the investigators agreed on a PSA score >0.2ng/mL as the main criteria for identifying biochemical recurrence after RP, and 67.4% of investigators did not consider any PSA score for ruling out salvage RT treatment. Most patients are referred to RO departments to receive salvage RT. Despite the publication of three IA evidence level randomized clinical trials, the patterns for using adjuvant and salvage RT did not change from 2006 to 2011, although patients' profile did. A consensus regarding postoperative RT indications should be reached in order to correct this controversial situation.

Salvage Radiation Therapy Improves Metastasis-free Survival for Clinically Aggressive and Indolent Prostate Cancer Recurrences After Radical Prostatectomy

To describe 5- and 10-year rates of metastasis-free survival (MFS) stratified by Gleason score (GS) and prostate-specific antigen doubling time (PSADT) for patients receiving salvage radiation therapy (SRT) after biochemical recurrence (BR) postradical prostatectomy (RP). A total of 236 patients who underwent SRT without receiving concomitant androgen deprivation therapy at a single institution after BR post-RP were retrospectively reviewed. The Kaplan-Meier methods and log-rank analysis were used to determine the MFS rates. Median follow-up post-SRT was 7.1 years. As of last follow-up, 59 men (25%) had developed metastasis. On univariate analysis, both GS and PSADT predicted MFS (P<0.001). Five- and 10-year rates of MFS were calculated for patients with GS 2 to 6, 7, and 8 to 10 and for patients with PSADT < 3, 3 to 9, 9 to 15, and >15 months, who received no additional salvage therapy until the development of metastases. The 5- and 10-year MFS for GS 8 to 10 were 62% and 50%, respectively, compared with 94% at both 5 and 10 years for GS 2 to 6. The 5- and 10-year MFS for PSADT < 3 months were 70% and 61%, respectively, compared with 100% and 90% at 5 and 10 years, respectively, for PSADT >15 months. After BR post-RP, SRT results in low 5- and 10-year rates of metastasis after initial BR. Importantly, a substantial proportion of patients with high-risk disease (GS 8 to 10 or PSADT < 3 mo) are free from metastasis at these same time points. Therefore, SRT should not be withheld from patients based solely on the presence of adverse disease risk factors.

MP62-14 LONG-TERM RESULTS OF POST-PROSTATECTOMY RADIOTHERAPY: A LARGE INSTITUTIONAL EXPERIENCE

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 2015MP62-14 LONG-TERM RESULTS OF POST-PROSTATECTOMY RADIOTHERAPY: A LARGE INSTITUTIONAL EXPERIENCE Rebecca Clayman, Adam Feldman, Sigolene Galland, Douglas Dahl, Francis McGovern, Aria Olumi, Alec Eidelman, Andrzej Niemierko, William Shipley, Anthony Zietman, and Jason Efstathiou Rebecca ClaymanRebecca Clayman More articles by this author , Adam FeldmanAdam Feldman More articles by this author , Sigolene GallandSigolene Galland More articles by this author , Douglas DahlDouglas Dahl More articles by this author , Francis McGovernFrancis McGovern More articles by this author , Aria OlumiAria Olumi More articles by this author , Alec EidelmanAlec Eidelman More articles by this author , Andrzej NiemierkoAndrzej Niemierko More articles by this author , William ShipleyWilliam Shipley More articles by this author , Anthony ZietmanAnthony Zietman More articles by this author , and Jason EfstathiouJason Efstathiou More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2388AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Randomized trials and consensus statements support the consideration of adjuvant radiation therapy (RT) following prostatectomy for adverse pathologic features (pT3 or positive margins) although its use remains low. Whether early salvage RT is as effective as immediate adjuvant therapy remains unknown. METHODS A retrospective single institutional analysis of 728 post-prostatectomy patients receiving RT between 1993 and 2012 was performed. Early salvage RT was defined as radiation received for a biochemical recurrence with postoperative PSA ≤0.5ng/ml. A Cox regression multivariable analysis (MVA) was used to identify clinical and treatment-related risk factors associated with biochemical recurrence-free survival, freedom from salvage androgen deprivation therapy (ADT), distant metastasis (DM), and overall survival (OS). RESULTS 187 patients were treated with adjuvant RT for adverse pathologic features, while 541 patients received salvage RT (184 of whom received early salvage and had initial pT3 disease and/or positive margins). Median follow-up from surgery was 7.0 and 8.9 years in the adjuvant and salvage cohorts, respectively. Median time from surgery to adjuvant RT was 4.5 months, and median time to first detectable PSA in the salvage cohort was 1.98 years (Range 0.014–15.4 years). In MVA, higher Gleason score, pT-stage, seminal vesicle involvement, and shorter interval between surgery and first detectable PSA were associated with increased risk of biochemical failure, DM, and subsequent need for ADT. Younger age (P<0.0001), lower pre-op PSA (p=0.005), and longer interval between surgery and first detectable PSA (P=0.007) were associated with increased OS. When compared to early salvage, adjuvant RT was associated with significantly improved 10-year freedom from biochemical failure (73.9% vs 59.5%, HR 0.60 (95%CI: 0.4-0.9), P=0.01); however there were no statistically significant differences in terms of 10-yr freedom from ADT (91.2% vs 83.2%, HR 0.67 (95%CI: 0.36-1.2), P=0.2), DM (95.8% vs 91.8%, HR 0.86 (95%CI: 0.3-2.2), P=0.8), and OS (97.8% vs 95.2%, HR 1.7 (95%CI: 0.6-4.6), P=0.3). CONCLUSIONS Postoperative RT confers excellent long-term disease control, a finding validated by the long follow-up in this series. Adjuvant RT is associated with reduced risk of PSA recurrence though not DM, OS, or need for subsequent ADT when compared to early salvage. Rational optimal timing of postoperative RT awaits report of the results of large ongoing randomized trials. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e786 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rebecca Clayman More articles by this author Adam Feldman More articles by this author Sigolene Galland More articles by this author Douglas Dahl More articles by this author Francis McGovern More articles by this author Aria Olumi More articles by this author Alec Eidelman More articles by this author Andrzej Niemierko More articles by this author William Shipley More articles by this author Anthony Zietman More articles by this author Jason Efstathiou More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Outcomes after radiation therapy for brain metastases from gastrointestinal primaries.

647 Background: There is limited data regarding outcomes of patients with colorectal cancer (CRC) and other gastrointestinal (GI) cancers metastatic to the brain. The aim of this study is assess intracranial disease control in GI patients treated with radiation therapy (RT) and the likelihood of receiving systemic therapy following the diagnosis of metastatic disease to the brain. Methods: From 1/2007 to 6/2013, 24 consecutive patients with adenocarcinoma of a GI primary were treated with RT for brain metastases. Patients were excluded if they had prior RT to the brain. The majority of patients had CRC (n = 15). Ten patients had resection of at least one brain tumor prior to radiation therapy. Patients were treated with the following RT modalities: stereotactic radiosurgery alone (n = 12), whole brain RT (n = 7), both (n = 1), and partial brain RT (n = 1). Survival and control rates were analyzed by the Kaplan-Meier method. Results: Twenty-one patients had died at the time of analysis and the median overall survival was 5.4 months (range, 0.5 – 58 months). Radiographic follow up was available in 20 patients and 60% (12/20) had intracranial disease progression. The 6- and 12-month control rates for the treated tumors were 60% and 30%, respectively. Seven patients received salvage radiation therapy following intracranial disease progression. Fifty-eight percent (14/24) did not receive further systemic therapy. On univariate analysis, only prior surgical resection predicted for improved survival (3.8 vs. 7.8 months, p = 0.018), while number of lesions, performance status, primary site, chemotherapy after RT, and RT modality were not significant. Conclusions: Survival and intracranial disease control following RT for brain metastasis from GI cancers are poor and many patients do not receive further systemic therapy. In this small series, outcomes are worse than published series for other disease sites metastatic to the brain and further research is warranted.

A prostate-specific antigen doubling time of &lt;6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy

BackgroundThe ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. We sought to assess what PSADT threshold is most clinically prognostic in this setting.Methods575 patients who received SRT at a single institution for biochemical recurrence after radical prostatectomy were retrospectively reviewed. We assessed the impact of pre-SRT PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Kaplan-Meier methods, hazard ratio (HR) assessment, and Cox Proportional Hazard models were used to assess the discriminatory ability of various PSADT thresholds.ResultsSufficient data to calculate PSADTs were available for 277 patients. PSADT was prognostic for BF, DM, PCSM, and OM on univariate analysis regardless of threshold. HR assessment identified 6 months as a strong threshold. No statistically significant difference was observed in BF, DM, PCSM, or OM between patients with PSADT <3 (n=40) and 3–6 months (n=61) or between 6–10 (n=62) and >10 months (n=114). However significant differences were seen in BF (HR:2.2, [95%CI: 1.4-3.5], p<0.01) and DM (HR:2.2, [95%CI: 1.2-4.3], p=0.02) between a PSADT of 3–6 and 6–10 months. On multivariate analysis a PSADT <6 months predicted BF (HR:2.0, [95%CI: 1.4-2.9], p=0.0001), DM (HR:2.0, [95%CI: 1.2-3.4], p=0.01), and PCSM (HR:2.6, [95%CI: 1.1-5.9], p=0.02).ConclusionsA pre-SRT PSADT <6 months was a strong predictor of outcomes in our data set, including PCSM. The most common nomogram for SRT uses a 10-month PSADT threshold for assigning points used to assess BF following SRT. If validated, our findings suggest that a PSADT threshold of <6 months should be considered for stratification of patients in future clinical trials in this setting.

Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer–specific death in patients receiving salvage radiation therapy following radical prostatectomy

The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level. A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models. On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP.

Gleason pattern 5 as a pathologic predictor of recurrence, development of metastasis, and prostate cancer-specific death for patients receiving salvage radiation therapy following radical prostatectomy.

151 Background: The presence of primary, secondary, and tertiary Gleason pattern 5 (GP5) in prostate cancer has been shown to predict outcomes and improve risk stratification following radical prostatectomy (RP) and external beam radiation therapy (EBRT). However, the predictive value of GP5 has not been assessed in salvage EBRT (SRT) for a rising PSA after RP. We sought to assess the prognostic capability of the presence of GP5 in this setting. Methods: 575 patients who received SRT at a single institution for biochemical recurrence after RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of GP5 on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. On pathologic evaluation, 563 patients had a documented Gleason score (GS). 60 patients (10.7%) had primary, secondary, or tertiary GP5. GP5 was the strongest pathologic predictor of DM (p&lt;0.01 HR: 1.9 [95%CI: 1.3-2.9]) and PCSM (p&lt;0.01 HR: 4.0 [95%CI: 2.1-7.7]) on univariate analysis. The presence of GP5 was a better predictor of BF, DM, PCSM, and OS than stratification by GS8-10. Patients with GP5 had clinically worse outcomes than GS8 patients without GP5. There was no difference in outcome between primary, secondary, and tertiary GP5. On multivariate analysis, GP5 was the strongest pathologic predictor of BF (p&lt;0.01 HR: 2.7 [95%CI: 1.6-4.5]), DM (p&lt;0.01 HR: 11.2 [95%CI: 3.9-32.2]), and PCSM (p&lt;0.01 HR: 6.0 [95%CI: 1.8-19.6]). Conclusions: In SRT, where pathologic factors including extra-capsular extension, seminal vesicle invasion, and margin status are known, the presence of GP5 is the strongest pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual GP’s for SRT patients following RP. Intensification of treatment regimens, such as early use of androgen deprivation therapy or adjuvant radiation, may be appropriate for patients with GP5 in this setting.

Predicting the Risk of Secondary Malignancies Associated With Pelvic Nodal Irradiation in the Treatment of Prostate Cancer

superiority in prostate cancer detection including local recurrence and lymph node metastases over F-18 fluorodeoxyglucose (FDG) PET and a higher sensitivity and specificity compared with other imaging studies in prostate cancer. We report our experience. Materials/Methods: From January 2010 to December 2011, a total of 76 patients with prostate cancer were referred for evaluation. Of these, 32 patients underwent primary radiation therapy treatment, 23 patients were for adjuvant radiation therapy, and 10 patients received salvage radiation therapy as well as 11 patients were treated with palliative radiation therapy for painful bone metastases. High risk and patients with metastatic disease also received hormonal therapy. Patients with suspicious lymph nodes on CAT scan or MRI during staging work up underwent C11-acetate PET. The findings and changes to original treatment plan are reported. Results: A total of 19 patients had C11-acetate PET. Eleven patients (57%) had high risk prostate cancer. Nine patients (47%) underwent primary radiation therapy treatment. Seven patients (37%) had increased SUV values (Above 6). The involved areas on C11-acetate PET included external iliac lymph nodes in five patients as well as both, iliac external and inguinal lymph nodes in two patients; Modification of radiation therapy treatment volumes, dose or both was required in three , one and three patients respectively. The decision to add hormone therapy remained the same without any change. With a mean follow up of 18 months, all of these patients remained under biochemical control and C11-acetate PET showed decrease in SUV at the previously affected regions. There was no correlation between PSA level and lymph node involvement but most of the patients with positive C11-acetate PET were in high risk category. Conclusions: C11-acetate PET was useful in detecting lymph node metastases especially in high risk prostate cancer patients. The findings of C11-acetate PET resulted in the change of radiation therapy treatment field/ volume or dose in more than one third of the patients (37%), hopefully leading to better local regional control. SUV values may serve as a tool for monitoring radiation therapy response. Further studies including prospective clinical trials are needed. Author Disclosure: J. Hinojosa Gomez: None. M. Blake: None. J.O. Hernandez: None. J. Balam: None. B.S. Teh: None.

Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at the University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores ≤7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.

Radiotherapy after subtotally resected or recurrent ganglioglioma

Gangliogliomas can recur after subtotal resection (STR). The role of postoperative radiation therapy (RT) is undefined. Eight consecutive patients with low-grade gangliogliomas (n = 7) or anaplastic gangliogliomas (n = 1) were treated with RT between 1987 and 2004. Median age was 17 years. Five patients received adjuvant RT after STR at a median time of 6 weeks after surgery. Three patients received salvage RT at a median time of 17 months after surgery. The median dose of RT was 54 Gy. Control was defined as no progressive disease on serial imaging. Median follow-up was 8.8 years. Of the 7 patients with low-grade gangliogliomas, 3 were controlled after RT and 4 recurred locally. Recurrences were controlled with further surgery (n = 2), chemotherapy (n = 1), or re-irradiation (n = 1) (median follow-up, 9 years after salvage therapy). Patients who received adjuvant RT after STR of their low-grade gangliogliomas had an overall local control rate of 75%. All 3 patients who were treated with salvage RT had recurrences in the treated area alone (n = 2) or in the treated area with leptomeningeal spread (n = 1). The patient with an anaplastic ganglioglioma was treated with adjuvant RT, and had recurrence in the radiation field after 4 months, then died 1 month later. Adjuvant RT may be indicated to treat select patients with subtotally resected gangliogliomas. Salvage RT for recurrence is probably less effective for long-term control; however, patients who recur may still be candidates for effective salvage therapies in the absence of malignant transformation.