Joseph Weiner

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

Purpose To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patients symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.

Impact of aspirin on clinical outcomes for African American men with prostate cancer undergoing radiation

Aims and background Preclinical and clinical studies have suggested that aspirin (ASA) may exhibit antineoplastic activity. Particularly in prostate cancer, several reports have suggested that ASA plays a role in improved outcomes. Therefore, we studied the role of ASA in a uniquely African American population, which is known to harbor more aggressive and biologically different disease compared to the general population. Methods We identified 289 African American men with prostate cancer who were treated with definitive radiation therapy to a dose of ≥7560 cGy. The median follow-up was 76 months. Kaplan-Meier analysis was used to analyze biochemical failure-free survival (bFFS), distant progression-free survival (DMPFS), and prostate cancer-specific survival (PCSS). Multivariate Cox regression was used to analyze the impact of covariates on all endpoints. Results There were 147 men who were ASA+ and 142 who were ASA-. The 7-year bFFS was 80.9% for ASA+ men and 70.3% for ASA− men (p = 0.03). On multivariate analysis, ASA use was associated with a significant reduction in biochemical recurrences (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.34-0.93, p = 0.03). The 7-year DMPFS was 98.4% for ASA+ and 91.8% for ASA− men (p = 0.04). On multivariate analysis, ASA use was associated with a decreased risk of distant metastases (HR 0.23, 95% CI 0.06-0.91, p = 0.04). The 7-year PCSS was 99.3% for ASA+ and 96.9% for ASA− men (p = 0.07). Conclusions In this study, ASA use was associated with improved biochemical outcomes and reduced distant metastases. This indicates that ASA appears to play an important antineoplastic role in African American men.

Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma

PURPOSE/OBJECTIVES Adjuvant treatment options following surgical staging for women with stage IIIC endometrial carcinoma include chemotherapy (CT) with or without radiation therapy (RT). We utilized the National Cancer Database (NCDB) to investigate utilization of adjuvant CT and RT for this group of patients and assess their impact on overall survival (OS). MATERIALS/METHODS The NCDB was queried for patients diagnosed with non-metastatic surgically staged uterine adenocarcinoma between 2004 and 2011 with at least one pathologically positive lymph node. Overall survival (OS) was analyzed using the Kaplan-Meier method. Comparison was made between patients receiving no additional therapy, RT alone, CT alone, or a combination of CT and RT (CMT). Multivariable cox regression analysis (MVA) was performed to evaluate the effect of covariates on OS. RESULTS A total of 6720 patients were included in this study. Of whom, 1409 received no adjuvant treatment, 1533 received CT only, 1265 received RT only, and 2522 received CMT. The 5-year OS for patients receiving no adjuvant therapy, RT alone, CT alone, and CMT were 54.9%, 63.9%, 64.4%, and 72.6%, respectively. On pairwise analysis, CMT was associated with improved survival compared to all other subgroups (p<0.001). On MVA, CMT (HR 0.58, 95% CI 0.52-0.66, p<0.001) was the strongest predictor for improved OS compared to RT alone (HR 0.79, 95% CI 0.69-0.89, p<0.001) or CT alone (HR 0.75, 95% CI 0.66-0.85, p<0.001). CONCLUSIONS Both adjuvant CT and adjuvant RT were associated with improved OS for women with stage IIIC endometrial adenocarcinoma, but CMT was associated with the largest improvement in OS.

Stereotactic radiotherapy of the prostate: fractionation and utilization in the United States

Purpose To analyze the utilization and fractionation of extreme hypofractionation via stereotactic body radiotherapy (SBRT) in the treatment of prostate cancer. Materials and Methods Data was analyzed on men diagnosed with localized prostate cancer between 2004–2012 and treated with definitive-intent radiation therapy, as captured in the National Cancer Database. This database is a hospital-based registry that collects an estimated 70% of all diagnosed malignancies in the United States. Results There were 299,186 patients identified, of which 4,962 (1.7%) were identified as receiving SBRT as primary treatment. Of those men, 2,082 had low risk disease (42.0%), 2,201 had intermediate risk disease (44.4%), and 679 had high risk disease (13.7%). The relative utilization of SBRT increased from 0.1% in 2004 to 4.0% in 2012. Initially SBRT was more commonly used in academic programs, though as time progressed there was a shift to favor an increased absolute number of men treated in the community setting. Delivery of five separate treatments was the most commonly utilized fractionation pattern, with 4,635 patients (91.3%) receiving this number of treatments. The most common dosing pattern was 725 cGy × 5 fractions (49.6%) followed by 700 cGy × 5 fractions (21.3%). conclusions Extreme hypofractionation via SBRT is slowly increasing acceptance. Currently 700-725 cGy × 5 fractions appears to be the most commonly employed scheme. As further long-term data regarding the safety and efficacy emerges, the relative utilization of this modality is expected to continue to increase.

Adjuvant radiation with hormonal therapy is associated with improved survival in men with pathologically involved lymph nodes after radical surgery for prostate cancer

PURPOSE Recent studies have suggested that the addition of adjuvant radiation therapy (aRT) may improve outcomes in men with pathologically involved lymph nodes (pN+). The objective of this study was to assess the treatment patterns and the overall survival (OS) outcomes in men with pN+prostate cancer using the National Cancer Data Base. METHODS Men diagnosed with nonmetastatic prostate cancer between 2004 and 2011, who underwent radical prostatectomy for pN+were identified in the National Cancer Data Base. Patients were stratified into subgroups of those receiving no adjuvant therapy and those receiving adjuvant hormonal therapy (aHT) alone, aRT alone, and aRT+aHT. OS was analyzed using Kaplan-Meier method and compared between the groups using the log-rank test. Multivariable Cox regression was used to identify covariates that affected OS. RESULTS A total of 7,225 patients were included in this analysis, of whom 3,636 (50.3%) received no adjuvant therapy, 2,041 (28.2%) received aHT alone, 350 (4.8%) received aRT alone, and 1,198 (16.5%) received aRT+aHT. The 5-year OS rates were 85.2% for no adjuvant therapy, 82.9% for aHT alone, 88.3% for aRT alone, and 88.8% for combination hormonal therapy, i.e., aRT+aHT (P<0.001). On multivariable analysis, aRT+aHT was associated with a significantly decreased risk of death (hazard ratio [HR] = 0.67; 95% CI: 0.54-0.83; P<0.001) compared with no adjuvant therapy, whereas aHT alone (HR = 0.99; 95% CI: 0.85-1.15; P = 0.90) and aRT alone (HR = 1.02; 95% CI: 0.74-1.40; P = 0.92) were not. CONCLUSION Patients treated with multimodal aRT+aHT had significantly higher OS rate than patients treated without adjuvant therapy or with aHT/aRT alone.

Patterns of adjuvant radiation usage and survival outcomes for stage I endometrial carcinoma in a large hospital-based cohort

OBJECTIVE Two randomized trials have demonstrated a local control advantage in the absence of a survival advantage for the addition of adjuvant radiation therapy (RT) to surgery in patients with stage I endometrial adenocarcinoma (EC). This study analyzed the National Cancer Data Base (NCDB) to evaluate the impact of adjuvant RT on overall survival (OS) for patients with stage I EC. METHODS Patients with EC who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011 were queried. Only those with AJCC stage pT1N0M0 were included. Patients surviving <4months excluded. Adjuvant RT included external beam RT (EBRT), brachytherapy, or external RT+brachytherapy. OS was analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis and propensity matched analysis were performed to assess the impact of covariates on OS. RESULTS There were 61,697 patients included. Most women (83.9%) did not receive adjuvant RT. Adjuvant RT usage increased with increasing stage/grade. Usage of brachytherapy alone decreased with increasing stage/grade (78.2% for IA/G1 to 36.1% for IB/G3) corresponding to an increase in the use of EBRT (21.8% for IA/G1 to 53.9% for IB/G3). On multivariable analysis, adjuvant EBRT (HR 0.83, 95%CI 0.74-0.93, p=0.002) and brachytherapy (HR 0.82, 95%CI 0.74-0.93, p=0.002) were each associated with improved survival for women with stage IB. In the propensity matched cohort, RT was associated with improved survival (0.85, 95% CI 0.78-0.92, p<0.001). CONCLUSION The use of adjuvant RT for women with stage I EC is highly dependent on stage/grade and is associated with improved survival for stage IB.

Does the Presence of a Major Psychiatric Disorder Affect Tolerance and Outcomes in Men With Prostate Cancer Receiving Radiation Therapy

Prior studies have suggested that men with prostate cancer and psychiatric disorders (+Psy) have worse outcomes compared with those without (−Psy), particularly due to delayed diagnosis or reduced access to definitive treatment. In the current study, the toxicity and outcomes of men who were primarily diagnosed through prostate-specific antigen screening and who underwent definitive treatment with external beam radiation was investigated. The charts of 469 men diagnosed with prostate cancer from 2003 to 2010 were reviewed. The presence of +Psy was based on a Diagnostic and Statistical Manual of Mental Disorders–Fourth edition diagnosis of posttraumatic stress disorder, depression, schizophrenia, bipolar disorder, and/or generalized anxiety disorder. Kaplan–Meier analysis was used to analyze biochemical control, distant control, prostate cancer–specific survival, and overall survival. One hundred patients (21.3%) were identified as +Psy. At a median follow-up of 73 months, there were no differences regarding 6-year biochemical control (79.8% −Psy vs. 80.4% +Psy, p = .50) or 6-year distant metastatic-free survival (96.4% −Psy vs. 98.0% +Psy, p = .36). There were also no differences regarding the 6-year prostate cancer–specific survival (98.4% −Psy vs. 99.0% +Psy, p = .45) or 6-year overall survival (80.2% −Psy vs. 82.2% +Psy, p = .35). Short- and long-term genitourinary and gastrointestinal toxicities were similar between the groups. On multivariate analyses with propensity score adjustment, +Psy was not a significant predictor for toxicity, biochemical recurrence, or survival. The presence of +Psy was not associated with higher toxicity or worse clinical outcomes, suggesting that effective removal of screening and treatment barriers may reduce the survival disparities of these patients.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer.

Purpose We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. Materials and Methods From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. Results The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Conclusion Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

The need for more aggressive therapy for men with Gleason 9-10 disease compared to Gleason ≤8 high-risk prostate cancer

Purpose To evaluate the outcomes of prostate cancer patients with high-risk disease stratified by Gleason Score (GS) (GS ≤8 vs GS ≥9) treated with external beam radiotherapy (EBRT). Methods The medical records of patients who underwent EBRT between 2003 and 2011 and had nonmetastatic high-risk disease were analyzed retrospectively. Patients were treated with EBRT and all patients received a dose ≥7,560 cGy. Androgen deprivation therapy was given in most patients (90%). Results A total of 155 patients were identified (GS ≤8 n = 104, GS ≥9 n = 51), and they had a median presenting prostate-specific antigen (PSA) of 14.7 ng/mL. At a median follow-up of 69 months, the 7-year biochemical failure-free survival was 59.1% in those with GS ≥9 and 69.2% in those with GS ≤8 (p = 0.12). On MVA, Gleason 9-10 (HR 1.83, p = 0.08) was not associated with an increased risk of biochemical recurrence, while a PSA >20 ng/mL (HR 2.39, p = 0.04) was associated with an increased likelihood of biochemical recurrence. Patients with GS ≥9 were noted to have worse 7-year distant metastatic-free survival (79.6% vs 90.5% p = 0.02) and cancer-specific survival (88.5% vs 97.9%, p = 0.006). On MVA, GS ≥9 was a significant indicator of distant metastatic failure and cancer-related death. Seven-year overall survival rates remained similar between the groups. Conclusions In this high-risk cohort, patients with GS 9-10 had significantly worse prostate cancer-related outcomes than other high-risk patients, suggesting that this group may warrant more aggressive treatment modalities than their high-risk counterparts.