ABSTRACT
BACKGROUND: The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9-10 PCa) is unknown. METHODS: We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9-10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis-free survival (DMFS), and salvage/adjuvant therapy-free survival (SAFS), as assessed by Kaplan-Meier analysis. RESULTS: We identified 1220 veterans with GS 9-10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow-up of 9.9 years, propensity score-matched analyses demonstrated that RP had superior 10-year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10-year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10-year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients. CONCLUSIONS: This analysis demonstrated higher 10-year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long-term cause-specific OS rates may be similar. We also highlight real-world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT.
Subject(s)
Prostatic Neoplasms , Veterans , Androgen Antagonists , Humans , Male , Prostatectomy , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Retrospective StudiesSubject(s)
Brachytherapy/adverse effects , Erectile Dysfunction/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lovastatin/therapeutic use , Prostatic Neoplasms/radiotherapy , Erectile Dysfunction/etiology , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Risk FactorsABSTRACT
PURPOSE: African American men have historically had poorer prostate cancer biochemical and survival outcomes than Caucasians. However, emerging data suggest nononcologic factors drive much of this disparity. Prior evidence has suggested an association between a transient prostate specific antigen (PSA) bounce and improved biochemical control. However, racial differences in this relationship have remained relatively unexplored. METHODS AND MATERIALS: We identified 4477 men treated for low- or intermediate-risk prostate cancer within the U.S. Department of Veterans Affairs (VA) from 2000 to 2010 with brachytherapy alone or in combination with external beam radiotherapy without androgen deprivation. Longitudinal PSA data were used to define to biochemical failure and PSA bounce. Cox proportional hazard models were used explore racial differences in the relationship between the PSA bounce and time to biochemical failure. RESULTS: Thirty-one percent of our sample experienced a PSA bounce, with African Americans more likely to experience a bounce (42%) compared with Caucasians (29%); p < 0.001. Despite this, African Americans had a higher likelihood of biochemical failure (hazard ratio [HR] 1.4; p = 0.006). However, African American men experiencing a PSA bounce were less likely to experience a biochemical failure (HR = 0.64; p = 0.046), whereas this relationship was not statistically significant for Caucasians (HR = 0.78; p = 0.092). On multivariate analysis, African Americans receiving brachytherapy alone were most sensitive to the protective benefit of the PSA bounce (HR = 0.64). CONCLUSIONS: A PSA bounce was associated with improved biochemical control among patients receiving brachytherapy as part of their treatment for low- or intermediate-risk prostate cancer at the VA. African American men treated with brachytherapy had a particularly pronounced biochemical control benefit of a PSA bounce.
Subject(s)
Black or African American , Brachytherapy , Kallikreins/blood , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/radiotherapy , White People , Aged , Humans , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Prostatic Neoplasms/ethnology , Treatment Outcome , United States , United States Department of Veterans AffairsABSTRACT
BACKGROUND: In this phase I/II trial, 5-year physician-assessed toxicity and patient reported quality of life data is reported for patients undergoing moderately hypofractionated intensity modulated radiation therapy (IMRT) for prostate cancer using a simultaneous integrated boost (SIB) and pelvic lymph node (LN) coverage. MATERIALS AND METHODS: Patients with T1-T2 localized prostate cancer were prospectively enrolled, receiving risk group based coverage of prostate ± seminal vesicles (SVs) ± pelvic lymph nodes (LNs). Low risk (LR) received 69.6 Gy/29 fractions to the prostate, while intermediate risk (IR) and high risk (HR) patients received 72 Gy/30fx to the prostate and 54Gy/30fx to the SVs. If predicted risk of LN involvement >15%, 50.4 Gy/30fx was delivered to pelvic LNs. Androgen deprivation therapy was given to IR and HR patients. RESULTS: There were 55 patients enrolled and 49 patients evaluable at a median follow up of 60 months. Included were 11 (20%) LR, 23 (41.8%) IR, and 21 (38.2%) HR patients. Pelvic LN treatment was given in 25 patients (51%). Prevalence rates of late grade 2 GI toxicity at 1, 3, and 5 years was 5.8, 3.9, and 5.8%, respectively, with no permanent grade 3 events. Prevalence rates of late grade 2 GU toxicity at 1, 3, and 5 years rates were 15.4, 7.7, and 13.5%, respectively, with three grade 3 events (5.8%). The biochemical relapse free survival at 5 years was 88.3%. There were no local, regional, or distant failures, with all patients still alive at last follow up. CONCLUSION: Moderate hypofractionation of localized prostate cancer utilizing a SIB technique and LN coverage produces tolerable acute/late toxicity. Given equivalent efficacy between moderate hypofractionation schedules, the optimal regimen will be determined by long-term toxicity reported from both the physician and patient perspective. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT01117935, Date of Registration: 5/6/2010.
Subject(s)
Neoplasm Metastasis , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapyABSTRACT
PURPOSE: This study evaluates the safety and efficacy of moderately hypofractionated radiation therapy (RT) with simultaneous integrated boost (HSIB) intensity modulated RT (IMRT) that includes coverage of the seminal vesicles (SVs) and pelvic lymph nodes (LNs). METHODS AND MATERIALS: Men with localized prostate cancer were prospectively enrolled in a phase 1/2 trial to receive HSIB-IMRT to the prostate, ± SV, ± pelvic LN using a risk-based method. Low-risk patients received 69.6 Gy to only the prostate in 29 fractions. Intermediate-risk (IR) and high-risk (HR) patients received 30 fractions with 72 Gy to the prostate, 54 Gy to the SV, and 50.4 Gy to the pelvic LN when risk of LN involvement exceeded 15% by the Roach formula. IR and HR patients received androgen deprivation therapy. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated with patient- and physician-reported surveys. RESULTS: Fifty-five men were enrolled, and 49 had at least 1 year of follow-up with 19.2% low-risk, 40.4% IR, and 40.4% HR disease. The median age was 69 years; median follow-up time was 36.9 months. Twenty-six patients received pelvic nodal HSIB-IMRT. At 2 years, the cumulative incidence of physician-reported late grade 2+ GU and GI toxicity was 32.6% and 18.4% respectively. At 2 years, only 10.2% grade 2+ GU toxicities and 2.0% grade 2+ GI toxicities remained unresolved. At last follow-up, the prevalence of unresolved physician-reported late grade 2+ GU and GI toxicity was 4.1% and 0%. The median patient-reported American Urologic Association-International Prostate Symptom Score fell from 10 at baseline to 7.5 at 2 years. The 3-year biochemical relapse-free survival rate for the cohort was 96%. CONCLUSIONS: HSIB-IMRT with risk-based nodal coverage results in excellent biochemical control. Although the cumulative incidence of physician-reported GU toxicity was higher than anticipated, late GI and GU toxicity was relatively transient.
Subject(s)
Radiotherapy, Intensity-Modulated/methods , Aged , Aged, 80 and over , Humans , Male , Middle AgedABSTRACT
PURPOSE: Physician reported symptomatic late rectal injury occurs in about 5% to 25% of patients treated with radiation therapy for prostate cancer, depending on the treatment technique. Patients, however, report clinically meaningful declines in bowel/rectal function regardless of the technique used. Lovastatin has been shown to protect mice from late radiation injury. This study was designed to determine if lovastatin might reduce the incidence of late rectal injury in patients receiving radiation therapy for prostate cancer. MATERIALS AND METHODS: Patients with adenocarcinoma of the prostate receiving radiotherapy with curative intent were eligible. A portion of the rectum had to receive at least 60 Gy. Gastrointestinal functioning was assessed using both physician-reported and patient-reported instruments at baseline and at prescribed intervals during and after treatment. Lovastatin (20 to 80 mg/d) was started on day 1 of radiation and continued for 12 months. Patients were followed for an additional 12 months. The primary endpoint was physician-reported rectal toxicity ≥grade 2 during the first 2 years after treatment. RESULTS: A total of 20/53 (38%) patients developed grade 2 or higher toxicity during the 2-year follow-up period. Seventeen patients had 1 or more unresolved gastrointestinal symptom at the end of 2 years, 3 (6%) of which were grade 2 and none were of higher grade. CONCLUSIONS: The primary endpoint of the study was not met. Lovastatin, as administered in this trial, did not reduce the incidence of grade 2 or higher rectal toxicity compared with historical controls.
Subject(s)
Adenocarcinoma/radiotherapy , Anticholesteremic Agents/therapeutic use , Lovastatin/therapeutic use , Prostatic Neoplasms/radiotherapy , Radiation Injuries/drug therapy , Radiotherapy, Conformal/adverse effects , Rectum/radiation effects , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Case-Control Studies , Follow-Up Studies , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/etiology , Humans , Male , Middle Aged , Prognosis , Prostatic Neoplasms/pathology , Radiation Injuries/diagnosis , Radiation Injuries/etiology , Radiation ProtectionABSTRACT
A prostate-specific antigen tracking system identifies patients who require intervention before they present with clinical problems, ensuring that testing occurs at appropriate intervals.
ABSTRACT
PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. METHODS AND MATERIALS: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). RESULTS: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. CONCLUSIONS: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/radiotherapy , Dacarbazine/analogs & derivatives , Glioblastoma/radiotherapy , Radiation-Sensitizing Agents/administration & dosage , Valproic Acid/administration & dosage , Adult , Age Factors , Aged , Antineoplastic Agents, Alkylating/adverse effects , Bone Marrow/drug effects , Bone Marrow/radiation effects , Brain Neoplasms/blood , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Glioblastoma/blood , Glioblastoma/drug therapy , Glioblastoma/mortality , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/therapeutic use , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/adverse effects , Radiation-Sensitizing Agents/metabolism , Temozolomide , Time Factors , Valproic Acid/adverse effects , Valproic Acid/bloodABSTRACT
OBJECTIVES: To assess the feasibility and toxicity of stereotactic body radiotherapy (SBRT) for patients with locally advanced or metastatic tumors in lung. METHODS: Twenty-five tumors in 17 patients were treated. All treatments were delivered in 3 daily fractions of 9 to 15 Gy per fraction. Normal tissue complication probability (NTCP) calculations (using the Lyman model) were performed to facilitate dose prescription, and doses were prescribed with a maximum allowable NTCP risk of pneumonitis of up to 20%, not to exceed 15 Gy per fraction. Planning target volumes were designed to allow for respiratory variation in tumor location. RESULTS: The median dose prescribed was 35 Gy (range, 24 to 45 Gy). Twenty-three of 25 tumors remained controlled at median follow-up of 14 months. Four patients experienced grade 1-2 acute toxicity. Late toxicity developed in 2 patients who received treatment to peri-hilar tumors, including one patient in whom bronchial stenosis developed with complete occlusion and lobar atelectasis 6 months after treatment. No patient had grade 3 or 4 radiation pneumonitis. CONCLUSIONS: SBRT prescribed within the confines of NTCP-restricted dosing on this protocol resulted in no radiation pneumonitis. Tissues other than lung parenchyma which are unaccounted for by NTCP may be dose-limiting when performing hypofractionated SBRT in the lung.