Chad G. Rusthoven

Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer

PURPOSE There is growing interest in the role of local therapies, including external beam radiotherapy (RT), for men with metastatic prostate cancer (mPCa). We used the National Cancer Database (NCDB) to evaluate the overall survival (OS) of men with mPCa treated with androgen deprivation (ADT) with and without prostate RT. METHODS The NCDB was queried for men with newly diagnosed mPCa, all treated with ADT, with complete datasets for RT, surgery, prostate-specific antigen (PSA) level, Gleason score, and Charlson-Deyo comorbidity score. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS From 2004 to 2012, 6,382 men with mPCa were identified, including 538 (8.4%) receiving prostate RT. At a median follow-up of 5.1 years, the addition of prostate RT to ADT was associated with improved OS on univariate (P < .001) and multivariate analysis (hazard ratio, 0.624; 95% CI, 0.551 to 0.706; P < .001) adjusted for age, year, race, comorbidity score, PSA level, Gleason score, T stage, N stage, chemotherapy administration, treating facility, and insurance status. Propensity score analysis with matched baseline characteristics demonstrated superior median (55 v 37 months) and 5-year OS (49% v 33%) with prostate RT plus ADT compared with ADT alone (P < .001). Landmark analyses limited to long-term survivors of ≥1, ≥3, and ≥5 years demonstrated improved OS with prostate RT in all subsets (all P < .05). Secondary analyses comparing the survival outcomes for patients treated with therapeutic dose RT plus ADT versus prostatectomy plus ADT during the same time interval demonstrated no significant differences in OS, whereas both therapies were superior to ADT alone. CONCLUSION In this large contemporary analysis, men with mPCa receiving prostate RT and ADT lived substantially longer than men treated with ADT alone. Prospective trials evaluating local therapies for mPCa are warranted.

The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

PURPOSE To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. METHODS AND MATERIALS The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. RESULTS A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. CONCLUSIONS In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

Assessment of Organ Motion in Postoperative Endometrial and Cervical Cancer Patients Treated With Intensity-Modulated Radiation Therapy

PURPOSE Intensity-modulated radiation therapy (IMRT) may be useful to reduce toxicity in gynecologic cancer patients requiring postoperative pelvic irradiation. This study was undertaken to quantify vaginal wall organ motion during the course of postoperative pelvic irradiation using pelvic IMRT. METHODS AND MATERIALS Twenty-two consecutive patients treated with postoperative pelvic IMRT on helical tomotherapy had fiducial markers placed at the vaginal apex prior to simulation then daily megavoltage computed tomography (CT) scans for positioning. The daily positions of the fiducials were registered and measured in reference to the initial CT scan to quantify the degree of vaginal wall organ motion during the entire course of therapy. RESULTS The total motion of the fiducials center of mass (COM) was a median of 5.8 mm (range, 0.6-20.2 mm), and 95% of all COM positions fell within 15.7 mm of their original position. Directional margins of 3.1 mm along the right-left axis, 9.5 mm along the superoinferior axis, and of 12.1 mm along the anteroposterior axis encompassed the vaginal fiducials in 95% of treatments. Mean organ deformation for all patients was 3.9 mm, (range, 0-27.5 mm; standard deviation, 3.1 mm), with significant distortions of greater than 10 mm in 17% of secondary image sets. CONCLUSIONS These data suggest a planning target volume margin of 16 mm will account for maximal organ motion in the majority of gynecologic patients undergoing postoperative pelvic IMRT, and it may be possible to incorporate directional motion into the planning target volume margin.

Gleason stratifications prognostic for survival in men receiving definitive external beam radiation therapy for localized prostate cancer

PURPOSE Histologic grade analyses for prostate cancer (PCa) have traditionally included Gleason scores (GS) of ≤6, 7, and 8-10. Stratified biochemical progression-free survival has increasingly been reported within these groups on analyses of primary-secondary patterns (PSPs) (e.g., 3+4 vs. 4+3) and overall GS (e.g., 8 vs. 9 vs. 10) but with limited data regarding stratified survival outcomes. In this analysis, outcomes for biopsy-assigned GS 6 to 10 were comprehensively evaluated to identify stratifications prognostic for survival in patients undergoing external beam radiation therapy (EBRT). METHODS The Surveillance, Epidemiology, and End Results database was examined for T1-4 N0 M0, GS 6 to 10 PCa managed with EBRT alone from 2004 to 2006. GS and PSP variations were analyzed for PCa-specific survival (PCSS) and overall survival (OS). RESULTS Overall, 26,885 patients were evaluated. Preliminary PSP analyses identified stratifications for 3+4 vs. 4+3 = 7 and 4+4 = 8 vs. GS 8 with pattern 5 (P5) (i.e., 3+5 and 5+3) as significant; however, no differences were observed for 4+5 vs. 5+4 = 9. The primary analysis included stratifications for GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10, where the 7.5-year PCSS rates were 99%, 97%, 95%, 91%, 86%, 81%, and 78% and 7.5-year OS rates were 83%, 76%, 72%, 67%, 66%, 58%, and 54%, respectively. PCSS differences for sequential score increases were all significant on univariate analyses (all P<0.05). In sequential multivariate analyses of PCSS accounting for age, prostate-specific antigen, T stage, year, marital status, race, and tumor registry, the identified GS stratifications remained significant (all P<0.05), with the exception of GS 8 w/P5 vs. 9 (P = 0.11). In overall multivariate analyses, the identified GS stratifications represented the strongest prognostic factor for survival. Subgroup analyses demonstrated that presence of any P5 was an independent prognostic factor for survival. CONCLUSION In the largest reported survival analysis of Gleason stratifications, biopsy-assigned GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10 represented sequential prognostic factors for survival in patients managed with definitive EBRT.

Combined-Modality Therapy With Radiation and Chemotherapy for Elderly Patients With Glioblastoma in the Temozolomide Era: A National Cancer Database Analysis

IMPORTANCE The optimal management for elderly patients with glioblastoma (GBM) is controversial. Following maximal safe resection or biopsy, accepted treatment paradigms for elderly patients with GBM include combined-modality therapy (CMT) with both radiotherapy (RT) and chemotherapy (CT), RT alone, and CT alone. OBJECTIVE To evaluate the overall survival (OS) outcomes associated with RT, CT, and CMT for elderly patients with GBM in the modern temozolomide era. DESIGN, SETTING, AND PARTICIPANTS In this retrospective cohort study of a prospectively maintained, multi-institutional national cancer registry, the National Cancer Database was queried for elderly patients (≥65 years) with newly diagnosed GBM from January 1, 2005, through December 31, 2011, with complete data sets for RT, CT, tumor resection, Charlson-Deyo comorbidity scores, age, sex, and year of diagnosis. Data analysis was performed from October 2015 through December 2015. INTERVENTIONS Combined-modality therapy, RT, CT. MAIN OUTCOMES AND MEASURES Survival by treatment cohort was estimated using the Kaplan-Meier method and analyzed using the log rank test, univariate and multivariate Cox models, and propensity score-matched analyses. RESULTS A total of 16 717 patients (median [range] age, 73 [65-≥90 y]; 8870 [53%] male) were identified. The median OS by treatment was 9.0 (95% CI, 8.8-9.3) months with CMT (8435 patients), 4.7 (95% CI, 4.5-5.0) months with RT alone (1693 patients), 4.3 (95% CI, 4.0-4.7) months with CT alone (1018 patients), and 2.8 (95% CI, 2.8-2.9) months with no therapy (5571 patients) (P < .001). On multivariate analysis, CMT was superior to both CT alone (hazard ratio, 1.50 [95% CI, 1.40-1.60]; P < .001) and RT alone (hazard ratio, 1.47 [95% CI, 1.39-1.55]; P < .001), whereas no differences were observed between CT alone vs RT alone (P = .60). Propensity score-matched analyses redemonstrated improved OS with CMT over CT alone (P = .002) and RT alone (P < .001); no differences were observed between CT alone vs RT alone (P = .44). On subgroup analyses, a consistent OS advantage was observed with CMT over both CT alone and RT alone across each age stratification (65-69, 70-74, 75-79, and ≥80 years) and among patients treated with or without tumor resection (all P < .001). CONCLUSIONS AND RELEVANCE In this analysis of multimodality therapy for elderly patients with GBM, OS was superior with CMT compared with CT alone and RT alone. Survival was similar between CT alone and RT alone, and both CT alone and RT alone were superior to no therapy. This analysis supports the use of CMT for suitable elderly candidates.

The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis

BACKGROUND Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB). PATIENTS AND METHODS Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan-Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses. RESULTS From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566-0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689-0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05). CONCLUSIONS In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.

The prognostic significance of Gleason scores in metastatic prostate cancer

PURPOSE Although the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of ≤7 vs. ≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer-specific survival (PCSS). RESULTS A total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS. CONCLUSIONS In this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting.

Association of health insurance with outcomes in adults ages 18 to 64 years with melanoma in the United States

BACKGROUND Studies evaluating insurance status and melanoma outcomes are limited. OBJECTIVE We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma. METHODS This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database. RESULTS Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001). LIMITATIONS This was a retrospective study. CONCLUSION Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes.

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

PURPOSE/OBJECTIVES The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). METHODS AND MATERIALS Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) using Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. RESULTS A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). CONCLUSION In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.

Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer: Theory and Practice.

Management paradigms for metastatic non-small cell lung cancer (mNSCLC) are evolving. Locally ablative therapies are now being increasingly integrated into combined-modality treatment strategies for mNSCLC patients with limited burdens of metastatic foci, termed oligometastases. Concurrently, techniques allowing for precise high-dose radiotherapy delivered over 1 to 5 total treatments, termed stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR), have emerged as a powerful means of noninvasive tumor ablation with broad patient candidacy. Strong rationale exists for ablative therapy in the setting of oligometastatic NSCLC, including patterns-of-failure analyses and data supporting local ablation of oligoprogressive disease for patients with oncogene-addicted mNSCLC treated with tyrosine kinase inhibitors. In this article, we examine the theoretical basis for ablation of oligometastatic NSCLC and review the growing clinical literature of mNSCLC patients treated with ablative radiation therapy.