Bernard L. Jones

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.

Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base

The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone.

Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the National Cancer Data Base

OBJECTIVES This study identifies clinical characteristics associated with HPV-positive oropharynx squamous cell carcinoma (OPSCC) and evaluates predictors of overall survival (OS) in HPV-positive patients undergoing definitive treatment within the National Cancer Data Base (NCDB). MATERIAL AND METHODS The NCDB was queried for patients ⩾18years old with OPSCC and known HPV status who underwent definitive treatment: surgery, radiation (RT), chemotherapy-RT (CRT), surgery+RT, surgery+CRT (S-CRT). Cox proportional hazards model was used for multivariate analysis (MVA) to evaluate predictors of OS by HPV status. RESULTS 3952 patients were included: 2454 (62%) were HPV-positive. Median follow up was 23.7months (range, 1.0-54.5). Unadjusted 2-year OS rates for HPV-positive vs. negative were 93.1% vs. 77.8% (p<0.001) with an adjusted hazard ratio of 0.44 (95% CI, 0.36-0.53; p<0.001). MVA identified multimodality treatment including CRT (HR, 0.42; p=0.024) and S-RT (HR, 0.30; p=0.024), but not S-CRT (HR, 0.51; p=0.086), as predictors for improved OS in HPV-positive stage III-IVB disease. Multimodality treatment including S-CRT was associated with longer OS in HPV-negative OPSCC. Nodal stage was poorly associated with OS in HPV-positive cancers. The presence of positive margins and/or extracapsular extension was associated with worse OS in HPV-negative (HR, 2.11; p=0.008) but not HPV positive OPSCC (HR, 1.61; p=0.154). CONCLUSION The established demographic and clinical features of HPV-positive OPSCC were corroborated in the NCDB. Population analysis suggests that AJCC staging is poorly associated with OS in HPV-positive cancer, and traditional high-risk features may be less impactful. Bimodality therapy appears beneficial in HPV-positive HNSCC.

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.

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.

Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma: Data From the National Cancer Data Base

Importance Data on adjuvant concurrent chemoradiotherapy (CRT) after resection of salivary gland carcinomas (SGCs) are limited. Objective To examine overall survival (OS) outcomes of patients who receive CRT vs radiotherapy (RT) alone after resection of SGCs. Design, Setting, and Participants The National Cancer Data Base (NCDB), a hospital-based registry that represents 70% of all cancer cases in the United States, was queried for patients who underwent resection of major SGCs with at least 1 high-risk feature (T3-T4 stage, N1-N3 stage, or positive margins). Included patients had histologic findings for malignant SGC with grades 2 to 3 disease and at least 1 high-risk feature. All patients underwent resection with postoperative CRT or RT alone. Patients were treated from 1998 to 2011. Data were analyzed from January to March 2016. Exposures Patients received CRT, defined as chemotherapy start within 14 days of RT initiation, or RT alone. Main Outcomes and Measures Univariate, multivariate, and propensity score-matched analyses were performed to compare OS for patients undergoing CRT vs RT alone. Results Analyses included 2210 eligible patients (1372 men [62.1%] and 838 women [37.9%]; median age [range], 63 [18-90] years); of these, 1842 (83.3%) received RT alone and 368 (16.7%) received CRT. Median follow-up was 39 (range, 2-188) months. Most of the resected major SGCs occurred at the parotid gland (1852 [83.8%]), followed by the submandibular gland (276 [12.5%]), major gland not otherwise specified (66 [3.0%]), and sublingual gland (16 [0.7%]). Unadjusted 2-year OS was worse with adjuvant CRT vs RT alone (71.3% vs 80.2%), as was 5-year OS (38.5% vs 54.2%) (hazard ratio [HR], 1.51; 95% CI, 1.29-1.76; P < .001). Overall survival was inferior with adjuvant CRT on multivariate analysis (HR, 1.22; 95% CI, 1.03-1.44; P = .02) and propensity score-matched analysis (HR, 1.20; 95% CI, 0.98-1.47; P = .08) compared with RT alone. Subgroup analyses by age, comorbidity score, primary site, histologic type, grade, T stage, N stage, margin status, and chemotherapy (single agent vs multiagent) demonstrated equivalent or shorter OS with the addition of chemotherapy to RT. Conclusions and Relevance This large analysis compared survival outcomes between postoperative CRT and RT alone in patients undergoing resection of high-risk major SGCs using a nationally representative database. The addition of concurrent chemotherapy to RT in patients with high-risk major SGCs did not offer an advantage in OS.

Dosimetric and deformation effects of image‐guided interventions during stereotactic body radiation therapy of the prostate using an endorectal balloon

PURPOSE During stereotactic body radiation therapy (SBRT) for the treatment of prostate cancer, an inflatable endorectal balloon (ERB) may be used to reduce motion of the target and reduce the dose to the posterior rectal wall. This work assessed the dosimetric impact of manual interventions on ERB position in patients receiving prostate SBRT and investigated the impact of ERB interventions on prostate shape. METHODS The data of seven consecutive patients receiving SBRT for the treatment of clinical stage T1cN0M0 prostate cancer enrolled in a multi-institutional, IRB-approved trial were analyzed. The SBRT dose was 50 Gy in five fractions to a planning target volume (PTV) that included the prostate (implanted with three fiducial markers) with a 3-5 mm margin. All plans were based on simulation images that included an ERB inflated with 60 cm(3) of air. Daily kilovoltage cone-beam computed tomography (CBCT) imaging was performed to localize the PTV, and an automated fusion with the planning images yielded displacements required for PTV relocalization. When the ERB volume and/or position were judged to yield inaccurate repositioning, manual adjustment (ERB reinflation and/or repositioning) was performed. Based on all 59 CBCT image sets acquired, a deformable registration algorithm was used to determine the dose received by, displacement of, and deformation of the prostate, bladder (BLA), and anterior rectal wall (ARW). This dose tracking methodology was applied to images taken before and after manual adjustment of the ERB (intervention), and the delivered dose was compared to that which would have been delivered in the absence of intervention. RESULTS Interventions occurred in 24 out of 35 (69%) of the treated fractions. The direct effect of these interventions was an increase in the prostate radiation dose that included 95% of the PTV (D95) from 9.6 ± 1.0 to 10.0 ± 0.2 Gy (p = 0.06) and an increase in prostate coverage from 94.0% ± 8.5% to 97.8% ± 1.9% (p = 0.03). Additionally, ERB interventions reduced prostate deformation in the anterior-posterior (AP) direction, reduced errors in the sagittal rotation of the prostate, and increased the similarity in shape of the prostate to the radiotherapy plan (increased Dice coefficient from 0.76 ± 0.06 to 0.80 ± 0.04, p = 0.01). Postintervention decreases in prostate volume receiving less than the prescribed dose and decreases in the voxel-wise displacement of the prostate, bladder, and anterior rectal wall were observed, which resulted in improved dose-volume histogram (DVH) characteristics. CONCLUSIONS Image-guided interventions in ERB volume and/or position during prostate SBRT were necessary to ensure the delivery of the dose distribution as planned. ERB interventions resulted in reductions in prostate deformations that would have prevented accurate localization of patient anatomy.

Impact of facility volume on outcomes in patients with squamous cell carcinoma of the anal canal: Analysis of the National Cancer Data Base

Given the rarity of anal cancer and the technical aspects involved in radiation (RT) planning, the authors conducted a population‐based analysis evaluating the impact of radiation oncology facility volume on overall survival (OS) in patients with squamous cell carcinoma (SCC) of the anal canal.

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.