V. Osborn

Characterization, treatment and outcomes of salivary ductal carcinoma using the National Cancer Database

OBJECTIVES To analyze clinical, treatment and outcome data for patients with salivary ductal carcinoma in a large population-based sample. MATERIALS AND METHODS The National Cancer Database was queried to identify patients diagnosed with salivary ductal carcinoma between 2004 and 2013. Kaplan Meier and Cox regression analysis were used to assess overall survival (OS) and identify impact of specific variables on OS. RESULTS A total of 495 patients were identified. The most common site of tumor origin was the parotid (80%). 130 patients (26.3%) presented with early stage (I-II) disease, 257 patients (51.9%) with locoregionally advanced pathologic stage (III-IVB) disease and 41 patients (8.3%) with metastatic disease. The 5year OS for these patients was 79.5%, 40.4% and 0% respectively. At presentation, 46.6% had node positive disease. Surgery was performed in 100% of patients with early stage disease, 98.4% with advanced disease and 90.2% with metastatic disease. Radiation therapy, generally postoperative radiation, was given to 58.5% of patients with stage I-II disease, 71.6% with stage III-IVB disease and 53.7% with metastatic disease. Chemotherapy was utilized in 5.4% of patients with stage I-II disease, 35% with stage III-IVB and 70.7% with metastatic disease. On multivariable analysis, there were no significant differences in OS based on receipt of adjuvant radiotherapy, chemotherapy, or chemoradiotherapy. CONCLUSION Salivary ductal carcinoma represents an uncommon and aggressive subset of salivary tumors for which current adjuvant treatments do not have a detectable impact on overall survival.

Patterns of care and survival of adjuvant radiation for major salivary adenoid cystic carcinoma: Adjuvant Radiation for Adenoid Cystic

National Cancer Care Network guidelines suggest consideration of adjuvant radiation even for early stage adenoid cystic carcinoma of the salivary glands. We used the National Cancer Data Base (NCDB) to analyze practice patterns and outcomes of postoperative radiotherapy for adenoid cystic carcinomas.

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.

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.

Impact of Adjuvant Radiotherapy for Malignant Salivary Gland Tumors

Objective Using the National Cancer Database (NCDB), we investigated the characteristics, outcomes, and benefits of adjuvant therapy for patients diagnosed with malignant salivary gland tumors between 2004 and 2012. Study Design Retrospective analysis. Setting NCDB. Subject and Methods The cases of patients diagnosed with a nonmetastatic major salivary gland tumor who underwent resection between 2004 and 2012 were abstracted from the NCDB. Patients were further included if they had pT1-4NX-1M0 high-grade disease or pT3-4NX-0M0 or pT1-4N1M0 low-grade disease. Patients were identified as having no postoperative radiation therapy or having received postoperative radiation therapy to a dose of 5000 and 7000 cGy to the head and neck region or the parotid region, and their characteristics and outcomes were compared. Results During the study period, 4068 patients met the inclusion criteria for this analysis, of which 2728 (67.1%) received postoperative radiation and 1340 (32.9%) did not. With a median follow-up of 49.1 months, there was a significant improvement in overall survival associated with those receiving postoperative radiation (5 years, 56% vs 50.6%). On multivariable analysis, radiation utilization (hazard ratio, 0.78; 95% CI, 0.71-0.86; P < 0.001) and female sex (hazard ratio, 0.88) were associated with improved survival. When the analysis was limited to patients ≤65 years old, the survival benefit was persistent on multivariable analysis. Conclusion In conclusion, in this large NCDB study of 4068 patients with locally advanced malignant salivary gland carcinoma, administering adjuvant radiotherapy was associated with improved overall survival.

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.

The utilization of MGMT promoter methylation testing in United States hospitals for glioblastoma and its impact on prognosis

Multiple studies have identified O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status to be an important prognostic factor in glioblastoma (GBM). We used the National Cancer Data Base (NCDB) to analyze completeness of coding for MGMT as well as to compare outcomes of GBM patients treated with adjuvant chemoradiation based on MGMT promoter methylation status (positive, negative, unknown). Patients diagnosed with GBM from 2010 to 2012 who received adjuvant chemoradiation were identified. MGMT promoter methylation status was obtained. The Kaplan-Meier method was used to assess overall survival (OS) by coding status of MGMT promoter methylation (positive, negative, unknown) and Cox regression analysis was used to assess impact of covariables on OS. There were 12,725 patients who met the study criteria, of which 626 (4.9%) were MGMT+, 1,037 (8.1%) were MGMT- and 11.062 (86.9%) were coded as unknown/not coded. Treatment at academic centers was strongly associated with MGMT promoter status testing (OR 2.23, p < 0.001), as well as hospital facility within the Northeast (OR 1.55, p < 0.001). The median and 2-year OS was 20 months and 40.2% for MGMT+ compared to 15 months and 24.1% for MGMT-, respectively (p < 0.001). For those coded as MGMT unknown, median and 2-year OS was 14.6 months and 27.5%, which was significantly worse compared to MGMT+ (p < 0.001) but not compared to MGMT- (p = 0.78). On multivariable analysis, MGMT+ was strongly associated with improved OS (HR 0.74, p < 0.001). Despite convincing evidence that MGMT promoter methylation status has a strong influence on prognosis; it appears to be a highly underutilized test in United States hospitals.

Patterns of care of IMRT usage in postoperative management of uterine cancer

OBJECTIVE To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. METHODS The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004-2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy. Multivariable logistic regression and multivariable Cox Regression were used to identify covariables that impact IMRT usage and improved survival respectively. RESULTS 7839 women were included in this study. IMRT utilization increased from 1.9% in 2004 to 32.4% in 2012 (p<0.001). The adjusted odds ratio (OR) for IMRT in 2012 compared with 2004 was 24.90, 95% CI 15.24-40.67 (p<0.001). Aside from year, other predictors of IMRT usage on multivariate analysis were positive nodes, higher dose, private insurance and higher income. Black race was associated with lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44-0.81 (p=0.001). IMRT was not associated with significantly increased survival (HR 0.86, 95% CI 0.73-1.01, p=0.06). Black race and positive nodes were associated with decreased survival within the group studied whereas private insurance and higher income were associated with improved survival. CONCLUSIONS In this hospital-based registry, IMRT has significantly increased in utilization for postoperative radiation in uterine cancer between 2004-2012 although not resulting in significantly improved survival. Socioeconomic and racial disparities exist in the allocation of IMRT usage.

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

Background The optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC. Materials and Methods The NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0‐20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21‐126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8‐ to 2‐Gy fractions. Kaplan‐Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS. Results A total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5‐year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5‐year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85‐0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94‐1.04; P = .53). Conclusion These data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC. Micro‐Abstract The present study examined the National Cancer Data Base to assess the practice patterns and survival stratified by thoracic radiation therapy (RT) timing in relation to chemotherapy for nonmetastatic small cell lung carcinoma. The early initiation of thoracic RT was associated with improved survival compared with late initiation, in particular, when hyperfractionated RT was used.

Impact of Timing of Adjuvant Chemoradiation for Glioblastoma in a Large Hospital Database

BACKGROUND Although the standard of care for glioblastoma remains maximal safe resection followed by chemoradiation, conflicting reports have emerged regarding the importance of the time interval between these 2 treatments. OBJECTIVE To assess whether differences in the duration between surgery and initiation of chemoradiation for glioblastoma had an impact on overall survival (OS) in a large hospital-based database. METHODS The National Cancer Database was queried to identify patients diagnosed with glioblastoma between 2010 and 2012 treated with surgery followed by chemoradiation. Patients who received biopsy only were excluded. The time from surgery to initiation of radiation therapy was divided into 4 equal quartiles of ≤24, 25 to 30, 31 to 37, and >37 d. Patient characteristics were compared between groups using Pearson Chi Square and Fishers Exact test. OS was analyzed via the Kaplan-Meier method and compared via the log-rank test. Univariable and multivariable Cox regression were performed to assess for impact of covariables on OS. RESULTS A total of 11 652 patients were included in the analysis. Median duration from surgery to radiation was 30 d. On multivariable regression, black race, larger tumor, gross-total resection, methyguanine-methyl transferase (MGMT+), and treatment at an academic facility were associated with a duration >30 d. On multivariable analysis, there were no significant differences when comparing start within 24 d to 25 to 30 d (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.90-1.01, P = .13) or > 37 d (HR 0.97, 95% CI 0.91-1.03, P = .26), although a small OS improvement was seen if initiated within 31 to 37 d (HR 0.93, 95% CI 0.88-0.99, P = .02). CONCLUSION There was no clear association between duration from surgery to initiation of chemoradiation on OS.