Justin Rineer

Prostate biopsy concordance in a large population-based sample: a Surveillance, Epidemiology and End Results study

Aims To use the Surveillance, Epidemiology and End Results database in order to evaluate prostate biopsy concordance in a large population-based sample. Methods We identified 34 195 men who were diagnosed with prostate cancer and underwent a radical prostatectomy from 2010 to 2011. All patients also had to have both clinical and pathological Gleason scores available for analysis. The concordance of the biopsy Gleason score to the pathological Gleason score was analysed using the coefficient of agreement (κ). Univariate and multivariate logistic regression analyses were performed to determine potential factors that may impact concordance of Gleason score. Results Overall, the clinical and pathological Gleason scores matched in 55.4% of patients. The concordance rates were 55.3% for Gleason 6, 66.9% for Gleason 3+4, 42.9% for Gleason 4+3 and 24.8% for Gleason 8, with frequent downgrading to Gleason 7. The κ for Gleason score concordance was 0.36 (95% CI 0.35 to 0.37), indicating fair agreement. The weighted κ for Gleason score concordance was 0.51 (95% CI 0.50 to 0.52), indicating moderate agreement. Additionally, the Bowker tests of symmetry were highly significant (p<0.001), indicating that when discordant findings were present, pathological upgrading was more common than downgrading. Conclusions This study is, to our knowledge, the largest contemporary study of prostate biopsy concordance. We found that there continues to be significant Gleason migration both upward from biopsy Gleason 6 or 3+4 and downgrading from biopsy Gleason ≥8. Further studies are needed to better determine other potential genomic or biologic factors that may help increase the biopsy Gleason concordance.

Radiation therapy for clinically localized prostate cancer: Long-term results of 469 patients from a single institution in the era of dose escalation

AIMS The aim of the following study is to analyze the long-term results of veterans treated with dose escalated radiation therapy for prostate cancer. MATERIALS AND METHODS This retrospective study analyzed 469 patients who were treated between 2003 and 2010 with dose escalated radiation therapy to a minimum dose of 7560 cGy for prostate cancer at the New York Harbor Department of Veterans Affairs. Biochemical failure-free survival (bFFS) and distant metastatic-free survival (DMFS) were compared using the Kaplan-Meier method. Univariate and multivariate Cox Regression were used to measure the impact of covariates on biochemical control. RESULTS The median follow-up was 61 months and 95.3% of patients were followed at least 2 years. The 5-year bFFS for National Cancer Care Network low, intermediate and high risk disease were 90.3%, 86.9% and 77.3% respectively (P=0.001). Patients with high risk disease were more likely to develop metastatic disease. The 5-year DMFS was 99.1% for low risk, 98.8% for intermediate risk and 94.5% for high-risk (P<0.001). There were 8 prostate cancer related deaths, of which 6 had high risk disease and 2 had intermediate risk disease. The 5-year prostate cancer specific survival was 98.4%. Toxicities were generally mild, however there were two genitourinary toxicity related deaths, though in both patients there were confounding medical issues that may have contributed to their deaths. CONCLUSIONS Dose escalated radiation in the treatment of United States Veterans appears to be well-tolerated with results in line with prior reports. Further follow-up is necessary to identify any additional late toxicities as well as to assess the durability of their biochemical control beyond 5 years.

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.

Utilization of Hyperfractionated Radiation in Small-Cell Lung Cancer and Its Impact on Survival

Introduction: Twice-daily radiation with concurrent chemotherapy is recognized as the standard of care for the treatment of limited stage small-cell lung carcinoma (SCLC), but its utilization in this setting is unclear. The objective of this study was to analyze modern patterns of treatment for limited stage SCLC and the impact on survival utilizing the National Cancer Database. Methods: Between 1999 and 2012, there were 25,045 patients diagnosed with nonmetastatic SCLC who met the selection criteria, of whom 22,626 had survival data. Those receiving 45 Gy in 1.5 Gy fractions twice-daily (BID) were compared with those receiving 45 to 72 Gy in 1.8 or 2.0 Gy fractions. Overall survival was analyzed via Kaplan–Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with survival. Results: The utilization of BID radiation overall was 11.3%. Treatment at an academic center was associated with a higher likelihood of receiving BID treatment (odds ratio: 2.29, 95% confidence interval [CI]: 1.95–2.69; p < 0.001). Median survival was 22.1, 17.2, 18.3, 19.2, and 19.5 months for patients receiving 45 Gy BID, 45 Gy once-daily, 46 to 59.4 Gy once-daily, 60 to 61.2 Gy once-daily, and 62 to 72 Gy once-daily, respectively (p < 0.001 for all pairwise comparisons to BID). On multivariate analysis, treatment at an academic center (hazard ratio: 0.88, 95% CI: 0.83–0.93; p < 0.001) and receipt of BID radiation (hazard ratio: 0.92, 95% CI: 0.86–0.98; p = 0.008) were associated with improved survival. Conclusions: The adoption of BID radiation remains very limited, but is more commonly utilized in the academic setting. In this hospital-based study, BID fractionation was associated with improved survival over once-daily fractionation, even at doses ≥60 Gy.

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.

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.