D.N. Yeboa

Increase in the use of lung stereotactic body radiotherapy without a preceding biopsy in the United States

BACKGROUND Stereotactic body radiotherapy (SBRT) is an efficacious treatment for early stage non-small cell lung cancer (NSCLC). Patients with clinically suspected NSCLC may have medical comorbidities that increase biopsy risks, making them more likely to receive SBRT without biopsy. This study characterizes the pervasiveness of this management approach nationally. METHODS Patients with stage I NSCLC who received SBRT from 2003 to 2011 were identified within National Cancer Database. Changes in the proportion treated without biopsy were compared by year of diagnosis using binomial logistic regression. Demographics were compared between patients with and without biopsy with Chi-square and t-tests. Multivariate logistic regression was used to determine factors independently associated with SBRT delivery without biopsy. RESULTS We identified 6960 patients. Most had biopsy before SBRT (95.5%). Over time the proportion treated without biopsy increased (OR 1.11, p=0.038). Univariate comparisons demonstrated that older, medically inoperable patients treated at academic centers located in the New England or Pacific regions were less likely to have biopsy before SBRT. Facility type and location (p<0.001), medical inoperability (p<0.001), and smaller tumor size (p=0.013) were associated with odds of SBRT without biopsy in multivariate analyses. A trend toward increased use of SBRT with a biopsy with later year of diagnosis (p=0.093) was observed in multivariate analysis. CONCLUSIONS The percentage of patients nationally undergoing SBRT without biopsy has increased over time. The reasons for this trend and ramifications of this approach on cost-effectiveness of care must be studied.

Contemporary Breast Radiotherapy and Cardiac Toxicity

Long-term cardiac effects are an important component of survivorship after breast radiotherapy. The pathophysiology of cardiotoxicity, history of breast radiotherapy, current methods of cardiac avoidance, modern outcomes, context of historical outcomes, quantifying cardiac effects, and future directions are reviewed in this article. Radiation-induced oxidative stress induces proinflammatory cytokines and is a process that potentiates late effects of fibrosis and intimal proliferation in endothelial vasculature. Breast radiation therapy has changed substantially in recent decades. Several modern technologies exist to improve cardiac avoidance such as deep inspiration breath hold, gating, accelerated partial breast irradiation, and use of modern 3-dimensional planning. Modern outcomes may vary notably from historical long-term cardiac outcomes given the differences in cardiac dose with modern techniques. Methods of quantifying radiation-related cardiotoxicity that correlate with future cardiac risks are needed with current data exploring techniques such as measuring computed tomography coronary artery calcium score, single-photon emission computed tomography imaging, and biomarkers. Placing historical data, dosimetric correlations, and relative cardiac risk in context are key when weighing the benefits of radiotherapy in breast cancer control and survival. Estimating present day cardiac risk in the modern treatment era includes challenges in length of follow-up and the use of confounding cardiotoxic agents such as evolving systemic chemotherapy and targeted therapies. Future directions in both multidisciplinary management and advancing technology in radiation oncology may provide further improvements in patient risk reduction and breast cancer survivorship.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness.

The evolving role of adjuvant radiotherapy for elderly women with early-stage breast cancer

Elderly patients with early‐stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)‐positive ESBC.

Adjuvant chemotherapy and overall survival in adult medulloblastoma

Background Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Methods Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Results Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). Conclusions This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

Concurrent chemoradiotherapy versus radiotherapy alone for “biopsy‐only” glioblastoma multiforme

Combined temozolomide and radiotherapy (RT) is the standard postoperative therapy for glioblastoma multiforme (GBM). However, the clearest benefit of concurrent chemoradiotherapy (CRT) observed in clinical trials has been among patients who undergo surgical resection. Whether the improved survival with CRT extends to patients who undergo “biopsy only” is less certain. The authors compared overall survival (OS) in a national cohort of patients with GBM who underwent biopsy and received either RT alone or CRT during the temozolomide era.

Trend in Age and Racial Disparities in the Receipt of Postlumpectomy Radiation Therapy for Stage I Breast Cancer: 2004-2009.

Objectives:Significant effort has been expended over the past decade to reduce racial disparities in breast cancer care. Whether disparities in receipt of appropriate radiotherapy care for breast cancer persisted despite these efforts is unknown, as is the impact of being eligible for Medicare. We therefore investigated trends in racial differences by age in postbreast lumpectomy radiation therapy (PLRT) from 2004 to 2009. Materials and Methods:We analyzed the Surveillance, Epidemiology and End Results registry database for women aged 40 to 85 years who underwent lumpectomy for stage I breast cancer and were eligible for PLRT. We examined variables potentially associated with the receipt of PLRT, including year of diagnosis, race, and examined women separately by age group. Results:Among 67,124 women aged 40 to 85 years undergoing lumpectomy, receipt of PLRT decreased from 80.7% in 2004 to 76.8% by 2009 (P<0.001). There remained a persistent disparity in PLRT among African American women (in 2004, 80.6% white vs. 78.9% African American and in 2009, 77.5% white vs. 72.0% African American). In multivariable logistic regression, African American race (odds ratio [OR], 0.82; 95% confidence interval [CI]. 0.76-0.89) and being diagnosed more recently were associated with lower odds of PLRT (OR for 2009 vs. 2004: 0.74; 95% CI, 0.69-0.79), whereas older women typically covered by public health insurance (aged 65 to 69 y) were more likely to receive PLRT (OR, 1.09; 95% CI, 1.02-1.15). Conclusions:PLRT decreased by a significant percentage of 3.9% among all women in recent years, and racial disparities in PLRT receipt have persisted. Medicare eligibility increased the likelihood of PLRT receipt.

The Association Between Evaluation at Academic Centers and the Likelihood of Expectant Management in Low-risk Prostate Cancer.

OBJECTIVE To identify factors associated with expectant management (EM) in a large cohort of men with low-risk prostate cancer based on cancer center type (community vs academic). EM, consisting of active surveillance or observation for men with low-risk prostate cancer, is an increasingly recognized management option, given the morbidity and lack of a survival benefit associated with definitive treatment. However, the influence of cancer center type on treatment selection is uncertain. MATERIALS AND METHODS We performed a retrospective analysis of the National Cancer Data Base from 2010 to 2013. Men with low-risk prostate cancer were divided by management strategy into groups consisting of EM or definitive treatment. The association between management strategy and facility type (community vs academic) was characterized using 2-level hierarchical mixed effects logistic regression models. RESULTS There were 52,417 (57%) men evaluated at community centers and 39,139 men (43%) evaluated at academic centers. Patients evaluated at academic centers were significantly more likely to receive EM than those at community centers (17% vs 8%, P < .001). After adjusting for pertinent covariates, evaluation at an academic vs community facility was independently associated with increased odds of EM utilization (adjusted odds ratio 2.70, 95% confidence interval 2.00-3.66). Fifty-one percent of the total variance was explained by interfacility variation. CONCLUSION The likelihood of receiving EM for low-risk prostate cancer was significantly lower in men evaluated at community centers. Further investigation is warranted to elucidate factors that influence the management of low-risk prostate cancer, including individual treatment center patterns.

Comparison of survival outcomes among standard radiotherapy regimens in limited-stage small cell lung cancer patients receiving concurrent chemoradiation

OBJECTIVES The optimal radiotherapy dose in concurrent chemoradiation (CRT) for limited-stage small cell lung cancer (SCLC) is controversial. We compared the effectiveness of several high-dose chemoradiation regimens using a large national dataset. MATERIALS AND METHODS Patients with non-metastatic SCLC treated with concurrent CRT were identified in the National Cancer Database base. Overall survival (OS) of patients receiving dose-fractionation regimens, matching those in the ongoing CALGB 30610 trial [45 Gy in 30 fractions (Fx) (45 Gy/30Fx), 70 Gy in 35 fractions (70 Gy/35Fx), and 61.2 Gy in 34 fractions (61.2 Gy/34Fx)], were compared using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. RESULTS We included 1228 patients treated between 1998 and 2006 with CRT. Mean age was 62 years and 50% of patients were women. Radiotherapy dose-fractionation was 45 Gy/30Fx in 707 (57.6%), 70 Gy/35Fx in 53 (4.3%), and 61.2 Gy/34Fx in 468 (38.1%). Overall survival was similar among patients treated with 45 Gy/30Fx, 70 Gy/35Fx, and 61.2 Gy/34Fx, with median survival times of 21.5, 21.5, and 20.2 months, respectively (p=0.438). Older age, male sex, larger tumor size, and more advanced stage were associated with inferior OS on Kaplan-Meier (all p<0.001). Cox proportional hazards modeling adjusting for these factors demonstrated similar OS among patients receiving these three dose-fractionation regimens (p=0.815). CONCLUSIONS We observed equivalent OS among patients with limited-stage SCLC being treated with three dose-fractionation regimens of concurrent CRT. This supports the use of any one of these regimens while awaiting the results of ongoing randomized trials.

Annual Facility Treatment Volume and Patient Survival for Mycosis Fungoides and Sézary Syndrome

Background: Management of mycosis fungoides and Sézary syndrome (MF/SS) is complex, and randomized evidence to guide treatment is lacking. The institutional treatment volumes for MF/SS might vary widely nationally and influence patient survival. Patients and Methods: Using the National Cancer Database, we identified patients with a diagnosis of MF/SS from 2004 to 2011 in the United States who had received treatment at a reporting facility. The patients were grouped into quintiles according to their treatment facilitys average annual treatment volume (ATV). The characteristics associated with ATV were identified and compared using χ2 tests. Overall survival (OS) was compared among the ATV quintiles using the Kaplan‐Meier method with log‐rank tests and multivariable Cox regression with hazard ratios (HRs). OS was also analyzed using the annual patient volume as a continuous variable. Results: A total of 2205 patients treated at 374 facilities were included for analysis. The ATV quintile cutoffs were 1, 3, 6, and 9 patients. With a median follow‐up period of 59 months, the 5‐year estimated OS survival increased with ATV from 56.7% in the lowest quintile (≤ 1 patient annually) to 83.8% in the highest quintile (> 9 patients annually; P < .001). On multivariable analysis, greater ATV was associated with improved survival when analyzed as a continuous variable (HR, 0.96 per patient per year; 95% confidence interval, 0.94‐0.98; P < .001) and when comparing the highest quintile to the lowest quintile (HR, 0.46; 95% confidence interval, 0.39‐0.55). Conclusion: The present national database analysis demonstrated that higher facility ATV is associated with improved OS for patients with MF/SS. Further study is needed to determine the underlying reasons for improved survival with higher facility ATV. &NA; Mycosis fungoides and Sézary syndrome (MF/SS) management is complex, with heterogeneous treatments. We analyzed a national registry of > 2200 MF/SS patients divided into cohorts by the annual treatment volume quintile of their treatment facility. A greater facility annual treatment volume was associated with improved survival for patients with MF/SS.