Eileen M. Harder

Central versus Peripheral Tumor Location: Influence on Survival, Local Control, and Toxicity Following Stereotactic Body Radiotherapy for Primary Non-Small-Cell Lung Cancer.

Introduction: Stereotactic body radiotherapy (SBRT) has been increasingly utilized for medically inoperable early stage non–small-cell lung cancer. However, a lower biological equivalent dose (BED) is often used for central tumors given toxicity concerns, potentially leading to decreased local control (LC). We compared survival, LC, and toxicity outcomes for SBRT patients with centrally versus peripherally located tumors. Methods: We included patients with primary cT1-2N0M0 non–small-cell lung cancer treated with SBRT at our institution from September 2007 to August 2013 with follow-up through August 2014. Central tumor location was defined as within 2 cm of the proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Kaplan–Meier analysis and multivariable Cox regression modeling were used for overall survival (OS) and LC, and the &khgr;2 test and multivariable logistic regression modeling were used for toxicity. Results: We included 251 patients (111 central, 140 peripheral) with median follow-up of 31.2 months. Patients with central tumors were more likely to be older (mean 75.8 versus 73.5 years; p = 0.04), have larger tumors (mean 2.5 cm versus 1.9 cm; p < 0.001), and be treated with a lower BED (mean 120.2 Gy versus 143.5 Gy; p < 0.001). Multivariable analysis revealed that tumor location was not associated with worse OS, LC, or toxicity. Patients with central tumors were less likely to have acute grade greater than or equal to three toxicity than those with peripheral tumors (odds ratio: 0.24; p = 0.02). Conclusions: Central tumor location did not predict for inferior OS, LC, or toxicity following SBRT when a lower mean BED was utilized.

Elderly patients undergoing SBRT for inoperable early-stage NSCLC achieve similar outcomes to younger patients

OBJECTIVES It is unclear whether elderly patients face an increased risk of complications following stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC), as has been reported following surgical resection. This study evaluates toxicity and outcomes achieved with SBRT in elderly versus non-elderly patients. MATERIALS AND METHODS We retrospectively identified patients treated with SBRT for cT1-3N0M0 NSCLC between 2007 and 2013. We defined elderly and non-elderly cohorts by age ≥75 and <75. We used chi-square and logistic regression analyses to compare toxicity, and employed Kaplan-Meier, log-rank, and multivariable Cox proportional hazard analyses to assess overall survival (OS), local control (LC), and distant control (DC). RESULTS We identified 251 patients (126 elderly, 125 non-elderly) with a median follow-up of 3.0 years. No differences in acute or late grade ≥3 toxicity were observed. Acute grade ≥3 toxicity was 11.1% in elderly vs. 8.0% in non-elderly (p=0.66). Late grade ≥3 toxicity was 10.3% in elderly vs. 7.2% in non-elderly (p=0.50). There was one grade 5 toxicity (hemoptysis). There were no 3-year OS or LC differences between elderly and non-elderly patients (OS 47.5% vs. 41.0%, p=0.75; LC 84.2% vs. 86.4%, p=0.89). However, 3-year DC was superior in elderly patients (89.1% vs. 76.0%, p=0.01). Improved DC remained associated with elderly age in Cox regression (HR 0.42, p=0.01). CONCLUSION Elderly patients undergoing SBRT for early stage NSCLC appear to have similar risk of toxicity and rate of efficacy as in younger patients. These findings support the use of SBRT in appropriately selected elderly patients.

Angiotensin-converting enzyme inhibitors decrease the risk of radiation pneumonitis after stereotactic body radiation therapy

PURPOSE Although angiotensin-converting enzyme (ACE) inhibitor use during conventionally fractionated radiation therapy has been associated with a decreased risk of radiation pneumonitis (RP), a similar effect has not been demonstrated in stereotactic body radiation therapy (SBRT). The purpose of this study was to examine the impact of ACE inhibitor use during SBRT on the risk of symptomatic (grade ≥2) RP. METHODS AND MATERIALS Patients with at least 1 follow-up treated with SBRT for primary lung cancer were included. ACE inhibitors, angiotensin receptor blockers, statins, nonsteroidal anti-inflammatory drugs, and glucocorticoids were examined. RP was determined from all available medical records, including follow-up appointments with radiation oncology, pulmonology, medical oncology, and hospitalizations. It was scored with the Common Terminology Criteria for Adverse Events, version 4.0. Analysis was performed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS A total of 257 patients met inclusion criteria. Seventy (27.2%) used an ACE inhibitor during SBRT. The overall rates of grade ≥2 and ≥3 RP were 19.1% (n = 49) and 7.0% (n = 18), respectively. ACE inhibitor users experienced greater freedom from symptomatic RP on univariate (vs nonusers, 89.8% vs 76.3% at 12 months, P = .029) and multivariate analysis (hazard ratio 0.373, 95% confidence interval 0.156-0.891, P =.026). The volume of normal lung tissue receiving ≥5 Gy, %, ≥10 Gy, ≥20 Gy, and mean lung dose were also significantly associated with RP on univariate and multivariate analysis. ACE inhibitor use was not associated with overall survival. Angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, glucocorticoids, and statin administration were not associated with symptomatic RP or survival. CONCLUSIONS ACE inhibitor use during SBRT was associated with significantly greater freedom from grade ≥2 RP, even after adjusting for pulmonary dose. Given the data on their protective effect in human and animal models, a prospective evaluation is warranted.

Dose-Volume Predictors of Esophagitis After Thoracic Stereotactic Body Radiation Therapy.

Objectives: Esophageal toxicity has become a major concern as stereotactic hypofractionated radiation therapy is increasingly utilized for central pulmonary tumors. Our purpose was to define esophageal dosimetric parameters that predict potentially dose-limiting toxicities. Materials and Methods: In total, 157 patients with a planning target volume ⩽5 cm from the esophagus were selected from an institutional database. Toxicity was scored with the CTCAE v4.0. Esophageal Dmax and Dv (dose D in Gy covering volume v in mL) in 0.5 mL increments were collected. Corresponding biologically effective dose (BED) was calculated for &agr;/&bgr;=10,3 (BED10, BED3). Normal tissue complication probability was computed with conventionally fractionated radiotherapy parameters and equivalent dose in 2 Gy per fraction (EQD2). Dosimetric predictors were identified with multivariate logistic regression with a manual forward stepwise selection technique. Results: The grade≥2 esophagitis rate was 5.7%. BED10 to 1.5 mL was the best predictor of esophagitis. BED10 to 0.5, 1.0, 2.0, 3.0, and 3.5 mL were also predictive but less strong. Results were similar when BED3 and physical dose were examined. Tumor-esophageal distance correlated with esophagitis (10.5% risk of≥grade 2 events with distance⩽3.9 cm vs. 1.3% when>3.9 cm, P=0.016). BED10 to 1.5 mL correlated well with EQD2 normal tissue complication probability estimates. Conclusions: BED to 1.5 mL was the strongest predictor of grade≥2 esophagitis (independent of &agr;/&bgr; ratio) with a 10.6% toxicity risk when BED10>21.1 Gy (14.3 Gy in 3 fractions, 16.0 Gy in 5). The overall rate of severe toxicity is low, suggesting that higher doses may be tolerable.