B.R. Mancini

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.

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.

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.

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.

Influence of a 21-Gene Recurrence Score Assay on Chemotherapy Delivery in Breast Cancer

BACKGROUND We performed an analysis to determine the relative contribution of the Oncotype DX (ODX) recurrence score (RS) results in adjuvant therapy delivery compared with traditional pathologic factors. METHODS AND MATERIALS We performed a retrospective review of women with stage I-IIIA breast cancer treated at the Yale Comprehensive Cancer Center from 2006 to 2012 with available ODX results. We constructed separate logistic models with the clinicopathologic factors alone and also integrating RS and compared these models using the likelihood ratio test and c-statistic to determine whether integration of the RS will result in better prediction of chemotherapy (CTx) delivery. RESULTS We identified 431 women with a median age of 58 years. The RS was low (< 18), intermediate (18-30), and high (> 30) in 56%, 37%, and 7%, respectively. CTx was delivered to 30% of the patients. Age, differentiation, lymphovascular invasion, and progesterone receptor (PR) positivity < 50% were associated with CTx delivery in multivariable logistic regression of clinicopathologic factors alone (P < .05). In the model integrating the RS, an intermediate or a high RS was the most influential factor for CTx delivery (odds ratio, 7.87 vs. 265.35, respectively; P < .0001). The PR results and grade were no longer significant (P = .74 and P = .06, respectively). The integration of the RS resulted in improved model fit and precision, indicated by the likelihood ratio test (ΔG2, 100.782; df = 2; P < .0001) and an improved c-statistic (0.720 vs. 0.856). CONCLUSION Gene expression profiling appears to account for a substantial amount of variability in CTx delivery in current practice. Further work is needed to ensure appropriate test usage and cost-effectiveness.

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.

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.

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.