Concurrent chemoradiotherapy versus radiotherapy alone for "biopsy-only" glioblastoma multiforme.

BACKGROUND: 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. METHODS: The US National Cancer Data Base was used to identify patients with histologically confirmed, biopsy-only GBM who received either RT alone or CRT from 2006 through 2011. Demographic and clinicopathologic predictors of treatment were analyzed using the chi-square test, the t test, and multivariable logistic regression. OS was evaluated using the log-rank test, multivariable Cox proportional hazard regression, and propensity score-matched analysis. RESULTS: In total, 1479 patients with biopsy-only GBM were included, among whom 154 (10.4%) received RT alone and 1325 (89.6%) received CRT. The median age at diagnosis was 61 years. CRT was associated with a significant OS benefit compared with RT alone (median, 9.2 vs 5.6 months; hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.54-0.76; P < .001). CRT was independently associated with improved OS compared with RT alone on multivariable analysis (HR, 0.71; 95% CI, 0.60-0.85; P < .001). A significant OS benefit for CRT persisted in a propensity score-matched analysis (HR, 0.72; 95% CI, 0.56-0.93; P = .009). CONCLUSIONS: The current data suggest that CRT significantly improves OS in patients with GBM who undergo biopsy only compared with RT alone and should remain the standard of care for patients who can tolerate therapy. Cancer 2016;122:2364-2370. © 2016 American Cancer Society.

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

BACKGROUND: 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. METHODS: Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed. RESULTS: This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P < .001) and a multivariate analysis (hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.837-0.953; P = .001). CRT remained associated with improved OS after propensity score matching (HR, 0.851; 95% CI, 0.793-0.913; P < .001). Subset analyses showed that CRT was associated with improved OS among patients with pT3 (HR, 0.892; 95% CI, 0.828-0.962; P = .003) or pN1 disease (HR, 0.856; 95% CI, 0.793-0.924; P < .001) and both R0 resection (HR, 0.901; 95% CI, 0.839-0.969; P = .005) and R1 resection (HR, 0.842; 95% CI, 0.722-0.983; P = .030). CONCLUSIONS: CRT was independently associated with improved OS after the resection of pancreatic adenocarcinoma in a large national cohort and particularly among patients with R1 resection and pN1 disease. Well-designed randomized comparisons of CRT and CT are urgently needed.

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

BACKGROUND: 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. METHODS: Patients aged ≥70 years with ER-positive ESBC measuring ≤2 cm after lumpectomy with negative resection margins and known RT details were identified in the National Cancer Data Base. Patients were classified by year of diagnosis and segregated into 3 groups relative to the initial publication and updated presentation of the Cancer and Leukemia Group B (CALGB) 9343 trial. RT use overall, prescription of hypofractionated RT, and use of boost RT were compared between groups using logistic regression analysis, and the influence of clinicopathologic covariates was determined with multivariable logistic regression analysis. RESULTS: A total of 122,796 elderly patients with ER-positive ESBC who were diagnosed between 1998 and 2011 were identified. Overall, 84,649 patients (68.9%) received adjuvant RT, with a decline observed between successive cohorts (71.3% in the pre-initial publication cohort, 69.5% in the pre-update cohort, and 64.7% in the post-update cohort; P <.001). Hypofractionated RT use increased among treated patients over time (P<.001). Boost RT was used in 67.5% of patients, with a decline noted between the pre-update and post-update cohorts (68.7% vs 57.7%; P<.001). Overall RT use as well as use of boost RT were found to be lower among older patients and those with lower-grade or smaller tumors (P<.001), whereas hypofractionated RT was used more commonly in these groups (P<.001). CONCLUSIONS: RT use appears to have declined in elderly patients with ER-positive ESBC, a finding that is reflective of evidence-based practice integrating mature trial data. Further research is needed to develop tools to aid in the decision-making process regarding the delivery or avoidance of RT in this setting.

Contemporary Practice Patterns for Palliative Radiation Therapy of Bone Metastases: Impact of a Quality Improvement Project on Extended Fractionation.

PURPOSE: Radiation therapy effectively palliates bone metastases, although variability exists in practice patterns. National recommendations advocate against using extended fractionation (EF) with courses greater than 10 fractions. We previously reported EF use of 14.8%. We analyzed practice patterns within a statewide quality consortium to assess EF use in a larger patient population after implementation of a quality measure focused on reducing EF. METHODS AND MATERIALS: Patients treated for bone metastases within a statewide radiation oncology quality consortium were prospectively enrolled from March 2018 through October 2020. The EF quality metric was implemented March 1, 2018. Data on patient, physician, and facility characteristics; fractionation schedules; and treatment planning and delivery techniques were collected. Multivariable binary logistic regression was used to assess EF. RESULTS: Twenty-eight facilities enrolled 1445 consecutive patients treated with 1934 plans. The median number of treatment plans per facility was 52 (range, 7-307). Sixty different fractionation schedules were used. EF was delivered in 3.4% of plans. Initially, EF use was lower than expected and remained low over time. Significant predictors for EF use included complicated metastasis (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.04-4.02; P = .04), lack of associated central nervous system or visceral disease (OR, 2.27; 95% CI, 1.2-4.2; P = .01), nonteaching versus teaching facilities (OR, 8.97; 95% CI, 2.1-38.5; P < .01), and treating physicians with more years in practice (OR, 12.82; 95% CI, 3.9-42.4; P < .01). CONCLUSIONS: Within a large, prospective population-based data set, fractionation schedules for palliative radiation therapy of bone metastases remain highly variable. Resource-intensive treatments including EF persist, although EF use was low after implementation of a quality measure. Complicated metastases, lack of central nervous system or visceral disease, and treatment at nonteaching facilities or by physicians with more years in practice significantly predict use of EF. These results support ongoing efforts to more clearly understand and address barriers to high-value radiation approaches in the palliative setting.

Chemoradiation after FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer.

BACKGROUND: The safety and efficacy of FOLFIRINOX (FX) followed by consolidative chemoradiation (CRT) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has not been extensively studied. We sought to evaluate outcomes and toxicities of this regimen. METHODS: A retrospective review was performed of 33 patients with BRPC or LAPC treated with FX followed by CRT. Radiotherapy was directed at the primary tumor and any involved nodes (84.8% received 50-50.4 Gy with standard fractionation and concurrent capecitabine, while 15.2% of patients received 36 Gy in 15 fractions with weekly gemcitabine). Toxicities of FX and CRT were graded using Common Terminology Criteria for Adverse Events (CTCAE v4.0), and radiographic response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS), distant metastasis-free survival (DMFS), and local control (LC) were calculated using Kaplan-Meier analyses, and a Cox proportional hazards model was used to assess the impact of clinicopathologic factors on OS. RESULTS: Median follow-up was 19.9 months and patients received a median of 6.4 months of chemotherapy (range, 2.2-12.0 months). There were more T4 tumors than T3 tumors (70% vs. 30%). Grade ≥3 toxicities were low, including fatigue (9.1%), diarrhea (6.1%), neuropathy (6.1%), and dehydration (6.1%). R0 surgical resection was achieved in 5 patients (15.2%) after CRT. Median OS was 22.0 months (91% at 1 year and 45% at 2 years). Median DMFS was 17.8 months (69% at 1 year and 35% at 2 years). LC was 84% at 1 year and 55% at 2 years. CONCLUSIONS: OS is promising with the use of FX in BRPC and LAPC, and consolidative CRT was well tolerated in this cohort. Therefore, the role of radiation after multi-agent chemotherapy should be further evaluated in prospective trials.

Contemporary Statewide Practice Pattern Assessment of the Palliative Treatment of Bone Metastasis.

PURPOSE: Palliative radiation therapy for bone metastases is often viewed as a single entity, despite national guidelines providing input principally only for painful uncomplicated bone metastases. Data surrounding the treatment of bone metastases are often gleaned from questionnaires of what providers would theoretically do in practice or from population-based data lacking critical granular information. We investigated the real-world treatment of bone metastases with radiation therapy. METHODS AND MATERIALS: Twenty diverse institutions across the state of Michigan had data extracted for their 10 most recent cases of radiation therapy delivered for the treatment of bone metastases at their institution between January and February 2017. Uni- and multivariable binary logistic regression was used to assess the use of single fraction (8 Gy × 1) radiation therapy. RESULTS: A total of 196 cases were eligible for inclusion. Twenty-eight different fractionation schedules were identified. The most common schedule was 3 Gy × 10 fractions (n = 100; 51.0%), 4 Gy × 5 fractions (n = 32; 16.3%), and 8 Gy × 1 (n = 15; 7.7%). The significant predictors for the use of single fraction radiation therapy were the presence of oligometastatic disease (P = .008), previous overlapping radiation therapy (P = .050), and academic practice type (P = .039). Twenty-nine cases (14.8%) received >10 fractions (median 15, range 11-20). Intensity modulated radiation therapy was used in 14 cases (7.1%), stereotactic body radiation therapy in 11 (5.6%), and image guidance with cone beam computed tomography in 11 (5.6%). Of the cases of simple painful bone metastases (no previous surgery, spinal cord compression, fracture, soft tissue extension, or overlapping previous radiation therapy; n = 70), only 12.9% were treated with 8 Gy × 1. CONCLUSIONS: Bone metastases represent a heterogeneous disease, and radiation therapy for bone metastases is similarly diverse. Future work is needed to understand the barriers to single fraction use, and clinical trials are necessary to establish appropriate guidelines for the breadth of this complex disease.

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 α/ß=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 α/ß 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.

Patterns of care and outcomes for use of concurrent chemoradiotherapy over radiotherapy alone for anaplastic gliomas.

BACKGROUND AND PURPOSE: The role of concurrent chemoradiotherapy (CRT) for anaplastic gliomas is undefined and patterns of care are under-reported. To address the knowledge gap, we examined use of CRT for grade III gliomas compared to radiotherapy (RT) alone. MATERIAL AND METHODS: In an observational study design cohort from the National Cancer Database, we identified 4437 adult patients receiving surgery followed by either CRT or RT for supratentorial anaplastic glioma in 2003-2011. Univariable and multivariable logistic regression analyses were used to assess factors associated with use of CRT. Overall survival (OS) was assessed by the Kaplan-Meier analysis with log-rank tests, Cox proportional hazards regression modeling, and propensity score matching. RESULTS: Receipt of CRT (vs. RT) was associated with recent year of diagnosis (OR for 2011 (vs. 2003) 3.36, 95% CI 2.49-4.54) and having astrocytoma (vs. oligodendroglioma) (OR 1.37, 95% CI 1.15-1.63). Patients receiving CRT had a lower adjusted hazard of death (hazard ratio 0.72, 95% CI 0.65-0.79). Outcomes were worse for patients ≥60 (HR 6.94, 95% CI 6.09-7.91) and astrocytomas (HR 2.08, 95% CI 1.85-2.34). CONCLUSION: Use of concurrent CRT is associated with more recent year of diagnosis and improved survival relative to RT alone.

Results of the 2013-2015 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States.

PURPOSE: The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice. METHODS AND MATERIALS: During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported. RESULTS: Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent of residents reported inadequate exposure to high-dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years. CONCLUSIONS: This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders.

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.

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.

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.

The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: To determine the effect of biologically effective dose (BED10) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED10 and radiation treatment schedule. The linear-quadratic equation was used to calculate BED10 and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED10. The primary outcome was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED10 was associated with OS. RESULTS: We identified 747 patients who met inclusion criteria. The median BED10 was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED10 had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED10 had a median survival of 22 months (log-rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED10 ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. CONCLUSIONS: We found that dose escalation to 105 Gy BED10 and beyond may improve survival in NSCLC patients treated with SBRT.

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.

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 χ 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.

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.

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.