Surgical Outcomes for Early Stage Non-small Cell Lung Cancer at Facilities With Stereotactic Body Radiation Therapy Programs.

BACKGROUND: Patients undergoing surgery for early stage non-small cell lung cancer (NSCLC) may be at high risk for postoperative mortality. Access to stereotactic body radiation therapy (SBRT) may facilitate more appropriate patient selection for surgery. RESEARCH QUESTION: Is postoperative mortality associated with early stage NSCLC lower at facilities with higher use of SBRT? STUDY DESIGN AND METHODS: Patients with early stage NSCLC reported to the National Cancer Database between 2004 and 2015 were included. Use of SBRT was defined by each facility's SBRT experience (in years) and SBRT to surgery volume ratios. Multivariate logistic regression was used to test for the associations between SBRT use and postoperative mortality. RESULTS: The study cohort consisted of 202,542 patients who underwent surgical resection of cT1-T2N0M0 NSCLC tumors. The 90-day postoperative mortality rate declined during the study period from 4.6% to 2.6% (P < .001), the proportion of facilities that used SBRT increased from 4.6% to 77.5% (P < .001), and the proportion of patients treated with SBRT increased from 0.7% to 15.4% (P < .001). On multivariate analysis, lower 90-day postoperative mortality rates were observed at facilities with > 6 years of SBRT experience (OR, 0.84; 95% CI, 0.76-0.94; P = .003) and SBRT to surgery volume ratios of more than 17% (OR, 0.85; 95% CI, 0.79-0.92; P < .001). Ninety-day mortality also was associated with surgical volume, region, year, age, sex, and race, among other covariates. Interaction testing between these covariates showed negative results. INTERPRETATION: Patients who underwent resection for early stage NSCLC at facilities with higher SBRT use showed lower rates of postoperative mortality. These findings suggest that the availability and use of SBRT may improve the selection of patients for surgery who are predicted to be at high risk of postoperative mortality.

Improved Progression-Free Survival for Bulky and Non-Bulky Advanced Stage Diffuse Large B-Cell Lymphoma With Consolidative Radiation Therapy: A Bi-Institutional Analysis.

Background The role of consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) is not fully established. A growing body of data suggests a role for consolidative RT in select stage III-IV DLBCL patients and emerging data from randomized studies further address the role of RT in advanced-stage patients initially presenting with bulky disease. Methods Patients with treatment-naive stage III-IV DLBCL treated at two institutions who achieved a clinically complete response to systemic therapy were included. Patients with either bulky or non-bulky disease were included, but those with the relapsed or refractory disease were excluded. Kaplan-Meier analysis was performed to determine the impact of consolidative RT. Univariate and multivariable analyses were performed using a Cox proportional hazards model. Results One hundred eighty-eight patients received systemic therapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 79%), another rituximab-based regimen (9%), or chemotherapy alone (12%). Clinical response was assessed using conventional CT or PET-CT. Sixty-eight patients (36%) received consolidative RT (median dose 30 Gy). Consolidative RT conferred a 36.7% absolute benefit in five-year progression-free survival (PFS; 85.9% vs. 49.2%, log rank p < 0.0001), a 14.5% absolute benefit in five-year overall survival (OS; 87.4% vs. 72.9%, log rank p = 0.0134), and a 37.0% absolute benefit in five-year LC (91.9% vs. 54.9%, log rank p < 0.0001). On multivariable analysis, consolidative RT was associated with improved PFS (HR 0.23, 95% CI 0.10-0.52, p < 0.001) and LC (HR 0.20, 95% CI 0.07-0.59, p = 0.003). Patients receiving consolidative RT demonstrated significantly improved PFS for tumors measuring both <5 cm (log rank p = 0.0454) and ≥5 cm (log rank p = 0.0003). Conclusions For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with the non-bulky disease. This benefit persists in the setting of rituximab-based systemic therapy.

Comparison of Single- and Three-fraction Schedules of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-Small-cell Lung Cancer.

BACKGROUND: To compare the clinical outcomes of patients with early-stage non-small-cell lung cancer (NSCLC) who had undergone either single-fraction (SF) or three-fraction (TF) stereotactic body radiation therapy (SBRT) at a single institution during over 8-year period. PATIENTS AND METHODS: Patients with peripherally located early-stage NSCLC who had undergone SBRT from February 2007 to November 2015 were included in the present study. SBRT was delivered without heterogeneity correction. Data were retrospectively reviewed and collected in an institutional review board-approved database. R software (version 3.3.2) was used for statistical analysis. RESULTS: Of 159 total lung tumors, 65 lesions received 30 Gy (median, 30 Gy) in 1 fraction, and 94 lesions received 48 to 60 Gy (median, 60 Gy) in 3 fractions. Patients with a Karnofsky performance status < 80 were more common in the SF-SBRT cohort (P = .050). After a median follow-up of 22.2 and 26.2 months for the SF-SBRT and TF-SBRT cohorts, respectively (P = .29), no statistically significant difference was found in overall survival (P = .86), progression-free survival (P = .95), local failure (P = .95), nodal failure (P = .91), and distant failure (P = .49) at 24 months. At 1 and 2 years, the overall survival rates were 86.1% and 63.2% for the SF-SBRT cohort and 80.8% and 61.6% for the TF-SBRT cohort, respectively. At 1 and 2 years, the local control rates were 95.1% and 87.8% for the SF-SBRT cohort and 92.7% and 86.2% for the TF-SBRT cohort, respectively. Both regimens were well tolerated. CONCLUSION: Despite more patients with poor performance status in the SF-SBRT cohort, the SF- and TF-SBRT regimens showed no differences in clinical outcomes. SF-SBRT is now our standard approach.

Three- Versus Five-Fraction Regimens of Stereotactic Body Radiotherapy for Peripheral Early-Stage Non-Small-Cell Lung Cancer: A Two-Institution Propensity Score-Matched Analysis.

PURPOSE: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database. RESULTS: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. CONCLUSION: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.

Stereotactic radiotherapy for prostate cancer: A review and future directions.

Prostate cancer affects over 200000 men annually in the United States alone. The role of conventionally fractionated external beam radiation therapy (RT) is well established as a treatment option for eligible prostate cancer patients; however, the use of stereotactic body radiotherapy (SBRT) in this setting is less well defined. Within the past decade, there have been a number of studies investigating the feasibility of SBRT as a potential treatment option for prostate cancer patients. SBRT has been well studied in other disease sites, and the shortened treatment course would allow for greater convenience for patients. There may also be implications for toxicity as well as disease control. In this review we present a number of prospective and retrospective trials of SBRT in the treatment of prostate cancer. We focus on factors such as biochemical progression-free survival, prostate specific antigen (PSA) response, and toxicity in order to compare SBRT to established treatment modalities. We also discuss future steps that the clinical community can take to further explore this new treatment approach. We conclude that initial studies examining the use of SBRT in the treatment of prostate cancer have demonstrated impressive rates of biochemical recurrence-free survival and PSA response, while maintaining a relatively favorable acute toxicity profile, though long-term follow-up is needed.

Comparison of single- and five-fraction schedules of stereotactic body radiation therapy for central lung tumours: a single institution experience.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer who are medically inoperable or decline surgery. Here we compare the outcome of patients with centrally located lung tumours who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years. METHODS: Between January 2009 and October 2014, patients with centrally located lung tumours who underwent SBRT were included in this study. Data were retrospectively collected using an institutional review board-approved database. For analysis, the Kaplan-Meier method and competing risks method were used. RESULTS: In total, 11 patients received 26-30 Gy in 1 fraction, whereas 31 patients received 50-60 Gy (median 55 Gy) in 5 fractions. After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p = 0.64), 1-year overall survival rates were 82 and 87%, respectively. SF- and FF-SBRT groups showed no significant difference in grade 3+ toxicity (p = 0·28). The only grade 4 toxicity (n = 1) was reported in the SF-SBRT group. All toxicities occurred >12 months after the SBRT. CONCLUSIONS: SF- and FF-SBRT have comparable overall survival. SF-SBRT may have some utility for patients unable to have multi-fraction SBRT.

Continuous-flow particle separation by 3D Insulative dielectrophoresis using coherently shaped, dc-biased, ac electric fields.

We present the development of a continuous-flow, "dielectrophoretic spectrometer" based on insulative DEP techniques and three-dimensional geometric design. Hot-embossed thermoplastic devices allow for high-throughput analysis and geometric control of electric fields via ridged microstructures patterned in a high width-to-depth aspect ratio (250:1) channel. We manipulate particles with dc-biased, ac electric fields and generate continuous-output streams of particles with a transverse outlet position specified by linear and nonlinear particle mobilities. We show, with simulation and experiment, that characteristic shape factors can be defined that capture the effects of constrictions in channel depth and that modulating the angle of these constrictions changes the resulting local DEP force. Microdevices are fabricated with an insulative constriction in channel depth, whose angle of incidence with the direction of flow varies continuously across the channel width. The resulting electric field gradients enable demonstration of a dielectrophoretic spectrometer that separates particles and controls their transverse channel position.