Project description:BackgroundThe purpose of this study is to describe stereotactic body radiation therapy (SBRT) use, outcomes, hospitalizations and costs compared to patients receiving chemotherapy among patients with metastatic non-small cell lung cancer (NSCLC).MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified patients aged ≥66 with metastatic NSCLC treated with SBRT as first-line treatment between 2004 and 2014. Multivariable logistic regression identified covariates associated with SBRT. Overall survival (OS) between SBRT and chemotherapy was compared using the Kaplan-Meier estimator and Cox proportional hazards regression. To compare hospitalizations and associated costs, we matched patients treated with SBRT to those with comparable prognostic factors receiving chemotherapy.ResultsWe identified 215 patients with metastatic NSCLC who received SBRT and 12,486 patients who received chemotherapy as first-line treatment. SBRT use increased from 0.5% to 3% and was associated with older age, female sex, poor disability status, and lower T- and N-stage. OS increased with SBRT, female sex, higher income and decreased with higher Charlson Comorbidity Score ≥2, poor disability status, higher T-stage and higher N-stage. Among a matched sample, SBRT patients underwent fewer hospitalizations vs. chemotherapy patients (73% vs. 81%, P=0.02). Among those hospitalized, SBRT patients incurred higher hospitalization costs ($33,063 vs. $23,865, P<0.001) but costs per month of survival were similar.ConclusionsSBRT is increasing among Medicare patients with metastatic NSCLC. Our findings suggest that SBRT may play a role in management of select metastatic NSCLC patients in addition to standard-of-care chemotherapy.
Project description:Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.
Project description:INTRODUCTION/BACKGROUND:Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. MATERIALS AND METHODS:We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. RESULTS:A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. CONCLUSION:GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.
Project description:IntroductionRadiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC).Materials and methodsRetrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006-2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p < 0.05.ResultsRIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL.DiscussionSBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.
Project description:PurposeNumerous dose and fractionation schedules have been used to treat medically inoperable stage I non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy. We evaluated published experiences with SBRT to determine local control (LC) rates as a function of SBRT dose.Methods and materialsOne hundred sixty published articles reporting LC rates after SBRT for stage I NSCLC were identified. Quality of the series was assessed by evaluating the number of patients in the study, homogeneity of the dose regimen, length of follow-up time, and reporting of LC. Clinical data including 1, 2, 3, and 5-year tumor control probabilities for stages T1, T2, and combined T1 and T2 as a function of the biological effective dose were fitted to the linear quadratic, universal survival curve, and regrowth models.ResultsForty-six studies met inclusion criteria. As measured by the goodness of fit χ2/ndf, with ndf as the number of degrees of freedom, none of the models were ideal fits for the data. Of the 3 models, the regrowth model provides the best fit to the clinical data. For the regrowth model, the fitting yielded an α-to-β ratio of approximately 25 Gy for T1 tumors, 19 Gy for T2 tumors, and 21 Gy for T1 and T2 combined. To achieve the maximal LC rate, the predicted physical dose schemes when prescribed at the periphery of the planning target volume are 43 ± 1 Gy in 3 fractions, 47 ± 1 Gy in 4 fractions, and 50 ± 1 Gy in 5 fractions for combined T1 and T2 tumors.ConclusionsEarly-stage NSCLC is radioresponsive when treated with SBRT or stereotactic ablative radiation therapy. A steep dose-response relationship exists with high rates of durable LC when physical doses of 43-50 Gy are delivered in 3 to 5 fractions.
Project description:The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an "abscopal effect" although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This "quadmodality" approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.
Project description:ObjectiveThe objective of this study was to characterize patients at an increased risk of distant metastasis (DM) following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC).Materials and methodsWe identified patients undergoing SBRT for stage I NSCLC between 2005 and 2016. Patients with a prior lung cancer diagnosis, receiving a biological effective dose <100 Gy, or receiving chemotherapy were excluded. Patients underwent pretreatment staging and were classified according to the American Joint Committee for Cancer (AJCC) 8th edition staging. The primary endpoint was DM. The Kaplan-Meier method and the Cox proportional hazards model were used for survival analysis and to identify predictors of DM.ResultsA total of 174 patients were included, with a median age 75 years (range, 49 to 96 y) and a median follow-up of 24 months (range, 3 to 123 mo). The 2- and 4-year cumulative incidences of DM were 14.2% and 19.1%, respectively. Patients who developed DM had worse overall survival versus patients developing a locoregional recurrence (P=0.023). On multivariable analysis, having stage IB disease (hazard ratio: 2.95; 95% confidence interval: 1.06-8.23; P=0.039) or a lower/middle lobe tumor (hazard ratio: 2.67; 95% confidence interval: 1.07-6.69; P=0.036) was associated with increased risk of DM. The 2-year cumulative incidences of DM were 10.9% and 35.7% (P=0.002) for patients with stage IA versus IB tumors, respectively, and 11.3% and 19.7% (P=0.049) for patients with upper lobe versus lower/middle lobe tumors, respectively.ConclusionsPatients with stage IB disease or lower/middle lobe tumors may have an increased risk of DM following SBRT. Randomized controlled trials are needed to further identify patients who may benefit from adjuvant systemic therapy after SBRT for stage I NSCLC.
Project description:IntroductionThe present study explores changes in pulmonary function, symptoms and radiological signs of pneumonitis after curatively intended stereotactic body radiation therapy (SBRT).MethodsAll inoperable, early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy (SBRT) from 2014-2017 were included in this single-centre study. They were followed regularly for 12 months after treatment. The patients were classified into three groups based on radiology and symptomatology: no radiation pneumonitis, asymptomatic and symptomatic radiation pneumonitis.ResultsForty-four patients with stage IA-IIB disease were treated with 45-56 Gy in 3-8 fractions. The median age was 75 years, 43% of the patients were female; 60% of the patients had a COPD in GOLD grade of 2-4, and 95.5% were active or former smokers. Symptomatic radiation pneumonitis occurred in 18% of the patients and asymptomatic pneumonitis as defined by radiology, in 39%. The mean of forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO) decreases for all patients during the first years were higher than one would expect from physiologic ageing. FEV1 and DLCO in percent decrease 7-8% at 1-1.5 months in the symptomatic radiation pneumonitis group. CT scan findings consistent with radiation pneumonitis occurred after a median of 2.9 months in the symptomatic and 5.4 months in the asymptomatic radiation pneumonitis groups. In the group with symptomatic radiation pneumonitis, symptoms, as measured by the Clinical COPD questionnaire score, significantly increased at 3 and 6 months. Significant higher maximum doses to the critical lung volumes DC1000cm3 (1000 cm3 of lung receiving a given dose or less) and DC 1500cm3 (1500 cm3 of lung receiving a given dose or less) were observed in patients who developed radiation pneumonitis.ConclusionEarly decrease in measured FEV1 and DLCO occurred before imaging changes and symptoms and might indicate the development of symptomatic radiation pneumonitis. The dose to critical lung volumes of DC1000 cm3 and DC1500 cm3 may predict the risk for the development of symptomatic radiation pneumonitis.