The fundamental problem of confounding by medical operability in retrospective comparisons of surgery versus stereotactic body radiation therapy for early-stage lung cancer.
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ABSTRACT:
SUBMITTER: Verma V
PROVIDER: S-EPMC6072946 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
The fundamental problem of confounding by medical operability in retrospective comparisons of surgery versus stereotactic body radiation therapy for early-stage lung cancer.
Verma Vivek V Rusthoven Chad G CG
Journal of thoracic disease 20180701 Suppl 18
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Project description:AimTo compare trends and outcomes in early stage bronchopulmonary carcinoid (BPC) tumors treated nonoperatively with conventionally fractionated radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT).Methods/materialsWe queried the National Cancer Database for primary (typical) BPC staged cT1-2N0M0 and treated nonsurgically with lung-directed radiation and ≥1 month of follow-up. Odds ratios were used to predict likelihood of SBRT treatment and multivariable Cox regression determined predictors of survival.ResultsOut of 154 patients, 84 (55%) were treated with SBRT and the remainder were treated with CFRT. Although SBRT use was 0% from 2004 to 2007, it varied from 50 to 70% per year thereafter. Propensity-matched Kaplan-Meier analysis revealed improved survival with lung SBRT (median: 66 vs 58 months; p = 0.034).ConclusionSBRT for early stage, primary BPC has increased over time and was associated with higher survival than CFRT.
| S-EPMC6891931 | biostudies-literature
Project description:The comparative effectiveness of stereotactic body radiation therapy (SBRT) and wedge resection in the treatment of early stage lung cancer is still under debate. This meta-analysis compares the 5-year overall survival (OS) of wedge resection and SBRT in patients with stage I non-small cell lung cancer (NSCLC). Original research articles published between 1995 and 2017 were identified through the National Library of Medicine and National Institutes of Health PubMed database and through the reference lists of reviewed articles. Data were processed and analyzed in R (version 3.4.2) and a summary estimate that accounted for the sample size of each study was calculated. The combined percent survival was calculated using random effect models. Funnel plots were used to assess publication bias. Heterogeneity was tested using the Q statistic and the I2 statistic. There were 16 studies totaling 1,984 patients with stage I NSCLC treated with wedge resection. The meta-estimate was 74% (95% CI, 66-81%), with significant heterogeneity across studies (Q =172.46, P<0.0001; I2=91.30%). Thirty-six studies including 3,309 patients with stage I NSCLC treated with SBRT/SABR produced a meta-estimate of 44% (95% CI, 38-50%), with significant heterogeneity (Q =423.55, P<0.0001; I2=91.74%). Two articles directly comparing stage I NSCLC patients treated with wedge resection to patients treated with SBRT both reported higher 5-year OS after wedge resection. SBRT is a treatment option reserved to medically inoperable patients, but could be an alternative to surgery in medically operable patients who prefer a less invasive treatment. More standardized methods for data collection and reporting are necessary to allow better comparisons across published studies.
| S-EPMC6236177 | biostudies-other
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.
| S-EPMC7703900 | biostudies-literature
Project description:SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.
| S-EPMC10136632 | biostudies-literature
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.
| S-EPMC9446070 | biostudies-literature
Project description:Recent data suggests that "ultra-central" tumors, generally defined as those abutting the proximal airways, are at particularly high risk for severe complications when treated with stereotactic ablative body radiation (SABR). However, this association has not been consistently demonstrated across reports, possibly due to small numbers, varying definitions of "ultra-central", and the lack of prospective data. New evidence suggests that exposure to VEGF-inhibiting agents may potentiate SABR toxicity and may partially explain the disproportionately high incidence of fatal complications in some reports. Efforts are underway to identify dose-volume limits that can predict complications involving central structures such as the proximal airways, heart, esophagus, and great vessels. The optimal dose for ultra-central SABR has not been determined, though there is a trend towards using more highly fractionated regimens. Further research into the safety of SABR for ultra-central tumors is needed, given the lack of other effective local therapy options for this clinical scenario.
| S-EPMC6795582 | biostudies-literature
Project description:Clinical use of stereotactic body radiation therapy (SBRT) has increased dramatically over the last 2 decades and is the current standard-of-care in cases of inoperable early stage non-small-cell lung cancer. While surgical resection remains the standard-of-care for operable patients, several ongoing clinical trials are investigating the role of SBRT in these operative candidates as well. Taking into consideration the expanding role and utility of SBRT, this paper will: review the historical basis of SBRT; examine landmark trials establishing the framework for the current body of evidence; discuss areas of active and future research; and identify epidemiological trends that are likely to further increase the use of SBRT.
| S-EPMC6488937 | biostudies-literature
Project description:Background: To investigate the role of stereotactic body RT (SBRT) in decreased total peripheral lymphocyte count (TLC) in patients with early-stage lung cancer and to explore possible risk factors for RT-induced lymphopenia. Materials and Methods: We analyzed the TLCs and lymphocyte subsets of 76 patients in our prospective clinical database who received SBRT for early-stage lung cancer treatment. Relationships between clinical factors or dosimetric parameters and TLC were evaluated using Spearman's correlation analysis and Chi-square tests for continuous and categorical variables, respectively. Multivariate linear regression analysis was used to control for confounding factors. Kaplan-Meier analysis with a log-rank test and a multivariate Cox regression model were used for survival analysis. Results: Most patients (64/76, 84.2%) experienced decreased absolute lymphocyte counts following SBRT, as well as shifts in lymphocyte subset distributions. Spearman's correlation coefficients between post-SBRT TLC and the percentage of the lung and heart receiving 5 to 50 Gy (in 5 Gy increments) shown that most lung DVH parameters [V(10)-V(50)] were significantly negatively correlated with post-SBRT TLC, while only heart V(5), V(20), V(25), V(30), and V(45) were significant. Univariate analyses revealed that a lower Pre-SBRT TLC level, higher mean lung dose, longer treatment duration, and longer TBT were significantly associated with a lower Post-SBRT TLC level (all P < 0.05). Stepwise multivariate linear regression, which incorporated all of the significantly clinical variables and SBRT-related parameters in univariate analysis, revealed that lower pre -SBRT TLC (P < 0.001), higher heart V5 (P = 0.002), and longer total beam-on time (TBT) (P = 0.001) were the independent risk factors for decrease in post-SBRT TLC. Patients with lower post-SBRT TLC and longer TBT exhibited significantly inferior progression-free survival (PFS) (P < 0.001 and P = 0.013) and overall survival (P = 0.006 and P = 0.043). Conclusions: G2 and more severe lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in early-stage lung cancer. Lowering heart V5 and TBT when designing SBRT plans may spare circulating lymphocytes and have the potential to further improve survival outcomes.
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Project description:Early-stage inclusion body formation is still mysterious. Literature is ambiguous about the existence of rod-shaped protein aggregates, a potential sponge-like inclusion body scaffold as well as the number of inclusion bodies per Escherichia coli cell. In this study, we verified the existence of rod-shaped inclusion bodies, confirmed their porous morphology, the presence of multiple protein aggregates per cell and modelled inclusion body formation as function of the number of generations.
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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.
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