Patterns of Care and Outcomes in Non-Operative, Early-Stage Non-Small Cell Lung Cancer when Stereotactic Body Radiation Therapy is not Feasible

Abstract

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is the standard of care treatment for non-operative patients with early-stage non-small cell lung cancer (NSCLC). However, there are cases where safe delivery of SBRT is precluded (e.g., ultracentral tumors or those abutting brachial plexus/stomach) or where SBRT is not available (e.g., centers without SBRT capability). The optimal management with regards to radiation dose/fractionation and whether sensitizing chemotherapy should be considered is unclear. <h3>Materials/Methods</h3> We identified node-negative NSCLC patients with tumors <3 cm (cT1 N0) who received definitive RT in the National Cancer Data Base from 2004-2016. Patients receiving SBRT (defined as 48-60 Gy in £5 fractions or BED₁₀≥100 Gy) were excluded. The use of chemotherapy (none vs. sequential vs. concurrent) and RT type was examined (conventionally fractionated, [CFRT], defined as 59.4-70.2 Gy in 30-39 fractions; and hypofractionated RT [HFRT] defined as 50-72 Gy in >5 fractions using >2 Gy/fraction). Factors associated with receipt of chemotherapy were analyzed via univariable (UV) and multivariable (MV) logistic regression. Overall survival (OS) was evaluated with Kaplan-Meier analyses and log-rank test as well as UV and MV Cox proportional hazards. Propensity score matching was also performed for comparison of OS between groups. P-values less than 0.05 were considered significant. <h3>Results</h3> A total of 2,851 patients were included with 69% receiving CFRT and 31% receiving HFRT. Nearly 26% of patients received chemotherapy, delivered either concurrently (21%) or sequentially (5%). On MV analysis, receipt of chemotherapy was associated with younger age (<70 years, p<0.001), larger tumor size (2+ cm, p<0.001), BED₁₀<80 Gy (p<0.001) and receipt of CFRT (p<0.001). OS was significantly improved for patients receiving concurrent chemotherapy with CFRT compared to patients receiving CFRT alone (p<0.001) and HFRT alone (p=0.003), which remained significant after propensity score matching. On MV analysis, improved OS remained associated with concurrent chemotherapy (p<0.001), as was younger age (<70 years, p=0.024), female gender (p<0.001), fewer comorbidities (Charlson-Deyo score <2, p<0.001), private insurance (p<0.001), treatment at an academic center (p=0.026), smaller tumor size (<2 cm, p<0.001), and non-squamous histology (p=0.004). <h3>Conclusion</h3> Patterns of care for non-operative early-stage NSCLC patients when SBRT is not feasible vary greatly. A surprising proportion of patients (21%) receive concurrent chemotherapy. Interestingly, concurrent chemotherapy with CFRT was associated with improved OS compared to HFRT or CFRT alone, however this finding requires additional validation given the inherent biases of our study.