Systematic Review of the Incidence of Chest Wall Toxicity Following Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer

Abstract

Stereotactic body radiation therapy (SBRT) is well tolerated with high local control rates in patients with stage I and stage II medically inoperable non-small cell lung cancer (NSCLC). Radiation-induced chest wall pain (CWP) and rib fracture (RF) are unique late adverse effects after hypo-fractionated SBRT, however there is variability in the literature on the true incidence and risk factors for CWP and RF in patients with long-term follow-up. We performed a systematic review to determine the pooled incidence of CWP and RF in patients with early stage NSCLC treated with SBRT. A comprehensive literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of English-language published records from 2001-2017 was undertaken using MEDLINE and EMBASE. Titles and abstracts were screened independently by a primary and secondary reviewer. A third reviewer resolved discrepancies. Full-text publication review and data extraction were performed by the primary reviewer. Observational studies and randomized controlled trials were included, while case reports, case series of <20 patients, letters and commentaries were excluded. A total of 548 records were identified through database search. Following abstract exclusion, 73 full-text articles were assessed for eligibility. Of these, 24 were excluded as they did not meet inclusion criteria. Forty-nine full text publications comprising 5919 patients met the inclusion criteria. The median patient age was 67-81 years and median follow-up varied from 12-84 months. Most studies were retrospective in nature. The number of patients evaluated in these studies varied from 22-772. Radiation doses ranged from 16-70 Gy in 1-10 fractions. Results across studies were heterogeneous due to differences in grading, tumor location and the observational nature of the studies. Nonetheless, the pooled incidence of reported CWP was estimated to be 6.8%, and the estimated pooled incidence of reported RF was 4.5%. A total of 24 studies reported grade of CWP toxicity; of these, 57 of 313 patients with CWP (18.2%) reported grade 3 and 4 pain (no grade 5 reported). A total of 18 studies reported RF toxicity grading; of these, grade 3 and 4 toxicity was observed in 13 of 114 patients (11%) who had RF. In the studies that reported SBRT dosimetry, a high chest wall V30 was an important common predictor of CWP and RF. Results from this review demonstrate low rates of CWP and RF following SBRT across a broad spectrum of stage I and II NSCLC patients. However, tumor location, accurate reporting of toxicity and dose-fractionation schemes may relatively increase or decrease these rates. Prospective correlation with dose/volume metrics and assessment of quality of life will further improve understanding of the effects of CWP and RF following SBRT.