Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors

Abstract

BackgroundAs stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated.MethodsBetween November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of α/β ratios (1–10 Gy). Receiver operating characteristics analysis was used to define the most appropriate α/β ratio.ResultsRib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy.ConclusionsRib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.

Exploratory analysis using machine learning to predict for chest wall pain in patients with stage I non‐small‐cell lung cancer treated with stereotactic body radiation therapy

“…In this cohort, 11 (5.6%) patients developed CTCAE v4 grade ≥2 chest wall pain. Prior studies suggest rates of CWS, or chest wall pain without evidence of rib fracture, range from 2% to 8%14, 17, 19 after SBRT, consistent with our observations. Conventional analyses struggle to identify meaningful clinically relevant thresholds for predicting toxicity due to the low number of absolute events.…”

“…One challenge in evaluating predictive factors for CWS is the low and varying range of events observed 14, 17, 19. Machine learning has previously been used in radiation oncology for a variety of problems, from quality assurance to outcome prediction 20, 21, 22, 23, 24, 25, 26.…”

Dosemetric Parameters Predictive of Rib Fractures after Proton Beam Therapy for Early-Stage Lung Cancer

“…In our study, grade 2 RFs occurred in 12 patients following PBT (19.4%), with a three-year cumulative incidence rate of 30.2%. With regard to SRT, several groups reported RFs frequencies ranging from 4% to 37.7% after SRT for earlystage NSCLC; these rates were not much higher compared with those observed in our study (30.2%) (Pettersson et al 2009;Dunlap et al 2010;Andolino et al 2011;Welsh et al 2011;Asai et al 2012;Creach et al 2012;Mutter et al 2012;Stephans et al 2012;Taremi et al 2012;Nambu et al 2013). Although PBT reportedly offers advantages over SRT, it has not been reported to dramatically reduce RFs incidence (Georg et al 2008;Kadoya et al 2011).…”

“…However, desired dose applications within target volumes are limited because of the proximity to critical normal tissues. Also, the incidence of rib fractures (RFs) following SRT for early-stage lung cancer ranges from 4% to 37.7% (Pettersson et al 2009;Dunlap et al 2010;Andolino et al 2011;Welsh et al 2011;Asai et al 2012;Creach et al 2012;Mutter et al 2012;Stephans et al 2012;Taremi et al 2012;Nambu et al 2013).…”

“…The risk factors and dose parameters for RFs have been analyzed in several previous studies (Taremi et al 2012;Nambu et al 2013). However, little is known regarding RFs following PBT, which often cause prolonged pain, long-term disability, and a decreased quality of life (Richardson et al 2007;Nirula and Mayberry 2010;Kanemoto et al 2013). Therefore, in the current study, we investigated the cumulative incidence and dose-volume responses of RFs following PBT for early-stage lung cancer.…”