Chest Wall Toxicity in Long-Term Follow-Up after Thoracic Stereotactic Body Radiation Therapy

Chest wall (CW) toxicity following SBRT in patients with peripheral lung tumors can significantly impact on the patients' quality of life, require chronic use of pain medication and limit physical function. The long term clinical course of CW toxicity has, however, not been well characterized. We hypothesize that CW toxicity has a prolonged healing period and that certain clinical and dosimetrical factors may be related to the development of CW pain and the risk for rib fracture. We retrospectively analyzed data from 67 peripheral lung lesions in 62 patients (30 male, 32 female) that were treated with SBRT and had a minimum follow up of 2 years. The most common fractionation regimen was 48Gy in 4 fractions (82%). The incidence, duration and severity of CW toxicity as well as associated clinical and dosimetrical factors were investigated. Mann-Whitney U-test and Chi-Square Test were applied to test significance. Mean age at the time of SBRT was 68 years (range 44-91). Mean duration of follow up was 49.6 months (range 24-93). Treatment of 21% (14/67) tumors resulted in CW pain (G1: 3, G2: 4, G3: 7 tumors), 71% of these patients had also radiographic rib fractures. Mean time to onset of pain was 15 months (range 2-50). Mean duration of CW pain was 37.3 months (range 6-79) and 33% of patients still had CW pain at last follow up. Overall, 21% (14/67) of treatments caused rib fractures, and 71% of these also resulted in CW pain. Mean time to occurrence of fracture was 23.5 months (range 7-42). On last follow up CT imaging, all patients had signs of either hypertrophic (callus formation in 7 patients) and/or atrophic (bone fragments in 9 patients) non-union as a result of osteoradionecrosis. Various dosimetric parameters, such as CW V10Gy - V40Gy, mean CW dose, D30cc and PTV volume were all significantly higher in patients with CW pain than those without (p<0.05). Mean PTV volume for patients with rib fracture was 43.55cc (±25.4) versus 32.5cc (±31) without rib fracture (p=0.009). Patients with rib fractures/CW pain were in 93% (13/14)/71% (10/14) female (p<0.001/p=0.25). Systemic steroid use was associated with increased risk of rib fracture (p=0.06) and NSAID use was higher in those who experienced CW pain (p=0.047). SBRT is associated with a significant risk of rib fracture and chest wall pain. These chest wall toxicities appear to be experienced more commonly by women, as well as those taking systemic steroids or NSAIDs. CW pain and rib fractures may take years to manifest and can result in a prolonged manifestation of symptoms. Every effort to decrease CW dose during the planning process should be undertaken to reduce the risk of this detrimental side effect.