Improved Local Control Associated With Dose-Escalated Stereotactic Body Radiation Therapy (SBRT) Indicates Dose-Response Relationship

Abstract

To determine prognostic factors for local control of primary or metastatic tumors within the lung, liver, or other extracranial sites treated with SBRT within a single institution. The records of 152 consecutive patients treated with SBRT from October 1999 through August 2005 were retrospectively reviewed on an IRB-approved protocol. A total of 261 lesions in the lungs, liver, or other extracranial sites were treated; 18% (27/152) of patients were treated on formal prospective Phase I/II studies. Patients ineligible or unwilling to participate in the dose-escalation studies were treated with the highest safe dose established at the time of treatment. A nominal dose of ≥30 Gy was prescribed to 84% of the lesions, and 97% were treated in a 3 fraction course (Fig.). Local control was assessed via serial imaging with CT, MRI, and/or PET/CT. The equivalent uniform dose (EUD) was tabulated for each lesion from dose-volume histogram (DVH) data, and local control was evaluated according to both nominal dose and EUD. A multivariate analysis was performed to identify patient or treatment factors associated with improved local control. The local control rate of treated tumors improved with increased dose, expressed as either nominal dose or EUD. At a median follow-up of 8.4 months (18.3 months for living patients, 5.9 months deceased), lesions treated to a nominal dose of ≥54 Gy had a 3-year actuarial local control rate of 89.3%, whereas the values for those treated to 36.1–53.9 Gy and <36 Gy were 59.7% and 8.7%. Likewise, lesions treated with the highest third of EUD (>64.3 Gy) had a 3-year local control rate of 90.6%, compared to 56.0% in the middle third (43.5–64.3 Gy, p = 0.0047) and 9.9% in the lowest third (<43.5 Gy, p < 0.0001). On univariate and multivariate analysis, increased dose (nominal or EUD) and smaller GTV were statistically significant predictors of improved local control. Patient age, gender, tumor histology, primary site, treatment site, duration of treatment, and clinical context (primary v metastasis) did not predict for local control on either univariate or multivariate analysis. Treatment was well tolerated; 3.4% of patients experienced a grade ≥3 toxicity. These single institution results demonstrate a dose-response relationship within the range of SBRT doses applied. Severe toxicity was uncommon. Excellent local control rates are achieved with a nominal dose of 54–60 Gy, corresponding to an EUD of >64.3 Gy. These results support the use of aggressive, high-dose SBRT regimens when durable tumor control is the primary objective.