Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

Purpose Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations. Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.