Improved local control using higher dose SBRT in metastatic sarcoma patients

Stereotactic Body Radiotherapy (SBRT) has been proven to be a safe and effective alternative to surgery in patients with metastatic primary sarcoma. However, data describing tumor response in relation to the given radiotherapy dose is lacking. Therefore, this study aims at analyzing efficacy and dose-response relationship in a retrospective cohort.

Patients with metastatic sarcoma treated with ablative SBRT and followed up at the Karolinska University Hospital between 2008 and 2021 were included. SBRT was delivered using an inhomogeneous dose distribution resulting in higher median doses within the planning target volume (PTV) than the dose prescribed. Local control (LC), progression-free survival (PFS), overall survival (OS), adverse events and dose-response relationship were assessed. Statistical analysis was performed to identify variables that correlate to outcome.

Forty-three patients with a total of 83 lesions were treated. The most frequent histology was leiomyosarcoma (44%). The most common site of metastases was the lung (84%), followed by the liver (11%). The median prescription dose was 45 Gy (range 30-56 Gy) delivered in 3 fractions (range 2-8) with a planned median CTV mean dose of 309 Gy in EQD₂ with α/β = 3 Gy. The local control at 1-year, 2-year and 5-year from SBRT treatment was 97, 93 and 84%, respectively. For tumors with a planned mean CTV dose above EQD₂ 278.8 Gy (corresponding to 60.3 Gy in 3 fractions) the 1, 2 and 5-year local control was 100, 100 and 93%, respectively. Tumors planned with a lower dose than EQD₂ 278.8 Gy (α/β = 3 Gy) had a 1, 2 and 5-year local control of 90, 70 and 52%, respectively. The difference in local control between the high dose and low dose groups was statistically significant (p < 0.001). The median OS for all patients was 43 months. When respecting dose constraints, there were only limited number of mild side effects.

In this analysis a strongly significant dose-response relationship with excellent LC rates and limited side effects for patients with metastatic lesions of sarcoma were seen. These results could be related to the inhomogeneous dose distribution of SBRT treatments utilized in this study.