Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases

Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1387-1395. doi: 10.1016/j.ijrobp.2020.12.012. Epub 2020 Dec 16.

Abstract

Purpose: We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.

Methods and materials: Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.

Results: Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%.

Conclusions: For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Follow-Up Studies
  • Humans
  • Liver / diagnostic imaging
  • Liver / radiation effects
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / mortality
  • Liver Neoplasms / radiotherapy*
  • Liver Neoplasms / secondary*
  • Magnetic Resonance Imaging
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Organs at Risk
  • Progression-Free Survival
  • Radiosurgery / methods*
  • Radiosurgery / mortality
  • Radiotherapy Dosage
  • Time Factors
  • Treatment Outcome
  • Tumor Burden