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Phase I Dose-Escalation Study of Stereotactic Body Radiotherapy in Patients With Hepatic Metastases

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To identify a tolerable and effective dose for 5-fraction stereotactic body radiotherapy for hepatic metastases.

Methods

Patients were enrolled onto three dose-escalation cohorts: 30 Gy in 3 fractions, 50 Gy in 5 fractions, and 60 Gy in 5 fractions. Eligible patients had one to five hepatic metastases, ability to spare a critical hepatic volume (volume receiving <21 Gy) of 700 ml, adequate baseline hepatic function, no concurrent antineoplastic therapy, and a Karnofsky performance score of ≥60. Dose-limiting toxicity included treatment-related grade 3 toxicity in the gastrointestinal, hepatobiliary/pancreas, and metabolic/laboratory categories. Any grade 4 or 5 event attributable to therapy was defined as a dose-limiting toxicity. Local control (LC) and complete plus partial response rates were assessed.

Results

Twenty-seven patients, 9 in each cohort, with 37 lesions were enrolled and treated: 17 men and 11 women; median age 62 (range 48–86) years; most common site of primary disease, colorectal (44.4%). Median follow-up was 20 (range 4–53) months. There was no grade 4 or 5 toxicity or treatment-related grade 3 toxicity. Actuarial 24-month LC rates for the 30-, 50-, and 60-Gy cohorts were 56%, 89%, and 100%, respectively. There was a statistically significant difference for LC between the 60- and 30-Gy cohorts (P = 0.009) but not between the 60- and 50-Gy cohorts (P = 0.56) or the 50- and 30-Gy cohorts (P = 0.091). The maximum tolerated dose was not reached.

Conclusions

A dose of 60 Gy in 5 fractions can be safely delivered to selected patients with hepatic metastases as long as the critical liver volume is respected. A dose of 60 Gy in 5 fractions yields an excellent level of LC.

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Acknowledgment

Supported in part by NIH CTSA grant UL1 RR024982. R.D.T. received research grants from Varian Medical Systems, Palo Alto, California, and Accuray Inc., Sunnyvale, California (both manufacturers of stereotactic radiation equipment).

Conflict of interest

The other authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Texas Southwestern, 5801 Forest Park Road, Dallas, TX, USA

    William Rule MD, Robert Timmerman MD, Ramzi Abdulrahman MD, Jeffrey Meyer MD & Thomas Boike MD

  2. Division of Biostatistics, University of Texas Southwestern, Dallas, TX, USA

    Liyue Tong MS

  3. Department of Surgical Oncology, University of Texas Southwestern, Dallas, TX, USA

    Roderich E. Schwarz MD

  4. Department of Radiology, University of Texas Southwestern, Dallas, TX, USA

    Paul Weatherall MD, PhD

  5. Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, USA

    L. Chinsoo Cho MD

  6. UT Southwestern Medical Center, Moncrief Radiation Oncology Center, Dallas, TX, USA

    Robert Timmerman MD

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  1. William Rule MD
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Correspondence to Robert Timmerman MD.

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Rule, W., Timmerman, R., Tong, L. et al. Phase I Dose-Escalation Study of Stereotactic Body Radiotherapy in Patients With Hepatic Metastases. Ann Surg Oncol 18, 1081–1087 (2011). https://doi.org/10.1245/s10434-010-1405-5

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  • DOI: https://doi.org/10.1245/s10434-010-1405-5

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