Originally published as JCO Early Release 10.1200/JCO.2009.23.6646 on July 6 2009

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Have We Established a Stereotactic Body Radiotherapy Regimen for Liver Metastases?

Academic Radiotherapy Department, Centre Oscar Lambret, Lille, France

To the Editor:

I read with great interest the results of the phase I/II study by Rusthoven et al¹ showing what is, to date, the best 1- and 2-year local control in a study of stereotactic body radiotherapy (SBRT) for liver metastases published. These excellent results were obtained with low levels of toxicity to liver and surrounding organs. Their study is well-controlled and conducted, and will be of great benefit to those of us treating liver with SBRT and to our patients. It appears that after several years of testing a wide variety of treatment regimens, we may be near to establishing an acceptable SBRT regimen for liver metastases.

Rusthoven et al¹ have applied rational liver dose constraints developed over the last few years and described in their previous work,^2,3 specifically, "a minimum volume of 700 mL should receive a total dose less than 15 Gy." Appropriate constraints were applied as well to kidney and spine, and probably to neighboring bowel, although this is not indicated. Their treatment technology included respiratory motion management either by abdominal compression (which required 7-mm radial and a 15-mm craniocaudal gross tumor volume [GTV] –to– planning target volume [PTV] margins) or active breathing control (which required 5-mm radial and a 10-mm craniocaudal margins). If movement beyond the PTV was noted on fluoroscopy, the PTV was extended further. The outcomes suggest that these margins were sufficient to ensure coverage of the moving tumor with the prescription dose without incurring undue complications. Nevertheless, GTV expansion to this extent can result in irradiation of a substantial volume of normal liver, and considerable dose spillage outside the PTV for seven-beam plans (Fig 1¹ for an extreme example). One wonders how many patients with multiple and/or larger tumors were not treated because the dose constraints (both within the tumor and for neighboring structures) would have been violated had these PTV margins been employed. Rusthoven et al¹ did not report the number of patients not enrolled for this reason. In such cases continuous tumor tracking, which can allow margin expansion to account for motion uncertainty to be reduced to 2 to 3 mm, has the potential to make this safe and effective treatment available to a larger number of patients.

We believe it is time to conduct much larger trials with the regimen of 3 fractions of 20 Gy. Although Rusthoven et al's¹ results suggest improvement over other studies with lower biologically equivalent doses, the error around the local control estimates is certainly large enough to overlap with the CIs of the other trials listed in Table 3.¹ Whether the higher-dose regimen is the better approach, therefore, still remains to be thoroughly tested.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Rusthoven KE, Kavanagh BD, Cardenes HR, et al: Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 27:1572–1578, 2009.[Abstract/Free Full Text]

2. Kavanagh BD, Schefter TE, Cardenes HR, et al: Interim analysis of a prospective phase I/II trial of SBRT for liver metastases. Acta Oncol 45:848–855, 2006.[CrossRef][Medline]

3. Schefter TE, Kavanagh BD, Timmerman RD, et al: A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys 62:1371–1378, 2005.[CrossRef][Medline]

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