방사선의학 웹진

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Abstract

BACKGROUND:

We evaluated the efficacy and safety of risk-adapted, proton-based stereotactic body radiation therapy (SBRT) for liver metastases from solid tumors.

METHODS:

This single-arm phase II single institutional study (NCT01239381) included patients with limited extrahepatic disease, 800 mL or greater of uninvolved liver, and no cirrhosis or Child-Pugh A, who had received proton-based SBRT to one to four liver metastases from solid tumors. Treatment comprised 30 to 50 Gray equivalent (GyE) in five fractions based on the effective volume of liver irradiated. Sample size was calculated to determine if local control (LC) at one year was greater than 70%. The cumulative incidence of local failure was used to estimate LC. The association of tumor characteristics, including genetic alterations in common cancer genes such as BRAF, EGFR, HER2, KRAS, NRAS, PIK3CA, and TP53 with local tumor control, was assessed. All statistical tests were two-sided.

RESULTS:

Eighty-nine patients were evaluable (colorectal, n = 34; pancreatic, n = 13; esophagogastric, n = 12; other, n = 30). Median tumor size was 2.5 cm (range = 0.5-11.9 cm). Median dose was 40 GyE (range = 30-50 GyE), and median follow-up was 30.1 months (range = 14.7-53.8 months). There was no grade 3 to 5 toxicity. Median survival time was 18.1 months. The one- and three-year LC rates were 71.9% (95% confidence limit [CL] = 62.3% to 80.9%) and 61.2% (95% CL = 50.8% to 71.8%), respectively. For large tumors (≥6 cm), one-year LC remained high at 73.9% (95% CL = 54.6% to 89.8%). Mutation in the KRAS oncogene was the strongest predictor of poor LC (P = .02). Tumor with both mutant KRAS and TP53 were particularly radioresistant, with a one-year LC rate of only 20.0%, compared with 69.2% for all others (P = .001).

CONCLUSIONS:

We report the largest prospective evaluation to date of liver SBRT for hepatic metastases, and the first with protons. Protons were remarkably well tolerated and effective even for metastases that were 6 cm or larger. KRAS mutation is a strong predictor of poor LC, stressing the need for tumor genotyping prior to SBRT and treatment intensification in this patient subset.​

Figure 3. Genotype predictors of local failure poststereotactic body radiation therapy in patients with mutational status available (excluding hepatocellular carcinoma; n ¼ 57). A) Influence of KRAS status on the cumulative incidence of local failure. B) Influence of TP53 status. C) Influence of combined KRAS and TP53 status. Statistical comparisons by Gray’s test, two-sided. MUT ¼ mutated; WT ¼ wild-type or no mutation detected.​

Author information​

Hong TS1, Wo JY1, Borger DR1, Yeap BY1, McDonnell EI1, Willers H1, Blaszkowsky LS1, Kwak EL1, Allen JN1, Clark JW1, Tanguturi S1, Goyal L1, Murphy JE1, Wolfgang JA1, Drapek LC1, Arellano RS1, Mamon HJ1, Mullen JT1, Tanabe KK1, Ferrone CR1, Ryan DP1, Iafrate AJ1, DeLaney TF1, Zhu AX1.

1 Department of Radiation Oncology, Department of Pathology, Division of Biostatistics, Department of Medicine, Division of Medical Oncology, Department of Medicine, Department of Radiology, and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA; Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.