Stereotactic body radiotherapy for colorectal liver metastases

Abstract

BACKGROUND: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort. METHODS: Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging 3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for >90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose. RESULTS: Forty-seven (72%) patients had 1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had 2 regimens. The median followup was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose (P ¼ .0015), dose/fraction (P ¼ .003), and BED (P ¼ .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P ¼ .046), and sustained local control was closely correlated (P ¼ .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control >90% is 46 to 52 Gy in 3 fractions. CONCLUSIONS: Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of 48 Gy should be considered, if normal tissue constraints allow. Cancer 2011;117:4060-

Radiobiology of stereotactic body radiation therapy (SBRT)

“…Converting this value into a 3-fraction SBRT regimen using the LQ-formula yields an estimated total dose between 46 and 52 Gy to achieve 90% local control. 24 The same calculation for a 5-fraction regimen results in a total dose around 55 Gy. Based on this publication, a total prescription dose of 48 Gy or higher in 3 fractions is recommended when possible.…”

“…Based on this publication, a total prescription dose of 48 Gy or higher in 3 fractions is recommended when possible. 24 Better outcome has been reported for non-colorectal liver metastases. This is perhaps because most patients with colorectal liver metastases had been heavily pretreated before SBRT.…”

“…8 In any case, literature of SBRT is full of examples where BED (biologically effective dose) or EQD2 (equivalent dose in 2 Gy fractions) are used to compare different fractionations. [8][9][10][11]24 The only parameter required to perform the calculations is the ˛/ˇ ratio. Although there are many uncertainties, the ˛/ˇ ratio normally used for earlyresponding tissues and most tumors is ≥10 Gy.…”

Determination and comparison of radiotherapy dose responses for hepatocellular carcinoma and metastatic colorectal liver tumours

“…A positive association between outcome and dose has previously been reported [11][12][13]. However, unlike other tumour sites [14][15][16][17][18], there is currently a paucity of explicit liver tumour dose-response modelling within the literature [11]. An improved understanding of radiation dose response is necessary to help better inform future dose prescriptions.…”

“…Stereotactic body radiotherapy (SBRT) has shown promise as a new method to safely and non-invasively treat liver tumours [8][9][10][11]. SBRT involves precise image-guided delivery of a high dose of radiation to the tumour in a small number of fractions and usually employs motion suppression or gating techniques.…”