Abstract

Background

Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection.

Methods

This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose limiting toxicities (DLTs) were assessed 6-8 weeks and 6 months after completing radiotherapy.

Results

All twelve patients had colorectal liver metastases and received prior hepatotoxic chemotherapy. Eight patients underwent prior liver resection. Median computed tomography (CT) anatomical non-tumor liver volume was 1,584 cc (range 764-2,699 cc). Median SPECT functional liver volume was 1,117 cc (range 570-1,928cc). Median non-target CT and SPECT liver volumes below the volumetric dose constraint were 997 cc (range 544-1,576 cc) and 684 cc (range 429-1,244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No DLTs were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%.

Conclusion

Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function.

Trial Registration

NCT02626312

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