Ryan G Price1, Smith Apisarnthanarax1, Stephanie K Schaub1, Matthew J Nyflot2, Tobias R Chapman3, Manuela Matesan4, Hubert J Vesselle4, Stephen R Bowen5. 1. Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington. 2. Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington; Department of Radiology, University of Washington School of Medicine, Seattle, Washington. 3. Beth-Israel Deaconess Medical Center, Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts. 4. Department of Radiology, University of Washington School of Medicine, Seattle, Washington. 5. Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington; Department of Radiology, University of Washington School of Medicine, Seattle, Washington. Electronic address: srbowen@uw.edu.
Abstract
PURPOSE: Hepatotoxicity risk in patients with hepatocellular carcinoma (HCC) is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [99mTc]sulfur colloid (SC) single-photon emission computed tomography (SPECT)/computed tomography (CT) liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. METHODS AND MATERIALS: SC SPECT/CT images of 15 patients with HCC with variable Child-Pugh (CP) status (8 CP-A, 7 CP-B/C) were acquired in treatment position before and 1 month (nominal) after stereotactic body radiation therapy (n = 6) or proton therapy (n = 9). Localized rigid registrations between pre/posttreatment CT to planning CT scans were performed, and transformations were applied to pre/posttreatment SC SPECT images. Radiation therapy doses were converted to EQD2 and Gy RBE (relative biological effectiveness) and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and posttreatment SPECT uptake, normalized to regions receiving <5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSCmax), dose midpoint (Dmid), and dose-response slope (αmid) parameters. RESULTS: Individual patient sigmoid dose-response curves had high goodness-of-fit (median R2 = 0.96, range 0.76-0.99). Large interpatient variability was observed, with median (range) in %ΔSCmax of 44% (20%-75%), Dmid of 13 Gy (4-27 GyEQD2), and αmid of 0.11 GyEQD2-1 (0.04-0.29 GyEQD2-1), respectively. Eight of 15 patients had %ΔSCmax of 20% to 45%, whereas 7 of 15 had %ΔSCmax of 60% to 75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2 of 15) with low total liver funcation (<0.12) and low Dmid (<7 GyEQD2). CONCLUSIONS: Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints.
PURPOSE:Hepatotoxicity risk in patients with hepatocellular carcinoma (HCC) is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [99mTc]sulfur colloid (SC) single-photon emission computed tomography (SPECT)/computed tomography (CT) liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. METHODS AND MATERIALS: SC SPECT/CT images of 15 patients with HCC with variable Child-Pugh (CP) status (8 CP-A, 7 CP-B/C) were acquired in treatment position before and 1 month (nominal) after stereotactic body radiation therapy (n = 6) or proton therapy (n = 9). Localized rigid registrations between pre/posttreatment CT to planning CT scans were performed, and transformations were applied to pre/posttreatment SC SPECT images. Radiation therapy doses were converted to EQD2 and Gy RBE (relative biological effectiveness) and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and posttreatment SPECT uptake, normalized to regions receiving <5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSCmax), dose midpoint (Dmid), and dose-response slope (αmid) parameters. RESULTS: Individual patient sigmoid dose-response curves had high goodness-of-fit (median R2 = 0.96, range 0.76-0.99). Large interpatient variability was observed, with median (range) in %ΔSCmax of 44% (20%-75%), Dmid of 13 Gy (4-27 GyEQD2), and αmid of 0.11 GyEQD2-1 (0.04-0.29 GyEQD2-1), respectively. Eight of 15 patients had %ΔSCmax of 20% to 45%, whereas 7 of 15 had %ΔSCmax of 60% to 75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2 of 15) with low total liver funcation (<0.12) and low Dmid (<7 GyEQD2). CONCLUSIONS: Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints.
Authors: Hannah Mary T Thomas; Jing Zeng; Howard J Lee; Balu Krishna Sasidharan; Paul E Kinahan; Robert S Miyaoka; Hubert J Vesselle; Ramesh Rengan; Stephen R Bowen Journal: Br J Radiol Date: 2019-08-12 Impact factor: 3.039