Functional dosimetric parameters have also been re- ported using Tc-99m galactosyl human serum albumin (GSA) scans. 3 Similar to the manuscript by Schaub et al, GSA analysis found that the FLV (defined as a liver uptake greater than tumor) receiving 20 Gy correlated with a Child-Pugh score increase of 1 (a different endpoint than in the current manuscript). A strength of the publication by Schaub et al is that the minimum threshold used to define FLV was based on phantom and patient investigations that correlated up- take with clinical liver function, making the parameters more likely to be reproducible between patients and/or institutions. 4,5 We agree with the authors’ conclusions that func- tional dosimetric parameters complement conventional clinical metrics for risk stratification and precision ra- diation therapy planning. It is crucial for studies that incorporate functional imaging techniques to report on clinical correlates of functional dosimetric parameters, as was done in this manuscript. Future studies may eluci- date changes in functional imaging that allow for earlier detection of potential hepatotoxicity. An adaptive approach could be used to reduce this risk in a manner similar to indocyanine green reassessment. 6 Institutional preferences/experiences or regulatory issues can influ- ence the choice of functional imaging method (eg, GSA is not currently a US Food and Drug Administrationeapproved radiotracer). Although these variations in institutional practices have led to a variety of promising approaches for functional image guided liver SBRT, prospective multi-institutional studies should be done to further evaluate the reproducibility and clinical utility of functional dosimetric parameters as a predictive biomarker. David E. Long, MD Susannah G. Ellsworth, MD Department of Radiation Oncology Indiana University Indianapolis, Indiana https://doi.org/10.1016/j.ijrobp.2018.12.013 References 1. Schaub SK, Apisarnthanarax S, Price RG, et al. Functional liver im- aging and dosimetry to predict hepatotoxicity risk in cirrhotic patients with primary liver cancer. Int J Radiat Oncol Biol Phys 2018;102: 1339-1348. 2. Long DE, Tann M, Huang KC, et al. Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans. Pract Radiat Oncol 2018;8:429-436. 3. Shirai S, Sato M, Noda Y, et al. Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepato- cellular carcinoma radiotherapy. World J Radiol 2014;6:598- 606. 4. Groshar D, Slobodin G, Zuckerman E. Quantitation of liver and spleen uptake of (99m)Tc-phytate colloid using SPECT: Detection of liver cirrhosis. J Nucl Med 2002;43:312-317. 5. Iosilevsky G, Israel O, Frenkel A, et al. A practical SPECT technique for quantitation of drug delivery to human tumors and organ absorbed radiation dose. Semin Nucl Med 1989;19:33-46. 6. Feng M, Suresh K, Schipper MJ, et al. Individualized adaptive stereotactic body radiotherapy for liver tumors in patients at high risk for liver damage: A phase 2 clinical trial. JAMA Oncol 2018;4: 40-47. In Reply to Long and Ellsworth To the Editor: We appreciate Ellsworth and Long’s comment on “Functional Liver Imaging and Dosimetry to Predict Hepatotoxicity Risk in Cirrhotic Patients with Pri- mary Liver Cancer.” 1,2 The authors compared our work using sulfur colloid (SC) single-photon emission tomogra- phy (SPECT) and their Practical Radiation Oncology article, “Functional Liver Image Guided Hepatic Therapy (FLIGHT) With Hepatobiliary Iminodiacetic Acid (HIDA) Scans.” 3 Long et al. demonstrated the feasibility of pre- radiation therapy (RT) HIDA SPECT-guided stereotac- tic body radiation therapy planning to maximize func- tional liver receiving <15 Gy (FRC 15 HIDA), 3 resulting in 41% of patients achieving a >5% increase in FRC 15 HIDA. We also concluded that patient selection is critical for differential hepatic avoidance radiation therapy planning based on SC SPECT. 4 Functional liver dosimetry should correlate to meaningful endpoints, including consensus definitions of radiation-induced liver disease. 5 We found that functional liver volume receiving 20 Gy (functional liver volume V20) was associated with Child-Pugh score increase (CPþ2) and radiation-induced liver diseaseerelated death. 2 Long et al identified cutoffs in global HIDA, FRC 15 HIDA, and the model for end-stage liver disease that predicted decompensation after stereotactic body radiation ther- apy. 3 Investigators have characterized in vivo dose- response relationships on functional liver imaging. Wang et al. correlated HIDA SPECT to indocyanine green clearance to form regional dose-response models with individual radiosensitivity. 6 Our group reported SC SPECT regional dose-response models with significant interpatient variability 7 and correlation to baseline total liver function. 8 We agree with Ellsworth and Long’s insight that imaging of functional liver response during treatment may enable earlier identification of potential treatment-related toxicity. Indiana University has launched a trial evaluating S.R.B. is supported in part by NIH/NCI R01CA204301, outside the submitted work. Conflict of interest: none. Volume 103  Number 5  2019 Comments 1285