PII S0360-3016(99)00201-1 CLINICAL INVESTIGATION Lung THE EFFECT OF PATIENT-SPECIFIC FACTORS ON RADIATION-INDUCED REGIONAL LUNG INJURY MELAHAT GARIPAGAOGLU, M.D.,* §1 MICHAEL T. MUNLEY,PH.D.,* DONNA HOLLIS, M.S., † JEAN M. POULSON, D.V.M.,* GUNILLA C. BENTEL, R.N., R.T.T.,* GREGORY SIBLEY, M.D.,* MITCHELL S. ANSCHER, M.D.,* MING FAN, M.D.,* RONALD J. JASZCZAK, M.D., ‡ R. EDWARD COLEMAN, M.D., ‡ AND LAWRENCE B. MARKS, M.D.* *Department of Radiation Oncology, † Comprehensive Cancer Center and ‡ Department of Nuclear Medicine, Duke University Medical Center, Durham, NC Purpose: To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion. Methods: Fifty patients (32 lung carcinoma, 7 Hodgkin’s disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and >24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose–response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction  coefficient 1  dose  coefficient 2  dose 2 ). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients. Results: None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used. Conclusion: Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient- specific factors will impact on how the summation of regional injury translates into whole organ injury. Refinements in our methods to generate and compare SPECT scans are needed. © 1999 Elsevier Science Inc. SPECT lung perfusion imaging, Lung damage, Radiation injury, Chemotherapy, Smoking, TGF-. INTRODUCTION Radiation-induced pulmonary injury is one of the most common complications in patients who receive external beam radiotherapy (RT) for tumors in and around the thorax (1–11). Symptomatic injury to the lung occurs in approxi- mately 5–20% of patients (2, 9, 11–14). A larger fraction of patients experience subclinical reductions in lung function determined by pulmonary function tests (PFTs) (6, 15–18). Methods to accurately predict changes in PFTs and/or the risk of symptomatic injury are lacking (19). Radiation- induced pulmonary injury is a complicated problem since different regions of the lung function relatively indepen- dently (i.e., parallel architecture). Since the radiation dose distribution throughout the lung is typically heterogeneous, the degree of radiation-induced regional injury is variable. Thus, changes in whole lung function probably reflect the summation of changes in regional function. In order to better study this issue, investigators at the Netherlands Can- cer Institute, Princess Margaret Hospital, and Duke Univer- sity have used computed tomography (CT) and perfusion single photon emission computed tomography (SPECT) im- aging to assess dose-dependent changes in regional function Reprint requests to: Lawrence B. Marks, M.D., Department of Radiation Oncology, Duke University Medical Center, PO Box 3085, Durham, NC 27710. Presented at the 40th annual ASTRO Meeting, Phoenix, Ari- zona, October 1998. Supported in part by PHS Grants R01-CA33541 and R29- CA69579, awarded by the National Cancer Institute, and Grant DE-FG05-89ER60894, awarded by the Department of Energy. 1 Current address: Department of Radiation Oncology, Akdeniz University School of Medicine, and Antalya, Turkey. Accepted for publication 14 May 1999. Int. J. Radiation Oncology Biol. Phys., Vol. 45, No. 2, pp. 331–338, 1999 Copyright © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0360-3016/99/$–see front matter 331