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Öğe The impact of induction chemotherapy and the associated tumor response on subsequent radiation-related changes in lung function and tumor response(Elsevier Science Inc, 2007) Mao, Jingfang; Kocak, Zafer; Zhou, Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang, Junan; Larrier, Nicole A.Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction. (c) 2007 Elsevier Inc.Öğe Prospective assessment of dosimetric/physiologic-based models for predicting radiation pneumonitis(Elsevier Science Inc, 2007) Kocak, Zafer; Borst, Gerben R.; Zeng, Jing; Zhou, Sumin; Hollis, Donna R.; Zhang, Junan; Evans, Elizabeth S.Purpose: Clinical and 3D dosimetric parameters are associated with symptomatic radiation pneumonitis rates in retrospective studies. Such parameters include: mean lung dose (MLD), radiation (RT) dose to perfused lung (via SPECT), and pre-RT lung function. Based on prior publications, we defined pre-RT criteria hypothesized to be predictive for later development of pneumonitis. We herein prospectively test the predictive abilities of these dosimetric/functional parameters on 2 cohorts of patients from Duke and The Netherlands Cancer Institute (NKI). Methods and Materials: For the Duke cohort, 55 eligible patients treated between 1999 and 2005 on a prospective IRB-approved study to monitor RT-induced lung injury were analyzed. A similar group of patients treated at the NKI between 1996 and 2002 were identified. Patients believed to be at high and low risk for pneumonitis were defined based on: (1) MLD; (2) OpRP (sum of predicted perfusion reduction based on regional dose-response curve); and (3) pre-RT DLCO. All doses reflected tissue density heterogeneity. The rates of grade >= 2 pneumonitis in the presumed high and low risk groups were compared using Fisher's exact test. Results: In the Duke group, pneumonitis rates in patients prospectively deemed to be at high vs. low risk are 7 of 20 and 9 of 35, respectively; p = 0.33 one-tailed Fisher's. Similarly, comparable rates for the NKI group are 4 of 21 and 6 of 44, respectively, p = 0.41 one-tailed Fisher's. Conclusion: The prospective model appears unable to accurately segregate patients into high vs. low risk groups. However, considered retrospectively, these data are consistent with prior studies suggesting that dosimetric (e.g., MLD) and functional (e.g., PFTs or SPECT) parameters are predictive for RT-induced pneumonitis. Additional work is needed to better identify, and prospectively assess, predictors of RT-induced lung injury. (c) 2007 Elsevier Inc.Öğe The role of functional imaging in the diagnosis and management of late normal tissue injury(W B Saunders Co-Elsevier Inc, 2007) Evans, Elizabeth S.; Hahn, Carol A.; Kocak, Zafer; Zhou, Su-Min; Marks, Lawrence B.Normal tissue injury after radiation therapy (RT) can be defined based on either clinical symptoms or laboratory/radiologic tests. In the research setting, functional imaging (eg, single-photon emission computed tomography [SPECT], positron-emission tomography [PET], and magnetic resonance imaging [MRI]) is useful because it provides objective quantitative data such as metabolic activity, perfusion, and soft-tissue contrast within tissues and organs. For RT-induced lung, heart, and parotid gland injury, pre- and post-RT SPECT images can be compared with the dose- and volume-dependent nature of regional injury. In the brain, SPECT can detect changes in perfusion and blood flow post-RT, and PET can detect metabolic changes, particularly to regions of the brain that have received doses above 40 to 50 Gy. On MRI, changes in contrast-enhanced images, T-1 and T-2 relaxation times, and pulmonary vascular resistance at different intervals pre- and post-RT show its ability to detect and distinguish different phases of radiation pneumonitis. Similarly, conventional and diffusion-weighted MRI can be used to differentiate between normal tissue edema, necrosis, and tumor in the irradiated brain, and magnetic resonance spectroscopy can measure changes in compounds, indicative of membrane and neuron disruption. The use of functional imaging is a powerful tool for early detection of RT-induced normal tissue injury, which may be related to long-term clinically significant injury.