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Tumor Perfusion and Metastatic Failure in Cervical Cancer
Proceedings of the 49th Annual ASTRO Meeting
210
Tumor Perfusion and Metastatic Failure in Cervical Cancer
D. Zhang1, N. A. Mayr1, J. Z. Wang1, D. D. Martin1, H. Zhang1, J. Fowler2, W. T. C. Yuh3 1 3
Department of Radiation Medicine, 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Department of Radiology, Ohio State University, Columbus, OH
Purpose/Objective(s): Despite improvements in therapy outcome, metastatic failure remains a challenge in advanced cervical cancer. The ability to predict metastasis, particularly early during therapy, would profoundly impact the treatment strategy aiming for better outcome. Dynamic contrast enhanced (DCE) MRI provides information on the underlying hemodynamics of the primary tumor, which may influence hematogenous dissemination of disease. The purpose of this study was to assess the value of the DCE MRI parameters obtained before and during radiation therapy (RT) for early prediction of metastatic spread and survival by quantitative analysis of the perfusion status of the primary tumor. Materials/Methods: Sixty-six cervical cancer patients, stages IB2-IVA, treated with radiation/chemotherapy, underwent serial DCE-MRI before RT, at 20–25 Gy/2–2.5 weeks, and at 40–50 Gy/4 weeks during RT. DCE MRI parameters were extracted from first-pass DCE imaging (rapid bolus injection and dynamic imaging at 3-seond intervals). Analyzed parameters of the DCE curve (Fig. 1a) included upslope of the curve (representing predominantly the early arterial phase), plateau-phase enhancement (mSI, representing predominantly the interstitial phase), and the pixel distribution of the plateau phase enhancement (SI10, the 10th percentile of signal intensity, representing poorly-perfused pixel populations within the tumor). Parameters were correlated with metastasis rate, local control and disease-free survival (median follow-up: 5.2 years). Results: The upslope of the MRI DCE curve obtained 2–2.5 weeks after RT start correlated with hematogenous metastases. A ‘‘steep’’ upslope (.3.5 SI/sec) was associated with a 5-year distant metastasis rate of 23%, compared to 4% for ‘‘shallower’’ upslope values (p = 0.044, Fig. 1b). Disease-free survival was 46% and 73%, respectively (p = 0.092, Fig. 1c). Metastasis rate did not correlate with the plateau-phase parameters mSI and SI10, or the DCE parameters pre-RT and at 4–5 weeks of RT. Local control did not correlate with upslope. Conclusions: These results suggest that parameters predominantly related to the arterial phase of the DCE curve of the primary tumor, obtained early during RT, can be early predictors of metastatic spread and may influence survival. Tumors with high and rapid contrast ‘‘in-flow’’ and high vascular permeability, evidenced by a ‘‘steep’’ upslope, have a higher tendency for hematogenous dissemination, supporting the role of hemodynamic factors in metastatic spread of cervical cancer. Non-invasive assessment of these parameters early during RT by first-pass DCE imaging may help guide individualized therapy strategies for better outcome. Supported by R01 CA 71906
Author Disclosure: D. Zhang, None; N.A. Mayr, None; J.Z. Wang, None; D.D. Martin, None; H. Zhang, None; J. Fowler, None; W.T.C. Yuh, None.
211
Expression of MDM2, p16, and HPV Status is Associated with Survival after Radiotherapy in Patients with Carcinoma of the Cervix
C. M. Doll1, P. S. Craighead1, S. P. Lees-Miller2, D. J. Demetrick3, M. Eliasziw4, A. M. Magliocco5 1 Department of Oncology, 2Department of Biochemistry and Molecular Biology, 3Departments of Oncology, Pathology, Biochemistry and Molecular Biology, 4Department of Community Health Sciences, 5Department of Oncology and Pathology, University of Calgary, Calgary, AB, Canada
Background: The majority of cervix cancers are attributed to effects of HPV viral infection, which may cause cellular dysregulation via viral associated protein interaction with p53 and Rb resulting in p16 over-expression as a cellular compensatory
S117
210
Tumor Perfusion and Metastatic Failure in Cervical Cancer
D. Zhang1, N. A. Mayr1, J. Z. Wang1, D. D. Martin1, H. Zhang1, J. Fowler2, W. T. C. Yuh3 1 3
Department of Radiation Medicine, 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Department of Radiology, Ohio State University, Columbus, OH
Purpose/Objective(s): Despite improvements in therapy outcome, metastatic failure remains a challenge in advanced cervical cancer. The ability to predict metastasis, particularly early during therapy, would profoundly impact the treatment strategy aiming for better outcome. Dynamic contrast enhanced (DCE) MRI provides information on the underlying hemodynamics of the primary tumor, which may influence hematogenous dissemination of disease. The purpose of this study was to assess the value of the DCE MRI parameters obtained before and during radiation therapy (RT) for early prediction of metastatic spread and survival by quantitative analysis of the perfusion status of the primary tumor. Materials/Methods: Sixty-six cervical cancer patients, stages IB2-IVA, treated with radiation/chemotherapy, underwent serial DCE-MRI before RT, at 20–25 Gy/2–2.5 weeks, and at 40–50 Gy/4 weeks during RT. DCE MRI parameters were extracted from first-pass DCE imaging (rapid bolus injection and dynamic imaging at 3-seond intervals). Analyzed parameters of the DCE curve (Fig. 1a) included upslope of the curve (representing predominantly the early arterial phase), plateau-phase enhancement (mSI, representing predominantly the interstitial phase), and the pixel distribution of the plateau phase enhancement (SI10, the 10th percentile of signal intensity, representing poorly-perfused pixel populations within the tumor). Parameters were correlated with metastasis rate, local control and disease-free survival (median follow-up: 5.2 years). Results: The upslope of the MRI DCE curve obtained 2–2.5 weeks after RT start correlated with hematogenous metastases. A ‘‘steep’’ upslope (.3.5 SI/sec) was associated with a 5-year distant metastasis rate of 23%, compared to 4% for ‘‘shallower’’ upslope values (p = 0.044, Fig. 1b). Disease-free survival was 46% and 73%, respectively (p = 0.092, Fig. 1c). Metastasis rate did not correlate with the plateau-phase parameters mSI and SI10, or the DCE parameters pre-RT and at 4–5 weeks of RT. Local control did not correlate with upslope. Conclusions: These results suggest that parameters predominantly related to the arterial phase of the DCE curve of the primary tumor, obtained early during RT, can be early predictors of metastatic spread and may influence survival. Tumors with high and rapid contrast ‘‘in-flow’’ and high vascular permeability, evidenced by a ‘‘steep’’ upslope, have a higher tendency for hematogenous dissemination, supporting the role of hemodynamic factors in metastatic spread of cervical cancer. Non-invasive assessment of these parameters early during RT by first-pass DCE imaging may help guide individualized therapy strategies for better outcome. Supported by R01 CA 71906
Author Disclosure: D. Zhang, None; N.A. Mayr, None; J.Z. Wang, None; D.D. Martin, None; H. Zhang, None; J. Fowler, None; W.T.C. Yuh, None.
211
Expression of MDM2, p16, and HPV Status is Associated with Survival after Radiotherapy in Patients with Carcinoma of the Cervix
C. M. Doll1, P. S. Craighead1, S. P. Lees-Miller2, D. J. Demetrick3, M. Eliasziw4, A. M. Magliocco5 1 Department of Oncology, 2Department of Biochemistry and Molecular Biology, 3Departments of Oncology, Pathology, Biochemistry and Molecular Biology, 4Department of Community Health Sciences, 5Department of Oncology and Pathology, University of Calgary, Calgary, AB, Canada
Background: The majority of cervix cancers are attributed to effects of HPV viral infection, which may cause cellular dysregulation via viral associated protein interaction with p53 and Rb resulting in p16 over-expression as a cellular compensatory
S117