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Dynamic Changes of 3-Dimensional DW-MRI for Primary Tumor and Cervical Lymph Nodes in Head and Neck Cancer During Radiation Therapy: A Phase 2 Prospective Study
S200
International Journal of Radiation Oncology Biology Physics
and to study the effects of molecular targeted agents in combination with radiation. Author Disclosure: C.R. Hauck: None. B.J. Thibodeau: None. S. Ahmed: None. M.D. Johnson: None. G.D. Wilson: None.
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Applied Cancer Science Institution, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7 Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 9Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
1068 Dynamic Changes of 3-Dimensional DW-MRI for Primary Tumor and Cervical Lymph Nodes in Head and Neck Cancer During Radiation Therapy: A Phase 2 Prospective Study M. Feng,1,2 J. Lang,1 F. Wu,3 J. Ren,3 X. Chen,3 F. LI,3 X. Peng,3 Y. Qi,3 S. Lu,1 Y. Huang,4 L. Li,5 S. Wang,3 K. Xu,6 and W. Wang7; 1Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 2Radiation Oncology Department, Sichuan Cancer Hospital and Institution, Chengdu, China, 3Sichuan Cancer Hospital and Institution, Chengdu, China, 4Sichuan Cancer Hospital, Chengdu, China, 5Guangxi Medical University, Nanning, China, 6Sichuan Cancer Hospital and Institute, Chengdu, China, 7Sichuan Cancer Hospital and Institute, Chengdu, China Purpose/Objective(s): DW-MRI becomes more and more important, recent study find it help to discriminate the metastatic lymph node and distinguish recurrent tumor. However, we still poorly understand the dynamic changes of it during treatment, especially for 3D-apparent diffusion coefficient (ADC). It is urgent to observe the dynamic changes of 3D-ADC for head and neck cancer during radiotherapy, and to investigate the correlation between the changes of ADC, radiation dose and volume reduction. Materials/Methods: Sixty patients with head and neck cancer treated with image-guided IMRT were enrolled. DW-MRI were performed on 3.0T MRI scanner (b Z 0, 500, 800 s/mm2) at pre-radiation, the 15th, the 25th and post-radiation. Region of interest was the primary tumor (GTV-T) and cervical lymph nodes (GTV-N). The volumes and the maximum, mean and minimum of 3D-ADC value were automatically measured by MIM software. Pearson analysis was used to assess the correlation between 3DADC values, delivered radiation dose and tumor volume reduction. Results: All the patients exhibited the mean 3D-ADC increase in GTV-T (0.640.24 x10-3 mm2/s) and GTV-N (0.350.09 x10-3 mm2/s), with the mean increased ratios of 0.500.20 and 0.440.08 between pre- and postradiation. The mean 3D-ADC for GTV-T and GTV-N both changed mostly at the 25th radiation. However, the changes of the maximum and minimum 3DADC values for GTV-T and GTV-N had no correlation with delivered dose and volume reduction. The maximum, mean, and minimum 3D-ADC changes in spinal cord were almost invisible ( 0.04 x10-3 mm2/s). The increased mean ADC had a strong positive correlation with the increased radiation delivered dose for GTV-T and GTV-N respectively (r Z 0.977, P Z 0.023; r Z 0.974, P Z 0.026), and a significantly negative correlation with the volume reduction (r Z -0.989，P Z 0.011; r Z -0.969, P Z 0.031). Conclusion: The mean 3D-ADC value of primary tumor and cervical lymph node can be increased greatly for head and neck cancer during radiotherapy. It had a strong negative correlation with the volume reduction, and a positive correlation with the increased delivered dose. Dynamic 3D-ADC changes during radiotherapy might be an early indicator to assess the treatment response and helps to make treatment strategy for head and neck cancer. Author Disclosure: M. Feng: None. J. Lang: None. F. Wu: None. J. Ren: None. X. Chen: None. F. LI: None. X. Peng: None. Y. Qi: None. S. Lu: None. Y. Huang: None. L. Li: None. S. Wang: None. K. Xu: None. W. Wang: None.
1069 RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy in Resected NoneSmall Cell Lung Cancer Y. Wang,1 J. Gudikote,2 J. Yan,3 W. Deng,4 W. Jiang,4 B. Hobbs,5 J. Wang,6 S.G. Swisher,7 J. Fujimoto,8 I. Wistuba,8 R.U. Komaki,4 J. Heymach,9 and S.H. Lin4; 1Department of Experimental Radiation
Purpose/Objective(s): Radiation therapy is a mainstay of therapy for locally advanced non-small cell lung cancer (NSCLC). However, both locoregional failure and distant metastasis remain problematic. Understanding the underlying mechanisms of therapeutic resistance against radiation by cancer cells is important to counteract treatment resistance. Materials/Methods: Using an integrative analysis approach, we assessed the activation of critical intracellular signaling pathways and potential therapeutic targets that may confer the radiation resistant phenotype using reverse-phase protein arrays (RPPA). Here, we utilized a panel of 70 NSCLC cell lines to profile the baseline expression of 170 total and phospho-proteins and correlated their expression levels with the intrinsic radiation response to categorize pathways that may contribute to resistance. We further carried out the tissue microarray analysis for the most significant markers indicated by RPPA in 127 patient tumor samples who received surgery and postoperative radiation therapy (PORT). The leading prognostic marker was identified by Cox regression analysis and log-rank test. The marker’s function in radiation resistance was validated by overexpression in NSCLC cell line in vitro. Results: Baseline RPPA profiling followed by unsupervised hierarchical clustering of the cell lines separated resistant from the sensitive cell lines at the first major branch of the cluster. Few subsets of the phospho-proteins or proteins correlated significantly with the cell lines’ radiation sensitivity parameters. Tissue microarray of 12 markers identified the significant correlation between RAD50 expression with distant relapse free survival (DMFS), locoregional relapse-free survival (LRRFS) and disease-free survival (DFS). Up-regulation of RAD50 in NSCLC cell line conferred radio resistance in vitro, and cell lines with up-regulated RAD50 recovered from the radiation-induced growth arrest faster than control cells. Conclusion: RAD50 is a potential prognostic biomarker for lung cancer patients who received radiotherapy. Author Disclosure: Y. Wang: None. J. Gudikote: None. J. Yan: None. W. Deng: None. W. Jiang: None. B. Hobbs: None. J. Wang: None. S.G. Swisher: None. J. Fujimoto: None. I. Wistuba: Research Grant; AstraZeneca, Ely-Lily, Genentech, Merck, Myriad Biotech, Pfizer. Honoraria; Boehringer Ingelheim, Genentech, General Electric, Glaxo SmithKline, Medscape, Novartis, Pfizer Pharmaceuticals, Roche. Translational Molecular Pathology; The University of Texas MD Anderson Cancer Center. R.U. Komaki: None. J. Heymach: None. S.H. Lin: Research Grant; Elekta, Inc., Hitachi Chemical, Inc., Peregrine Pharmaceuticals, Inc., Roche/Genentech, STCube Pharmaceuticals, Inc.
1070 BCN057 Mitigates Radiation Induced Gastrointestinal Syndrome P. Bhanja,1 A.J. Norris,2 D. Nag,3 S. Choudhury,3 A. Hoover,1 and S. Saha3; 1University of Kansas School of Medicine, Department of Radiation Oncology, Kansas City, KS, 2BCN Biosciences, Pasadena, CA, 3 University of Kansas School of Medicine, Department of Radiation Oncology, Kansas City, KS Purpose/Objective(s): Radiation Induced Gastro Intestinal Syndrome (RIGS) limits the survival of victims in a mass casualty setting from nuclear accidents or terrorism. Currently there is no approved therapy for
International Journal of Radiation Oncology Biology Physics
and to study the effects of molecular targeted agents in combination with radiation. Author Disclosure: C.R. Hauck: None. B.J. Thibodeau: None. S. Ahmed: None. M.D. Johnson: None. G.D. Wilson: None.
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Applied Cancer Science Institution, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7 Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 9Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
1068 Dynamic Changes of 3-Dimensional DW-MRI for Primary Tumor and Cervical Lymph Nodes in Head and Neck Cancer During Radiation Therapy: A Phase 2 Prospective Study M. Feng,1,2 J. Lang,1 F. Wu,3 J. Ren,3 X. Chen,3 F. LI,3 X. Peng,3 Y. Qi,3 S. Lu,1 Y. Huang,4 L. Li,5 S. Wang,3 K. Xu,6 and W. Wang7; 1Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 2Radiation Oncology Department, Sichuan Cancer Hospital and Institution, Chengdu, China, 3Sichuan Cancer Hospital and Institution, Chengdu, China, 4Sichuan Cancer Hospital, Chengdu, China, 5Guangxi Medical University, Nanning, China, 6Sichuan Cancer Hospital and Institute, Chengdu, China, 7Sichuan Cancer Hospital and Institute, Chengdu, China Purpose/Objective(s): DW-MRI becomes more and more important, recent study find it help to discriminate the metastatic lymph node and distinguish recurrent tumor. However, we still poorly understand the dynamic changes of it during treatment, especially for 3D-apparent diffusion coefficient (ADC). It is urgent to observe the dynamic changes of 3D-ADC for head and neck cancer during radiotherapy, and to investigate the correlation between the changes of ADC, radiation dose and volume reduction. Materials/Methods: Sixty patients with head and neck cancer treated with image-guided IMRT were enrolled. DW-MRI were performed on 3.0T MRI scanner (b Z 0, 500, 800 s/mm2) at pre-radiation, the 15th, the 25th and post-radiation. Region of interest was the primary tumor (GTV-T) and cervical lymph nodes (GTV-N). The volumes and the maximum, mean and minimum of 3D-ADC value were automatically measured by MIM software. Pearson analysis was used to assess the correlation between 3DADC values, delivered radiation dose and tumor volume reduction. Results: All the patients exhibited the mean 3D-ADC increase in GTV-T (0.640.24 x10-3 mm2/s) and GTV-N (0.350.09 x10-3 mm2/s), with the mean increased ratios of 0.500.20 and 0.440.08 between pre- and postradiation. The mean 3D-ADC for GTV-T and GTV-N both changed mostly at the 25th radiation. However, the changes of the maximum and minimum 3DADC values for GTV-T and GTV-N had no correlation with delivered dose and volume reduction. The maximum, mean, and minimum 3D-ADC changes in spinal cord were almost invisible ( 0.04 x10-3 mm2/s). The increased mean ADC had a strong positive correlation with the increased radiation delivered dose for GTV-T and GTV-N respectively (r Z 0.977, P Z 0.023; r Z 0.974, P Z 0.026), and a significantly negative correlation with the volume reduction (r Z -0.989，P Z 0.011; r Z -0.969, P Z 0.031). Conclusion: The mean 3D-ADC value of primary tumor and cervical lymph node can be increased greatly for head and neck cancer during radiotherapy. It had a strong negative correlation with the volume reduction, and a positive correlation with the increased delivered dose. Dynamic 3D-ADC changes during radiotherapy might be an early indicator to assess the treatment response and helps to make treatment strategy for head and neck cancer. Author Disclosure: M. Feng: None. J. Lang: None. F. Wu: None. J. Ren: None. X. Chen: None. F. LI: None. X. Peng: None. Y. Qi: None. S. Lu: None. Y. Huang: None. L. Li: None. S. Wang: None. K. Xu: None. W. Wang: None.
1069 RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy in Resected NoneSmall Cell Lung Cancer Y. Wang,1 J. Gudikote,2 J. Yan,3 W. Deng,4 W. Jiang,4 B. Hobbs,5 J. Wang,6 S.G. Swisher,7 J. Fujimoto,8 I. Wistuba,8 R.U. Komaki,4 J. Heymach,9 and S.H. Lin4; 1Department of Experimental Radiation
Purpose/Objective(s): Radiation therapy is a mainstay of therapy for locally advanced non-small cell lung cancer (NSCLC). However, both locoregional failure and distant metastasis remain problematic. Understanding the underlying mechanisms of therapeutic resistance against radiation by cancer cells is important to counteract treatment resistance. Materials/Methods: Using an integrative analysis approach, we assessed the activation of critical intracellular signaling pathways and potential therapeutic targets that may confer the radiation resistant phenotype using reverse-phase protein arrays (RPPA). Here, we utilized a panel of 70 NSCLC cell lines to profile the baseline expression of 170 total and phospho-proteins and correlated their expression levels with the intrinsic radiation response to categorize pathways that may contribute to resistance. We further carried out the tissue microarray analysis for the most significant markers indicated by RPPA in 127 patient tumor samples who received surgery and postoperative radiation therapy (PORT). The leading prognostic marker was identified by Cox regression analysis and log-rank test. The marker’s function in radiation resistance was validated by overexpression in NSCLC cell line in vitro. Results: Baseline RPPA profiling followed by unsupervised hierarchical clustering of the cell lines separated resistant from the sensitive cell lines at the first major branch of the cluster. Few subsets of the phospho-proteins or proteins correlated significantly with the cell lines’ radiation sensitivity parameters. Tissue microarray of 12 markers identified the significant correlation between RAD50 expression with distant relapse free survival (DMFS), locoregional relapse-free survival (LRRFS) and disease-free survival (DFS). Up-regulation of RAD50 in NSCLC cell line conferred radio resistance in vitro, and cell lines with up-regulated RAD50 recovered from the radiation-induced growth arrest faster than control cells. Conclusion: RAD50 is a potential prognostic biomarker for lung cancer patients who received radiotherapy. Author Disclosure: Y. Wang: None. J. Gudikote: None. J. Yan: None. W. Deng: None. W. Jiang: None. B. Hobbs: None. J. Wang: None. S.G. Swisher: None. J. Fujimoto: None. I. Wistuba: Research Grant; AstraZeneca, Ely-Lily, Genentech, Merck, Myriad Biotech, Pfizer. Honoraria; Boehringer Ingelheim, Genentech, General Electric, Glaxo SmithKline, Medscape, Novartis, Pfizer Pharmaceuticals, Roche. Translational Molecular Pathology; The University of Texas MD Anderson Cancer Center. R.U. Komaki: None. J. Heymach: None. S.H. Lin: Research Grant; Elekta, Inc., Hitachi Chemical, Inc., Peregrine Pharmaceuticals, Inc., Roche/Genentech, STCube Pharmaceuticals, Inc.
1070 BCN057 Mitigates Radiation Induced Gastrointestinal Syndrome P. Bhanja,1 A.J. Norris,2 D. Nag,3 S. Choudhury,3 A. Hoover,1 and S. Saha3; 1University of Kansas School of Medicine, Department of Radiation Oncology, Kansas City, KS, 2BCN Biosciences, Pasadena, CA, 3 University of Kansas School of Medicine, Department of Radiation Oncology, Kansas City, KS Purpose/Objective(s): Radiation Induced Gastro Intestinal Syndrome (RIGS) limits the survival of victims in a mass casualty setting from nuclear accidents or terrorism. Currently there is no approved therapy for