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Effect of thermal properties on the production behavior from water-saturated methane hydrate-bearing sediments using depressurization
Volume 105 Number 1S Supplement 2019
Mini Oral Sessions S213
was 6.6% [95% confident intervals (CI): 4.5-8.5%] at 10 years after RT, 13.9% (95% CI: 10.7-16.9%) at 15 years and 23.6% (95% CI 15.8-30.6%) at 20 years. The incidence of CVA in NPC survivors were significantly higher compared with general populations in the age groups (the age when NPC was diagnosed) e risk ratio was 5.56 (95% CI: 3.34-8.73, p<0.001) for 45-54 years old, 3.39 (95% CI: 2.25-4.92, p<0.001) for 55-64 years old, 2.74 (95% CI: 1.79-4.02, P<0.001) for 65-74 years old. In multivariate analysis, age of NPC at diagnosis >55 years old [hazard ratio (HR): 2.65, 95% CI: 1.63-4.3, p<0.001], hypertension (HR 1.87, 95% CI: 1.123.14, p<0.017), male gender (HR 1.90, 95% CI 1.11-3.21, pZ0.018), hyperlipidemia (HR 2.01, 95% CI 1.3-3.4, p<0.004) were significant risk factors of development of CVA. Conclusion: Incidence of CVA in NPC survivors progressively increased beyond 10 years after radical RT and it was markedly elevated compared with general population. The gross incidence rate of >20% beyond 20 years of follow-up was alarming which indicated the urgent unmet need of survivorship care in NPC patients Abstract 1209; Table 1 Cumulative Incidence of CVA After Radical RT for Nasopharyngeal Cancer Patients Years After Radical RT for NPC 5 10 15 20 25 30
Number at risk
Number of event between last time point
610 458 262 26 13 4
14 25 31 14 0 3
Cumulative incidence of CVA (%, 95% CI) 2.0 6.6 13.9 23.6 23.6 53.7
(0.9-3.0) (4.5-8.5) (10.7-16.9) (15.8-30.6) (15.8-30.6) (15.3-74.7)
Author Disclosure: T. Lam: Research Grant; Roche, Mundipharma. H.C. Choi: None. I. Yeung: None.
1210 Radiation-Induced Hypoglossal Nerve Palsy after Definitive Radiotherapy for Nasopharyngeal Carcinoma: Clinical Predictors and Dose-Toxicity Relationship J.C.H. Chow,1 K.M. Cheung,1 K.H. Au,1 B.C.Y. Zee,2 J. Lee,2 R.K.C. Ngan,3 A.W.M. Lee,4 H.H.Y. Yiu,1 K.W.S. Li,1 K.C.A. Leung,1 J.C.H. Chan,1 F.C.H. Lee,1 and K.H. Wong1; 1Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, 2Division of Biostatistics, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong, 3Department of Clinical Oncology, Gleneagles Hong Kong Hospital, Hong Kong, Hong Kong, 4 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Purpose/Objective(s): Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning. Materials/Methods: We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Clinical predictive factors were analyzed using the Cox proportional hazard model. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling. Results: With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. The 5-year and 8-year cumulative incidences were 2.1% and 12.4% respectively. The median latency time to development of palsy was 6.4 years. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological
hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC Z 0.826). Hypoglossal nerves with D1cc of 74Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74Gy EQD2 had significantly lower risk of palsy than those 74Gy EQD2 (2.4% vs 20.8%, p<0.001). Conclusion: Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5%. Author Disclosure: J. Chow: None. K. Cheung: None. K. Au: None. B.C. Zee: None. J. Lee: None. R.K. Ngan: None. A.W. Lee: None. H.H. Yiu: None. K.W. Li: None. K. Leung: None. J.C.H. Chan: None. F.C. Lee: None. K. Wong: None.
1211 Depicting Distant Metastatic Risk by Refined Subgroups Derived From the 8th Edition Nasopharyngeal Carcinoma TNM Q. Guo,1,2 T. Lu,3 S.H. Huang,4 B. O’Sullivan,5 J. Zong,1 Y. Xiao,6 W. Xu,7 C. Chen,1 S. Qiu,1 L.X. Xu,1 W. Zheng,1 Y. Chen,6 S. Lin,1 and J. Pan1; 1Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China, 2Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, 3Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China, 4 Department of Radiation Oncology, Princess Margaret Cancer Centre/ University of Toronto, Toronto, ON, Canada, 5Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada, 6Department of Radiology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China, 7 Department of Biostatistics, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada Purpose/Objective(s): Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensitymodulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. Materials/Methods: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. Results: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.482.4) and 63.6% (56.3-70.9), respectively (p<0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell’s concordance index (c-index) for DMFS. Conclusion: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intragroup hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials. Author Disclosure: Q. Guo: None. T. Lu: None. S. Huang: None. B. O’Sullivan: None. J. Zong: None. Y. Xiao: None. W. Xu: None. C. Chen: None. S. Qiu: None. L. Xu: None. W. Zheng: None. Y. Chen: None. S. Lin: None. J. Pan: None.
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was 6.6% [95% confident intervals (CI): 4.5-8.5%] at 10 years after RT, 13.9% (95% CI: 10.7-16.9%) at 15 years and 23.6% (95% CI 15.8-30.6%) at 20 years. The incidence of CVA in NPC survivors were significantly higher compared with general populations in the age groups (the age when NPC was diagnosed) e risk ratio was 5.56 (95% CI: 3.34-8.73, p<0.001) for 45-54 years old, 3.39 (95% CI: 2.25-4.92, p<0.001) for 55-64 years old, 2.74 (95% CI: 1.79-4.02, P<0.001) for 65-74 years old. In multivariate analysis, age of NPC at diagnosis >55 years old [hazard ratio (HR): 2.65, 95% CI: 1.63-4.3, p<0.001], hypertension (HR 1.87, 95% CI: 1.123.14, p<0.017), male gender (HR 1.90, 95% CI 1.11-3.21, pZ0.018), hyperlipidemia (HR 2.01, 95% CI 1.3-3.4, p<0.004) were significant risk factors of development of CVA. Conclusion: Incidence of CVA in NPC survivors progressively increased beyond 10 years after radical RT and it was markedly elevated compared with general population. The gross incidence rate of >20% beyond 20 years of follow-up was alarming which indicated the urgent unmet need of survivorship care in NPC patients Abstract 1209; Table 1 Cumulative Incidence of CVA After Radical RT for Nasopharyngeal Cancer Patients Years After Radical RT for NPC 5 10 15 20 25 30
Number at risk
Number of event between last time point
610 458 262 26 13 4
14 25 31 14 0 3
Cumulative incidence of CVA (%, 95% CI) 2.0 6.6 13.9 23.6 23.6 53.7
(0.9-3.0) (4.5-8.5) (10.7-16.9) (15.8-30.6) (15.8-30.6) (15.3-74.7)
Author Disclosure: T. Lam: Research Grant; Roche, Mundipharma. H.C. Choi: None. I. Yeung: None.
1210 Radiation-Induced Hypoglossal Nerve Palsy after Definitive Radiotherapy for Nasopharyngeal Carcinoma: Clinical Predictors and Dose-Toxicity Relationship J.C.H. Chow,1 K.M. Cheung,1 K.H. Au,1 B.C.Y. Zee,2 J. Lee,2 R.K.C. Ngan,3 A.W.M. Lee,4 H.H.Y. Yiu,1 K.W.S. Li,1 K.C.A. Leung,1 J.C.H. Chan,1 F.C.H. Lee,1 and K.H. Wong1; 1Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, 2Division of Biostatistics, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong, 3Department of Clinical Oncology, Gleneagles Hong Kong Hospital, Hong Kong, Hong Kong, 4 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Purpose/Objective(s): Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning. Materials/Methods: We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Clinical predictive factors were analyzed using the Cox proportional hazard model. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling. Results: With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. The 5-year and 8-year cumulative incidences were 2.1% and 12.4% respectively. The median latency time to development of palsy was 6.4 years. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological
hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC Z 0.826). Hypoglossal nerves with D1cc of 74Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74Gy EQD2 had significantly lower risk of palsy than those 74Gy EQD2 (2.4% vs 20.8%, p<0.001). Conclusion: Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5%. Author Disclosure: J. Chow: None. K. Cheung: None. K. Au: None. B.C. Zee: None. J. Lee: None. R.K. Ngan: None. A.W. Lee: None. H.H. Yiu: None. K.W. Li: None. K. Leung: None. J.C.H. Chan: None. F.C. Lee: None. K. Wong: None.
1211 Depicting Distant Metastatic Risk by Refined Subgroups Derived From the 8th Edition Nasopharyngeal Carcinoma TNM Q. Guo,1,2 T. Lu,3 S.H. Huang,4 B. O’Sullivan,5 J. Zong,1 Y. Xiao,6 W. Xu,7 C. Chen,1 S. Qiu,1 L.X. Xu,1 W. Zheng,1 Y. Chen,6 S. Lin,1 and J. Pan1; 1Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China, 2Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, 3Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China, 4 Department of Radiation Oncology, Princess Margaret Cancer Centre/ University of Toronto, Toronto, ON, Canada, 5Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada, 6Department of Radiology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China, 7 Department of Biostatistics, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada Purpose/Objective(s): Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensitymodulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. Materials/Methods: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. Results: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.482.4) and 63.6% (56.3-70.9), respectively (p<0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell’s concordance index (c-index) for DMFS. Conclusion: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intragroup hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials. Author Disclosure: Q. Guo: None. T. Lu: None. S. Huang: None. B. O’Sullivan: None. J. Zong: None. Y. Xiao: None. W. Xu: None. C. Chen: None. S. Qiu: None. L. Xu: None. W. Zheng: None. Y. Chen: None. S. Lin: None. J. Pan: None.