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Salvage Intensity Modulated Radiation Therapy (IMRT) for Locally Recurrent Nasopharyngeal Cancer After Definitive IMRT: Treatment Outcomes of a Clinically Distinct Condition in the Modern Era
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Volume 96 Number 2S Supplement 2016 epiglottis, infrahyoid epiglottis, total epiglottis, aryepiglottic folds, supraglottic larynx, glottic larynx, subglottic larynx and total larynx. Of these 49 patients, 30 were included for this analysis. Nineteen patients were excluded due to either prevalent aspiration at baseline, or because they did not come to have their 12 month evaluation. The incidence of aspiration 1 year following CRT was correlated with dose-volume data to laryngeal substructures. Doses were compared between those with and without aspiration at 12 months using the Wilcoxon rank sum test. Data are reported as mean (standard deviation). There were few data points at 24 months. Results: For the 30 included patients, the median age for the group was 50 years, 23 males, 7 females, 63% were smokers and 93% had stage IV disease. None of the 30 patients aspirated prior to CRT. One year following CRT, 10/30 (33%) showed aspiration on VFG. The following dose-volume associations were observed. Aryepiglottic Folds: The mean dose was significantly higher in patients who aspirated than in non-aspirating patients (6600 cGy (521) vs 5830 cGy (1024), P Z 0.048), V50, V60, D20 and D1.5cc also were significantly associated with aspiration (P < .05). Suprahyoid Epiglottis and Total Epiglottis: Mean dose and D1.5cc were significantly associated with aspiration (mean 7280 cGy (442) in aspirators, 6755 cGy (661) in non-aspirators, P Z 0.048). Cricoid Cartilage: V40 was significantly associated with aspiration (P < .05). Entire Larynx: The mean dose was higher in aspirators, 7090 cGy (572) compared with nonaspirators, 6290 cGy (943), P Z 0.059. V40, V60, D15 and D20were significantly associated with aspiration. Conclusion: These are hypothesis-generating data that require further research and validation in a larger number of patients to assess the importance of laryngeal substructures in aspiration so IMRT can be used to reduce radiation doses to the selected OAR within the larynx. Author Disclosure: B.B. Mittal: None. T. Refaat: None. A. Rademaker: None. B.R. Pauloski: None. M. Choi: None. T.O. Thomas: None. J.A. Logemann: None.
2809 Salvage Intensity Modulated Radiation Therapy (IMRT) for Locally Recurrent Nasopharyngeal Cancer After Definitive IMRT: Treatment Outcomes of a Clinically Distinct Condition in the Modern Era L. Kong,1,2 L. Wang,3 C. Shen,1 C. Hu,1 L. Wang,1 and J.J. Lu2; 1Fudan University Shanghai Cancer Center, Shanghai, China, 2Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China, 3Second Hospital of Kashi, Xinjiang, China Purpose/Objective(s): Despite advances in imaging and the use of highprecision IMRT in the definitive treatment of nasopharyngeal carcinoma, the local recurrence rate remains at 10%. Further, since the previous technical limitations of 2D and 3D conformal therapy have largely been eliminated, locally recurrent nasopharyngeal carcinoma (rNPC) after IMRT represents a distinct clinical entity that has been selectively enriched by radio-resistant cancer cells. Therefore, we report of the outcomes of repeat salvage-IMRT for only patients with rNPC after a definitive course of IMRT. Materials/Methods: Between May 2009 and May 2014, a total of 77 patients with rNPC who failed initial IMRT (66 to 70.4 Gy to gross disease) with curative intent were treated with salvage IMRT. Seventyone patients received salvage IMRT alone to a median dose of 66Gy (range 46.2-70) prescribed to the PTV(s) at 2.0-2.1Gy/day (5 days per week. Six patients received IMRT (50-56Gy) plus a brachytherapy boost. Overall survival time (OS), duration of local control (LC), local and regional progression-free and distant metastasis-free survival time (LPFS, RPFS, and DMFS), and progression-free survival time (PFS) were measured from the time of diagnosis of recurrent until documented locoregional or distant failure/progression. Univariate Log-rank tests were used to detect differences in the survival outcomes between factor-defined subgroups. Multivariate analysis was performed using the Cox proportional hazard model. The level of significance was set at a two-tailed P value of <0.05.
Results: Median interval between the completion of initial RT and the start of re-irradiation for local recurrence was 27.9 months (range 11.779.0). The median follow-up time was 25.7 months (range 3.0-75.7 months) measured from the time of recurrence. The median overall survival time and progression-free survival time of the entire cohort was 37.0 and 20.5 months, respectively. Thirty-four patients (44.2%) died. Approximately 35% of these patients died from disease progression, but 53% were from treatment-induced severe adverse effects (SAEs) without evidence of disease progression. Late SAEs, namely, mucosal and temporal lobe necrosis, occurred in 50 (64.9%) patients during follow up. The 3-year OS in patients not experiencing SAEs was 69.3% vs. 26.1% for those not having SAEs, respectively (P Z 0.034). Higher T-stage of the recurrent tumor and the development of SAEs were found to be the only independent and significant prognostic factors on multi-variable analysis. Conclusion: These outcomes underscore the particularly virulent characteristics of rNPC after definitive IMRT, when compared to historical recurrences after conventional radiation therapy. The impact on survival by SAEs was especially concerning. These data further demonstrate the need for safer treatment strategies to address this difficult clinical problem. Author Disclosure: L. Kong: None. L. Wang: None. C. Shen: None. C. Hu: None. L. Wang: None. J.J. Lu: None.
2810 Correlation of Plasma Epstein-Barr Virus DNA Level With Tumor Volume and Pattern of Tumor Extension and Metastasis in Pretreatment Nasopharyngeal Carcinoma X. Zhou1,2 and C. Hu2; 1Shanghai Medical College Fudan University, Shanghai, China, 2Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): To investigate the association of pretreatment concentration of plasma Epstein-Barr virus DNA (pEBV DNA) to tumor volume and characteristics of tumor invasion in patients with nasopharyngeal carcinoma (NPC), and to develop a prediction model for pEBV DNA. Materials/Methods: 108 patients newly diagnosed with non-disseminated NPC were enrolled in this study. Pretreatment pEBV DNA (copies/mL) was quantified using a real-time PCR technique. Volume (cm3) of the primary tumor (GTV-NX), metastatic lymph nodes (GTV-LN) and total neoplasm (GTV-Tol) were measured using the 3-dimensional quantitative tool of a commercial workstation. Tumor characteristics were evaluated, including anatomical structures invaded by primary mass as well as the level, laterality, multiplicity, size, the presence of extracapsular spread or necrosis of metastatic lymph nodes. All evaluation was performed on MR images. Relationship among natural logarithm of pEBV DNA (lnDNA), cubic root of GTV (crGTV) and tumor characteristics was analyzed using Mann-Whitney U test or one-way analysis of variance (ANOVA). The prediction value of tumor volume and tumor characteristics on pEBV DNA was tested in a stepwise multivariate linear regression model. Results: lnDNA showed significant correlation with crGTV-LN (adjusted R2 Z 0.534, P<0.001) and crV-Tol (adjusted R2 Z 0.457, P<0.001), compared to a weaker correlation with crGTV-NX (adjusted R2 Z 0.053, P Z 0.011). Pretreatment pEBV DNA was closely related to N classification (median count for N0-N3:54, 380, 1737, 16326 copies/mL, P<0.001) and overall stage (median count for N0-N3:118, 181, 1057, 2143 copies/mL, P Z 0.012). Several tumor characteristics were associated with lnDNA (P<0.01). According to the multivariate linear regression, crGTVLN and skull base invasion (Ib) (adjusted R2 Z 0.055, P<0.001) are two strongest predictors for lnDNA (R2 Z 0.589); a fitted equation was: lnDNA Z 2.528+1.622*crGTV-LN+1.256*Ib. Conclusion: Larger regional lymph nodes and invasion of skull base predict higher pretreatment pEBV DNA level. Based on the acquired equation, a severe bias of pEBV DNA from the predicted value might imply a potential of distant metastasis. Author Disclosure: X. Zhou: None. C. Hu: None.
Volume 96 Number 2S Supplement 2016 epiglottis, infrahyoid epiglottis, total epiglottis, aryepiglottic folds, supraglottic larynx, glottic larynx, subglottic larynx and total larynx. Of these 49 patients, 30 were included for this analysis. Nineteen patients were excluded due to either prevalent aspiration at baseline, or because they did not come to have their 12 month evaluation. The incidence of aspiration 1 year following CRT was correlated with dose-volume data to laryngeal substructures. Doses were compared between those with and without aspiration at 12 months using the Wilcoxon rank sum test. Data are reported as mean (standard deviation). There were few data points at 24 months. Results: For the 30 included patients, the median age for the group was 50 years, 23 males, 7 females, 63% were smokers and 93% had stage IV disease. None of the 30 patients aspirated prior to CRT. One year following CRT, 10/30 (33%) showed aspiration on VFG. The following dose-volume associations were observed. Aryepiglottic Folds: The mean dose was significantly higher in patients who aspirated than in non-aspirating patients (6600 cGy (521) vs 5830 cGy (1024), P Z 0.048), V50, V60, D20 and D1.5cc also were significantly associated with aspiration (P < .05). Suprahyoid Epiglottis and Total Epiglottis: Mean dose and D1.5cc were significantly associated with aspiration (mean 7280 cGy (442) in aspirators, 6755 cGy (661) in non-aspirators, P Z 0.048). Cricoid Cartilage: V40 was significantly associated with aspiration (P < .05). Entire Larynx: The mean dose was higher in aspirators, 7090 cGy (572) compared with nonaspirators, 6290 cGy (943), P Z 0.059. V40, V60, D15 and D20were significantly associated with aspiration. Conclusion: These are hypothesis-generating data that require further research and validation in a larger number of patients to assess the importance of laryngeal substructures in aspiration so IMRT can be used to reduce radiation doses to the selected OAR within the larynx. Author Disclosure: B.B. Mittal: None. T. Refaat: None. A. Rademaker: None. B.R. Pauloski: None. M. Choi: None. T.O. Thomas: None. J.A. Logemann: None.
2809 Salvage Intensity Modulated Radiation Therapy (IMRT) for Locally Recurrent Nasopharyngeal Cancer After Definitive IMRT: Treatment Outcomes of a Clinically Distinct Condition in the Modern Era L. Kong,1,2 L. Wang,3 C. Shen,1 C. Hu,1 L. Wang,1 and J.J. Lu2; 1Fudan University Shanghai Cancer Center, Shanghai, China, 2Shanghai Proton and Heavy Ion Center (SPHIC), Shanghai, China, 3Second Hospital of Kashi, Xinjiang, China Purpose/Objective(s): Despite advances in imaging and the use of highprecision IMRT in the definitive treatment of nasopharyngeal carcinoma, the local recurrence rate remains at 10%. Further, since the previous technical limitations of 2D and 3D conformal therapy have largely been eliminated, locally recurrent nasopharyngeal carcinoma (rNPC) after IMRT represents a distinct clinical entity that has been selectively enriched by radio-resistant cancer cells. Therefore, we report of the outcomes of repeat salvage-IMRT for only patients with rNPC after a definitive course of IMRT. Materials/Methods: Between May 2009 and May 2014, a total of 77 patients with rNPC who failed initial IMRT (66 to 70.4 Gy to gross disease) with curative intent were treated with salvage IMRT. Seventyone patients received salvage IMRT alone to a median dose of 66Gy (range 46.2-70) prescribed to the PTV(s) at 2.0-2.1Gy/day (5 days per week. Six patients received IMRT (50-56Gy) plus a brachytherapy boost. Overall survival time (OS), duration of local control (LC), local and regional progression-free and distant metastasis-free survival time (LPFS, RPFS, and DMFS), and progression-free survival time (PFS) were measured from the time of diagnosis of recurrent until documented locoregional or distant failure/progression. Univariate Log-rank tests were used to detect differences in the survival outcomes between factor-defined subgroups. Multivariate analysis was performed using the Cox proportional hazard model. The level of significance was set at a two-tailed P value of <0.05.
Results: Median interval between the completion of initial RT and the start of re-irradiation for local recurrence was 27.9 months (range 11.779.0). The median follow-up time was 25.7 months (range 3.0-75.7 months) measured from the time of recurrence. The median overall survival time and progression-free survival time of the entire cohort was 37.0 and 20.5 months, respectively. Thirty-four patients (44.2%) died. Approximately 35% of these patients died from disease progression, but 53% were from treatment-induced severe adverse effects (SAEs) without evidence of disease progression. Late SAEs, namely, mucosal and temporal lobe necrosis, occurred in 50 (64.9%) patients during follow up. The 3-year OS in patients not experiencing SAEs was 69.3% vs. 26.1% for those not having SAEs, respectively (P Z 0.034). Higher T-stage of the recurrent tumor and the development of SAEs were found to be the only independent and significant prognostic factors on multi-variable analysis. Conclusion: These outcomes underscore the particularly virulent characteristics of rNPC after definitive IMRT, when compared to historical recurrences after conventional radiation therapy. The impact on survival by SAEs was especially concerning. These data further demonstrate the need for safer treatment strategies to address this difficult clinical problem. Author Disclosure: L. Kong: None. L. Wang: None. C. Shen: None. C. Hu: None. L. Wang: None. J.J. Lu: None.
2810 Correlation of Plasma Epstein-Barr Virus DNA Level With Tumor Volume and Pattern of Tumor Extension and Metastasis in Pretreatment Nasopharyngeal Carcinoma X. Zhou1,2 and C. Hu2; 1Shanghai Medical College Fudan University, Shanghai, China, 2Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): To investigate the association of pretreatment concentration of plasma Epstein-Barr virus DNA (pEBV DNA) to tumor volume and characteristics of tumor invasion in patients with nasopharyngeal carcinoma (NPC), and to develop a prediction model for pEBV DNA. Materials/Methods: 108 patients newly diagnosed with non-disseminated NPC were enrolled in this study. Pretreatment pEBV DNA (copies/mL) was quantified using a real-time PCR technique. Volume (cm3) of the primary tumor (GTV-NX), metastatic lymph nodes (GTV-LN) and total neoplasm (GTV-Tol) were measured using the 3-dimensional quantitative tool of a commercial workstation. Tumor characteristics were evaluated, including anatomical structures invaded by primary mass as well as the level, laterality, multiplicity, size, the presence of extracapsular spread or necrosis of metastatic lymph nodes. All evaluation was performed on MR images. Relationship among natural logarithm of pEBV DNA (lnDNA), cubic root of GTV (crGTV) and tumor characteristics was analyzed using Mann-Whitney U test or one-way analysis of variance (ANOVA). The prediction value of tumor volume and tumor characteristics on pEBV DNA was tested in a stepwise multivariate linear regression model. Results: lnDNA showed significant correlation with crGTV-LN (adjusted R2 Z 0.534, P<0.001) and crV-Tol (adjusted R2 Z 0.457, P<0.001), compared to a weaker correlation with crGTV-NX (adjusted R2 Z 0.053, P Z 0.011). Pretreatment pEBV DNA was closely related to N classification (median count for N0-N3:54, 380, 1737, 16326 copies/mL, P<0.001) and overall stage (median count for N0-N3:118, 181, 1057, 2143 copies/mL, P Z 0.012). Several tumor characteristics were associated with lnDNA (P<0.01). According to the multivariate linear regression, crGTVLN and skull base invasion (Ib) (adjusted R2 Z 0.055, P<0.001) are two strongest predictors for lnDNA (R2 Z 0.589); a fitted equation was: lnDNA Z 2.528+1.622*crGTV-LN+1.256*Ib. Conclusion: Larger regional lymph nodes and invasion of skull base predict higher pretreatment pEBV DNA level. Based on the acquired equation, a severe bias of pEBV DNA from the predicted value might imply a potential of distant metastasis. Author Disclosure: X. Zhou: None. C. Hu: None.