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Association of Human Papillomavirus Infection and p16 status in Nonendemic Nasopharyngeal Carcinoma: Incidence, Prevalence, and Prognostic Role
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Volume 99 Number 2S Supplement 2017 and plan strategy forthe Task Force and Committee; Union for International Cancer Control (UICC). A.J. Hope: Travel Expenses; Elekta, Inc.
2785 Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients Who Received Defintive Radiation Therapy for Head and Neck Squamous Cell Carcinoma Y. Cho II,1 H.I. Yoon,2 C.G. Lee Jr,3 and K.C. Keum4; 1Yonsei Cancer Center, Yonsei University Health System, Seoul 120-752, Korea, Republic of (South), 2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 3Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South), 4Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea, Republic of (South) Purpose/Objective(s): With growing evidence on the role of inflammation in carcinogenesis, the presence of a systemic inflammatory response has been proposed as having prognostic significance in a wide range of cancers. The purpose of this study was to investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiotherapy (RT). Materials/Methods: We retrospectively analyzed 498 patients with stage I-IVB HNSCC including oral cavity, nasopharyngeal, oropharyngeal, hypopharyngeal and laryngeal cancer who received definitive RT with (62.7%) or without (37.3%) chemotherapy between 2006 and 2015. The median age of all patients was 60 years. Patients with high NLR had more advanced stage (p<0.001) and they received induction or concurrent chemotherapy more frequently (76.2% vs. 52.5%, p <0.001). progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Cox’s regression model was used for multivariate analysis of selected variables (p<0.05 in univariate analysis) as prognostic factors. Results: The median follow up time was 38 months and 5-year PFS and OS for all patients were 62.3% and 72.1%. With NLR >2.7 considered as high according to receiver operating characteristic curve using PFS as an endpoint, 172 patients had a high NLR. Patients with high NLR showed significantly higher regional failure rate (37.8% vs, 28.6%, p <0.001) while incidence of local and distant failure were comparable to those with low NLR. PFS and OS were significantly lower in high NLR patients (5-year PFS 39.7% vs. 74.8%; 5-year OS. 51.0% vs. 83.7%, p <0.001, respectively). In subgroup analysis according to subsite of HNSCC, patients with high NLR showed significantly better PFS and OS in oral cavity, nasopharyngeal, hypopharyngeal and laryngeal cancer as well, while difference between two groups showed borderline significance in oropharyngeal cancer. In multivariate analysis, high NLR still remained as a independent prognostic factor for PFS and OS (HR for PFS 2.863, 95% CI 1.755-4.670, p<0.001; HR for OS 2.863, 95% CI 1.755-4.670, p<0.001). Conclusion: The patients with high NLR showed poorer survival and different patterns of failure. The optimal therapeutic approaches should be considered for these patients. Author Disclosure: Y. Cho: None. H. Yoon: None. C. Lee: None. K. Keum: None.
2786 Association of Human Papillomavirus Infection and p16 status in Nonendemic Nasopharyngeal Carcinoma: Incidence, Prevalence, and Prognostic Role A. Chundury,1 P. Cosper,1 A. Srivastava,2 D. Gondim,3 J. Contreras,2 W.R. Kennedy,2 P.J. Parikh,2 H.A. Gay,2 X. Wang,1 R. Chernock,3 and W.L. Thorstad2; 1Department of Radiation Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 2 Washington University School of Medicine, Department of Radiation
Oncology, St. Louis, MO, 3Washington University School of Medicine, Department of Pathology, St. Louis, MO Purpose/Objective(s): The purpose of this study was to determine the expression of high risk human papillomavirus (HPV) in nasopharyngeal carcinomas (NPC) and its association with p16 status for a select population of patients with non-endemic NPC treated with definitive chemoradiation therapy (CRT). Materials/Methods: A total of 24 patients with paraffin-embedded tumor specimens who received definitive CRT from 1997 to 2014 for NPC were identified in a prospectively maintained institutional database. Epstein-Barr virus-encoded small RNAs (EBER) in-situ hybridization (ISH) and p16 immunohistochemistry (IHC) were performed on all specimens. Slides were then reviewed by an experienced head and neck pathologist who confirmed diagnosis and identified tumor regions. Macrodissection was performed to remove non-tumor regions, then total RNA was isolated and reverse transcribed. Quantitative PCR (qPCR) for E6 and E7 of 13 different high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 66 and 68) was performed. Gene expression was normalized to the averaged expression levels of both GAPDH and b-actin. The log-rank test and Cox proportional hazard models were used to evaluate the impact of clinical and patient variables on overall survival (OS). Kaplan Meier method was used to derive estimates of OS. Statistical significance was considered as a p <0.05. All levels of significance were two-sided. Results: Median follow up time was 52.3 months (range, 9.5-163.2). Median age was 48.5 years (range, 18.8-68.2). Fifteen (62.5%) patients were Caucasian, 6 (25%) were African American, and 3 (12.5%) were Asian. A total of 7 (29.2%) tumors were HPV-positive/EBV-negative, 15 (62.5%) were HPV-negative/EBV-positive, and 2 (8.3%) were HPVnegative/EBV negative. All tumor specimens positive for p16 on IHC were also positive for HPV mRNA expression, and all the specimens negative for p16 on IHC were also negative for HPV mRNA expression. Given such, the sensitivity and specificity of p16 IHC and high-risk HPV mRNA expression were both 100%. Five year actuarial rates of OS for patients with a HPV-positive tumor and for patients with a HPV-negative tumor were 100% and 69.4% (p Z 0.048), respectively. On multivariate analysis, older age (HR 1.15, 95% CI 1.01-1.28, p Z 0.038) and advanced nodal stage (HR 33, 95% CI 1.19-914.44, p Z 0.039) remained independently predictive for overall survival. Conclusion: p16 IHC is a reliable surrogate marker for high risk HPV mRNA expression in patients with non-endemic NPC and furthermore, HPV-positive tumors are associated with improved overall survival when compared to HPV-negative tumors. Given discordance in previously published data, a larger confirmatory study is required to validate these findings. Author Disclosure: A. Chundury: Research Grant; Washington University Department of Radiation Oncology. P. Cosper: Research Grant; RSNA. A. Srivastava: None. D. Gondim: None. J. Contreras: None. W.R. Kennedy: None. P.J. Parikh: Research Grant; Varian Medical. Stock; Holaira. H.A. Gay: None. X. Wang: None. R. Chernock: None. W.L. Thorstad: None.
2787 A 7-Year Institutional Experience in Dosimetric Quality Improvement for Oropharyngeal Cancer: Progress to Date T. Cui,1 M.C. Ward,1 E.J. Murray,1 J. Potter,1 A. Dorfmeyer,1 C. Belfi,1 N.P. Joshi,1 J.F. Greskovich Jr,2 S. Koyfman,1 and P. Xia1; 1Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 2Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Florida, Weston, FL Purpose/Objective(s): We have previously reported a low incidence of treatment-related toxic effects after treatment for oropharyngeal carcinoma compared to historical data. Multiple quality improvement steps have been taken at our institution over the past 7 years: the adoption of volumetric modulated arc therapy (VMAT) over step-and-shoot IMRT (SS-IMRT),
Volume 99 Number 2S Supplement 2017 and plan strategy forthe Task Force and Committee; Union for International Cancer Control (UICC). A.J. Hope: Travel Expenses; Elekta, Inc.
2785 Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients Who Received Defintive Radiation Therapy for Head and Neck Squamous Cell Carcinoma Y. Cho II,1 H.I. Yoon,2 C.G. Lee Jr,3 and K.C. Keum4; 1Yonsei Cancer Center, Yonsei University Health System, Seoul 120-752, Korea, Republic of (South), 2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 3Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South), 4Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea, Republic of (South) Purpose/Objective(s): With growing evidence on the role of inflammation in carcinogenesis, the presence of a systemic inflammatory response has been proposed as having prognostic significance in a wide range of cancers. The purpose of this study was to investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiotherapy (RT). Materials/Methods: We retrospectively analyzed 498 patients with stage I-IVB HNSCC including oral cavity, nasopharyngeal, oropharyngeal, hypopharyngeal and laryngeal cancer who received definitive RT with (62.7%) or without (37.3%) chemotherapy between 2006 and 2015. The median age of all patients was 60 years. Patients with high NLR had more advanced stage (p<0.001) and they received induction or concurrent chemotherapy more frequently (76.2% vs. 52.5%, p <0.001). progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Cox’s regression model was used for multivariate analysis of selected variables (p<0.05 in univariate analysis) as prognostic factors. Results: The median follow up time was 38 months and 5-year PFS and OS for all patients were 62.3% and 72.1%. With NLR >2.7 considered as high according to receiver operating characteristic curve using PFS as an endpoint, 172 patients had a high NLR. Patients with high NLR showed significantly higher regional failure rate (37.8% vs, 28.6%, p <0.001) while incidence of local and distant failure were comparable to those with low NLR. PFS and OS were significantly lower in high NLR patients (5-year PFS 39.7% vs. 74.8%; 5-year OS. 51.0% vs. 83.7%, p <0.001, respectively). In subgroup analysis according to subsite of HNSCC, patients with high NLR showed significantly better PFS and OS in oral cavity, nasopharyngeal, hypopharyngeal and laryngeal cancer as well, while difference between two groups showed borderline significance in oropharyngeal cancer. In multivariate analysis, high NLR still remained as a independent prognostic factor for PFS and OS (HR for PFS 2.863, 95% CI 1.755-4.670, p<0.001; HR for OS 2.863, 95% CI 1.755-4.670, p<0.001). Conclusion: The patients with high NLR showed poorer survival and different patterns of failure. The optimal therapeutic approaches should be considered for these patients. Author Disclosure: Y. Cho: None. H. Yoon: None. C. Lee: None. K. Keum: None.
2786 Association of Human Papillomavirus Infection and p16 status in Nonendemic Nasopharyngeal Carcinoma: Incidence, Prevalence, and Prognostic Role A. Chundury,1 P. Cosper,1 A. Srivastava,2 D. Gondim,3 J. Contreras,2 W.R. Kennedy,2 P.J. Parikh,2 H.A. Gay,2 X. Wang,1 R. Chernock,3 and W.L. Thorstad2; 1Department of Radiation Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 2 Washington University School of Medicine, Department of Radiation
Oncology, St. Louis, MO, 3Washington University School of Medicine, Department of Pathology, St. Louis, MO Purpose/Objective(s): The purpose of this study was to determine the expression of high risk human papillomavirus (HPV) in nasopharyngeal carcinomas (NPC) and its association with p16 status for a select population of patients with non-endemic NPC treated with definitive chemoradiation therapy (CRT). Materials/Methods: A total of 24 patients with paraffin-embedded tumor specimens who received definitive CRT from 1997 to 2014 for NPC were identified in a prospectively maintained institutional database. Epstein-Barr virus-encoded small RNAs (EBER) in-situ hybridization (ISH) and p16 immunohistochemistry (IHC) were performed on all specimens. Slides were then reviewed by an experienced head and neck pathologist who confirmed diagnosis and identified tumor regions. Macrodissection was performed to remove non-tumor regions, then total RNA was isolated and reverse transcribed. Quantitative PCR (qPCR) for E6 and E7 of 13 different high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 66 and 68) was performed. Gene expression was normalized to the averaged expression levels of both GAPDH and b-actin. The log-rank test and Cox proportional hazard models were used to evaluate the impact of clinical and patient variables on overall survival (OS). Kaplan Meier method was used to derive estimates of OS. Statistical significance was considered as a p <0.05. All levels of significance were two-sided. Results: Median follow up time was 52.3 months (range, 9.5-163.2). Median age was 48.5 years (range, 18.8-68.2). Fifteen (62.5%) patients were Caucasian, 6 (25%) were African American, and 3 (12.5%) were Asian. A total of 7 (29.2%) tumors were HPV-positive/EBV-negative, 15 (62.5%) were HPV-negative/EBV-positive, and 2 (8.3%) were HPVnegative/EBV negative. All tumor specimens positive for p16 on IHC were also positive for HPV mRNA expression, and all the specimens negative for p16 on IHC were also negative for HPV mRNA expression. Given such, the sensitivity and specificity of p16 IHC and high-risk HPV mRNA expression were both 100%. Five year actuarial rates of OS for patients with a HPV-positive tumor and for patients with a HPV-negative tumor were 100% and 69.4% (p Z 0.048), respectively. On multivariate analysis, older age (HR 1.15, 95% CI 1.01-1.28, p Z 0.038) and advanced nodal stage (HR 33, 95% CI 1.19-914.44, p Z 0.039) remained independently predictive for overall survival. Conclusion: p16 IHC is a reliable surrogate marker for high risk HPV mRNA expression in patients with non-endemic NPC and furthermore, HPV-positive tumors are associated with improved overall survival when compared to HPV-negative tumors. Given discordance in previously published data, a larger confirmatory study is required to validate these findings. Author Disclosure: A. Chundury: Research Grant; Washington University Department of Radiation Oncology. P. Cosper: Research Grant; RSNA. A. Srivastava: None. D. Gondim: None. J. Contreras: None. W.R. Kennedy: None. P.J. Parikh: Research Grant; Varian Medical. Stock; Holaira. H.A. Gay: None. X. Wang: None. R. Chernock: None. W.L. Thorstad: None.
2787 A 7-Year Institutional Experience in Dosimetric Quality Improvement for Oropharyngeal Cancer: Progress to Date T. Cui,1 M.C. Ward,1 E.J. Murray,1 J. Potter,1 A. Dorfmeyer,1 C. Belfi,1 N.P. Joshi,1 J.F. Greskovich Jr,2 S. Koyfman,1 and P. Xia1; 1Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 2Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Florida, Weston, FL Purpose/Objective(s): We have previously reported a low incidence of treatment-related toxic effects after treatment for oropharyngeal carcinoma compared to historical data. Multiple quality improvement steps have been taken at our institution over the past 7 years: the adoption of volumetric modulated arc therapy (VMAT) over step-and-shoot IMRT (SS-IMRT),