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HPV-Positive Oropharyngeal Cancer Increased for Both Black and White Patients Over Time, 1992-2007
494
International Journal of Radiation Oncology Biology Physics
combination chemoradiation therapy with Nimotuzumab was well tolerated. Addition of Nimotuzumab to concurrent chemoradiation therapy regimen was not associated with added toxicity. Conclusions: Addition of Nimotuzumab to concurrent chemotherapy and radiation is safe and efficacious based on the locoregional response and confirms the available phase 2 data in HNSCC patients. The survival benefits of this combination need further evaluation in a larger study setting Author Disclosure: S. Sundaram: None. B. Venkatanarayanan: None. N. Sridharan: None. G. Kakumudi Rajagopal: None.
unknown if the incidence of unknown primary carcinoma of the head and neck is rising at a rate similar to that of HPV-associated oropharynx cancer. Materials/Methods: The institutional databases of SCCUPS from 1990 2013 of two tertiary care cancer centers (Fox Chase Cancer Center, Philadelphia, PA and University of Pittsburgh Medical Center) were combined. To be assigned a diagnosis of unknown primary squamous cell carcinoma all patients were required to have: 1.) pathologically proven squamous cell carcinoma in a neck lymph node, 2.) cross sectional imaging that failed to demonstrate a mucosal primary, and 3.) a negative flexible scope examination +/- directed biopsies and/or tonsillectomy. A subset of patients underwent lingual tonsillectomy, in an effort to identify the primary. HPV status was determined by immunohistochemistry (IHC) using antibody against p16 (G175-405, BD Pharmingen, USA). A positive test was defined as intermediate/strong nuclear and cytoplasmic staining in 70% of cells. Incidence rates were calculated by linear regression. Prevalence of HPV status as a function of time of diagnosis was calculated. Results: Unknown primary carcinoma of the head and neck was diagnosed 175 times at the two institutions during the designated time frame. N stage distribution was: N1 (n Z 40, 23%); N2 (n Z 108, 62%); N3 (n Z 27, 15%). An overwhelming majority of cases were diagnosed in the year 2000 or later (n Z 144, 83%). Assignment of a diagnosis of squamous carcinoma of unknown primary exhibited linear growth since 1990 at the two institutions, with an average of 6.6 additional cases per additional 10 years, with unabated increases through the last complete year of data in 2012. A total of 126 (72%) of patients have had samples tested for HPV, almost all of which (n Z 115, 91%) were treated in 2000 or later. Among those with a known HPV status, 95 (75%) were determined to be HPV associated tumors. Conclusions: The majority of patient diagnosed with SCCUPS are p16+, indicative of HPV association. Our date demonstrate that the incidence of SCCUPS is increasing at a rate consistent with that of HPV associated oropharynx cancer. Prospective study of toxicity mitigation for this good prognosis disease indicated. Author Disclosure: T.J. Galloway: None. K.S. Davis: None. B. Burtness: Q. Leadership; ECOG Head and Neck Committee. R.L. Ferris: Q. Leadership; ECOG Head and Neck Committee. R. Mehra: None. J.A. Ridge: Q. Leadership; ECOG Head and Neck Committee, RTOG Surgical Oncology. D. Flieder: None. U. Duvvuri: None.
276 Dosimetric Comparison of Field-in-Field Technique to Conventional Wedge Planned Technique for Early-Stage Glottic Cancer Definitive Management of Head-and-Neck Squamous Cell Carcinoma M. Gurka,1 T. Campbell,2 E. Bullock,1 J. Hoon,3 K. Unger,1 N. Nasr,3 and K. Harter1; 1Medstar Georgetown University Hospital, Washington, DC, 2RadAmerica, Clinton, MD, 3Virginia Hospital Center, Arlington, VA Purpose/Objective(s): To analyze conventional wedged beam and fieldin-field (FIF) techniques in patients with early stage (T1-T2) glottic cancer using dosimetric parameters. Materials/Methods: In five patients with early stage glottic cancer, two plans were generated for each patient: a conventional wedged plan and a FIF plan both utilizing opposed lateral fields. A CTV was contoured that included the entire glottic area (top of thyroid cartilage to cricoid ring). Conventional larynx fields were used that extended from the bottom of the hyoid bone inferiorly to the cricoid cartilage. Anteriorly 1-2 cm of flash was given and the field extended posteriorly to the anterior margin of the cervical spine. The dose was prescribed to a reference point 1-2 cm anterior to the cervical spine. For T1 tumors, the prescribed dose was 63 Gy in 2.25 Gy and 65.25 in 2.25 Gy for T2 tumors. The FIF plans included one to two subfields for each open field. The wedge angle was chosen that provided the best coverage with an acceptable Dmax. The plans were compared in regards to the global Dmax, CTV coverage expressed as dose to 95% of the CTV (D95) as well as volume of CTV receiving 100% of the prescribed dose (V100%), and homogeneity index defined as D5/D95, where D5 Z dose to 5% of the target volume and D95 Z dose to 95% of the target volume. Results: Overall, both plans performed similarly. The median global Dmax was slightly higher FIF plans compared to the wedges plans, 106.1% (range 103.8% - 107.0%) and 104.9% (range 103.4% - 107.4%). The D95% was higher with the field-in-field technique in three of the five plans. In terms of V100%, FIF performed better with a median of 89% (range 31% - 99%) compared to 73% (range 34% - 95%) for the wedged plans. Homogeneity was also minimally improved with the FIF plans, median 1.06 (range 1.04 -1.16) compared to 1.07 (range 1.05-1.11) with a wedge fields. Conclusions: In these five patients, a FIF plan yields similar coverage and homogeneity compared to wedged plans and can be considered as an alternative to using wedges. Author Disclosure: M. Gurka: None. T. Campbell: None. E. Bullock: None. J. Hoon: None. K. Unger: None. N. Nasr: None. K. Harter: None.
101 HPV Association and the Increasing Incidence of Unknown Primary Head-and-Neck Squamous Cell Carcinoma Epidemiology and Prevention T.J. Galloway,1 K.S. Davis,2 B. Burtness,1 R.L. Ferris,2 R. Mehra,1 J.A. Ridge,1 D. Flieder,1 and U. Duvvuri2; 1Fox Chase Cancer Center, Philadelphia, PA, 2University of Pittsburgh Medical Center, Pittsburgh, PA Purpose/Objective(s): Unknown primary head and neck squamous cell carcinoma (SCCUPS) typically has a favorable prognosis. It is suspected that the historical good outcome is a reflection of a high percentage of previously unrecognized HPV (Human papillomavirus) association. It is
107 HPV-Positive Oropharyngeal Cancer Increased for Both Black and White Patients Over Time, 1992-2007 Epidemiology and Prevention D.P. Zandberg,1 S.Z. Liu,2 O. Goloubeva,1 L.M. Schumaker,1 and K.J. Cullen1; 1University of Maryland Greenebaum Cancer Center, Baltimore, MD, 2Department of Pathology University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): While we previously reported a striking racial difference in the prevalence of human papillomavirus (HPV) positive oropharyngeal cancer (OPSCC), which has been corroborated by other groups, less is known about differences by HPV status and race over time. To investigate we analyzed tissue samples from OPSCC patients treated at the University of Maryland Greenebaum Cancer Center (UMGCC) over a 15-year time period. Materials/Methods: We conducted a retrospective study of 467 OPSCC patients treated between 1992 and 2007, of which 200 had tissue available for HPV16 testing (by PCR for E6 and E7 genes). Baseline characteristics included race, gender, age, smoking and alcohol status, staging, and treatment. Overall Survival (OS) included only those with first primary tumors and was estimated by the Kaplan-Meier approach and compared by the log-rank test. The Cox regression model was applied to identify risk factors and their impact on OS. Results: Of 200 patients, 67 were HPV16 positive, 127 were HPV16 negative and 6 were not evaluable. Overall racial distribution was 62.5% white, 36.5% black, 1% other; and of HPV16 positive, 83.6% were white, 15% black, 1.4% other. White race was associated with a higher
Volume 88 Number 2 Supplement 2014 percentage of HPV16 positive tumors (p<.0001). There was a significant increase in HPV16 positive OPSCC over time from 15.6% in 1992-1995 to 43.3% in 2004-2007 (pZ.01). An increase in percentage of HPV16 positive cases was seen for both blacks and whites; however this trend was not significant when each race was analyzed separately. HPV16 was not seen in black patients from 1992 to 1995 but was present in 17.7% of blacks in 2004-2007. During the same time period the percentage of white HPV16 positive patients increased from 33.3% to 53.5%. During each 4 year interval between 1992 and 2007, white patients had a significantly higher percentage of HPV16 positive OPSCC compared to blacks. White and black patients with HPV16 positive tumors had similar baseline characteristics and a significantly favorable nearly identical OS (median 8.08 and 8.10 years, respectively). However, among HPV16 negative patients, whites had a significantly improved OS compared to blacks (median 2.33 and 0.89 years, respectively, pZ0.02), including after controlling for age, gender, stage, smoking and drinking in the multivariable Cox regression model. Conclusions: From 1992 to 2007 the percentage of HPV16 positive OPSCCs increased for both black and white patients and whites had a significantly higher percentage of positive tumors compared to blacks during every time interval examined. While survival for HPV16 positive black and white patients was similar and favorable, outcomes for HPV16 negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics. Author Disclosure: D.P. Zandberg: None. S.Z. Liu: None. O. Goloubeva: None. L.M. Schumaker: None. K.J. Cullen: None.
115 Epigenetic Alterations Are Associated With Survival From Headand-Neck Cancer Epidemiology and Prevention S. Virani, M. Sartor, J. McHugh, D.B. Chepeha, T.E. Carey, L.A. Peterson, E. Bellile, J.M. Taylor, G.T. Wolf, and L.S. Rozek; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Head and neck cancer makes up 5% of new cancer cases each year in the US. Although treatment outcomes have improved, the overall 5-year survival rate of w60% in the United States has not significantly changed in the last decade. Tumor and patient characteristics such as clinical subtype or smoking status influence the probability of survival making it necessary to identify new biomarkers of survival that can be used to tailor individualized treatment. Epigenetic marks are easily identifiable and potentially reversible, providing ideal candidates for targeted therapeutic intervention. Materials/Methods: We measured methylation in six genes (CCNA1, DCC, NDN, CD1A, p16, and GADD45a) in formalin-fixed, paraffin-embedded tumors collected from 358 newly diagnosed, previously untreated patients from the UM HNSPORE. Thirty-five percent of the subjects had cancer of the oropharynx, 37% in the oral cavity, and 28% of the larynx. Thirty-eight percent of the sample was HPV positive, the majority of which were in cancers of the oropharynx (78%). Log-rank tests were used to compare survival distributions by quartiles of methylation levels. Cox proportional hazards models were developed using a backwards selection algorithm with clinical and epidemiological variables collected from medical records and baseline health surveys including gender, site, stage, age, comorbidities, HPV, and smoking status. Results: Probability for survival was lowest, overall and at 24 months, for those in the lowest quartile of methylation for NDN, CD1A, DCC and CCNA1. NDN, and CD1A and DCC were significantly associated with survival (pZ0.01, pZ0.005, pZ0.05, respectively) after controlling for age, site, and stage in multivariable models. There was no difference in survival for GADD45a, and p16 (pZ0.34 and pZ0.36, respectively). The association between CCNA1 and survival was borderline (pZ0.10). Conclusions: Overall, we found that higher methylation of these genes was associated with survival from head and neck cancer. DCC, NDN, and CD1A are novel biomarkers of survival identified in this study.
Poster Presentations
495
Methylation status of these genes may aid in directing personalized treatment strategies. Author Disclosure: S. Virani: None. M. Sartor: None. J. McHugh: None. D.B. Chepeha: None. T.E. Carey: None. L.A. Peterson: None. E. Bellile: None. J.M. Taylor: None. G.T. Wolf: None. L.S. Rozek: None.
137 The Effects of Geography on Survival in Patients With Oral Cavity Squamous Cell Carcinoma Epidemiology and Prevention H. Zhang,1 P.T. Dziegielewski,2 T.J. Nguyen,3 C.C. Jeffery,1 D.A. O’Connell,1 J.R. Harris,1 and H. Seikaly1; 1University of Alberta, Edmonton, AB, Canada, 2University of Florida, Gainesville, FL, 3 University of Sherbrooke, Sherbrooke, QC, Canada Purpose/Objective(s): Cancer-related death rates demonstrate inequalities even within the same disease-specific population. Associated factors with this disparity include access to care and socioeconomic status, which are often influenced by geographical location. However, the effect of a patient’s home location on survival has not been studied for oral cavity squamous cell carcinoma (OCSCC). To assess the survival outcomes of OCSCC by differing geographical location. The secondary goal was to identify factors associated with the survival differences amongst the geographic groups. Materials/Methods: Demographic, pathologic, treatment, and survival data was obtained from OCSCC patients from 1998-2010 in Alberta, Canada. 554 patients were included from 660 OCSCC patients. Overall, disease-specific, and disease-free survivals were estimated with KaplanMeier and Cox regression analyses. Patients were grouped by geographic locations as well as distance from place of residence to cancer centers. Results: Patients from urban locations had improved overall, diseasespecific, and disease-free survival compared to rural locations (p<0.05). Two and five year estimates of overall survival were significantly higher in the urban cohort at 84% and 78%, versus rural with 48% and 44%, respectively (p<0.05). Disease-specific and disease-free survival rates were also superior in the urban group (p<0.05). In addition, increasing distance of residence from a tertiary cancer center was associated with lower rates of overall, disease-specific, and disease-free survival. Two and five year estimates of overall survival were significantly higher in the cohort residing less than 50 kilometers from the cancer center at 85% and 71%, versus 65% and 52% for the group living greater than 100 kilometers away (p<0.05). Disease-specific and disease-free survival were also superior within the cohort less than 50 kilometers away from a cancer center (p<0.05). Conclusions: This study shows that patients with OCSCC living in urban settings have improved survival compared to rural groups. While access to initial treatment does not seem to be a factor, patients who live farther demonstrated worse outcomes. A potential cause may be adherence to post-treatment surveillance. Such patients should be identified early and provided with closer local follow-up. Author Disclosure: H. Zhang: None. P.T. Dziegielewski: None. T.J. Nguyen: None. C.C. Jeffery: None. D.A. O’Connell: None. J.R. Harris: None. H. Seikaly: None.
141 The New Epidemiology of Head-and-Neck Squamous Cell Carcinoma: A Description of Age-Related and Subsite-Specific Shifts in the US Since 2000 Epidemiology and Prevention V.A. Fritsch, C.A. Banks, and T.A. Day; Medical University of South Carolina, Charleston, SC Purpose/Objective(s): Head and neck squamous cell carcinoma (HNSCC) epidemiologic trends are shifting. We continue to face a growing epidemic of HPV-related oropharynx SCC, while the incidence of cancers involving other subsites is decreasing. There is currently a lack of published quantitative data regarding demographic shifts in non-oropharynx
International Journal of Radiation Oncology Biology Physics
combination chemoradiation therapy with Nimotuzumab was well tolerated. Addition of Nimotuzumab to concurrent chemoradiation therapy regimen was not associated with added toxicity. Conclusions: Addition of Nimotuzumab to concurrent chemotherapy and radiation is safe and efficacious based on the locoregional response and confirms the available phase 2 data in HNSCC patients. The survival benefits of this combination need further evaluation in a larger study setting Author Disclosure: S. Sundaram: None. B. Venkatanarayanan: None. N. Sridharan: None. G. Kakumudi Rajagopal: None.
unknown if the incidence of unknown primary carcinoma of the head and neck is rising at a rate similar to that of HPV-associated oropharynx cancer. Materials/Methods: The institutional databases of SCCUPS from 1990 2013 of two tertiary care cancer centers (Fox Chase Cancer Center, Philadelphia, PA and University of Pittsburgh Medical Center) were combined. To be assigned a diagnosis of unknown primary squamous cell carcinoma all patients were required to have: 1.) pathologically proven squamous cell carcinoma in a neck lymph node, 2.) cross sectional imaging that failed to demonstrate a mucosal primary, and 3.) a negative flexible scope examination +/- directed biopsies and/or tonsillectomy. A subset of patients underwent lingual tonsillectomy, in an effort to identify the primary. HPV status was determined by immunohistochemistry (IHC) using antibody against p16 (G175-405, BD Pharmingen, USA). A positive test was defined as intermediate/strong nuclear and cytoplasmic staining in 70% of cells. Incidence rates were calculated by linear regression. Prevalence of HPV status as a function of time of diagnosis was calculated. Results: Unknown primary carcinoma of the head and neck was diagnosed 175 times at the two institutions during the designated time frame. N stage distribution was: N1 (n Z 40, 23%); N2 (n Z 108, 62%); N3 (n Z 27, 15%). An overwhelming majority of cases were diagnosed in the year 2000 or later (n Z 144, 83%). Assignment of a diagnosis of squamous carcinoma of unknown primary exhibited linear growth since 1990 at the two institutions, with an average of 6.6 additional cases per additional 10 years, with unabated increases through the last complete year of data in 2012. A total of 126 (72%) of patients have had samples tested for HPV, almost all of which (n Z 115, 91%) were treated in 2000 or later. Among those with a known HPV status, 95 (75%) were determined to be HPV associated tumors. Conclusions: The majority of patient diagnosed with SCCUPS are p16+, indicative of HPV association. Our date demonstrate that the incidence of SCCUPS is increasing at a rate consistent with that of HPV associated oropharynx cancer. Prospective study of toxicity mitigation for this good prognosis disease indicated. Author Disclosure: T.J. Galloway: None. K.S. Davis: None. B. Burtness: Q. Leadership; ECOG Head and Neck Committee. R.L. Ferris: Q. Leadership; ECOG Head and Neck Committee. R. Mehra: None. J.A. Ridge: Q. Leadership; ECOG Head and Neck Committee, RTOG Surgical Oncology. D. Flieder: None. U. Duvvuri: None.
276 Dosimetric Comparison of Field-in-Field Technique to Conventional Wedge Planned Technique for Early-Stage Glottic Cancer Definitive Management of Head-and-Neck Squamous Cell Carcinoma M. Gurka,1 T. Campbell,2 E. Bullock,1 J. Hoon,3 K. Unger,1 N. Nasr,3 and K. Harter1; 1Medstar Georgetown University Hospital, Washington, DC, 2RadAmerica, Clinton, MD, 3Virginia Hospital Center, Arlington, VA Purpose/Objective(s): To analyze conventional wedged beam and fieldin-field (FIF) techniques in patients with early stage (T1-T2) glottic cancer using dosimetric parameters. Materials/Methods: In five patients with early stage glottic cancer, two plans were generated for each patient: a conventional wedged plan and a FIF plan both utilizing opposed lateral fields. A CTV was contoured that included the entire glottic area (top of thyroid cartilage to cricoid ring). Conventional larynx fields were used that extended from the bottom of the hyoid bone inferiorly to the cricoid cartilage. Anteriorly 1-2 cm of flash was given and the field extended posteriorly to the anterior margin of the cervical spine. The dose was prescribed to a reference point 1-2 cm anterior to the cervical spine. For T1 tumors, the prescribed dose was 63 Gy in 2.25 Gy and 65.25 in 2.25 Gy for T2 tumors. The FIF plans included one to two subfields for each open field. The wedge angle was chosen that provided the best coverage with an acceptable Dmax. The plans were compared in regards to the global Dmax, CTV coverage expressed as dose to 95% of the CTV (D95) as well as volume of CTV receiving 100% of the prescribed dose (V100%), and homogeneity index defined as D5/D95, where D5 Z dose to 5% of the target volume and D95 Z dose to 95% of the target volume. Results: Overall, both plans performed similarly. The median global Dmax was slightly higher FIF plans compared to the wedges plans, 106.1% (range 103.8% - 107.0%) and 104.9% (range 103.4% - 107.4%). The D95% was higher with the field-in-field technique in three of the five plans. In terms of V100%, FIF performed better with a median of 89% (range 31% - 99%) compared to 73% (range 34% - 95%) for the wedged plans. Homogeneity was also minimally improved with the FIF plans, median 1.06 (range 1.04 -1.16) compared to 1.07 (range 1.05-1.11) with a wedge fields. Conclusions: In these five patients, a FIF plan yields similar coverage and homogeneity compared to wedged plans and can be considered as an alternative to using wedges. Author Disclosure: M. Gurka: None. T. Campbell: None. E. Bullock: None. J. Hoon: None. K. Unger: None. N. Nasr: None. K. Harter: None.
101 HPV Association and the Increasing Incidence of Unknown Primary Head-and-Neck Squamous Cell Carcinoma Epidemiology and Prevention T.J. Galloway,1 K.S. Davis,2 B. Burtness,1 R.L. Ferris,2 R. Mehra,1 J.A. Ridge,1 D. Flieder,1 and U. Duvvuri2; 1Fox Chase Cancer Center, Philadelphia, PA, 2University of Pittsburgh Medical Center, Pittsburgh, PA Purpose/Objective(s): Unknown primary head and neck squamous cell carcinoma (SCCUPS) typically has a favorable prognosis. It is suspected that the historical good outcome is a reflection of a high percentage of previously unrecognized HPV (Human papillomavirus) association. It is
107 HPV-Positive Oropharyngeal Cancer Increased for Both Black and White Patients Over Time, 1992-2007 Epidemiology and Prevention D.P. Zandberg,1 S.Z. Liu,2 O. Goloubeva,1 L.M. Schumaker,1 and K.J. Cullen1; 1University of Maryland Greenebaum Cancer Center, Baltimore, MD, 2Department of Pathology University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): While we previously reported a striking racial difference in the prevalence of human papillomavirus (HPV) positive oropharyngeal cancer (OPSCC), which has been corroborated by other groups, less is known about differences by HPV status and race over time. To investigate we analyzed tissue samples from OPSCC patients treated at the University of Maryland Greenebaum Cancer Center (UMGCC) over a 15-year time period. Materials/Methods: We conducted a retrospective study of 467 OPSCC patients treated between 1992 and 2007, of which 200 had tissue available for HPV16 testing (by PCR for E6 and E7 genes). Baseline characteristics included race, gender, age, smoking and alcohol status, staging, and treatment. Overall Survival (OS) included only those with first primary tumors and was estimated by the Kaplan-Meier approach and compared by the log-rank test. The Cox regression model was applied to identify risk factors and their impact on OS. Results: Of 200 patients, 67 were HPV16 positive, 127 were HPV16 negative and 6 were not evaluable. Overall racial distribution was 62.5% white, 36.5% black, 1% other; and of HPV16 positive, 83.6% were white, 15% black, 1.4% other. White race was associated with a higher
Volume 88 Number 2 Supplement 2014 percentage of HPV16 positive tumors (p<.0001). There was a significant increase in HPV16 positive OPSCC over time from 15.6% in 1992-1995 to 43.3% in 2004-2007 (pZ.01). An increase in percentage of HPV16 positive cases was seen for both blacks and whites; however this trend was not significant when each race was analyzed separately. HPV16 was not seen in black patients from 1992 to 1995 but was present in 17.7% of blacks in 2004-2007. During the same time period the percentage of white HPV16 positive patients increased from 33.3% to 53.5%. During each 4 year interval between 1992 and 2007, white patients had a significantly higher percentage of HPV16 positive OPSCC compared to blacks. White and black patients with HPV16 positive tumors had similar baseline characteristics and a significantly favorable nearly identical OS (median 8.08 and 8.10 years, respectively). However, among HPV16 negative patients, whites had a significantly improved OS compared to blacks (median 2.33 and 0.89 years, respectively, pZ0.02), including after controlling for age, gender, stage, smoking and drinking in the multivariable Cox regression model. Conclusions: From 1992 to 2007 the percentage of HPV16 positive OPSCCs increased for both black and white patients and whites had a significantly higher percentage of positive tumors compared to blacks during every time interval examined. While survival for HPV16 positive black and white patients was similar and favorable, outcomes for HPV16 negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics. Author Disclosure: D.P. Zandberg: None. S.Z. Liu: None. O. Goloubeva: None. L.M. Schumaker: None. K.J. Cullen: None.
115 Epigenetic Alterations Are Associated With Survival From Headand-Neck Cancer Epidemiology and Prevention S. Virani, M. Sartor, J. McHugh, D.B. Chepeha, T.E. Carey, L.A. Peterson, E. Bellile, J.M. Taylor, G.T. Wolf, and L.S. Rozek; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Head and neck cancer makes up 5% of new cancer cases each year in the US. Although treatment outcomes have improved, the overall 5-year survival rate of w60% in the United States has not significantly changed in the last decade. Tumor and patient characteristics such as clinical subtype or smoking status influence the probability of survival making it necessary to identify new biomarkers of survival that can be used to tailor individualized treatment. Epigenetic marks are easily identifiable and potentially reversible, providing ideal candidates for targeted therapeutic intervention. Materials/Methods: We measured methylation in six genes (CCNA1, DCC, NDN, CD1A, p16, and GADD45a) in formalin-fixed, paraffin-embedded tumors collected from 358 newly diagnosed, previously untreated patients from the UM HNSPORE. Thirty-five percent of the subjects had cancer of the oropharynx, 37% in the oral cavity, and 28% of the larynx. Thirty-eight percent of the sample was HPV positive, the majority of which were in cancers of the oropharynx (78%). Log-rank tests were used to compare survival distributions by quartiles of methylation levels. Cox proportional hazards models were developed using a backwards selection algorithm with clinical and epidemiological variables collected from medical records and baseline health surveys including gender, site, stage, age, comorbidities, HPV, and smoking status. Results: Probability for survival was lowest, overall and at 24 months, for those in the lowest quartile of methylation for NDN, CD1A, DCC and CCNA1. NDN, and CD1A and DCC were significantly associated with survival (pZ0.01, pZ0.005, pZ0.05, respectively) after controlling for age, site, and stage in multivariable models. There was no difference in survival for GADD45a, and p16 (pZ0.34 and pZ0.36, respectively). The association between CCNA1 and survival was borderline (pZ0.10). Conclusions: Overall, we found that higher methylation of these genes was associated with survival from head and neck cancer. DCC, NDN, and CD1A are novel biomarkers of survival identified in this study.
Poster Presentations
495
Methylation status of these genes may aid in directing personalized treatment strategies. Author Disclosure: S. Virani: None. M. Sartor: None. J. McHugh: None. D.B. Chepeha: None. T.E. Carey: None. L.A. Peterson: None. E. Bellile: None. J.M. Taylor: None. G.T. Wolf: None. L.S. Rozek: None.
137 The Effects of Geography on Survival in Patients With Oral Cavity Squamous Cell Carcinoma Epidemiology and Prevention H. Zhang,1 P.T. Dziegielewski,2 T.J. Nguyen,3 C.C. Jeffery,1 D.A. O’Connell,1 J.R. Harris,1 and H. Seikaly1; 1University of Alberta, Edmonton, AB, Canada, 2University of Florida, Gainesville, FL, 3 University of Sherbrooke, Sherbrooke, QC, Canada Purpose/Objective(s): Cancer-related death rates demonstrate inequalities even within the same disease-specific population. Associated factors with this disparity include access to care and socioeconomic status, which are often influenced by geographical location. However, the effect of a patient’s home location on survival has not been studied for oral cavity squamous cell carcinoma (OCSCC). To assess the survival outcomes of OCSCC by differing geographical location. The secondary goal was to identify factors associated with the survival differences amongst the geographic groups. Materials/Methods: Demographic, pathologic, treatment, and survival data was obtained from OCSCC patients from 1998-2010 in Alberta, Canada. 554 patients were included from 660 OCSCC patients. Overall, disease-specific, and disease-free survivals were estimated with KaplanMeier and Cox regression analyses. Patients were grouped by geographic locations as well as distance from place of residence to cancer centers. Results: Patients from urban locations had improved overall, diseasespecific, and disease-free survival compared to rural locations (p<0.05). Two and five year estimates of overall survival were significantly higher in the urban cohort at 84% and 78%, versus rural with 48% and 44%, respectively (p<0.05). Disease-specific and disease-free survival rates were also superior in the urban group (p<0.05). In addition, increasing distance of residence from a tertiary cancer center was associated with lower rates of overall, disease-specific, and disease-free survival. Two and five year estimates of overall survival were significantly higher in the cohort residing less than 50 kilometers from the cancer center at 85% and 71%, versus 65% and 52% for the group living greater than 100 kilometers away (p<0.05). Disease-specific and disease-free survival were also superior within the cohort less than 50 kilometers away from a cancer center (p<0.05). Conclusions: This study shows that patients with OCSCC living in urban settings have improved survival compared to rural groups. While access to initial treatment does not seem to be a factor, patients who live farther demonstrated worse outcomes. A potential cause may be adherence to post-treatment surveillance. Such patients should be identified early and provided with closer local follow-up. Author Disclosure: H. Zhang: None. P.T. Dziegielewski: None. T.J. Nguyen: None. C.C. Jeffery: None. D.A. O’Connell: None. J.R. Harris: None. H. Seikaly: None.
141 The New Epidemiology of Head-and-Neck Squamous Cell Carcinoma: A Description of Age-Related and Subsite-Specific Shifts in the US Since 2000 Epidemiology and Prevention V.A. Fritsch, C.A. Banks, and T.A. Day; Medical University of South Carolina, Charleston, SC Purpose/Objective(s): Head and neck squamous cell carcinoma (HNSCC) epidemiologic trends are shifting. We continue to face a growing epidemic of HPV-related oropharynx SCC, while the incidence of cancers involving other subsites is decreasing. There is currently a lack of published quantitative data regarding demographic shifts in non-oropharynx