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Impact of Human Papillomavirus on Clinicopathological Characteristics of Oropharyngeal Carcinomas
Volume 84 Number 3S Supplement 2012 1 failure occurred in a patient receiving CRT. 6/8 of the HPV- T4 tumors failed locoregionally including 3/5 treated with RT and 3/3 receiving CRT failed. Conclusions: In our retrospective experience, LRC was excellent for all HPV+ patients regardless of whether or not they received chemotherapy, with expected worse results for HPV- patients. Additionally, DMFS was similar for RT versus CRT for all patients. HPV- patients with T4 tumors had high rates of locoregional failure, regardless of type of therapy. RT alone should be considered for future prospective trials of HPV + SCCOP. Author Disclosure: M.L. Mierzwa: None. L.E. Imwalle: None. K.A. Casper: None. A. Dwivedi: None. Q. Zhai: None. K.P. Redmond: None. W.L. Barrett: None.
2675 Total Metabolic Tumor Volume Predicts Outcomes in p16-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma A.A. Garsa, A.J. Chang, T. DeWees, F. Dehdashti, D.R. Adkins, H. Gay, and W.L. Thorstad; Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To evaluate whether pre-treatment metabolic parameters obtained from positron emission tomography (PET) with [18F] fluorodeoxyglucose (FDG) can improve risk prediction for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive intensity modulated radiation therapy (IMRT). We also evaluated the interaction with p16 status. Methods/Materials: Between 2003 and 2009, 86 patients with a new diagnosis of OPSCC had FDG-PET/CT prior to treatment with definitive IMRT. Chemotherapy was administered to 90% of the patients. Metabolic tumor volume (MTV) was defined as the tumor volume with 50% of the local maximum standardized uptake value (SUVmax). Total lesion glycolysis (TLG) was defined as the product of SUVmean and MTV. MTV, TLG, SUVmax and SUVmean were analyzed for the primary tumor alone and the total of the primary tumor and all involved lymph nodes. Survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association between PET parameters and disease-free survival (DFS) and overall survival (OS). Graphical diagnostic plots, minimum p-value approach, and receiver operator characteristic (ROC) analysis were performed to identify the optimal total MTV cutpoint with regard to OS. Results: Median follow-up time for surviving patients was 41 months. The median radiation therapy dose was 70 Gy (range 66-75 Gy). The estimated 3-year DFS and OS were 47.6% and 51.1%, respectively. On univariate analysis, total MTV and total TLG were significant predictors of DFS and OS. Tumor MTV and TLG were also significant predictors of OS. SUVmax and SUVmean failed to predict DFS or OS. On multivariate analysis controlling for T and N stage, total MTV remained a significant predictor of DFS (p Z <0.0001, HR Z 1.04) and OS (p Z 0.0005, HR Z 1.03). The optimal cutpoint for total MTV was calculated to be 20.5 mL. Total MTV > 20.5 mL was associated with a 4.13-fold increased risk of death (p<0.0001). In the subset of patients with p16+ cancer (n Z 26), total MTV was a significant predictor of DFS (p Z 0.019, HR Z 1.05) and OS (p Z 0.024, HR Z 1.05). Similarly, for the subset of patients with p16cancer (n Z17), total MTV was predictive of DFS (p Z 0.043, HR Z 1.05) and OS (p Z 0.035, HR Z 1.05). A total MTV > 20.5 mL was associated with a 13.6-fold increased risk of death (p Z 0.014) for p16+ group, compared to a 3.97-fold increased risk of death (p Z 0.028) in the p16- group. Conclusions: Total MTV is an independent predictor of DFS and OS for patients with OPSCC treated with definitive radiation therapy. Total MTV > 20.5 mL was associated with a 4.1-fold increased risk of death. Total MTV remained predictive of DFS and OS for both p16+ and p16- cancer. Our data suggest that a larger total MTV (> 20.5 mL) may be more prognostic for p16+ cancer. Author Disclosure: A.A. Garsa: None. A.J. Chang: None. T. DeWees: None. F. Dehdashti: None. D.R. Adkins: None. H. Gay: None. W.L. Thorstad: None.
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2676 Radiologic Assessment of Lymph Node Involvement in HPV/p16+ Oropharyngeal Cancers C. Tang, S. Komakula, C. Chan, J. Murphy, C. Kong, K. Jensen, and Q. Le; Stanford University, Stanford, CA Purpose/Objective(s): Retropharyngeal (RP) nodes represent a therapeutic dilemma due to their proximity to radiosensitive structures. The purpose of this study was to analyze patterns of RP nodal involvement (RPN+) in patients in HPV/p16+ oropharynx (OPX) cancer. Materials/Methods: We analyzed 125 patients with OPX cancer and known p16 status treated between Feb 2006 and Aug 2011. Nodal status was determined with pre-treatment MRI (nZ46) and PET/CT (nZ79). RP node positivity was defined as SUV > 3 or short axis > 6 mm on MRI or PET/CT. Primary tumor subsites were classified as anterior (base of tongue and vallecula, nZ55), lateral (tonsil, tonsillar fossa, glossotonsillar sulcus, nZ68), or posterior (posterior pharyngeal wall, nZ2). P16 status served as a proxy for HPV status, (14 p16- and 111 p16+ patients). Proportions and means were compared with Fisher’s exact and Wilcoxon sum rank tests, respectively. Results: Fourteen patients were found to be RPN+ (12%). There was no statistically significant association between RP and p16 status (pZ0.66). Pre-treatment MRI trended towards a higher proportion of RPN+ compared to PET/CT (RRZ2.29, pZ0.14). Given the relatively low numbers of p16- patients, the remainder of the analysis is restricted to p16+ OPX patients (nZ111), of which 12 (11%) and 99 (89%) were RPN+ and RPN-, respectively. Among p16+ OPX cancers, there was no association between anatomical subsite and RP status. RPN+ was generally ipsilateral to the primary site (93%) and observed in patients with higher stage disease (T-stage2 and N-stage2). Involvement of nodes outside the RP space was the best predictor of RP involvement. RPN+ patients exhibited more nodal involvement outside the RP space compared to RPN- patients (median 4 nodes vs. median 1 node; p<0.001). In fact, all RPN+ patients had at least 2 lymph nodes outside the RP space. Broken down by node level, RPN+ patients had higher rates of involved neck nodes at every level: level I (33% vs. 4%, pZ0.0045), level II (100% vs. 81%), level III (75% vs. 34%, pZ0.010), level IV (8% vs. 7%), and level V (8% vs. 4%). All patients with both RP and level I involvement also exhibited involvement of levels II and III. Concurrent involvement of levels I-III was higher in RPN+ compared to RPN- patients (33% vs. 2%, pZ0.0011). Conclusions: In p16+ OPX patients, RPN+ was present with concurrent involvement of multiple other nodal groups. These results suggest that RP involvement results from serial nodal progression and that involvement of neck node stations is a strong predictor of RP status. Author Disclosure: C. Tang: None. S. Komakula: None. C. Chan: None. J. Murphy: None. C. Kong: None. K. Jensen: None. Q. Le: None.
2677 Impact of Human Papillomavirus on Clinicopathological Characteristics of Oropharyngeal Carcinomas Z. Rakusic, S. Seiwerth, A. Jakovcevic, D. Prgomet, and A. Juretic; Clinical Hospital Center Zagreb, Zagreb, Croatia Purpose/Objective(s): Recent data demonstrate important role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC). At least 90% HPV-positive OPSCC are associated with HPV type 16. The p16-positive OPSCC have better prognosis. Relation between p16 and epidermal growth factor receptor (EGFR) expression is ambiguous. Materials/Methods: In this retrospective study, it has been performed immunohistochemical analysis of p16 and EGFR expression on tumor tissues embedded on paraffin blocks. p16 immunohistochemistry was used as a surrogate for HPV status. It was analyzed histopathological samples of 108 patients with oropharyngeal carcinomas who were diagnosed and treated in the period from January 2002. to June 2007. All
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patients were treated with 2D external-beam radiation therapy exclusively, postoperatively or concurrent with chemotherapy, in dose of 6070 Gy. Results: Overexpression of p16 was detected in 40 of 108 examined samples (37.0%). p16 overexpression statistically significantly correlates with higher levels of tumor grade (pZ0.0016), while subsite of primary tumor, T stage , N stage and clinical stage of disease were not in correlation with p16 overexpression. Overall 5 year survival (OS) of p16 positive patients with oropharyngeal carcinomas were 45% (median survival 3.18 years), and 34% in p16 negative (median survival 1,29 years), respectively (pZ0.0652). In multivariate analysis, p16 overexpression (HR 0.329; pZ0.002), T stage (HR 2.374; pZ0.0002), and age of patients (HR 1.088; pZ0.0001), had statistically significant impact on overall survival of analyzed group of patients, while EGFR overexpression did not have significant impact on survival of observed patients. Conclusions: The p16 expression is a reliable surrogate marker of HPV status. The study showed that p16 positive patients have a better OS compared to p16 negative. Defining p16 expression is necessary as a routine procedure in all OPSCC due to better stratification of patients, making therapeutic algorithms and successful treatment of this heterogeneous group of tumors. Correlation between p16 and EGFR expression has to be investigated. Author Disclosure: Z. Rakusic: None. S. Seiwerth: None. A. Jakovcevic: None. D. Prgomet: None. A. Juretic: None.
Conclusions: Our results showed an improvement in outcome with IMRT vs. 3D CRT with respect to local control and the incidence of post-treatment esophageal strictures in patients with locally advanced oropharyngeal cancers. In our series, the extent of nodal involvement was a strong predictor of any recurrence or death. Distant metastases however, remained a major pattern of relapse. Author Disclosure: G.A. Hobeika: None. Y. Zia: None. G. Walker: None. M. Samuels: None. M. Abramowitz: None. N. Elsayyad: None.
2678 Definitive Radiation Therapy for Locally Advanced Oropharyngeal Carcinoma G.A. Hobeika, Y. Zia, G. Walker, M. Samuels, M. Abramowitz, and N. Elsayyad; University of Miami Affiliated Hospitals, Miami, FL Purpose/Objective(s): To report outcomes, patterns of failures, and toxicities in patients treated with definitive radiation therapy for locally advanced squamous cell carcinoma of the oropharynx. Materials/Methods: Between June 1995 and March 2010, 108 patients with loco-regionally advanced oropharyngeal cancers were treated with radiation therapy (RT) with a curative intent. Of these, 91 (87%) received concurrent systemic therapy with 18 of them also receiving chemotherapy neoadjuvantly. Systemic therapy was Platinum-based in 76/91 patients (83%), Taxane-based in 10/91 (11%) and Cetuximab-based in 5/91 (5%). The median prescribed dose to gross disease was 70 Gy (65.9 -76.0 Gy). Fractionation was conventional in 101 patients and accelerated in 7.IMRT was used in 74 patients and 3D CRT was in 34. Results: The median follow-up was 39 (5-191) months among surviving patients. The 3-year cumulative actuarial rates of local failure (LF), regional failure (RF), and distant metastasis (DM) were 6.5%, 7.9%, and 13.5%, respectively. The 3-year local failure rate was 17.6% (95% CI: 7.0 -32.2%) or 6/34 for those treated using 3DCRT compared with 1.4% (95% CI: 0.1 to 6.5%) or 1/74 for those treated using IMRT. Among the 6 LF treated with 3DCRT, 2 recurred out of RT field and 3 did not receive chemotherapy. The only LR that occurred in the IMRT group was located within the high dose volume. There was no statistically significant difference in RF or DM with respect to the treatment modality. On Univariate analysis, the likelihood of LF correlated with higher T stage (T4-T3 vs. T1-T2 pZ0.05), absence of systemic therapy (pZ0.02) and use of 3D-CRT technique (pZ0.01) whereas the likelihood of DM was associated with an advanced N-stage (N2c-N3 vs.N0-2b pZ0.007). On Multivariate analysis, RT technique (3D-CRT) remained a strong predictor for LF (pZ0.05), whereas advanced N stage predicted any type of recurrence or death (pZ0.02). No statistical difference was found with regards to treatment breaks between the two modalities, However, lower incidence of esophageal stricture and lower rates of PEG tube placement were noted in the IMRT group versus those treated with 3D CRT (1.4% vs 11.8% (pZ0.033), and 18.9% vs 24.2% respectively.
2679 Metabolic Tumor Volume Is Superior to Gross Tumor Volume in Predicting Outcomes in Patients With Oropharyngeal Cancer Treated With IMRT P. Romesser, N. Riaz, B.H. Lok, J. Setton, S. Rao, and N.Y. Lee; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Volumetric based metrics including the gross tumor volume (GTV) and metabolic tumor volume (MTV), derived from [18F]fluorodeoxyglucose positron emission tomography/computed tomography scans (PET-CT), correlate with locoregional control and overall survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). The purpose of this retrospective review was to compare the predictive utility of GTV versus MTV in patients with OPSCC treated with definitive chemoradiation. Materials/Methods: From January 2004 through April 2009, 126 oropharyngeal cancer patients with pre-treatment PET-CT, performed at our institution, were treated with definitive chemoradiation. We retrospectively reviewed radiation oncology treatment planning dose volume histograms and PET-CTs, utilizing a 42% threshold, to define the GTV and MTV, respectively. Cox proportional hazard models were performed with GTV and MTV evaluated as continuous variables. Results: The median overall follow up of survivors was 33.5 months (range, 6.5-67.0 months). The cohort included 55 (43.7%) patients with T3/4 disease and 109 (86.5%) patients with N2/3 disease. The median GTV and MTV were 40.7 cc and 9.7, respectively, both of which were moderately correlated (R2Z 0.376). The 2-year rates of local failure (LF), locoregional failure (LRF), distant metastases (DM), and death were 10%, 13%, 22%, and 19%, respectively. Larger GTVs and MTVs, respectively, correlated with a greater risk of LF (HR 1.12, PZ0.03 versus HR 2.36, P<0.001), LRF (HR 1.08, PZ0.09 versus HR 2.05, PZ<0.001), DM (HR 1.07, PZ0.05 versus HR 1.83, P<0.001), and death (HR 1.10, PZ0.002 versus HR 1.84, P<0.001). Multivariate analyses confirmed MTV as independently predictive of LF (HR 2.20, PZ0.008), LRF (HR 2.27, P<0.001), DM (HR 1.92, P<0.001), and death (HR 1.74, PZ0.002) when adjusted for GTV, while GTV failed to reach significance when accounting for MTV. Conclusions: In a direct comparison, MTV demonstrated superiority over GTV as an independent predictor of LF, LRF, DM, and death in a cohort of oropharyngeal cancer patients treated with definitive chemoradiation. Author Disclosure: P. Romesser: None. N. Riaz: None. B.H. Lok: None. J. Setton: None. S. Rao: None. N.Y. Lee: None.
2680 Locoregional Patterns of Failure in Oropharyngeal Carcinoma: Implications for Treatment De-escalation N. Riaz, E. Katsoulakis, L. Ong, B. Youssef, S. Wolden, G. Niyazov, S. Rao, and N. Lee; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Loco-regional failure (LRF) in oropharyngeal carcinoma (OPC) has markedly dropped in the past decade. Improved outcomes have led many investigators to seek methods for de-escalating treatment. We examined our patterns of LRF to identify areas at low
2675 Total Metabolic Tumor Volume Predicts Outcomes in p16-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma A.A. Garsa, A.J. Chang, T. DeWees, F. Dehdashti, D.R. Adkins, H. Gay, and W.L. Thorstad; Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To evaluate whether pre-treatment metabolic parameters obtained from positron emission tomography (PET) with [18F] fluorodeoxyglucose (FDG) can improve risk prediction for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive intensity modulated radiation therapy (IMRT). We also evaluated the interaction with p16 status. Methods/Materials: Between 2003 and 2009, 86 patients with a new diagnosis of OPSCC had FDG-PET/CT prior to treatment with definitive IMRT. Chemotherapy was administered to 90% of the patients. Metabolic tumor volume (MTV) was defined as the tumor volume with 50% of the local maximum standardized uptake value (SUVmax). Total lesion glycolysis (TLG) was defined as the product of SUVmean and MTV. MTV, TLG, SUVmax and SUVmean were analyzed for the primary tumor alone and the total of the primary tumor and all involved lymph nodes. Survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association between PET parameters and disease-free survival (DFS) and overall survival (OS). Graphical diagnostic plots, minimum p-value approach, and receiver operator characteristic (ROC) analysis were performed to identify the optimal total MTV cutpoint with regard to OS. Results: Median follow-up time for surviving patients was 41 months. The median radiation therapy dose was 70 Gy (range 66-75 Gy). The estimated 3-year DFS and OS were 47.6% and 51.1%, respectively. On univariate analysis, total MTV and total TLG were significant predictors of DFS and OS. Tumor MTV and TLG were also significant predictors of OS. SUVmax and SUVmean failed to predict DFS or OS. On multivariate analysis controlling for T and N stage, total MTV remained a significant predictor of DFS (p Z <0.0001, HR Z 1.04) and OS (p Z 0.0005, HR Z 1.03). The optimal cutpoint for total MTV was calculated to be 20.5 mL. Total MTV > 20.5 mL was associated with a 4.13-fold increased risk of death (p<0.0001). In the subset of patients with p16+ cancer (n Z 26), total MTV was a significant predictor of DFS (p Z 0.019, HR Z 1.05) and OS (p Z 0.024, HR Z 1.05). Similarly, for the subset of patients with p16cancer (n Z17), total MTV was predictive of DFS (p Z 0.043, HR Z 1.05) and OS (p Z 0.035, HR Z 1.05). A total MTV > 20.5 mL was associated with a 13.6-fold increased risk of death (p Z 0.014) for p16+ group, compared to a 3.97-fold increased risk of death (p Z 0.028) in the p16- group. Conclusions: Total MTV is an independent predictor of DFS and OS for patients with OPSCC treated with definitive radiation therapy. Total MTV > 20.5 mL was associated with a 4.1-fold increased risk of death. Total MTV remained predictive of DFS and OS for both p16+ and p16- cancer. Our data suggest that a larger total MTV (> 20.5 mL) may be more prognostic for p16+ cancer. Author Disclosure: A.A. Garsa: None. A.J. Chang: None. T. DeWees: None. F. Dehdashti: None. D.R. Adkins: None. H. Gay: None. W.L. Thorstad: None.
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2676 Radiologic Assessment of Lymph Node Involvement in HPV/p16+ Oropharyngeal Cancers C. Tang, S. Komakula, C. Chan, J. Murphy, C. Kong, K. Jensen, and Q. Le; Stanford University, Stanford, CA Purpose/Objective(s): Retropharyngeal (RP) nodes represent a therapeutic dilemma due to their proximity to radiosensitive structures. The purpose of this study was to analyze patterns of RP nodal involvement (RPN+) in patients in HPV/p16+ oropharynx (OPX) cancer. Materials/Methods: We analyzed 125 patients with OPX cancer and known p16 status treated between Feb 2006 and Aug 2011. Nodal status was determined with pre-treatment MRI (nZ46) and PET/CT (nZ79). RP node positivity was defined as SUV > 3 or short axis > 6 mm on MRI or PET/CT. Primary tumor subsites were classified as anterior (base of tongue and vallecula, nZ55), lateral (tonsil, tonsillar fossa, glossotonsillar sulcus, nZ68), or posterior (posterior pharyngeal wall, nZ2). P16 status served as a proxy for HPV status, (14 p16- and 111 p16+ patients). Proportions and means were compared with Fisher’s exact and Wilcoxon sum rank tests, respectively. Results: Fourteen patients were found to be RPN+ (12%). There was no statistically significant association between RP and p16 status (pZ0.66). Pre-treatment MRI trended towards a higher proportion of RPN+ compared to PET/CT (RRZ2.29, pZ0.14). Given the relatively low numbers of p16- patients, the remainder of the analysis is restricted to p16+ OPX patients (nZ111), of which 12 (11%) and 99 (89%) were RPN+ and RPN-, respectively. Among p16+ OPX cancers, there was no association between anatomical subsite and RP status. RPN+ was generally ipsilateral to the primary site (93%) and observed in patients with higher stage disease (T-stage2 and N-stage2). Involvement of nodes outside the RP space was the best predictor of RP involvement. RPN+ patients exhibited more nodal involvement outside the RP space compared to RPN- patients (median 4 nodes vs. median 1 node; p<0.001). In fact, all RPN+ patients had at least 2 lymph nodes outside the RP space. Broken down by node level, RPN+ patients had higher rates of involved neck nodes at every level: level I (33% vs. 4%, pZ0.0045), level II (100% vs. 81%), level III (75% vs. 34%, pZ0.010), level IV (8% vs. 7%), and level V (8% vs. 4%). All patients with both RP and level I involvement also exhibited involvement of levels II and III. Concurrent involvement of levels I-III was higher in RPN+ compared to RPN- patients (33% vs. 2%, pZ0.0011). Conclusions: In p16+ OPX patients, RPN+ was present with concurrent involvement of multiple other nodal groups. These results suggest that RP involvement results from serial nodal progression and that involvement of neck node stations is a strong predictor of RP status. Author Disclosure: C. Tang: None. S. Komakula: None. C. Chan: None. J. Murphy: None. C. Kong: None. K. Jensen: None. Q. Le: None.
2677 Impact of Human Papillomavirus on Clinicopathological Characteristics of Oropharyngeal Carcinomas Z. Rakusic, S. Seiwerth, A. Jakovcevic, D. Prgomet, and A. Juretic; Clinical Hospital Center Zagreb, Zagreb, Croatia Purpose/Objective(s): Recent data demonstrate important role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC). At least 90% HPV-positive OPSCC are associated with HPV type 16. The p16-positive OPSCC have better prognosis. Relation between p16 and epidermal growth factor receptor (EGFR) expression is ambiguous. Materials/Methods: In this retrospective study, it has been performed immunohistochemical analysis of p16 and EGFR expression on tumor tissues embedded on paraffin blocks. p16 immunohistochemistry was used as a surrogate for HPV status. It was analyzed histopathological samples of 108 patients with oropharyngeal carcinomas who were diagnosed and treated in the period from January 2002. to June 2007. All
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patients were treated with 2D external-beam radiation therapy exclusively, postoperatively or concurrent with chemotherapy, in dose of 6070 Gy. Results: Overexpression of p16 was detected in 40 of 108 examined samples (37.0%). p16 overexpression statistically significantly correlates with higher levels of tumor grade (pZ0.0016), while subsite of primary tumor, T stage , N stage and clinical stage of disease were not in correlation with p16 overexpression. Overall 5 year survival (OS) of p16 positive patients with oropharyngeal carcinomas were 45% (median survival 3.18 years), and 34% in p16 negative (median survival 1,29 years), respectively (pZ0.0652). In multivariate analysis, p16 overexpression (HR 0.329; pZ0.002), T stage (HR 2.374; pZ0.0002), and age of patients (HR 1.088; pZ0.0001), had statistically significant impact on overall survival of analyzed group of patients, while EGFR overexpression did not have significant impact on survival of observed patients. Conclusions: The p16 expression is a reliable surrogate marker of HPV status. The study showed that p16 positive patients have a better OS compared to p16 negative. Defining p16 expression is necessary as a routine procedure in all OPSCC due to better stratification of patients, making therapeutic algorithms and successful treatment of this heterogeneous group of tumors. Correlation between p16 and EGFR expression has to be investigated. Author Disclosure: Z. Rakusic: None. S. Seiwerth: None. A. Jakovcevic: None. D. Prgomet: None. A. Juretic: None.
Conclusions: Our results showed an improvement in outcome with IMRT vs. 3D CRT with respect to local control and the incidence of post-treatment esophageal strictures in patients with locally advanced oropharyngeal cancers. In our series, the extent of nodal involvement was a strong predictor of any recurrence or death. Distant metastases however, remained a major pattern of relapse. Author Disclosure: G.A. Hobeika: None. Y. Zia: None. G. Walker: None. M. Samuels: None. M. Abramowitz: None. N. Elsayyad: None.
2678 Definitive Radiation Therapy for Locally Advanced Oropharyngeal Carcinoma G.A. Hobeika, Y. Zia, G. Walker, M. Samuels, M. Abramowitz, and N. Elsayyad; University of Miami Affiliated Hospitals, Miami, FL Purpose/Objective(s): To report outcomes, patterns of failures, and toxicities in patients treated with definitive radiation therapy for locally advanced squamous cell carcinoma of the oropharynx. Materials/Methods: Between June 1995 and March 2010, 108 patients with loco-regionally advanced oropharyngeal cancers were treated with radiation therapy (RT) with a curative intent. Of these, 91 (87%) received concurrent systemic therapy with 18 of them also receiving chemotherapy neoadjuvantly. Systemic therapy was Platinum-based in 76/91 patients (83%), Taxane-based in 10/91 (11%) and Cetuximab-based in 5/91 (5%). The median prescribed dose to gross disease was 70 Gy (65.9 -76.0 Gy). Fractionation was conventional in 101 patients and accelerated in 7.IMRT was used in 74 patients and 3D CRT was in 34. Results: The median follow-up was 39 (5-191) months among surviving patients. The 3-year cumulative actuarial rates of local failure (LF), regional failure (RF), and distant metastasis (DM) were 6.5%, 7.9%, and 13.5%, respectively. The 3-year local failure rate was 17.6% (95% CI: 7.0 -32.2%) or 6/34 for those treated using 3DCRT compared with 1.4% (95% CI: 0.1 to 6.5%) or 1/74 for those treated using IMRT. Among the 6 LF treated with 3DCRT, 2 recurred out of RT field and 3 did not receive chemotherapy. The only LR that occurred in the IMRT group was located within the high dose volume. There was no statistically significant difference in RF or DM with respect to the treatment modality. On Univariate analysis, the likelihood of LF correlated with higher T stage (T4-T3 vs. T1-T2 pZ0.05), absence of systemic therapy (pZ0.02) and use of 3D-CRT technique (pZ0.01) whereas the likelihood of DM was associated with an advanced N-stage (N2c-N3 vs.N0-2b pZ0.007). On Multivariate analysis, RT technique (3D-CRT) remained a strong predictor for LF (pZ0.05), whereas advanced N stage predicted any type of recurrence or death (pZ0.02). No statistical difference was found with regards to treatment breaks between the two modalities, However, lower incidence of esophageal stricture and lower rates of PEG tube placement were noted in the IMRT group versus those treated with 3D CRT (1.4% vs 11.8% (pZ0.033), and 18.9% vs 24.2% respectively.
2679 Metabolic Tumor Volume Is Superior to Gross Tumor Volume in Predicting Outcomes in Patients With Oropharyngeal Cancer Treated With IMRT P. Romesser, N. Riaz, B.H. Lok, J. Setton, S. Rao, and N.Y. Lee; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Volumetric based metrics including the gross tumor volume (GTV) and metabolic tumor volume (MTV), derived from [18F]fluorodeoxyglucose positron emission tomography/computed tomography scans (PET-CT), correlate with locoregional control and overall survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). The purpose of this retrospective review was to compare the predictive utility of GTV versus MTV in patients with OPSCC treated with definitive chemoradiation. Materials/Methods: From January 2004 through April 2009, 126 oropharyngeal cancer patients with pre-treatment PET-CT, performed at our institution, were treated with definitive chemoradiation. We retrospectively reviewed radiation oncology treatment planning dose volume histograms and PET-CTs, utilizing a 42% threshold, to define the GTV and MTV, respectively. Cox proportional hazard models were performed with GTV and MTV evaluated as continuous variables. Results: The median overall follow up of survivors was 33.5 months (range, 6.5-67.0 months). The cohort included 55 (43.7%) patients with T3/4 disease and 109 (86.5%) patients with N2/3 disease. The median GTV and MTV were 40.7 cc and 9.7, respectively, both of which were moderately correlated (R2Z 0.376). The 2-year rates of local failure (LF), locoregional failure (LRF), distant metastases (DM), and death were 10%, 13%, 22%, and 19%, respectively. Larger GTVs and MTVs, respectively, correlated with a greater risk of LF (HR 1.12, PZ0.03 versus HR 2.36, P<0.001), LRF (HR 1.08, PZ0.09 versus HR 2.05, PZ<0.001), DM (HR 1.07, PZ0.05 versus HR 1.83, P<0.001), and death (HR 1.10, PZ0.002 versus HR 1.84, P<0.001). Multivariate analyses confirmed MTV as independently predictive of LF (HR 2.20, PZ0.008), LRF (HR 2.27, P<0.001), DM (HR 1.92, P<0.001), and death (HR 1.74, PZ0.002) when adjusted for GTV, while GTV failed to reach significance when accounting for MTV. Conclusions: In a direct comparison, MTV demonstrated superiority over GTV as an independent predictor of LF, LRF, DM, and death in a cohort of oropharyngeal cancer patients treated with definitive chemoradiation. Author Disclosure: P. Romesser: None. N. Riaz: None. B.H. Lok: None. J. Setton: None. S. Rao: None. N.Y. Lee: None.
2680 Locoregional Patterns of Failure in Oropharyngeal Carcinoma: Implications for Treatment De-escalation N. Riaz, E. Katsoulakis, L. Ong, B. Youssef, S. Wolden, G. Niyazov, S. Rao, and N. Lee; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): Loco-regional failure (LRF) in oropharyngeal carcinoma (OPC) has markedly dropped in the past decade. Improved outcomes have led many investigators to seek methods for de-escalating treatment. We examined our patterns of LRF to identify areas at low