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Evaluation of Prognostic Groupings for Overall Survival in Human Papillomavirus–Associated Oropharyngeal Cancer
Volume 93 Number 3S Supplement 2015 Author Disclosure: M.A. Weller: None. M.C. Ward: None. C.A. Berriochoa: None. C.A. Reddy: None. S. Trosman: None. J.F. Greskovich: None. T. Nwizu: None. B.B. Burkey: None. D.J. Adelstein: None. S. Koyfman: None.
173 Pathological Factors Predicting the Risk of Distant Failure for Human PapillomavirusePositive Oropharyngeal Squamous Cell Carcinoma (OPSCC) J.N. Lukens,1 K. Tangsriwong,1 N. Mitra,1 R. Cohen,1 G.S. Weinstein,1 B. O’Malley,1 A. Chalian,1 C. Rassekh,1 J. Newman,1 S. Cannady,1 K.T. Montone,1 P. Ahn,1 H. Quon,2 and A. Lin1; 1University of Pennsylvania, Philadelphia, PA, 2Johns Hopkins University, Baltimore, MD Purpose/Objective(s): Despite superior locoregional control for human papillomavirusepositive (HPV+) OPSCC compared to HPV-negative tumors, a similar proportion (approximately 10%) will develop distant metastases (DM). Current American Joint Committee on Cancer (AJCC) pathological staging does not adequately identify patients (pts) at high risk of DM. There are emerging data on risk factors for DM in pts treated with chemoradiation therapy (CRT), but very little information on risk factors for DM in pts treated with initial surgery. Materials/Methods: We performed a retrospective analysis of 174 HPV+ OPSCC pts with 20 months of follow-up, treated with transoral robotic resection (TORS) and neck dissection followed by adjuvant CRT. Pathologic data included the number and proportion of involved lymph nodes, lowest level of involved nodes, and presence and extent of extracapsular extension (ECE) classified as none, microscopic/focal, or macroscopic/gross. The Wilcoxon rank sum test was used to compare continuous variables, multivariable logistic regression to assess for predictors of DM, and Kaplan-Meier to estimate survival probabilities. Results: With a median follow-up of 38 months, 12 pts (7%) developed DM. The number of positive nodes (PNs) was the strongest predictor of the risk of DM, with the probability increasing in proportion to the number of PNs 4. Risk of DM was 14% for 4 PNs (vs. 3.4%, P Z .021), 18% for 5 PNs (vs. 3%, P Z .002), 22% for 6 PNs (vs. 3.5%, P Z .002), and 28% for 7 PNs (vs. 3.4%, P < .001). Median PNs for pts with and without subsequent DM was 7 versus 2, P Z .004. Number of nodes examined was similar between pts with and without DM (median 41). On univariate analysis, macroscopic/gross ECE was a predictor of DM, with 20% of these pts developing DM versus 4.2% of pts with no or microscopic-only ECE (P Z .007). Neither microscopic ECE nor clinical or (AJCC) pathologic staging predicted for subsequent DM. A multivariable logistic regression model revealed that the number of PNs (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.07e1.40, P Z .004) remained a significant predictor of DM, while macroscopic/gross ECE was of borderline significance (OR 3.30, 95% CI Z 0.85e12.8, P Z .084). ROC analysis suggests that 6 PNs is a reasonable cut-point for prediction of the risk of DM (AUC Z 0.75). Pts with 6 PNs had inferior 4-year distant metastasis-free survival (DMFS) and overall survival (OS) compared to pts with <6 PNs: DMFS 80% versus 95% (P Z .002), and OS 88% versus 97% (P Z .022). Conclusion: The number of PNs appears to be the strongest predictor of DM in pts with pathologically staged HPV+ OPSCC undergoing primary surgery followed by adjuvant CRT. Pts with 6 PNs have a 22% risk of developing DM and appear to have inferior OS. If validated, the number of PNs could be incorporated into a revised pathologic staging system for HPV+ OPSCC to select pts for intensified or investigational adjuvant systemic therapy. Author Disclosure: J.N. Lukens: None. K. Tangsriwong: None. N. Mitra: None. R. Cohen: None. G.S. Weinstein: None. B. O’Malley: None. A. Chalian: None. C. Rassekh: None. J. Newman: None. S. Cannady: None. K.T. Montone: None. P. Ahn: None. H. Quon: None. A. Lin: None.
Oral Scientific Sessions
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174 Impact of Retropharyngeal Adenopathy on Distant Control and Survival in Human PapillomavirusePositive Oropharyngeal Cancer Treated With Chemoradiation Therapy S. Samuels,1 J.M. Vainshtein,2 M.E. Spector,1 M. Ibrahim,1 J.B. McHugh,1 Y. Tao,1 M. Schipper,1 W. Francis,1 and A. Eisbruch1; 1University of Michigan, Ann Arbor, MI, 2Emory University, Atlanta, GA Purpose/Objective(s): Retropharyngeal adenopathy (RPA), a wellestablished poor prognostic factor in head and neck squamous cell carcinoma (HNSCC), predicts worse local and distant control. Human papillomavirusepositive (HPV+) oropharyngeal cancer (OPC) patients are a distinct population of HNSCC patients with superior tumor control and survival compared to smoking- and drinking-related HSNCC. However, the prognostic significance of RPA in HPV+ OPC is unknown. Therefore, we reviewed our institutional experience of HPV+ OPC patients treated with chemoradiation to determine the impact of RPA on tumor control and survival. Materials/Methods: We retrospectively reviewed of 231 consecutive OPC cancer patients treated from 2003 to 2010 with chemoeintensity modulated radiation therapy (weekly carboplatin [AUC1] and docetaxel [30mg/m2]). HPV tumor status was determined for 198 patients, 184 of whom were HPV+ by PCR (184 patients), 93% of whom were p16+ by immunohistochemistry (1 additional patient was p16+, HPV-). Pretherapy images were reviewed for the purpose of this study by a single head and neck radiologist blinded to treatment outcome to determine RPA. Doses to the RP nodal regions were determined from treatment plans. Outcomes were analyzed using Kaplan-Meier method, log-rank tests determined statistically significant differences, and correlations were determined using Spearman rank analyses (r). Results: Twenty-nine (16%) of the 185 HPV+ patients had RPA. Among these, 3 had N1/N2a disease (RPA only), and 26 had additional nodal involvements in levels IIeIV (12 had N2b, 9 had N2c, and 5 had N3 nodal stages). There was no statistically significant correlation between RPA and involvement of other lymph nodes (r Z 0.07, P Z .36) or N stage (r Z 0.12, P Z .11). All patients received 70 Gy to the involved RPA. At median 49 months follow-up, there were no failures in the RPA anatomical compartments. Patients with RPA had overall worse outcomes compared to those without RPA. Five-year overall survival (OS), cancer-specific survival (CSS), and failure-free survival (FFS) were 57% versus 81% (P Z .02), 63% versus 85% (P Z .02), and 63% versus 80% (P Z .015) for patients with and without RPA, respectively. Patterns of failure analysis revealed that presence of RPA was associated with worse distant failurefree survival (DFFS) (70% vs 91%, P Z .002), without any impact on either local (P Z .87) or regional (P Z .88) control rates, which exceeded 95% and 90%, respectively, in both groups. In multivariable analysis T4, N3, and presence of RPA were independently associated with worse OS, CSS, FFS, and DFFS while age, disease site, N2c classification, and smoking status were not. Conclusion: RPA in HPV+ OPC was found to be an independent prognostic factor for distant failure, independent of established risk factors such as T4 and N3 stages, which translated into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment deescalation. Author Disclosure: S. Samuels: None. J.M. Vainshtein: None. M.E. Spector: None. M. Ibrahim: None. J.B. McHugh: None. Y. Tao: None. M. Schipper: None. W. Francis: None. A. Eisbruch: None.
175 Evaluation of Prognostic Groupings for Overall Survival in Human PapillomaviruseAssociated Oropharyngeal Cancer J.J. Caudell, J.M. Frakes, T. Strom, J. Russell, L.B. Harrison, and A. Trotti; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): Human papillomavirus (HPV)eassociated squamous cell carcinomas of the oropharynx are increasingly seen as a separate disease entity from smoking-associated oropharyngeal cancers, with a
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International Journal of Radiation Oncology Biology Physics
much higher likelihood of cure. Several prognostic groupings have been proposed and we evaluate these in a large independent cohort. Materials/Methods: After institutional review board approval, an institutional database was queried for patients with HPV or p16 positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT), and 247 cases were identified. Patient, tumor, and treatment factors were abstracted from the charts. Tested groupings included the American Joint Committee on Cancer (AJCC) TNM staging system, the Radiation Therapy Oncology Group (RTOG) 0129 risk groups (Low Risk Z 10 pack years or >10 pack years with N0e2a, Intermediate Risk Z >10 pack years and N2be3), and the Princess Margaret Hospital (PMH) prognostic groups (I Z T1e3N0e2b, II Z T1e3N2c, III Z T4 or N3). Outcomes, including locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated from the end of RT and estimated via Kaplan-Meier method. Comparisons were made via log-rank test. Results: Median follow-up of patients alive at last contact was 24 months. All patients were treated with definitive RT alone (n Z 38, 15.4%) or concurrent chemotherapy and RT (n Z 209, 84.6%). For the entire cohort 2 year LRC was 94.6%, FFDM 92%, and OS 92.5%. AJCC stage was I in 4 patients (1.6%), II in 13 (5.3%), III in 35 (14.2%) or IVAeB in 195 (78.9%). AJCC stage was not prognostic for LRC (P Z .30), FFDM (P Z .90), or OS (P Z .31). Per RTOG risk groups, 170 were low risk (68.8%), and 77 were intermediate risk (31.2%). RTOG risk groups were not prognostic for LRC (P Z .94), FFDM (P Z .86), or OS (P Z .08). Per PMH prognostic groups, 180 were stage I (72.9%), 37 were stage II (15%), and 30 were stage III (12.1%). PMH prognostic groups were not significant for LRC (P Z .72), but were significant for FFDM (P Z .03) and OS (P Z .003). Actuarial OS at 2 years for PMH stage I was 94.8%, for stage II was 94.5%, and for stage III was 76.6%. Conclusion: Outcomes for patients with HPV-associated oropharyngeal cancer treated with definitive RT are excellent. The proposed PMH stage grouping resulted in improved survival prediction at 2 years compared with RTOG risk groups or AJCC TNM staging. Author Disclosure: J.J. Caudell: None. J.M. Frakes: None. T. Strom: None. J. Russell: None. L.B. Harrison: None. A. Trotti: None.
Purpose/Objective(s): Multiple management options exist for stage IIIeIV oropharyngeal squamous cell cancer, including definitive chemoradiation therapy (CRT), surgery (S) plus adjuvant radiation therapy (S-RT) with or without chemotherapy (S-CRT), or induction chemotherapy followed by definitive treatment. Level I evidence comparing modalities is not available. In our province patients may be treated with either primary surgery (oropharyngeal resection) followed by adjuvant therapy or definitive CRT. We sought to compare the approaches and hypothesized that recurrence rates and survival would not differ. Materials/Methods: This study selected all stage IIIeIV nonmetastatic oropharyngeal squamous cell cancer patients treated with curative intent in our province between 2006 and 2012. Institutional ethics board approval was granted. Patient data was extrapolated from a prospective registry and retrospective review of medical records. KaplaneMeier estimates of the median recurrence-free survival (RFS) and overall survival (OS) and 95% confidence interval (CI) were obtained for both groups. Logistic regression was used to explore the association between patient, tumor, and treatment factors for the primary chemoradiation therapy and surgery groups with 2- and 5-year RFS. Results: Four hundred and twenty-one patients were eligible. Median follow up was 4.3 years. Patient characteristics are shown in Table 1. RFS was not significantly different between groups. The 2- and 5-year RFS rates for CRT versus S were 85% versus 84% and 80% versus 79%. Distant metastases occurred in 47% of CRT patients and 76% of S patients who recurred. Overall survival was no different between groups: 83% versus 82% and 73% versus 71% for CRT versus surgery at 2 and 5 years, respectively. For both groups, the cause of death was oropharyngeal cancer in 51% of patients, noncancer causes in 34%, and second cancers in 15%. Multivariate analysis on all patients showed an increased risk of recurrence associated with advanced stage (IVB, HR Z 2.5, 95% CI Z 1.3e5.1, P Z .007) and p16 negativity (HR Z 3.4, 95% CI Z 1.4e8.0, P Z .006). Smoking status was not identified as a negative prognostic factor. Conclusion: No difference in RFS or OS was observed in advanced oropharyngeal cancer patients treated with primary CRT or primary surgery. Given equivalent outcomes, cost effectiveness analysis and morbidity assessment should determine the most appropriate treatment for these patients. Author Disclosure: R.N. Banerjee: None. B.J. Debenham: None. K. Martell: None. R. Scrimger: None. N. Jha: None. H. Lau: None. M.B. Parliament: None.
176 A Comparison of Primary Chemoradiation Therapy Versus Primary Surgery for Stage III-IV Squamous Cell Carcinoma of the Oropharynx R.N. Banerjee,1 B.J. Debenham,2 K. Martell,1 R. Scrimger,2 N. Jha,2 H. Lau,1 and M.B. Parliament3; 1University of Calgary, Calgary, AB, Canada, 2University of Alberta, Edmonton, AB, Canada, 3Cross Cancer Institute e Alberta Health Services, Edmonton, AB, Canada
Oral Scientific Abstracts 176; Table 1
Age (mean) Gender (male) Smoking status (%) Never smoker Ex-smoker Current smoker Stage (%) III IVA IVB p16 status + e unknown Charlson Comorbidity (age-adjusted) Treatment modality Surgery Surgery + RT Surgery + CRT RT Alone CRT
Patient Characteristics Overall
Primary RT
57 87% 26% 46% 28% 14 74 12 38 6 56 3.9 4% 6% 24% 2% 64%
57 87 28 42 30 14 74 12 48 5 47 4.1 66
Primary Surgery
P value
56 87 22 51 26 15 75 10 20 5 75 3.6 34
.29 .96 .16
.75
.001
.001
177 Use of Human Papillomavirus 16 (HPV16) Cell Free DNA for Assessment of Response to Chemoradiation in HPV-Associated Oropharyngeal Cancer D.S. Higginson,1 E.D. Scher,1 B. Yarusi,1 S. Chan,1 L. Mitrani,2 C. Thompson,1 C.R. Cleary,1 S.M. McBride,1 N. Riaz,1 and N. Lee1; 1 Memorial Sloan Kettering Cancer Center, New York, NY, 2Columbia University, College of Physicians and Surgeons, New York, NY Purpose/Objective(s): Circulating cell free plasma DNA (cfDNA) can be a sensitive biomarker of tumor burden that is accessible by simple phlebotomy. The key challenges include 1) discrimination of cell free DNA derived from tumor and from normal tissue and 2) inherent genetic heterogeneity. Virally induced cancers present unique advantages for cfDNA technologies in that viral genomes present a cancer-specific, broadly applicable target for assessment by quantitative PCR (qPCR) without any additional DNA processing steps that reduce DNA yield. Assessment of EBV cfDNA by qPCR at the conclusion of chemoradiation has been shown to be prognostic of eventual distant metastases and is now investigated as a clinical decision-making tool for use of adjuvant chemotherapy for nasopharyngeal carcinoma. In this pilot study, we hypothesize that qPCR of HPV16 cfDNA can likewise serve as a marker of disease burden after a course of chemoradiation for HPV-associated oropharyngeal cancer (OPC).
173 Pathological Factors Predicting the Risk of Distant Failure for Human PapillomavirusePositive Oropharyngeal Squamous Cell Carcinoma (OPSCC) J.N. Lukens,1 K. Tangsriwong,1 N. Mitra,1 R. Cohen,1 G.S. Weinstein,1 B. O’Malley,1 A. Chalian,1 C. Rassekh,1 J. Newman,1 S. Cannady,1 K.T. Montone,1 P. Ahn,1 H. Quon,2 and A. Lin1; 1University of Pennsylvania, Philadelphia, PA, 2Johns Hopkins University, Baltimore, MD Purpose/Objective(s): Despite superior locoregional control for human papillomavirusepositive (HPV+) OPSCC compared to HPV-negative tumors, a similar proportion (approximately 10%) will develop distant metastases (DM). Current American Joint Committee on Cancer (AJCC) pathological staging does not adequately identify patients (pts) at high risk of DM. There are emerging data on risk factors for DM in pts treated with chemoradiation therapy (CRT), but very little information on risk factors for DM in pts treated with initial surgery. Materials/Methods: We performed a retrospective analysis of 174 HPV+ OPSCC pts with 20 months of follow-up, treated with transoral robotic resection (TORS) and neck dissection followed by adjuvant CRT. Pathologic data included the number and proportion of involved lymph nodes, lowest level of involved nodes, and presence and extent of extracapsular extension (ECE) classified as none, microscopic/focal, or macroscopic/gross. The Wilcoxon rank sum test was used to compare continuous variables, multivariable logistic regression to assess for predictors of DM, and Kaplan-Meier to estimate survival probabilities. Results: With a median follow-up of 38 months, 12 pts (7%) developed DM. The number of positive nodes (PNs) was the strongest predictor of the risk of DM, with the probability increasing in proportion to the number of PNs 4. Risk of DM was 14% for 4 PNs (vs. 3.4%, P Z .021), 18% for 5 PNs (vs. 3%, P Z .002), 22% for 6 PNs (vs. 3.5%, P Z .002), and 28% for 7 PNs (vs. 3.4%, P < .001). Median PNs for pts with and without subsequent DM was 7 versus 2, P Z .004. Number of nodes examined was similar between pts with and without DM (median 41). On univariate analysis, macroscopic/gross ECE was a predictor of DM, with 20% of these pts developing DM versus 4.2% of pts with no or microscopic-only ECE (P Z .007). Neither microscopic ECE nor clinical or (AJCC) pathologic staging predicted for subsequent DM. A multivariable logistic regression model revealed that the number of PNs (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.07e1.40, P Z .004) remained a significant predictor of DM, while macroscopic/gross ECE was of borderline significance (OR 3.30, 95% CI Z 0.85e12.8, P Z .084). ROC analysis suggests that 6 PNs is a reasonable cut-point for prediction of the risk of DM (AUC Z 0.75). Pts with 6 PNs had inferior 4-year distant metastasis-free survival (DMFS) and overall survival (OS) compared to pts with <6 PNs: DMFS 80% versus 95% (P Z .002), and OS 88% versus 97% (P Z .022). Conclusion: The number of PNs appears to be the strongest predictor of DM in pts with pathologically staged HPV+ OPSCC undergoing primary surgery followed by adjuvant CRT. Pts with 6 PNs have a 22% risk of developing DM and appear to have inferior OS. If validated, the number of PNs could be incorporated into a revised pathologic staging system for HPV+ OPSCC to select pts for intensified or investigational adjuvant systemic therapy. Author Disclosure: J.N. Lukens: None. K. Tangsriwong: None. N. Mitra: None. R. Cohen: None. G.S. Weinstein: None. B. O’Malley: None. A. Chalian: None. C. Rassekh: None. J. Newman: None. S. Cannady: None. K.T. Montone: None. P. Ahn: None. H. Quon: None. A. Lin: None.
Oral Scientific Sessions
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174 Impact of Retropharyngeal Adenopathy on Distant Control and Survival in Human PapillomavirusePositive Oropharyngeal Cancer Treated With Chemoradiation Therapy S. Samuels,1 J.M. Vainshtein,2 M.E. Spector,1 M. Ibrahim,1 J.B. McHugh,1 Y. Tao,1 M. Schipper,1 W. Francis,1 and A. Eisbruch1; 1University of Michigan, Ann Arbor, MI, 2Emory University, Atlanta, GA Purpose/Objective(s): Retropharyngeal adenopathy (RPA), a wellestablished poor prognostic factor in head and neck squamous cell carcinoma (HNSCC), predicts worse local and distant control. Human papillomavirusepositive (HPV+) oropharyngeal cancer (OPC) patients are a distinct population of HNSCC patients with superior tumor control and survival compared to smoking- and drinking-related HSNCC. However, the prognostic significance of RPA in HPV+ OPC is unknown. Therefore, we reviewed our institutional experience of HPV+ OPC patients treated with chemoradiation to determine the impact of RPA on tumor control and survival. Materials/Methods: We retrospectively reviewed of 231 consecutive OPC cancer patients treated from 2003 to 2010 with chemoeintensity modulated radiation therapy (weekly carboplatin [AUC1] and docetaxel [30mg/m2]). HPV tumor status was determined for 198 patients, 184 of whom were HPV+ by PCR (184 patients), 93% of whom were p16+ by immunohistochemistry (1 additional patient was p16+, HPV-). Pretherapy images were reviewed for the purpose of this study by a single head and neck radiologist blinded to treatment outcome to determine RPA. Doses to the RP nodal regions were determined from treatment plans. Outcomes were analyzed using Kaplan-Meier method, log-rank tests determined statistically significant differences, and correlations were determined using Spearman rank analyses (r). Results: Twenty-nine (16%) of the 185 HPV+ patients had RPA. Among these, 3 had N1/N2a disease (RPA only), and 26 had additional nodal involvements in levels IIeIV (12 had N2b, 9 had N2c, and 5 had N3 nodal stages). There was no statistically significant correlation between RPA and involvement of other lymph nodes (r Z 0.07, P Z .36) or N stage (r Z 0.12, P Z .11). All patients received 70 Gy to the involved RPA. At median 49 months follow-up, there were no failures in the RPA anatomical compartments. Patients with RPA had overall worse outcomes compared to those without RPA. Five-year overall survival (OS), cancer-specific survival (CSS), and failure-free survival (FFS) were 57% versus 81% (P Z .02), 63% versus 85% (P Z .02), and 63% versus 80% (P Z .015) for patients with and without RPA, respectively. Patterns of failure analysis revealed that presence of RPA was associated with worse distant failurefree survival (DFFS) (70% vs 91%, P Z .002), without any impact on either local (P Z .87) or regional (P Z .88) control rates, which exceeded 95% and 90%, respectively, in both groups. In multivariable analysis T4, N3, and presence of RPA were independently associated with worse OS, CSS, FFS, and DFFS while age, disease site, N2c classification, and smoking status were not. Conclusion: RPA in HPV+ OPC was found to be an independent prognostic factor for distant failure, independent of established risk factors such as T4 and N3 stages, which translated into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment deescalation. Author Disclosure: S. Samuels: None. J.M. Vainshtein: None. M.E. Spector: None. M. Ibrahim: None. J.B. McHugh: None. Y. Tao: None. M. Schipper: None. W. Francis: None. A. Eisbruch: None.
175 Evaluation of Prognostic Groupings for Overall Survival in Human PapillomaviruseAssociated Oropharyngeal Cancer J.J. Caudell, J.M. Frakes, T. Strom, J. Russell, L.B. Harrison, and A. Trotti; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): Human papillomavirus (HPV)eassociated squamous cell carcinomas of the oropharynx are increasingly seen as a separate disease entity from smoking-associated oropharyngeal cancers, with a
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International Journal of Radiation Oncology Biology Physics
much higher likelihood of cure. Several prognostic groupings have been proposed and we evaluate these in a large independent cohort. Materials/Methods: After institutional review board approval, an institutional database was queried for patients with HPV or p16 positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT), and 247 cases were identified. Patient, tumor, and treatment factors were abstracted from the charts. Tested groupings included the American Joint Committee on Cancer (AJCC) TNM staging system, the Radiation Therapy Oncology Group (RTOG) 0129 risk groups (Low Risk Z 10 pack years or >10 pack years with N0e2a, Intermediate Risk Z >10 pack years and N2be3), and the Princess Margaret Hospital (PMH) prognostic groups (I Z T1e3N0e2b, II Z T1e3N2c, III Z T4 or N3). Outcomes, including locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated from the end of RT and estimated via Kaplan-Meier method. Comparisons were made via log-rank test. Results: Median follow-up of patients alive at last contact was 24 months. All patients were treated with definitive RT alone (n Z 38, 15.4%) or concurrent chemotherapy and RT (n Z 209, 84.6%). For the entire cohort 2 year LRC was 94.6%, FFDM 92%, and OS 92.5%. AJCC stage was I in 4 patients (1.6%), II in 13 (5.3%), III in 35 (14.2%) or IVAeB in 195 (78.9%). AJCC stage was not prognostic for LRC (P Z .30), FFDM (P Z .90), or OS (P Z .31). Per RTOG risk groups, 170 were low risk (68.8%), and 77 were intermediate risk (31.2%). RTOG risk groups were not prognostic for LRC (P Z .94), FFDM (P Z .86), or OS (P Z .08). Per PMH prognostic groups, 180 were stage I (72.9%), 37 were stage II (15%), and 30 were stage III (12.1%). PMH prognostic groups were not significant for LRC (P Z .72), but were significant for FFDM (P Z .03) and OS (P Z .003). Actuarial OS at 2 years for PMH stage I was 94.8%, for stage II was 94.5%, and for stage III was 76.6%. Conclusion: Outcomes for patients with HPV-associated oropharyngeal cancer treated with definitive RT are excellent. The proposed PMH stage grouping resulted in improved survival prediction at 2 years compared with RTOG risk groups or AJCC TNM staging. Author Disclosure: J.J. Caudell: None. J.M. Frakes: None. T. Strom: None. J. Russell: None. L.B. Harrison: None. A. Trotti: None.
Purpose/Objective(s): Multiple management options exist for stage IIIeIV oropharyngeal squamous cell cancer, including definitive chemoradiation therapy (CRT), surgery (S) plus adjuvant radiation therapy (S-RT) with or without chemotherapy (S-CRT), or induction chemotherapy followed by definitive treatment. Level I evidence comparing modalities is not available. In our province patients may be treated with either primary surgery (oropharyngeal resection) followed by adjuvant therapy or definitive CRT. We sought to compare the approaches and hypothesized that recurrence rates and survival would not differ. Materials/Methods: This study selected all stage IIIeIV nonmetastatic oropharyngeal squamous cell cancer patients treated with curative intent in our province between 2006 and 2012. Institutional ethics board approval was granted. Patient data was extrapolated from a prospective registry and retrospective review of medical records. KaplaneMeier estimates of the median recurrence-free survival (RFS) and overall survival (OS) and 95% confidence interval (CI) were obtained for both groups. Logistic regression was used to explore the association between patient, tumor, and treatment factors for the primary chemoradiation therapy and surgery groups with 2- and 5-year RFS. Results: Four hundred and twenty-one patients were eligible. Median follow up was 4.3 years. Patient characteristics are shown in Table 1. RFS was not significantly different between groups. The 2- and 5-year RFS rates for CRT versus S were 85% versus 84% and 80% versus 79%. Distant metastases occurred in 47% of CRT patients and 76% of S patients who recurred. Overall survival was no different between groups: 83% versus 82% and 73% versus 71% for CRT versus surgery at 2 and 5 years, respectively. For both groups, the cause of death was oropharyngeal cancer in 51% of patients, noncancer causes in 34%, and second cancers in 15%. Multivariate analysis on all patients showed an increased risk of recurrence associated with advanced stage (IVB, HR Z 2.5, 95% CI Z 1.3e5.1, P Z .007) and p16 negativity (HR Z 3.4, 95% CI Z 1.4e8.0, P Z .006). Smoking status was not identified as a negative prognostic factor. Conclusion: No difference in RFS or OS was observed in advanced oropharyngeal cancer patients treated with primary CRT or primary surgery. Given equivalent outcomes, cost effectiveness analysis and morbidity assessment should determine the most appropriate treatment for these patients. Author Disclosure: R.N. Banerjee: None. B.J. Debenham: None. K. Martell: None. R. Scrimger: None. N. Jha: None. H. Lau: None. M.B. Parliament: None.
176 A Comparison of Primary Chemoradiation Therapy Versus Primary Surgery for Stage III-IV Squamous Cell Carcinoma of the Oropharynx R.N. Banerjee,1 B.J. Debenham,2 K. Martell,1 R. Scrimger,2 N. Jha,2 H. Lau,1 and M.B. Parliament3; 1University of Calgary, Calgary, AB, Canada, 2University of Alberta, Edmonton, AB, Canada, 3Cross Cancer Institute e Alberta Health Services, Edmonton, AB, Canada
Oral Scientific Abstracts 176; Table 1
Age (mean) Gender (male) Smoking status (%) Never smoker Ex-smoker Current smoker Stage (%) III IVA IVB p16 status + e unknown Charlson Comorbidity (age-adjusted) Treatment modality Surgery Surgery + RT Surgery + CRT RT Alone CRT
Patient Characteristics Overall
Primary RT
57 87% 26% 46% 28% 14 74 12 38 6 56 3.9 4% 6% 24% 2% 64%
57 87 28 42 30 14 74 12 48 5 47 4.1 66
Primary Surgery
P value
56 87 22 51 26 15 75 10 20 5 75 3.6 34
.29 .96 .16
.75
.001
.001
177 Use of Human Papillomavirus 16 (HPV16) Cell Free DNA for Assessment of Response to Chemoradiation in HPV-Associated Oropharyngeal Cancer D.S. Higginson,1 E.D. Scher,1 B. Yarusi,1 S. Chan,1 L. Mitrani,2 C. Thompson,1 C.R. Cleary,1 S.M. McBride,1 N. Riaz,1 and N. Lee1; 1 Memorial Sloan Kettering Cancer Center, New York, NY, 2Columbia University, College of Physicians and Surgeons, New York, NY Purpose/Objective(s): Circulating cell free plasma DNA (cfDNA) can be a sensitive biomarker of tumor burden that is accessible by simple phlebotomy. The key challenges include 1) discrimination of cell free DNA derived from tumor and from normal tissue and 2) inherent genetic heterogeneity. Virally induced cancers present unique advantages for cfDNA technologies in that viral genomes present a cancer-specific, broadly applicable target for assessment by quantitative PCR (qPCR) without any additional DNA processing steps that reduce DNA yield. Assessment of EBV cfDNA by qPCR at the conclusion of chemoradiation has been shown to be prognostic of eventual distant metastases and is now investigated as a clinical decision-making tool for use of adjuvant chemotherapy for nasopharyngeal carcinoma. In this pilot study, we hypothesize that qPCR of HPV16 cfDNA can likewise serve as a marker of disease burden after a course of chemoradiation for HPV-associated oropharyngeal cancer (OPC).