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Comparing the Survival, Recurrence, and Toxicities Between Surgery With Adjuvant Therapy Versus Surgery Alone for Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma
S76
International Journal of Radiation Oncology Biology Physics
Author Disclosure: S.S. Khwaja: None. C. Baker: None. W. Haynes: None. C.R. Spencer: None. H.A. Gay: None. W.L. Thorstad: None. J.S. Lewis Jr.: None. X. Wang: None.
1.89e13.15; P Z .001). When examining all toxic events, 19.6% (29/148) of AT patients experienced toxicity (12.8% dysphagia and 8.9% osteoradionecrosis). None of the SA patients experienced the 2 toxicities scored in this study (P < .01). Conclusion: Among HPV+ patients, those treated with AT were 3 times less likely to develop LRR. AT patients also enjoyed improved survival at 1 year, 2 years, and 5 years. However, this came at the cost of a higher rate of dysphagia and osteonecrosis. Author Disclosure: D. Pasalic: None. R.K. Funk: None. E.J. Moore: None. J.J. Garcia: None. K. Price: None. D.L. Price: None. R.L. Foote: None. D.J. Ma: None.
171 Comparing the Survival, Recurrence, and Toxicities Between Surgery With Adjuvant Therapy Versus Surgery Alone for Human PapillomavirusePositive Oropharyngeal Squamous Cell Carcinoma D. Pasalic, R.K. Funk, E.J. Moore, J.J. Garcia, K. Price, D.L. Price, R.L. Foote, and D.J. Ma; Mayo Clinic, Rochester, MN Purpose/Objective(s): The purpose of this study was to compare survival, tumor control, and toxicity in patients with human papillomavirusepositive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) treated with surgery alone or combined with adjuvant therapy. Given that HPV+ patients tend to be younger and higher performing, we hypothesized that adjuvant therapy may not be necessary in this unique population so as to spare them from accrued toxicities. Materials/Methods: An institutional review boardeapproved retrospective review of 317 surgically treated OPSCC between 2005 and 2013 revealed 173 HPV+ patients, 148 of whom received adjuvant intensity modulated radiation therapy with or without chemotherapy (AT) and 25 patients who elected not to receive AT, although they were candidates (SA). HPV status was determined by either p16 staining or DNA in situ hybridization. Recorded toxicities included 3 grade dysphagia with >6 months of feeding tube, or osteonecrosis requiring surgery or hyperbaric oxygen. First recurrence after initial therapy was tracked at the local, regional, or distant metastatic level. Hazard ratios (HR) were calculated and reported with 95% confidence interval (CI). Results: Patient demographics are listed in Table 1. Median follow-up was 2.6 years. The Kaplan-Meier local-regional recurrence (LRR)efree survival at 1 year, 2 years, and 5 years was 99.3%, 98.5%, and 98.5% for AT and 79.2%, 79.2%, and 59.4% for SA, respectively. Disease recurrence (HR Z 3.16, CI 1.29e7.75; P Z .01) and specifically LRR (HR Z 17.64, CI 3.72e83.52; P < .001) was significantly higher in SA patients. Among high-risk extracapsular extension (ECE)epositive patients, the KaplanMeier disease-free survival at 1 year and 2 years was 92.1% and 86.3% for AT and 57.1% and 57.1% for SA, respectively (HR Z 4.98, CI
Oral Scientific Abstracts 171; Table 1
HPV+ Median age Male Any smoking history Chemotherapy Location Tongue base Tonsil Recurrence Local Regional Distant Tumor stage 1 2 3 4a Nodal stage 0 1 2a 2b 2c 3 Metastasis stage 0
AT (# of patients)
SA (# of patients)
148 57.4 128 78 99
25 58.5 23 10 0
71 77
10 15
0 2 13
2 4 1
49 65 19 15
3 15 7 0
5 12 24 90 9 8
4 5 8 7 1 0
148
25
172 Cetuximab-based Bioradiation Therapy Is Associated With Higher Rates of Distant Metastases Than Platinum-based Chemoradiation Therapy in Human PapillomavirusePositive Oropharyngeal Cancer M.A. Weller, M.C. Ward, C.A. Berriochoa, C.A. Reddy, S. Trosman, J.F. Greskovich, Jr, T. Nwizu, B.B. Burkey, D.J. Adelstein, and S. Koyfman; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): To identify predictors of distant metastases (DM) in patients with human papillomavirus (HPV)epositive oropharyngeal cancer (OPC) treated with cisplatin-based chemoradiation therapy (CisRT) or cetuximab-based bioradiation therapy (CetRT). Materials/Methods: Between 2002 and 2013, 310 patients with stage IIIeIVb HPV-positive OPC were managed with definitive nonsurgical treatment: 267 patients (86%) received CisRT, and 43 patients (14%) received CetRT. HPV association was confirmed by in situ hybridization for HPV DNA, or strong and diffuse staining for p16 in >75% of the tissue by immunohistochemistry in all patients. Student t tests and Pearson chi-square tests were used to compare baseline patient and tumor characteristics between treatment groups. Kaplan-Meier analysis was used to calculate rates of DM, with the log-rank test used to compare rates between patient and treatment groups. Univariate and multivariate analyses (MVA) were used to identify factors associated with distant metastases, including age, smoking status, T stage, N stage, and type of systemic therapy. Results: The median follow-up for all patients was 44 months (range, 2e151 months), 49 months for CisRT versus 24 months for CetRT patients. T and N stage breakdown was as follows: T1e3, 74%; T4, 16%; N0eN2a, 21%; N2b, 42%; N2c, 26%; and N3, 11%. CisRT patients were more likely to have T4 tumors (18% vs 5%, P Z .03) and be active smokers (18% vs 9%, P Z .14). Otherwise groups were well balanced for N stage and Karnofsky Performance Status. Overall, 20 patients (6.5%) experienced a locoregional failure. For all patients, DM rates at 2 and 5 years were 7% and 13%, respectively. Rates of DM at 2 and 5 years were significantly higher with CetRT compared to CisRT (2 years: 23% vs 5%; 5 years: 23% vs 11%; P Z .0035). Significantly increased DM rates were also noted in active smokers at diagnosis (n Z 53) versus never/former smokers (n Z 257) (2 years: 22% vs 5%; 5 years: 32% vs 9%, P < .0001), and for T4 versus T1e3 (2 years: 15% vs 6%; 5 years: 21% vs 11%, P Z .045). On MVA, active smoking (hazard ratio [HR] 5.41; P < .0001), the use of CetRT (HR Z 5.24; P Z .0003), and T4 disease (HR Z 2.78; P Z .018) were the only factors associated with higher rates of DM. Overall pack-years (PY), >10 PY, >20 PY, and N stage were not significantly associated with DM. Conclusion: Despite a more favorable case mix, patients with HPV-positive OPC who received concurrent cetuximab with radiation therapy had a significantly higher rate of distant metastases compared to those who received platinum-based CRT. While we await mature results from Radiation Therapy Oncology Group 1016, cisplatin delivered concurrently with radiation therapy should remain the standard of care for these patients. T4 tumors and active smoking also predict for DM, and these patients should be the primary target of intensification.
International Journal of Radiation Oncology Biology Physics
Author Disclosure: S.S. Khwaja: None. C. Baker: None. W. Haynes: None. C.R. Spencer: None. H.A. Gay: None. W.L. Thorstad: None. J.S. Lewis Jr.: None. X. Wang: None.
1.89e13.15; P Z .001). When examining all toxic events, 19.6% (29/148) of AT patients experienced toxicity (12.8% dysphagia and 8.9% osteoradionecrosis). None of the SA patients experienced the 2 toxicities scored in this study (P < .01). Conclusion: Among HPV+ patients, those treated with AT were 3 times less likely to develop LRR. AT patients also enjoyed improved survival at 1 year, 2 years, and 5 years. However, this came at the cost of a higher rate of dysphagia and osteonecrosis. Author Disclosure: D. Pasalic: None. R.K. Funk: None. E.J. Moore: None. J.J. Garcia: None. K. Price: None. D.L. Price: None. R.L. Foote: None. D.J. Ma: None.
171 Comparing the Survival, Recurrence, and Toxicities Between Surgery With Adjuvant Therapy Versus Surgery Alone for Human PapillomavirusePositive Oropharyngeal Squamous Cell Carcinoma D. Pasalic, R.K. Funk, E.J. Moore, J.J. Garcia, K. Price, D.L. Price, R.L. Foote, and D.J. Ma; Mayo Clinic, Rochester, MN Purpose/Objective(s): The purpose of this study was to compare survival, tumor control, and toxicity in patients with human papillomavirusepositive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) treated with surgery alone or combined with adjuvant therapy. Given that HPV+ patients tend to be younger and higher performing, we hypothesized that adjuvant therapy may not be necessary in this unique population so as to spare them from accrued toxicities. Materials/Methods: An institutional review boardeapproved retrospective review of 317 surgically treated OPSCC between 2005 and 2013 revealed 173 HPV+ patients, 148 of whom received adjuvant intensity modulated radiation therapy with or without chemotherapy (AT) and 25 patients who elected not to receive AT, although they were candidates (SA). HPV status was determined by either p16 staining or DNA in situ hybridization. Recorded toxicities included 3 grade dysphagia with >6 months of feeding tube, or osteonecrosis requiring surgery or hyperbaric oxygen. First recurrence after initial therapy was tracked at the local, regional, or distant metastatic level. Hazard ratios (HR) were calculated and reported with 95% confidence interval (CI). Results: Patient demographics are listed in Table 1. Median follow-up was 2.6 years. The Kaplan-Meier local-regional recurrence (LRR)efree survival at 1 year, 2 years, and 5 years was 99.3%, 98.5%, and 98.5% for AT and 79.2%, 79.2%, and 59.4% for SA, respectively. Disease recurrence (HR Z 3.16, CI 1.29e7.75; P Z .01) and specifically LRR (HR Z 17.64, CI 3.72e83.52; P < .001) was significantly higher in SA patients. Among high-risk extracapsular extension (ECE)epositive patients, the KaplanMeier disease-free survival at 1 year and 2 years was 92.1% and 86.3% for AT and 57.1% and 57.1% for SA, respectively (HR Z 4.98, CI
Oral Scientific Abstracts 171; Table 1
HPV+ Median age Male Any smoking history Chemotherapy Location Tongue base Tonsil Recurrence Local Regional Distant Tumor stage 1 2 3 4a Nodal stage 0 1 2a 2b 2c 3 Metastasis stage 0
AT (# of patients)
SA (# of patients)
148 57.4 128 78 99
25 58.5 23 10 0
71 77
10 15
0 2 13
2 4 1
49 65 19 15
3 15 7 0
5 12 24 90 9 8
4 5 8 7 1 0
148
25
172 Cetuximab-based Bioradiation Therapy Is Associated With Higher Rates of Distant Metastases Than Platinum-based Chemoradiation Therapy in Human PapillomavirusePositive Oropharyngeal Cancer M.A. Weller, M.C. Ward, C.A. Berriochoa, C.A. Reddy, S. Trosman, J.F. Greskovich, Jr, T. Nwizu, B.B. Burkey, D.J. Adelstein, and S. Koyfman; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): To identify predictors of distant metastases (DM) in patients with human papillomavirus (HPV)epositive oropharyngeal cancer (OPC) treated with cisplatin-based chemoradiation therapy (CisRT) or cetuximab-based bioradiation therapy (CetRT). Materials/Methods: Between 2002 and 2013, 310 patients with stage IIIeIVb HPV-positive OPC were managed with definitive nonsurgical treatment: 267 patients (86%) received CisRT, and 43 patients (14%) received CetRT. HPV association was confirmed by in situ hybridization for HPV DNA, or strong and diffuse staining for p16 in >75% of the tissue by immunohistochemistry in all patients. Student t tests and Pearson chi-square tests were used to compare baseline patient and tumor characteristics between treatment groups. Kaplan-Meier analysis was used to calculate rates of DM, with the log-rank test used to compare rates between patient and treatment groups. Univariate and multivariate analyses (MVA) were used to identify factors associated with distant metastases, including age, smoking status, T stage, N stage, and type of systemic therapy. Results: The median follow-up for all patients was 44 months (range, 2e151 months), 49 months for CisRT versus 24 months for CetRT patients. T and N stage breakdown was as follows: T1e3, 74%; T4, 16%; N0eN2a, 21%; N2b, 42%; N2c, 26%; and N3, 11%. CisRT patients were more likely to have T4 tumors (18% vs 5%, P Z .03) and be active smokers (18% vs 9%, P Z .14). Otherwise groups were well balanced for N stage and Karnofsky Performance Status. Overall, 20 patients (6.5%) experienced a locoregional failure. For all patients, DM rates at 2 and 5 years were 7% and 13%, respectively. Rates of DM at 2 and 5 years were significantly higher with CetRT compared to CisRT (2 years: 23% vs 5%; 5 years: 23% vs 11%; P Z .0035). Significantly increased DM rates were also noted in active smokers at diagnosis (n Z 53) versus never/former smokers (n Z 257) (2 years: 22% vs 5%; 5 years: 32% vs 9%, P < .0001), and for T4 versus T1e3 (2 years: 15% vs 6%; 5 years: 21% vs 11%, P Z .045). On MVA, active smoking (hazard ratio [HR] 5.41; P < .0001), the use of CetRT (HR Z 5.24; P Z .0003), and T4 disease (HR Z 2.78; P Z .018) were the only factors associated with higher rates of DM. Overall pack-years (PY), >10 PY, >20 PY, and N stage were not significantly associated with DM. Conclusion: Despite a more favorable case mix, patients with HPV-positive OPC who received concurrent cetuximab with radiation therapy had a significantly higher rate of distant metastases compared to those who received platinum-based CRT. While we await mature results from Radiation Therapy Oncology Group 1016, cisplatin delivered concurrently with radiation therapy should remain the standard of care for these patients. T4 tumors and active smoking also predict for DM, and these patients should be the primary target of intensification.