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Locoregional Patterns of Failure in Oropharyngeal Carcinoma: Implications for Treatment De-escalation
S474
International Journal of Radiation Oncology Biology Physics
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
Volume 84 Number 3S Supplement 2012 risk for isolated failure, which could be considered for dose deescalation. Materials/Methods: Our center treated 412 consecutive OPC patients between September 1998 and April 2009 with definitive IMRT. The majority (nZ389) received chemotherapy. The GTV was defined by the extent of tumor on clinical exam or imaging. The high risk CTV59.4 was defined as the GTV with a 1-1.5 cm margin and included coverage of the pterygopalatine fossa for tonsil and vallecula for the base of tongue (BOT). For the involved neck (N+), levels Ib-V and the retropharyngeal nodes (RPN) were included in the CTV59.4. For the negative neck (N-), levels IIIV and the RPN were always treated. Level Ib and V were treated at the discretion of the treating physician. Thirty-three patients developed a LRF or had persistent disease, of whom 28 had restorable treatment plans. Target volume delineation was reviewed visually on a slice-by-slice basis alongside axial imaging documenting LRF. Imaging for difficult cases was rigidly fused to treatment planning CT scan. Pathology for patients who underwent salvage surgery was also reviewed. Results: Median time to LRF was 9.7 months (range: 3.4 - 63.4) for the 28 patients who had restorable treatment plans. The tonsil was the primary site in 12 patients and the BOT in 16 patients. T stage was T1 in 3 patients, T2 in 14, T3 in 4, and T4 in 7. N stage was N0 in 3 patients, N1 in 2, N2 in 21, and N3 in 2. 20 patients developed a local failure (LF), 18 patients developed a regional failure (RF), and 10 patients developed both a local and regional failure. The majority of LF were in the center of the PTV70Gy, (17/20) suggesting treatment refractory disease as the cause rather than inadequate targeting. 2 patients had LF marginal to the PTV70, but, both recurrences were within the 59.4Gy volume. One LF was not evaluable because there was no axial imaging documenting the location of recurrence. Thirteen of 18 regional recurrences involved level II. Two recurrences occurred in level I; these also had synchronous LF. Two RF occurred in indeterminate nodes on pre-treatment evaluation, which were not boosted, to 70 Gy. Two RF involved the base of skull (BOS), however, neither was isolated. One case involved gross disease present at diagnosis and the other case was a patient’s second recurrence. Conclusions: In our cohort of OPC patients, the majority of LRF occurred at the primary site and at the level II nodal region. The lack of isolated failures in Level I or at the BOS, indicate that these areas could be considered for dose de-escalation. Areas to consider for de-escalation may be especially relevant for HPV related tumors, which already have an excellent prognosis. Author Disclosure: N. Riaz: None. E. Katsoulakis: None. L. Ong: None. B. Youssef: None. S. Wolden: None. G. Niyazov: None. S. Rao: None. N. Lee: None.
2681 Diffusion-Weighted Imaging Compared to 3-month PET/CT to Predict Response in the Irradiated Neck W.R. Silveira, P.Y. Shen, J. Tan, C.M. Glastonbury, J.M. Quivey, W.R. Ryan, S.J. Wang, and S.S. Yom; University of California San Francisco, San Francisco, CA Purpose/Objective(s): To determine the utility of diffusion-weighted magnetic resonance imaging (DWI) in the assessment of nodal response at 6-8 weeks after definitive radiation therapy for squamous cell carcinoma (SCC) of the oropharynx, as compared to positron emission tomography with contrast-enhanced CT (PET/CT) performed at 12-14 weeks. Materials/Methods: We conducted a retrospective review of all patients with oropharyngeal SCC who had concurrent chemoradiation between 2009 to 2011 with DWI and PET/CT imaging at 6-8 and 12-14 weeks, respectively, post-treatment. The mean apparent diffusion coefficient (ADC), measured from the nodal cross-sectional area, was investigated as a marker for persistent nodal disease. ROC analysis was applied to determine the optimal ADC cutoff. Results: Nineteen patients with a median age of 58 years were identified, consisting of 16 men and 3 women. Primary sites were: 8 tonsil, 7 base
Poster Viewing Abstracts S475 of tongue, 1 with tonsil and base of tongue involvement and 3 with clinically diagnosed oropharynx SCC without pathologic primary site confirmation. Thirteen of 19 patients had p16 positive disease. The prescription dose was 6996 cGy in 33 fractions to gross disease. A total of 23 residual nodal sites were assessed. Two patients (one p16 positive, one p16 negative) had post-treatment FDG-avidity with SUVmax of 2.56 and 3.44 and underwent neck dissection with findings of residual pathology. The averages of the mean ADC values for patients with pathologically proven residual disease in the neck versus all others were 1.81 x 10-3 mm^2/s (range, 1.52-2.09 x 10-3 mm^2/s) and 1.90 x 10-3 mm^2/s (range, 0.25-3.45 x 10-3 mm^2/s), respectively. ROC analysis yielded a cutoff ADC of 2.10 x 10-3 mm^2/s, resulting in sensitivity Z 100%, specificity Z 36%, PPV Z 12.5%, and NPV Z 100%. The averages of the mean ADC values for patients with persistent FDGavidity in the neck versus all others were 1.59 x 10-3 mm^2/s (range, 1.04-2.09 x 10-3 mm^2/s) and 1.95 x 10-3 mm^2/s (range, 0.25-3.45 x 10-3 mm^2/s), respectively. Using positive post-treatment PET activity at 3 months as the gold standard for likely residual disease at that time, an ADC cutoff of 1.70 x 10-3 mm^2/s yielded sensitivity Z 75%, specificity Z 75%, PPV Z 37.5%, and NPV Z 93.8%. Conclusions: After definitive chemoradiation for oropharyngeal cancer, diffusion-weighted imaging is a highly sensitive and reasonably specific means of detecting persistent nodal disease at an earlier timepoint than PET/CT. ADC values can be derived to predict results of PET/CT at 12-14 weeks and/or predict pathologic disease at neck dissection. Analysis was complicated by the rarity of failure seen in this population. Author Disclosure: W.R. Silveira: None. P.Y. Shen: None. J. Tan: None. C.M. Glastonbury: None. J.M. Quivey: None. W.R. Ryan: None. S.J. Wang: None. S.S. Yom: None.
2682 Intensity Modulated Proton Therapy for Head-and-Neck Cancer: The First Clinical Experience S.J. Frank, J.D. Cox, M. Gillin, D.I. Rosenthal, A.S. Garden, K. Ang, R. Mohan, M.B. Palmer, M. Amin, and X.R. Zhu; M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Intensity-modulated radiation therapy (IMXT) results in improved conformality but often produces unacceptable beampath toxicity (i.e. oral mucositis, nausea and vomiting) from use of multiple coplanar beams for head and neck cancer. We sought to test the feasibility, toxicity, and effectiveness of multi-field optimization (MFO) intensity-modulated proton therapy (IMPT) with discrete spot scanning beam technology for patients with head and neck tumors. Materials/Methods: Fifteen patients with head and neck cancer [8 oropharynx, 4 nasopharynx, 2 paranasal sinus, and 1 unknown primary], enrolled on an approved protocol, underwent MFO IMPT with a simultaneous integrated boost; 10 had squamous cell carcinoma and 5 had adenoid cystic carcinoma. Doses for patients, who were to receive concurrent chemoradiation therapy, were 70 Gy(RBE), to be given in 33 fractions of 2.12 Gy(RBE). Organs at risk were brain, brainstem, spinal cord, optical apparatus, cochleas, parotids, submandibular glands, oral cavity, larynx, and esophagus. Results: All 15 patients completed treatment with MFO IMPT with no need for treatment breaks and no hospitalizations; 12 patients (80%), 4 of whom had induction chemotherapy, also received concurrent chemotherapy. Toxicity profile was favorable; there were no treatment-related deaths and only 1 grade 4 toxicity (vomiting). Ten patients (67%) experience no anterior oral mucositis with the other five patients experiencing Grade 1. Six patients (40%) experienced no nausea or vomiting (2 with base-of-tongue, 2 tonsil, 1 nasopharynx, and 1 paranasal sinus tumors); 8 had nausea (4 grade 2, 4 grade 3); and 11 patients experienced no vomiting. No patient had disease progression during treatment, and 14 of 15 patients (93%) experienced clinical complete response of the primary and nodal disease.
International Journal of Radiation Oncology Biology Physics
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
Volume 84 Number 3S Supplement 2012 risk for isolated failure, which could be considered for dose deescalation. Materials/Methods: Our center treated 412 consecutive OPC patients between September 1998 and April 2009 with definitive IMRT. The majority (nZ389) received chemotherapy. The GTV was defined by the extent of tumor on clinical exam or imaging. The high risk CTV59.4 was defined as the GTV with a 1-1.5 cm margin and included coverage of the pterygopalatine fossa for tonsil and vallecula for the base of tongue (BOT). For the involved neck (N+), levels Ib-V and the retropharyngeal nodes (RPN) were included in the CTV59.4. For the negative neck (N-), levels IIIV and the RPN were always treated. Level Ib and V were treated at the discretion of the treating physician. Thirty-three patients developed a LRF or had persistent disease, of whom 28 had restorable treatment plans. Target volume delineation was reviewed visually on a slice-by-slice basis alongside axial imaging documenting LRF. Imaging for difficult cases was rigidly fused to treatment planning CT scan. Pathology for patients who underwent salvage surgery was also reviewed. Results: Median time to LRF was 9.7 months (range: 3.4 - 63.4) for the 28 patients who had restorable treatment plans. The tonsil was the primary site in 12 patients and the BOT in 16 patients. T stage was T1 in 3 patients, T2 in 14, T3 in 4, and T4 in 7. N stage was N0 in 3 patients, N1 in 2, N2 in 21, and N3 in 2. 20 patients developed a local failure (LF), 18 patients developed a regional failure (RF), and 10 patients developed both a local and regional failure. The majority of LF were in the center of the PTV70Gy, (17/20) suggesting treatment refractory disease as the cause rather than inadequate targeting. 2 patients had LF marginal to the PTV70, but, both recurrences were within the 59.4Gy volume. One LF was not evaluable because there was no axial imaging documenting the location of recurrence. Thirteen of 18 regional recurrences involved level II. Two recurrences occurred in level I; these also had synchronous LF. Two RF occurred in indeterminate nodes on pre-treatment evaluation, which were not boosted, to 70 Gy. Two RF involved the base of skull (BOS), however, neither was isolated. One case involved gross disease present at diagnosis and the other case was a patient’s second recurrence. Conclusions: In our cohort of OPC patients, the majority of LRF occurred at the primary site and at the level II nodal region. The lack of isolated failures in Level I or at the BOS, indicate that these areas could be considered for dose de-escalation. Areas to consider for de-escalation may be especially relevant for HPV related tumors, which already have an excellent prognosis. Author Disclosure: N. Riaz: None. E. Katsoulakis: None. L. Ong: None. B. Youssef: None. S. Wolden: None. G. Niyazov: None. S. Rao: None. N. Lee: None.
2681 Diffusion-Weighted Imaging Compared to 3-month PET/CT to Predict Response in the Irradiated Neck W.R. Silveira, P.Y. Shen, J. Tan, C.M. Glastonbury, J.M. Quivey, W.R. Ryan, S.J. Wang, and S.S. Yom; University of California San Francisco, San Francisco, CA Purpose/Objective(s): To determine the utility of diffusion-weighted magnetic resonance imaging (DWI) in the assessment of nodal response at 6-8 weeks after definitive radiation therapy for squamous cell carcinoma (SCC) of the oropharynx, as compared to positron emission tomography with contrast-enhanced CT (PET/CT) performed at 12-14 weeks. Materials/Methods: We conducted a retrospective review of all patients with oropharyngeal SCC who had concurrent chemoradiation between 2009 to 2011 with DWI and PET/CT imaging at 6-8 and 12-14 weeks, respectively, post-treatment. The mean apparent diffusion coefficient (ADC), measured from the nodal cross-sectional area, was investigated as a marker for persistent nodal disease. ROC analysis was applied to determine the optimal ADC cutoff. Results: Nineteen patients with a median age of 58 years were identified, consisting of 16 men and 3 women. Primary sites were: 8 tonsil, 7 base
Poster Viewing Abstracts S475 of tongue, 1 with tonsil and base of tongue involvement and 3 with clinically diagnosed oropharynx SCC without pathologic primary site confirmation. Thirteen of 19 patients had p16 positive disease. The prescription dose was 6996 cGy in 33 fractions to gross disease. A total of 23 residual nodal sites were assessed. Two patients (one p16 positive, one p16 negative) had post-treatment FDG-avidity with SUVmax of 2.56 and 3.44 and underwent neck dissection with findings of residual pathology. The averages of the mean ADC values for patients with pathologically proven residual disease in the neck versus all others were 1.81 x 10-3 mm^2/s (range, 1.52-2.09 x 10-3 mm^2/s) and 1.90 x 10-3 mm^2/s (range, 0.25-3.45 x 10-3 mm^2/s), respectively. ROC analysis yielded a cutoff ADC of 2.10 x 10-3 mm^2/s, resulting in sensitivity Z 100%, specificity Z 36%, PPV Z 12.5%, and NPV Z 100%. The averages of the mean ADC values for patients with persistent FDGavidity in the neck versus all others were 1.59 x 10-3 mm^2/s (range, 1.04-2.09 x 10-3 mm^2/s) and 1.95 x 10-3 mm^2/s (range, 0.25-3.45 x 10-3 mm^2/s), respectively. Using positive post-treatment PET activity at 3 months as the gold standard for likely residual disease at that time, an ADC cutoff of 1.70 x 10-3 mm^2/s yielded sensitivity Z 75%, specificity Z 75%, PPV Z 37.5%, and NPV Z 93.8%. Conclusions: After definitive chemoradiation for oropharyngeal cancer, diffusion-weighted imaging is a highly sensitive and reasonably specific means of detecting persistent nodal disease at an earlier timepoint than PET/CT. ADC values can be derived to predict results of PET/CT at 12-14 weeks and/or predict pathologic disease at neck dissection. Analysis was complicated by the rarity of failure seen in this population. Author Disclosure: W.R. Silveira: None. P.Y. Shen: None. J. Tan: None. C.M. Glastonbury: None. J.M. Quivey: None. W.R. Ryan: None. S.J. Wang: None. S.S. Yom: None.
2682 Intensity Modulated Proton Therapy for Head-and-Neck Cancer: The First Clinical Experience S.J. Frank, J.D. Cox, M. Gillin, D.I. Rosenthal, A.S. Garden, K. Ang, R. Mohan, M.B. Palmer, M. Amin, and X.R. Zhu; M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Intensity-modulated radiation therapy (IMXT) results in improved conformality but often produces unacceptable beampath toxicity (i.e. oral mucositis, nausea and vomiting) from use of multiple coplanar beams for head and neck cancer. We sought to test the feasibility, toxicity, and effectiveness of multi-field optimization (MFO) intensity-modulated proton therapy (IMPT) with discrete spot scanning beam technology for patients with head and neck tumors. Materials/Methods: Fifteen patients with head and neck cancer [8 oropharynx, 4 nasopharynx, 2 paranasal sinus, and 1 unknown primary], enrolled on an approved protocol, underwent MFO IMPT with a simultaneous integrated boost; 10 had squamous cell carcinoma and 5 had adenoid cystic carcinoma. Doses for patients, who were to receive concurrent chemoradiation therapy, were 70 Gy(RBE), to be given in 33 fractions of 2.12 Gy(RBE). Organs at risk were brain, brainstem, spinal cord, optical apparatus, cochleas, parotids, submandibular glands, oral cavity, larynx, and esophagus. Results: All 15 patients completed treatment with MFO IMPT with no need for treatment breaks and no hospitalizations; 12 patients (80%), 4 of whom had induction chemotherapy, also received concurrent chemotherapy. Toxicity profile was favorable; there were no treatment-related deaths and only 1 grade 4 toxicity (vomiting). Ten patients (67%) experience no anterior oral mucositis with the other five patients experiencing Grade 1. Six patients (40%) experienced no nausea or vomiting (2 with base-of-tongue, 2 tonsil, 1 nasopharynx, and 1 paranasal sinus tumors); 8 had nausea (4 grade 2, 4 grade 3); and 11 patients experienced no vomiting. No patient had disease progression during treatment, and 14 of 15 patients (93%) experienced clinical complete response of the primary and nodal disease.