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Sparing Level IB in Node-Positive, Human Papillomavirus–Associated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis
E336
International Journal of Radiation Oncology Biology Physics
2824
Purpose/Objective(s): Patients with head and neck squamous cell carcinoma (HNSCC) and N3 nodal disease are underrepresented in randomized trials creating uncertainty regarding their optimal management. We utilized a large national registry to evaluate patterns of care and outcome in this N3 population. Materials/Methods: Patients with N3 HNSCC who underwent curative intent treatment between 2004 and 2012 were identified from the National Cancer Data Base. Univariate and multiple-logistic regression were performed to identify predictors of treatment modality. Cox-proportional hazards analysis was used to determine predictors of survival. Results: We identified 3,877 patients with N3 HNSCC treated with curative intent with a median follow-up of 59.4 months. From this cohort, 2,832 patients were treated with radiation alone and 1,045 were treated with combined surgery and radiation. Chemotherapy was delivered to 90.8% of all patients. Patients with lower T-stage, oral cavity sub-site, and younger age were more likely to undergo surgery. Overall survival at 5 years for all patients was 46.3%. Patients treated with radiation alone versus combined surgery and radiation exhibited 5 year OS of 41.8% and 58.3%, respectively (P<0.001). When analyzed by site of the primary tumor, a similar survival advantage for combined surgery and radiation was observed. Predictors for survival included oropharynx sub-site (P<0.001), surgery as part of treatment (P<0.001), use of chemotherapy (P<0.001), treatment at an academic facility (P Z 0.02), lower T-stage (P<0.001), younger age (P<0.001), and lower Charlson-Deyo score (P Z 0.03). Conclusion: This analysis of N3 HNSCC demonstrates that patients who received combined surgery and radiation exhibited the best survival outcomes. However, only 27% of the N3 patients underwent surgery, possibly reflecting the advanced nature of their primary tumors and/or neck disease, poor performance status or other factors. The N3 patients who were selected for surgery were younger, had smaller T-stage tumors and were more likely to have oral cavity primary sites. N3 oropharynx patients had statistically longer survival compared to oral cavity and hypopharynx subsites, and this may reflect the presumed higher incidence of HPV-associated cancers of the oropharynx that carries a more favorable prognosis. This represents the largest cohort of N3 HNSCC patients reported to date and provides opportunities for hypothesis testing to improve future outcomes. Author Disclosure: H.C. Ko: None. J.V. Brower: None. A.M. Baschnagel: None. C.R. Hullett: None. A. Wieland: None. P.M. Harari: None. M.E. Witek: None.
Positron Emission Tomography (PET)eBased Adaptive Radiation Therapy for Locally Advanced Squamous Carcinoma of the Head and Neck: Initial Results of a Prospective Trial D.J. Krauss,1 H. Ye,1 D. Yan,2 Q. Liu,3 J. Liang,4 K. Marvin,1 T. Dimeglio,3 J. Akervall,5 and P. Chen3; 1Beaumont Health, Royal Oak, MI, 2Beaumont Health System, Royal Oak, MI, 3Oakland University William Beaumont School of Medicine, Royal Oak, MI, 4William Beaumont Health System, Royal Oak, MI, 5William Beaumont Hospital, Royal Oak, MI Purpose/Objective(s): To report initial clinical outcomes of a prospective, non-randomized protocol of a PET-based adaptive radiation therapy (RT) approach for patients with locally advanced head and neck squamous carcinoma (HNSCC). Materials/Methods: Patients with a diagnosis of clinically node-positive nasopharyngeal, oropharyngeal, laryngeal, or hypopharyngeal squamous carcinoma were eligible and treated on an IRB-approved protocol. Patients underwent concurrent cisplatin-based chemotherapy with RT. Prescription doses were 70 Gy to sites of gross disease (both primary and nodal) and 60 Gy to at-risk but uninvolved nodal basins. Treatment was delivered in a concomitant boost technique over 35 fractions. Simulation was performed using a thermoplastic mask on a PET-CT simulator and was repeated following treatment fractions 10 and 22. Plans were modified at those points taking into account reduction in disease burden and anatomical changes secondary to weight loss. Additional weekly PET-CT scans were considered optional and acquired on all agreeable patients to monitor response. The primary study endpoint was locoregional failure (LRF). Secondary endpoints included treatment toxicity, distant metastases, and both overall (OS) and disease-free survival (DFS). Toxicity rates were scored using CTCAE v4.0. Results: A total of 25 patients have enrolled, 20 of whom with > 6 months’ follow up form the basis for this analysis. Median follow up time is 15 months (range 6-39). Median age at diagnosis was 61 years (range 48-76). Primary tumor site was oropharynx in 13 patients, oral cavity in 1, supraglottic larynx in 3, hypopharynx in 1, and unknown in 3. 11 patients were p16 positive, 8 negative, and 1 unknown. Primary tumor stage was Tx in 3 patients, T1 in 2, T2 in 7, T3 in 7, and T4 in 1. Nodal stage was N1 in 2 patients, N2b in 13, N2c in 4, and N3 in 1. All patients completed cisplatin based chemotherapy concurrently, with 1 switched to cetuximab mid-treatment due to toxicity. 3 LRF events occurred, yielding a 2-year local control rate of 83%. All LRF events occurred in p16-negative patients. 4 patients developed distant metastases (2-yr rate Z 22.5%), 2 synchronous with LRF. 2-year OS and DFS estimates were 100% and 72.3%, respectively. The most common chronic grade 2 toxicities were dysgeusia (54%), xerostomia (31%), and dysphagia (23%). No chronic grade 3 toxicities have occurred to date. Conclusion: Target volume reduction likely may be safely performed based on radiographic and PET responses occurring during a course of concurrent chemoradiation therapy for node-positive HNSCC. Toxicity rates are favorable, and additional investigation will continue to define the optimal integration of such approaches into disease management paradigms. Author Disclosure: D.J. Krauss: None. H. Ye: None. D. Yan: None. Q. Liu: None. J. Liang: None. K. Marvin: None. T. Dimeglio: None. J. Akervall: None. P. Chen: None.
2825 Patterns of Care and Outcome for N3 Head and Neck Squamous Cell Carcinoma: Review of the National Cancer Data Base H.C. Ko,1 J.V. Brower,1 A.M. Baschnagel,1 C.R. Hullett,1 A. Wieland,2 P.M. Harari,1 and M.E. Witek1; 1Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, 2Department of Otolaryngology, University of Wisconsin Hospital and Clinics, Madison, WI
2826 Sparing Level IB in Node-Positive, Human PapillomaviruseAssociated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis N.P. Joshi,1 A. Juloori,2 M.C. Ward,3 H. Qu,2 J.F. Greskovich, Jr,4 E. Murray,2 J. Potter,3 A. Dorfmeyer,3 P. Xia,2 and S. Koyfman3; 1Taussig Cancer Institute Cleveland Clinic, Cleveland, OH, 2Cleveland Clinic, Cleveland, OH, 3Cleveland Clinic Foundation, Cleveland, OH, 4Cleveland Clinic Florida, Weston, FL Purpose/Objective(s): The conformality of modern intensity-modulated radiation therapy (IMRT) allows meaningful avoidance of the submandibular glands (SMG) in select patients, thereby potentially improving late xerostomia. This study explores the safety and efficacy of this approach in select node-positive oropharyngeal carcinoma patients, comparing it with traditional level IB coverage. Materials/Methods: From a retrospective IRB-approved registry, patients with T1-2, node-positive HPV-associated oropharyngeal carcinoma treated with definitive IMRT at a single institution from August 2009 to January 2014 were identified. While in the earlier portion of this study, routine avoidance of level Ib was uncommon, in recent years, we routinely avoid clinically uninvolved level Ib, even in the presence of level 2a LN. We reviewed and verified all treatment plans. Mean doses to the SMG were compared for instances where level Ib LN were targeted and when level Ib LN were avoided. We then examined mean doses to the oral cavity as well
Volume 96 Number 2S Supplement 2016 as predictors of late grade 2 xerostomia on a per patient basis, for which patients were divided into three groups: bilateral level IB targeted (A), a single level IB targeted (B) and bilateral IB not targeted (C). We also reviewed every failure location to identify the rate of level Ib regional recurrence. Differences in continuous variables were compared using the Wilcoxon rank-sums test and Pearson’s Chi-square test was used for categorical variables. Results: Among 87 patients and 174 level Ib stations, level Ib was targeted in 95 instances and avoided in 79 instances. Mean SMG doses were significantly lower when level IB was spared compared to where it was targeted (44.5% reduction; 37.5 Gy vs. 67.5 Gy; P < 0.0001). We examined predictors of late grade 2 xerostomia on a per patient basis which included 17 pts in Group A, 61 in group B and 9 in group C. Age, KPS, smoking pack-years, T stage, N stage and type of chemotherapy did not differ amongst the 3 groups. Median doses to oral cavity decreased with increasing level Ib sparing (42.2 Gy (Group A) vs. 35.4 Gy (Group B) vs. 30.7 (Group C); P Z 0.001). Rates of late grade 2 xerostomia were numerically but not statistically lower in group C vs. A and B (11% vs. 59% and 52%, P Z 0.17). With a median follow-up of 29.8 months, no regional failures were identified in levels IB in any patient. Conclusion: Sparing level IB, either contralaterally, or bilaterally, is safe in T1-2, node positive HPV + oropharyngeal cancer. Avoiding level Ib appears to translate into significantly lower SMG doses as well as oral cavity doses. Larger studies are needed to validate these early findings and the impact of this technique on late xerostomia and other functional outcomes. Author Disclosure: N.P. Joshi: None. A. Juloori: None. M.C. Ward: None. H. Qu: None. J.F. Greskovich: None. E. Murray: None. J. Potter: None. A. Dorfmeyer: None. P. Xia: Research Grant; Phillips, Siemens. S. Koyfman: None.
Poster Viewing E337 outcomes including overall survival (OS), local control rate (LCR) and incidence and grades of treatment-related toxicities. Results: A total of 339 patients were analyzed. The median follow-up duration was 64 months ranging from 20-91 months, and male/female was 164/175, respectively. Distribution of primary sites was 258 (76%) in sinonasal cavity, 28 in salivary gland, 22 in oral cavity and 31 patients in others, and histological diagnosis was 141 (42%) in malignant melanoma, 83 in adenoid cystic carcinoma, 63 in olfactory neuroblastoma and 62 patients in others. Overall survival, progression-free and local control rate of all patients at 5 years was 61.2%, 36.8% and 71.2%, respectively. According to histologies, OS and LCR at 5 years was 40.2%, 64.2% in malignant melanoma, 72.9%, 71.5% in adenoid cystic carcinoma, 86.2%, 79.0% in olfactory neuroblastoma and 60.0%, 74.7% in others. Among all patients analyzed, 254 (75%) patients were not suited for photon radiation therapy because doses to OARs exceeded tolerance dose in the evaluation of dose volume histogram. However, OS at 5years of these patients was 65.5%. Regarding the incidence and grades of late toxicities, 34 (10%) patients developed grade 3 or 4 late toxicities such as brain injuries and neuropathy. None experienced grade 5 toxicities. Conclusion: The results of multi-institutional study demonstrated excellent long-term clinical outcomes and acceptable late toxicities, indicating that PBT would be highly effective treatment option for head and neck cancer patients with non-squamous cell histologies. Author Disclosure: T. Akimoto: None. S. Zenda: None. N. Nakamura: None. Y. Demizu: None. T. Okimoto: None. S. Murayama: None. M. Mizumoto: None. H. Sakurai: None. T. Nakamura: None. Y. Kikuchi: None. K. Yamamoto: None. H. Shirato: None. T. Onoe: None.
2828 2827 A Retrospective Multi-institutional Study of Proton Beam Therapy for Head and Neck Cancer With Non-Squamous Cell Histologies T. Akimoto,1 S. Zenda,2 N. Nakamura,1 Y. Demizu,3 T. Okimoto,3 S. Murayama,4 M. Mizumoto,5 H. Sakurai,5 T. Nakamura,6 Y. Kikuchi,6 K. Yamamoto,7 H. Shirato,8 and T. Onoe9; 1National Cancer Center Hospital East, Division of Radiation Oncology and Particle Therapy, Kashiwa, Japan, 2National Cancer Center Hospital East, Chiba, Japan, 3 Hyogo Ion Beam Medical Center, Hyogo, Japan, 4Shizuoka Cancer Center Hospital, Shizuoka, Japan, 5University of Tsukuba, Tsukuba, Japan, 6Southern Tohoku Proton Therapy Center, Koriyama, Japan, 7 Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Japan, 8 Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 9Division of Radiation Oncology, Shizuoka Cancer Center, Shizuoka, Japan Purpose/Objective(s): Head and neck cancers with non-squamous histologies such as adenoid cystic carcinoma and mucosal malignant melanoma tend to show relatively radioresistant profiles and frequently extend along organs at risk (OARs) such as optic nerves and brainstem. Therefore, proton beam therapy (PBT) has been used as an effective non-invasive treatment option, and superior local control rates have been reported. Actually, a systematic review and meta-analysis regarding the studies of nasal cavity and paranasal sinus tumors demonstrated that charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses compared with photon therapy. However, median follow-up duration of patients analyzed in the systematic review was 38 months and patients with squamous cell histology were also included. The purpose of this multi-institutional study is to evaluate the long-term clinical outcomes and toxicities of PBT for head and neck cancer with non-squamous cell histologies to clarify the efficacy of PBT. Materials/Methods: We collected clinical data of patients who had biopsy-proven head and neck cancers with non-squamous histologies and were treated with PBT between 2003 and 2013 in 5 institutions. The study was approved by the institutional review boards. We analyzed clinical
Prospective Comparative Study of Diffusion-Weighted MRI Versus FDG Positron Emission Tomography/Computed Tomography for the Detection of Recurrent Head and Neck Squamous Cell Carcinomas After (Chemo)Radiation Therapy J. Driessen,1 M. Philippens,2 J. Huijbregts,3 F. Pameijer,2 L. Janssen,2 W. Grolman,4 and C. Terhaard2; 1UMCU, Utrecht, Netherlands, 2UMC Utrecht, Utrecht, Netherlands, 3UMCU, Utrecht, Netherlands, 4UMCU, Utrecht, Netherlands Purpose/Objective(s): This prospective study aimed to compare the diagnostic accuracy of diffusion weighted MRI (DW-MRI) to FDG PETCT in the detection of local recurrent head and neck squamous cell carcinomas after (chemo)radiation ((C)RT). Materials/Methods: The institutional ethical committee approved this study and all patients signed written informed consent. Seventy-five patients clinically suspected of local recurrence after (C)RT for laryngeal, hypopharyngeal or oropharyngeal cancer underwent a DW-MRI and an FDG PET-CT. Qualitative assessment of DW-MRI and FDG PET-CT was performed independently by a blinded experienced radiologist and a nuclear medicine physician respectively. Reference standard was the absence of biopsy proven local recurrence within 6 months following imaging. Results: Seventy patients were suitable for analysis. Fifty percent (35/70) had local recurrence. Seventy-three percent (51/70) of the FDG PET-CTs were positive compared to 46% (32/70) of the DW-MRI. FDG PET-CT had an area under the curve 0.71 compared to 0.73 for MR-DWI (P Z 0.85). The sensitivity of FDG PET-CT was 97% compared to 69% for DW-MRI (P Z <0.01). The specificity of FDG PET-CT was 77% compared to 46% for DW-MRI (P Z <0.01). Conclusion: DW-MRI showed similar diagnostic accuracy, superior specificity but inferior sensitivity compared to FDG PET-CT. False negative results will cause delay in the detection of a recurrence and this will potentially influence the chance of successful salvage surgery. Therefore, based on these results, we consider FDG PET-CT to be superior to MRDWI for the detection of early recurrent oropharyngeal, hypopharyngeal or laryngeal cancer after (chemo)radiation. Author Disclosure: J. Driessen: None. M. Philippens: None. J. Huijbregts: None. F. Pameijer: None. L. Janssen: None. W. Grolman: None. C. Terhaard: None.
International Journal of Radiation Oncology Biology Physics
2824
Purpose/Objective(s): Patients with head and neck squamous cell carcinoma (HNSCC) and N3 nodal disease are underrepresented in randomized trials creating uncertainty regarding their optimal management. We utilized a large national registry to evaluate patterns of care and outcome in this N3 population. Materials/Methods: Patients with N3 HNSCC who underwent curative intent treatment between 2004 and 2012 were identified from the National Cancer Data Base. Univariate and multiple-logistic regression were performed to identify predictors of treatment modality. Cox-proportional hazards analysis was used to determine predictors of survival. Results: We identified 3,877 patients with N3 HNSCC treated with curative intent with a median follow-up of 59.4 months. From this cohort, 2,832 patients were treated with radiation alone and 1,045 were treated with combined surgery and radiation. Chemotherapy was delivered to 90.8% of all patients. Patients with lower T-stage, oral cavity sub-site, and younger age were more likely to undergo surgery. Overall survival at 5 years for all patients was 46.3%. Patients treated with radiation alone versus combined surgery and radiation exhibited 5 year OS of 41.8% and 58.3%, respectively (P<0.001). When analyzed by site of the primary tumor, a similar survival advantage for combined surgery and radiation was observed. Predictors for survival included oropharynx sub-site (P<0.001), surgery as part of treatment (P<0.001), use of chemotherapy (P<0.001), treatment at an academic facility (P Z 0.02), lower T-stage (P<0.001), younger age (P<0.001), and lower Charlson-Deyo score (P Z 0.03). Conclusion: This analysis of N3 HNSCC demonstrates that patients who received combined surgery and radiation exhibited the best survival outcomes. However, only 27% of the N3 patients underwent surgery, possibly reflecting the advanced nature of their primary tumors and/or neck disease, poor performance status or other factors. The N3 patients who were selected for surgery were younger, had smaller T-stage tumors and were more likely to have oral cavity primary sites. N3 oropharynx patients had statistically longer survival compared to oral cavity and hypopharynx subsites, and this may reflect the presumed higher incidence of HPV-associated cancers of the oropharynx that carries a more favorable prognosis. This represents the largest cohort of N3 HNSCC patients reported to date and provides opportunities for hypothesis testing to improve future outcomes. Author Disclosure: H.C. Ko: None. J.V. Brower: None. A.M. Baschnagel: None. C.R. Hullett: None. A. Wieland: None. P.M. Harari: None. M.E. Witek: None.
Positron Emission Tomography (PET)eBased Adaptive Radiation Therapy for Locally Advanced Squamous Carcinoma of the Head and Neck: Initial Results of a Prospective Trial D.J. Krauss,1 H. Ye,1 D. Yan,2 Q. Liu,3 J. Liang,4 K. Marvin,1 T. Dimeglio,3 J. Akervall,5 and P. Chen3; 1Beaumont Health, Royal Oak, MI, 2Beaumont Health System, Royal Oak, MI, 3Oakland University William Beaumont School of Medicine, Royal Oak, MI, 4William Beaumont Health System, Royal Oak, MI, 5William Beaumont Hospital, Royal Oak, MI Purpose/Objective(s): To report initial clinical outcomes of a prospective, non-randomized protocol of a PET-based adaptive radiation therapy (RT) approach for patients with locally advanced head and neck squamous carcinoma (HNSCC). Materials/Methods: Patients with a diagnosis of clinically node-positive nasopharyngeal, oropharyngeal, laryngeal, or hypopharyngeal squamous carcinoma were eligible and treated on an IRB-approved protocol. Patients underwent concurrent cisplatin-based chemotherapy with RT. Prescription doses were 70 Gy to sites of gross disease (both primary and nodal) and 60 Gy to at-risk but uninvolved nodal basins. Treatment was delivered in a concomitant boost technique over 35 fractions. Simulation was performed using a thermoplastic mask on a PET-CT simulator and was repeated following treatment fractions 10 and 22. Plans were modified at those points taking into account reduction in disease burden and anatomical changes secondary to weight loss. Additional weekly PET-CT scans were considered optional and acquired on all agreeable patients to monitor response. The primary study endpoint was locoregional failure (LRF). Secondary endpoints included treatment toxicity, distant metastases, and both overall (OS) and disease-free survival (DFS). Toxicity rates were scored using CTCAE v4.0. Results: A total of 25 patients have enrolled, 20 of whom with > 6 months’ follow up form the basis for this analysis. Median follow up time is 15 months (range 6-39). Median age at diagnosis was 61 years (range 48-76). Primary tumor site was oropharynx in 13 patients, oral cavity in 1, supraglottic larynx in 3, hypopharynx in 1, and unknown in 3. 11 patients were p16 positive, 8 negative, and 1 unknown. Primary tumor stage was Tx in 3 patients, T1 in 2, T2 in 7, T3 in 7, and T4 in 1. Nodal stage was N1 in 2 patients, N2b in 13, N2c in 4, and N3 in 1. All patients completed cisplatin based chemotherapy concurrently, with 1 switched to cetuximab mid-treatment due to toxicity. 3 LRF events occurred, yielding a 2-year local control rate of 83%. All LRF events occurred in p16-negative patients. 4 patients developed distant metastases (2-yr rate Z 22.5%), 2 synchronous with LRF. 2-year OS and DFS estimates were 100% and 72.3%, respectively. The most common chronic grade 2 toxicities were dysgeusia (54%), xerostomia (31%), and dysphagia (23%). No chronic grade 3 toxicities have occurred to date. Conclusion: Target volume reduction likely may be safely performed based on radiographic and PET responses occurring during a course of concurrent chemoradiation therapy for node-positive HNSCC. Toxicity rates are favorable, and additional investigation will continue to define the optimal integration of such approaches into disease management paradigms. Author Disclosure: D.J. Krauss: None. H. Ye: None. D. Yan: None. Q. Liu: None. J. Liang: None. K. Marvin: None. T. Dimeglio: None. J. Akervall: None. P. Chen: None.
2825 Patterns of Care and Outcome for N3 Head and Neck Squamous Cell Carcinoma: Review of the National Cancer Data Base H.C. Ko,1 J.V. Brower,1 A.M. Baschnagel,1 C.R. Hullett,1 A. Wieland,2 P.M. Harari,1 and M.E. Witek1; 1Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, 2Department of Otolaryngology, University of Wisconsin Hospital and Clinics, Madison, WI
2826 Sparing Level IB in Node-Positive, Human PapillomaviruseAssociated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis N.P. Joshi,1 A. Juloori,2 M.C. Ward,3 H. Qu,2 J.F. Greskovich, Jr,4 E. Murray,2 J. Potter,3 A. Dorfmeyer,3 P. Xia,2 and S. Koyfman3; 1Taussig Cancer Institute Cleveland Clinic, Cleveland, OH, 2Cleveland Clinic, Cleveland, OH, 3Cleveland Clinic Foundation, Cleveland, OH, 4Cleveland Clinic Florida, Weston, FL Purpose/Objective(s): The conformality of modern intensity-modulated radiation therapy (IMRT) allows meaningful avoidance of the submandibular glands (SMG) in select patients, thereby potentially improving late xerostomia. This study explores the safety and efficacy of this approach in select node-positive oropharyngeal carcinoma patients, comparing it with traditional level IB coverage. Materials/Methods: From a retrospective IRB-approved registry, patients with T1-2, node-positive HPV-associated oropharyngeal carcinoma treated with definitive IMRT at a single institution from August 2009 to January 2014 were identified. While in the earlier portion of this study, routine avoidance of level Ib was uncommon, in recent years, we routinely avoid clinically uninvolved level Ib, even in the presence of level 2a LN. We reviewed and verified all treatment plans. Mean doses to the SMG were compared for instances where level Ib LN were targeted and when level Ib LN were avoided. We then examined mean doses to the oral cavity as well
Volume 96 Number 2S Supplement 2016 as predictors of late grade 2 xerostomia on a per patient basis, for which patients were divided into three groups: bilateral level IB targeted (A), a single level IB targeted (B) and bilateral IB not targeted (C). We also reviewed every failure location to identify the rate of level Ib regional recurrence. Differences in continuous variables were compared using the Wilcoxon rank-sums test and Pearson’s Chi-square test was used for categorical variables. Results: Among 87 patients and 174 level Ib stations, level Ib was targeted in 95 instances and avoided in 79 instances. Mean SMG doses were significantly lower when level IB was spared compared to where it was targeted (44.5% reduction; 37.5 Gy vs. 67.5 Gy; P < 0.0001). We examined predictors of late grade 2 xerostomia on a per patient basis which included 17 pts in Group A, 61 in group B and 9 in group C. Age, KPS, smoking pack-years, T stage, N stage and type of chemotherapy did not differ amongst the 3 groups. Median doses to oral cavity decreased with increasing level Ib sparing (42.2 Gy (Group A) vs. 35.4 Gy (Group B) vs. 30.7 (Group C); P Z 0.001). Rates of late grade 2 xerostomia were numerically but not statistically lower in group C vs. A and B (11% vs. 59% and 52%, P Z 0.17). With a median follow-up of 29.8 months, no regional failures were identified in levels IB in any patient. Conclusion: Sparing level IB, either contralaterally, or bilaterally, is safe in T1-2, node positive HPV + oropharyngeal cancer. Avoiding level Ib appears to translate into significantly lower SMG doses as well as oral cavity doses. Larger studies are needed to validate these early findings and the impact of this technique on late xerostomia and other functional outcomes. Author Disclosure: N.P. Joshi: None. A. Juloori: None. M.C. Ward: None. H. Qu: None. J.F. Greskovich: None. E. Murray: None. J. Potter: None. A. Dorfmeyer: None. P. Xia: Research Grant; Phillips, Siemens. S. Koyfman: None.
Poster Viewing E337 outcomes including overall survival (OS), local control rate (LCR) and incidence and grades of treatment-related toxicities. Results: A total of 339 patients were analyzed. The median follow-up duration was 64 months ranging from 20-91 months, and male/female was 164/175, respectively. Distribution of primary sites was 258 (76%) in sinonasal cavity, 28 in salivary gland, 22 in oral cavity and 31 patients in others, and histological diagnosis was 141 (42%) in malignant melanoma, 83 in adenoid cystic carcinoma, 63 in olfactory neuroblastoma and 62 patients in others. Overall survival, progression-free and local control rate of all patients at 5 years was 61.2%, 36.8% and 71.2%, respectively. According to histologies, OS and LCR at 5 years was 40.2%, 64.2% in malignant melanoma, 72.9%, 71.5% in adenoid cystic carcinoma, 86.2%, 79.0% in olfactory neuroblastoma and 60.0%, 74.7% in others. Among all patients analyzed, 254 (75%) patients were not suited for photon radiation therapy because doses to OARs exceeded tolerance dose in the evaluation of dose volume histogram. However, OS at 5years of these patients was 65.5%. Regarding the incidence and grades of late toxicities, 34 (10%) patients developed grade 3 or 4 late toxicities such as brain injuries and neuropathy. None experienced grade 5 toxicities. Conclusion: The results of multi-institutional study demonstrated excellent long-term clinical outcomes and acceptable late toxicities, indicating that PBT would be highly effective treatment option for head and neck cancer patients with non-squamous cell histologies. Author Disclosure: T. Akimoto: None. S. Zenda: None. N. Nakamura: None. Y. Demizu: None. T. Okimoto: None. S. Murayama: None. M. Mizumoto: None. H. Sakurai: None. T. Nakamura: None. Y. Kikuchi: None. K. Yamamoto: None. H. Shirato: None. T. Onoe: None.
2828 2827 A Retrospective Multi-institutional Study of Proton Beam Therapy for Head and Neck Cancer With Non-Squamous Cell Histologies T. Akimoto,1 S. Zenda,2 N. Nakamura,1 Y. Demizu,3 T. Okimoto,3 S. Murayama,4 M. Mizumoto,5 H. Sakurai,5 T. Nakamura,6 Y. Kikuchi,6 K. Yamamoto,7 H. Shirato,8 and T. Onoe9; 1National Cancer Center Hospital East, Division of Radiation Oncology and Particle Therapy, Kashiwa, Japan, 2National Cancer Center Hospital East, Chiba, Japan, 3 Hyogo Ion Beam Medical Center, Hyogo, Japan, 4Shizuoka Cancer Center Hospital, Shizuoka, Japan, 5University of Tsukuba, Tsukuba, Japan, 6Southern Tohoku Proton Therapy Center, Koriyama, Japan, 7 Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Japan, 8 Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 9Division of Radiation Oncology, Shizuoka Cancer Center, Shizuoka, Japan Purpose/Objective(s): Head and neck cancers with non-squamous histologies such as adenoid cystic carcinoma and mucosal malignant melanoma tend to show relatively radioresistant profiles and frequently extend along organs at risk (OARs) such as optic nerves and brainstem. Therefore, proton beam therapy (PBT) has been used as an effective non-invasive treatment option, and superior local control rates have been reported. Actually, a systematic review and meta-analysis regarding the studies of nasal cavity and paranasal sinus tumors demonstrated that charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses compared with photon therapy. However, median follow-up duration of patients analyzed in the systematic review was 38 months and patients with squamous cell histology were also included. The purpose of this multi-institutional study is to evaluate the long-term clinical outcomes and toxicities of PBT for head and neck cancer with non-squamous cell histologies to clarify the efficacy of PBT. Materials/Methods: We collected clinical data of patients who had biopsy-proven head and neck cancers with non-squamous histologies and were treated with PBT between 2003 and 2013 in 5 institutions. The study was approved by the institutional review boards. We analyzed clinical
Prospective Comparative Study of Diffusion-Weighted MRI Versus FDG Positron Emission Tomography/Computed Tomography for the Detection of Recurrent Head and Neck Squamous Cell Carcinomas After (Chemo)Radiation Therapy J. Driessen,1 M. Philippens,2 J. Huijbregts,3 F. Pameijer,2 L. Janssen,2 W. Grolman,4 and C. Terhaard2; 1UMCU, Utrecht, Netherlands, 2UMC Utrecht, Utrecht, Netherlands, 3UMCU, Utrecht, Netherlands, 4UMCU, Utrecht, Netherlands Purpose/Objective(s): This prospective study aimed to compare the diagnostic accuracy of diffusion weighted MRI (DW-MRI) to FDG PETCT in the detection of local recurrent head and neck squamous cell carcinomas after (chemo)radiation ((C)RT). Materials/Methods: The institutional ethical committee approved this study and all patients signed written informed consent. Seventy-five patients clinically suspected of local recurrence after (C)RT for laryngeal, hypopharyngeal or oropharyngeal cancer underwent a DW-MRI and an FDG PET-CT. Qualitative assessment of DW-MRI and FDG PET-CT was performed independently by a blinded experienced radiologist and a nuclear medicine physician respectively. Reference standard was the absence of biopsy proven local recurrence within 6 months following imaging. Results: Seventy patients were suitable for analysis. Fifty percent (35/70) had local recurrence. Seventy-three percent (51/70) of the FDG PET-CTs were positive compared to 46% (32/70) of the DW-MRI. FDG PET-CT had an area under the curve 0.71 compared to 0.73 for MR-DWI (P Z 0.85). The sensitivity of FDG PET-CT was 97% compared to 69% for DW-MRI (P Z <0.01). The specificity of FDG PET-CT was 77% compared to 46% for DW-MRI (P Z <0.01). Conclusion: DW-MRI showed similar diagnostic accuracy, superior specificity but inferior sensitivity compared to FDG PET-CT. False negative results will cause delay in the detection of a recurrence and this will potentially influence the chance of successful salvage surgery. Therefore, based on these results, we consider FDG PET-CT to be superior to MRDWI for the detection of early recurrent oropharyngeal, hypopharyngeal or laryngeal cancer after (chemo)radiation. Author Disclosure: J. Driessen: None. M. Philippens: None. J. Huijbregts: None. F. Pameijer: None. L. Janssen: None. W. Grolman: None. C. Terhaard: None.