1. www.siteman.wustl.edu A Phase II Study to Evaluate the Safety and Toxicity of Sparing Radiation to the Pathologic N0 Side of the Neck in Squamous Cell Carcinoma: Quality of Life Outcomes Christopher R. Spencer 1, H. Gay 1, T. DeWees 1, T. Wildes 3, L. S. Michel 3, D. Adkins 3, B. H. Haughey 2, B. Nussenbaum 2, Wade L. Thorstad 1 1 Department of Radiation Oncology, 2 Division of Head and Neck Surgical Oncology, 3 Division of Oncology, Washington University School of Medicine, St. Louis, MO Purpose/Objectives At Washington University we began utilizing IMRT in 1997 for Head and Neck Squamous Cell Carcinoma (HNSCC). We previously showed reducing radiotherapy volumes improves quality of life (QoL) while maintaining locoregional control for patients with oral cavity, oropharynx, hypopharynx, larynx and unknown primary HNSCC. In that study the contralateral low neck was treated electively. Here we advance volume reduction another step and review its effect on patient reported QoL. The goal of this study was to evaluate safety and toxicity of using postoperative IMRT to eliminate treatment to the pathologically N0 side(s) of the neck. Accrual began in 2007 and completed in 2014. The trial fully accrued 73 patients and 65 had evaluable QOL data. Median follow up was 22 months for both trial and matched cohort patients. More patients in the matched cohort received chemotherapy and had N2c neck disease; otherwise there were no differences in clinicopathologic variables between groups. There was no baseline difference in any QOL domain or xerostomia between the two groups. Overall global QOL (59.1 v. 53.8; p=0.036) and xerostomia (60.5 v. 55.4; p=0.024) were improved on trial compared to standard of care. There was a trend for improvement in the emotional (64.2 v. 61.8; p=0.08) and functional (65.9 v. 63.1; p=0.06) domains. Fewer patients treated on trial, sparing the pN0 neck, required a temporary feeding tube (38% v. 54%; p=0.046). Results Patients with pathologically-proven tumors of the oral cavity, oropharynx, larynx, or hypopharynx treated with surgical resection and with PN0 status of one (or both) side(s) of the neck were eligible. Patients were also required to have high-risk features indicating radiation therapy at the primary site or involved neck. The CTV1 and CTV2 were treated to 66 Gy and 54 Gy in 33 fractions or 60 Gy and 52 Gy in 30 fractions. The primary endpoint was local control in the unirradiated neck. Secondary endpoints included patient-reported quality of life (QOL) outcomes related to dysphagia and xerostomia, locoregional control, disease free and overall survival. QOL data was compared to a matched cohort of patients treated with standard of care IMRT over the same time frame on an institutional prospective registry. Fisher’s exact test was used to test for association between clinical variables and cohorts. The previously validated 20 question MD Anderson Dysphagia Inventory and 8 question University of Michigan Patient-reported Xerostomia Questionnaire were used to collect swallowing and xerostomia QOL data. Wilcoxon rank sum test was used to test the significance between trial participants and the matched cohort in emotional, physical, functional, xerostomia, and global QOL domains. These were scaled from 0 to 100 with 0 being the worst QOL and 100 the best QOL. Materials and Methods Elimination of radiotherapy to the pN0 side(s) of the neck is associated with improved patient-reported quality of life and xerostomia. Efficacy data will be presented after patient follow- up matures. Conclusions

2. www.siteman.wustl.edu Eligibility Criteria Pathologically Diagnosed Squamous cell carcinoma of the; Oral Cavity, Oropharynx, Hypopharynx, Larynx, or Unknown Primary Cancer Treated with surgical resection with one (or both) side(s) of the neck undergoing a lymph node dissection demonstrating a pathologically N0 neck And have an indication for radiotherapy at the primary site or neck consisting of any of the below characteristics Close Margin (< 0.5 cm) Positive Margin Perineural Invasion LVSI Metastatic disease in more than one lymph node or lymph node group Extracapsular extension in any lymph node Any other risk factor thought to be an indicator for radiotherapy after discussion at multidisciplinary tumor board. No previous head and neck cancer or head and neck surgery, Age 18+

3. www.siteman.wustl.edu T2N1 Oropharynx patient treated on protocol eliminating the contralateral pN0 neck T3N1 Oropharynx patient treated with a standard IMRT Head and Neck treatment Plan

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5. Study Participants Reported Improved Xerostomia and Global QOL

6. www.siteman.wustl.edu Study Participants also had a decreased rate of PEG tube dependence

7. www.siteman.wustl.edu Conclusions Eliminating Radiotherapy to the pathologically N0 Neck improves patient reported xerostomia and quality of life. It also reduces PEG-Tube dependency rates. After follow up matures safety and efficacy data will be presented.