1. 1 Poster # 1100: Temporal Regression of Cervical Lymph Node in N2-N3 Head and Neck Cancer Treated with Primary Radiotherapy  Chemotherapy: stratified by HPV status S Huang, B O’Sullivan, W Xu, H Zhao, A Chen, K Chan, J Kim, A Bayley, D Goldstein, J Waldron The Princess Margaret Hospital / University of Toronto, Canada Objective: To compare neck response after radiotherapy (RT)  chemotherapy (RT/CRT) for N2-N3 HPV(+) vs. HPV(-) head & neck cancer (HNC):  Temporal regression of gross LN after RT/CRT: K-M Method  Initial radiological involution and ultimate nodal resolution HPV(+) HNC: included 257 p16 positive oropharyngeal cancers (OPC) HPV(-) HNC: included 60 p16 negative OPC, 107 laryngeal, and 69 hypopharyngeal cancers Excluded 171 HPV status unascertained OPCs and 43 post-RT LN un-assessable cases

2. 2 Huang et al.(#1100): Temporal regression of gross LN in HPV(+) vs. HPV(-) HNC Definition:Initial radiological complete response (CR): Involution of the initial gross LN to ≤1.0 cm in CT/MR 8~12 weeks after RT or CRT Percentage of gross LN involution at 8-12 weeks after RT/CRT: (1-size of radiological residual LN / size of initial gross LN) x 100% Elective neck dissection (END) Neck dissection performed ≤20 weeks following RT (by RTOG 1016 protocol) Ultimate LN resolution: Previous gross LN involute to <1.0 cm without adverse features HPV(+) HPV(  ) All HPV+ OPC & HPV(-) HNC* (n=493) CR: 125 (49%) HPV(+): 257HPV(-) : 236 No-CR: 132 (51%)CR: 129 (55%)No-CR: 107 (45%) END 6 (5%) all (-) END 5 (4%) 4 (-); 1 (+) No-END 119 (95%) No-END 124 (96%) END 63 (48%) 17 (+) (27%) No-END 69 (52%) rN 6 (9%) END 25 (23%) 11 (+) (44%) No-END 82 (77%) rN 34 (41%) Assess at 8-12 weeks by CT/MRI CR: all LN ≤1.0cm rN: nodal failure In the no-CR cohort: END was not possible in 17/69 HPV(+) and 35/82 HPV(-) patients

3. 3 Huang et al.(#1100): Temporal regression of gross LN in HPV(+) vs. HPV(-) HNC Residual LN # 12 wks (3m) 24 wks (6m) 36 wks (9m) 48 wks (12m) p HPV(+)257 58% (52-64) 20% (15-26) 10% (6-14) 6% (3-10)0.006 HPV(-)236 56% (50-63) 29% (22-35) 23% (17-29) 19% (13-25) Initial Radiological CR Multivariate OR95% CIp Age (continuous) 1.000.981.020.92 HPV(+) vs. HPV(-) 0.980.681.540.92 Pre-RT Nodal Size 0.560.470.66<0.01 Non-cystic vs. cystic 1.360.832.210.22 T4 vs. T1-3 0.950.611.490.83 RT-alone vs. CRT 0.880.581.330.55 Ultimate LN Resolution Multivariate OR95% CIp Age (continuous)0.990.981.000.10 HPV(-) vs. HPV(+)0.730.580.92<0.001 Pre-RT Nodal Size0.780.710.85<0.001 Non-cystic vs. cystic1.170.911.490.22 T4 vs. T1-30.740.580.940.015 RT-alone vs. CRT0.990.981.000.10 In HPV(+) HNC, lymph node continued to involute to a greater extent beyond 24 weeks Gross LN Duration RC 3-years5-yearsp >=40% involution74%73%<0.001 <40% involution92%91% HPV(+): p16(+) oropharynx (OPC) HPV(-): p16(-) oropharynx (n=60); larynx (n=107); hypopharynx (n=69)

4. 4 Huang et al.(#1100): Temporal regression of gross LN in HPV(+) vs. HPV(-) HNC Take home Message:  The temporal regression of initial gross LN following RT is different for HPV(+) vs. HPV(-) HNC  LN resolution in HPV(+) is a more prolonged process and more reliably achieved beyond 24 weeks  HPV status was not a predictor for initial radiological CR at 8- 12 weeks following RT but was a strong predictor for ultimate LN resolution  Initial gross LN size is a predictor for both initial radiological CR & ultimate LN resolution  Neck response assessment protocols and management approaches may need modification for HPV(+) HNC in terms of timing, size criteria, and use of additional interventions such as END