The Efficacy of Reduced Radiotherapy Dose for Human Papilloma Virus-associated (HPV+) Squamous Cell Carcinoma (SCC) of the Oropharynx Treated with Concurrent Chemoradiation

Abstract

HPV+ oropharyngeal SCC (OPSCC) is chemo- and radiation therapy (RT) sensitive, carrying a better prognosis (Gillison, ASTRO 2009). We investigated whether lower RT doses could eradicate gross nodal disease as effectively as standard RT doses (≥70Gy) in HPV+ OPSCC. We retrospectively reviewed T1-4N2-3 HPV+ OPSCC patients treated with definitive chemoRT on IRB approved studies with ≥1 year follow-up. In-situ hybridization for high-risk HPV subtypes was positive in all cases. ChemoRT consisted of once or twice daily RT with concurrent, standard dose CDDP/5FU wk 1, 4 or CDDP wk 1, 4, 7. All patients previously underwent CT simulation and conventional planning. Conventional fields consisted of a single isocenter, shrinking field technique (opposed laterals, AP supraclav, supplemental electrons). Because neck dissection was planned, gross nodal disease was not intentionally included in the high-dose, boost fields. The pre-RT, diagnostic FDG PET-CT scan was co-registered to the simulation CT scan to aid in lymph node gross tumor volume (LNGTV) delineation. LNGTV was contoured using MIMVista software and exported to Pinnacle for composite plan dose-volume analysis. Mean dose and D95 for each LNGTV was recorded. Student's t-test was used to compare mean dose/D95 anto level II vs. levels III-IV- retropharyngeal (RP) nodes. Nineteen patients with 43 LNGTVs were included. Median age was 61; median follow-up was 16 mos. Never, former, and active smokers comprised 47%, 58% and 5%, respectively. Primary tumor site was base of tongue (11 pts) and tonsil (8 pts). The number of level II, III, IV and RP nodes that were involved were 28, 11, 1 and 3, respectively. The mean LNGTV was 7.7cc (range: 0.8-22.3cc) and 3.8cc (range: 0.9-13.5cc) for level II, and level III-IV-RP nodes, respectively. The mean dose to the level II and level III-IV-RP LNGTV was 70.0Gy (range: 56.2-75.9Gy) and 62.8Gy (range: 55.3-69.5Gy), respectively. The mean D95 to the level II and level III-IV-RP LNGTV was 66.0Gy (range: 46.8-74.2Gy) and 58.9Gy (range: 45.8-68.2Gy), respectively. The mean dose and D95 for level III-IV-RP nodes was significantly lower than level II nodes (p = 0.0003). The D95 was ≤60Gy in 15 of 43 (35%) LNGTVs and ≤55Gy in 7 LNGTVs (16%). All patients achieved a complete response on follow-up PET/CT, and remain disease free. No patients required post-RT neck dissection. HPV+ OPSCC LNs respond to RT doses significantly lower than standard definitive doses when combined with concurrent, high dose CDDP/5FU or CDDP. A randomized study to compare de-escalated RT (55-60Gy) vs. standard dose (70Gy) with concurrent CDDP-based chemotherapy should be considered.