Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus–Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy
Authors: C. Jillian Tsai, Sean M. McBride, Nadeem Riaz, Jung J. Kang, Daniel J. Spielsinger, Todd Waldenberg, Daphna Gelblum, Yao Yu, Linda C. Chen, Kaveh Zakeri, Richard J. Wong, Lara Dunn, David G. Pfister, Eric J. Sherman, Nancy Y. Lee
Journal: JAMA Oncology (2022)

<h3>Importance</h3> Several de-escalation strategies for human papillomavirus (HPV)–associated oropharyngeal carcinoma (OPC) have focused on deintensifying gross disease treatment. Reduction of radiotherapy dose and target volume to subclinical regions may achieve good clinical outcomes with favorable patient quality of life (QOL). <h3>Objective</h3> To determine outcomes from a systematic approach of reducing radiotherapy dose and target volume to the elective treatment regions in patients with HPV-associated OPC undergoing concurrent chemoradiotherapy (CCRT). <h3>Design, Setting, and Participants</h3> This retrospective cohort study included 276 consecutive patients with HPV-positive OPC receiving CCRT from March 1, 2017, to July 31, 2019. Data were analyzed from February 23 to September 13, 2021. <h3>Interventions</h3> Elective nodal and subclinical regions received 30 Gy of radiotherapy in 15 fractions, followed by a cone down of 40 Gy in 20 fractions to gross disease for a total dose of 70 Gy. The high retropharyngeal nodal basins in the node-negative neck and bilateral levels IB and V basins were omitted. <h3>Main Outcomes and Measures</h3> Patients were followed up to evaluate locoregional control as the primary outcome and distant metastasis–free survival, progression-free survival, and overall survival as secondary outcomes. Quality-of-life data were obtained at each visit when feasible. <h3>Results</h3> Among the 276 patients included in the analysis, the median age was 61 (range, 36-87) years; 247 (89.5%) were men; and 183 (66.3%) had less than 10 pack-years of smoking history. Most patients (251 [90.9%]) were White. Overall, 87 (31.5%) had cT3-cT4 disease and 65 (23.5%) had cN2-cN3 disease per the 8th edition of the<i>American Joint Committee on Cancer Staging Manual</i>. One hundred seventy-two patients (62.3%) completed 300-mg/m<sup>2</sup>high-dose cisplatin therapy. During a median follow-up of 26 (range, 21-32) months, 8 patients developed locoregional recurrence, including 7 at the primary site or gross nodes that received a total dose of 70 Gy and 1 with a persistent node not previously identified as gross disease that received a total dose of only 30 Gy. The 24-month locoregional control was 97.0%; progression-free survival, 88.0%; distant metastasis–free survival, 95.2%; and overall survival, 95.1%. During treatment, 17 patients (6.2%) required a feeding tube. At 24 months, most of the QOL composite scores (jaw-related problems, pain, social contact, eating, speech, and swallow) were comparable or superior to baseline measures except for senses, dry mouth, muscular tension, and cognitive functioning, which improved over time but remained marginally worse than baseline. <h3>Conclusions and Relevance</h3> This cohort study found that the evaluated de-escalation strategy for elective regions showed favorable clinical outcomes and QOL profiles. Long-term follow-up data will help affirm the efficacy of this strategy as a care option for treating HPV-associated OPC with primary CCRT.