Dose and Volume De-Escalation for Elective Nodal Regions in Patients With Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer (OPC) Undergoing Curative-Intent Concurrent Chemoradiation (CCRT).

PURPOSE/OBJECTIVE(S) Several de-escalation strategies for HPV-associated OPC have focused on treatment de-intensification to the gross disease. We propose that by systematically reducing the volume and dose to the elective regions, toxicity can be decreased without compromising tumor control. Here we report our long-term results. MATERIALS/METHODS Since 2010, we started our systemic de-escalation approach by first reducing the treatment volumes for the node-negative neck. Retropharyngeal, level IB, high level II, and levels IV-V nodal basins were not included in the subclinical target volume. For the node-positive neck, levels IB and V were not covered unless involved. Using this approach, we have observed high control rates. Starting March 2017, we subsequently reduced the dose to all elective regions to 30 Gy in 15 fractions for all patients with HPV-positive OPC undergoing curative CCRT. This is followed by a cone-down to the gross disease with a 3-5 mm margin delivering 40 Gy in 20 fractions. Patients were required to receive concurrent cisplatin or other chemotherapy. RESULTS From March 2017 to July 2019, 276 consecutive HPV-positive OPC patients underwent CCRT. Median age was 61 (range: 34-87), 90% were male, and 26% had ≥ 15 pack-year of smoking history. Overall, 35% had cT3-4 and 24% had cN2-3 per AJCC 8th Edition. The majority (77%) received high-dose cisplatin and 81% of them had a cumulative dose of 300mg/m2. With a median follow-up of 23 months (range: 1-42), 7 patients (2.5%) developed locoregional recurrence - 6 had disease recurrence in the primary site and/or gross nodes that received 70 Gy and 1 patient had a gross nodal recurrence in the 30 Gy region due to mistargeting. All patients with gross nodal recurrence in the neck were successfully salvaged with surgery. There was no disease recurrence in the subclinical fields receiving 30 Gy or in the omitted radiation fields. Seventeen (6.2%) patients developed distant metastasis. The 2-year locoregional recurrence-free survival was 92.5%, distant metastasis-free survival 90.0%, and overall survival 94.6%. Fifty-six of the 276 patients were also enrolled on an adaptive radiotherapy protocol (NCT03096808) to study modification of the radiation treatment plan during treatment course to account for temporal variations in anatomy, with toxicities and quality-of-life (QoL) metrics evaluated at baseline and follow-up visits. Of the 56 patients on adaptive protocol, 5.8% had feeding tube placement during treatment. No patient had feeding tube dependence at 6 months after radiotherapy. At 2-year follow-up, most of the QoL metrics (pain, social contact, social eating, speech, and swallow) were comparable or superior to baseline measures except for taste and xerostomia. CONCLUSION The systematic de-escalation strategy of volume and dose resulted in favorable locoregional control and acute toxicities profile. This regimen can be adapted for treating a wide range of HPV-associated OPC patients undergoing primary CCRT.