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Top Line: There are several ongoing attempts to reduce the intensity of treatment for favorable risk, HPV-associated oropharyngeal cancer.

The Study: In 2018, we read about a de-intensified definitive chemoradiation approach being used at MSKCC, and here is a retrospective review of that experience. This attempts to reduce treatment intensity in three ways: reduction or omission of the high-to-intermediate dose CTV around gross disease, reduced dose to elective sites, and selected omission of low-risk nodal regions in the negative neck. In contrast to other de-escalation approaches (e.g., HN002), standard dose (70 Gy in 35 fractions) was given to gross disease. PTV70 consisted of a 5mm expansion from primary and nodal GTVs with no CTV expansion. Chemotherapy was also standard with cisplatin every 3 weeks. The elective CTV encompassed the primary GTV with a 1cm margin as well as the retropharyngeal, retrostyloid, and II-IV nodal levels in the node positive neck. In the node-negative neck, retropharyngeal nodes were omitted but levels II-IV were included. Levels IB and V were not routinely treated. The bilateral neck was treated except for T1 tonsil primaries with up to 2 ipsilateral nodes < 3cm who could receive treatment of the ipsilateral neck alone. The elective treatment volume received 30 Gy in 15 fractions followed by the remaining 40 Gy in 20 fractions to PTV70. Nearly a third of patients (31.5%) also received 50 Gy to an intermediate dose level adjacent to gross disease at physician discretion. Since 2017, 276 patients were treated with this approach. Most patients had base of tongue or tonsil primaries (93.8%) with 31.5% having T3-4 disease and 23.5% having AJCC 8 N2-3 disease. At 24 months, locoregional control was 97%, progression-free survival was 88%, distant metastasis-free survival was 95%, and overall survival was 95%. Of the 3% of patients with locoregional recurrence, all but one had recurrence at GTV sites within the high dose region. A single patient had progression in a node initially thought benign that was within the 30 Gy volume. Only 6.2% of patients required feeding tube placement. 

TBL: This large retrospective experience suggests that lower doses and volumes for microscopic disease may be adequate for HPV-associated oropharyngeal cancer, but as we’ve seen before, randomized trials are needed to safely apply treatment de-intensification strategies. | Tsai, JAMA Oncol 2022

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