A Phase 2 Exploratory Trial Evaluating Computed Tomography-Based Midtreatment Nodal Response to Select for De-escalated Chemoradiation Therapy in the Definitive Management of p16+ Oropharyngeal Cancer.
| Publication Type | Academic Article |
| Authors | Kim J, Tam M, Kim S, Solomon E, Hill C, Karp J, Hung C, Oh C, Concert C, Rybstein M, Li Z, Zan E, Goldberg J, Hochman T, Jacobson A, Duvvuri U, Persky M, Persky M, Harrison L, Hu K |
| Journal | Int J Radiat Oncol Biol Phys |
| Date Published | 10/14/2025 |
| ISSN | 1879-355X |
| Abstract | PURPOSE: This prospective, nonrandomized phase 2 single-arm pilot trial aimed to explore favorable midtreatment nodal response (FMNR) through computed tomography (CT) imaging to guide de-escalated chemoradiation therapy (CRT) in patients with favorable risk, node-positive human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). METHODS AND MATERIALS: Eligible patients included p16+ OPC (AJCC 8th: cT1-3 N1 M0, <10 pack-year smokers). All patients were initially planned to receive 70 Gy with concurrent weekly cisplatin 40 mg/m2. At week 4, CT imaging evaluated the nodal response: ≥40% reduction warranted de-escalation to 60 Gy, whereas <40% reduction continued standard CRT. The primary endpoint was 2-year progression-free survival (PFS) from initiation of dose de-escalated CRT. Tumor tissue modified viral (TTMV) HPV DNA samples and diffusion-weighted magnetic resonance imaging (MRI) were collected at baseline and week 4. MD Anderson Dysphagia Inventory questionnaires were collected at baseline, 1, 3, 6, 12, and 24 months. RESULTS: Of 39 patients, 26 had FMNR and underwent de-escalated treatment. Thirteen patients had slow midtreatment nodal shrinkage and received a standard dose. At a median follow-up of 47.4 months, the 2-year PFS was 92.1% (95% CI, 0.72-0.98) for the de-escalated dose group and 92.3% for the standard dose patients (95% CI, 0.57-0.99), P = .96. With a median survival follow-up of 48.9 months (range, 16.7-77.8 months), there were no deaths or distant failures. FMNR was associated with rapid TTMV HPV DNA clearance, reduced TTMV HPV DNA flare, lower baseline and week 4 MRI diffusivity, and higher baseline and week 4 MRI diffusional kurtosis. No differences in acute or late maximum grade 3 to 4 toxicity by patient were noted. MD Anderson Dysphagia Inventory composite scores showed minimal clinically important difference in the de-escalated group at 1-month posttreatment, whereas the standard group had minimal clinically important difference up to 1-year posttreatment. No patients required feeding tube placement. CONCLUSIONS: De-escalated CRT using CT-based midtreatment nodal response in favorable risk, node-positive HPV-associated OPC achieved excellent 2-year PFS and overall survival rates, and represents a potential approach in better selecting patients for treatment de-escalation. |
| DOI | 10.1016/j.ijrobp.2025.09.054 |
| PubMed ID | 41101558 |