A Phase II Exploratory Trial Evaluating CT-based Mid-Treatment 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, non-randomized phase II single-arm pilot trial aimed to explore favorable mid-treatment nodal response (FMNR) through CT imaging to guide de-escalated chemoradiation therapy (CRT) in patients with favorable risk, node-positive HPV-associated oropharyngeal cancer (OPC). MATERIALS AND METHODS: 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 nodal response: ≥40% reduction warranted de-escalation to 60 Gy, while <40% reduction continued standard CRT. Primary endpoint was 2-year PFS from initiation of dose de-escalated CRT. Tissue tumor modified viral (TTMV) HPV DNA samples and DW-MRI were collected at baseline and week 4. MDADI questionnaires were collected at baseline, 1, 3, 6, 12, and 24 months. RESULTS: Of 39 patients, 26 had FMNR and underwent de-escalated treatment. 13 pts had slow mid-treatment nodal shrinkage and received 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 deescalated dose group and 92.3% for the standard dose patients (95% CI: 0.57-0.99), p=0.96. 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 3-4 toxicity by patient were noted. MDADI composite scores showed minimal clinical important difference (MCID) in the de-escalated group at 1-month post-treatment while the standard group had MCID up to 1-year post-treatment. No patients required feeding tube placement. CONCLUSIONS: De-escalated CRT using CT-based mid-treatment nodal response in favorable risk, node-positive HPV-associated OPC achieved excellent 2-year PFS and OS 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 |