KEY POINTS
- A multidisciplinary international panel of radiation, clinical, and medical oncologists evaluated 28 unresolved questions across four settings: locally advanced squamous cell carcinoma, recurrent or metastatic squamous cell carcinoma, locally advanced nasopharyngeal carcinoma, and recurrent or metastatic nasopharyngeal carcinoma.
- Fifteen complete expert responses were analyzed using a weighted Borda ranking system. Experts also described an ideal trial for the highest-priority question in each setting, considering clinical impact, feasibility, patient selection, innovation, and safety.
- In locally advanced squamous cell carcinoma, risk-based prognostic and predictive assessment at diagnosis ranked first with a Borda score of 94. Tailoring chemoradiotherapy after perioperative immunotherapy ranked second with a score of 87, ahead of treatment selection for cisplatin-unfit patients.
- Proposed curative trials should integrate established and emerging biomarkers—including HPV or p16 status, PD-L1, circulating tumor DNA, and circulating HPV DNA—with event-free survival, disease-free survival, functional outcomes, and quality of life.
- In recurrent or metastatic squamous cell carcinoma, the leading questions concerned locoregional radiotherapy after response to first-line treatment in de novo metastatic disease and the sequencing of ablative radiotherapy with immunotherapy in PD-L1-positive oligometastatic disease.
- For locally advanced nasopharyngeal carcinoma, experts prioritized biomarker-guided intensification for high-risk disease and de-escalation after a favourable response to induction chemoimmunotherapy. Baseline and longitudinal EBV-DNA kinetics were considered central, although assay harmonization remains necessary.
- In metastatic nasopharyngeal carcinoma, priorities included fractionation and target-volume selection for primary-site consolidation after systemic response, followed by sequencing of metastasis-directed radiotherapy. Topic selection was not based on a systematic review, European experts were overrepresented, and the formal modified-Delphi consensus process had not yet begun.
CLINICAL TAKEAWAY
The paper is a research agenda, not a treatment guideline. Its most useful message is that future head and neck trials should stop testing uniform combinations and instead use biological response, disease burden, and patient-reported outcomes to determine who needs intensification, de-escalation, or consolidative radiotherapy.