KEY POINTS
- Among 10,273 newly diagnosed HNSCC cases, 222 patients (2.2%) presented with de novo metastatic disease. HPV-associated disease accounted for 48 cases, while 174 were classified as HPV-independent; median overall survival for the entire metastatic cohort was only 7 months (95% CI 6.0-8.8).
- Metastatic patterns were broadly similar by HPV status. Oligometastatic disease, defined as 1-5 lesions, occurred in 31% vs 43% of HPV-associated and HPV-independent cases (p=0.21), while lung-only metastases occurred in 83% vs 77% (p=0.46). Mediastinal involvement was more frequent with HPV-associated disease (40% vs 23%, p=0.034).
- Locoregional radiotherapy was delivered to 191/222 patients (86%). Common schedules included 50 Gy/20 fractions (24%), 60 Gy/25 fractions (9%), and 70 Gy/35 fractions (9%); 23% of patients starting locoregional radiotherapy did not complete the planned course.
- Survival remained poor but differed substantially across clinical groups. Two-year overall survival was 33% vs 12% for HPV-associated versus HPV-independent disease, 18% vs 4% with versus without locoregional radiotherapy, and 53% vs 11% with versus without first-line immunotherapy.
- On multivariable analysis, locoregional radiotherapy was associated with longer survival (aHR 0.49, 95% CI 0.32-0.75), as were HPV-associated disease (aHR 0.62, 95% CI 0.43-0.88), ECOG 0-1 (aHR 0.63, 95% CI 0.47-0.86), first-line immunotherapy (aHR 0.52, 95% CI 0.33-0.82) and lung-only metastatic disease (aHR 0.67, 95% CI 0.48-0.95).
- Among patients receiving locoregional radiotherapy, a dose of ≥50 Gy remained associated with better survival (aHR 0.53, 95% CI 0.34-0.83, p=0.006). Conversely, involvement of ≥3 metastatic organs was strongly associated with worse survival (aHR 4.64, 95% CI 1.99-10.80).
- Patient selection is a major limitation: those not receiving locoregional radiotherapy had substantially greater metastatic burden, and treatments spanned 2001-2024, during major changes in systemic therapy and imaging. The study therefore cannot establish that locoregional radiotherapy itself improves survival.
CLINICAL TAKEAWAY
Locoregional radiotherapy may have a role beyond symptom control in carefully selected patients with de novo metastatic HNSCC, particularly those with good performance status and limited systemic disease. The ≥50 Gy signal is clinically interesting, but it remains retrospective and requires prospective validation before it should change treatment sequencing.