Bespoke prescriptions | van den Bosch, J Clin Oncol 2025
Top Line: De-escalation of radiation dose–as opposed to systemic therapy–remains an intriguing option for head and neck cancer.
The Study: One reason is our detection of even small deposits of nodal disease have improved with modern imaging techniques making our “elective” nodal volumes more elective than ever. In the prospective UPGRADE-RT trial, 300 patients receiving definitive radiation alone for cT2-4N0-2M0 H&N mucosal squamous cell carcinoma were randomized 2:1 to standard versus de-escalated elective nodal irradiation. In both arms, gross disease received 68 Gy in 34 fractions over 5.5 weeks (6 fractions per week). In the standard arm, elective nodal volumes received 50 Gy in 34 fractions versus 43 Gy in the experimental arm. Note: that’s <1.3 Gy daily for elective nodes. Also note, an intermediate dose of 60 Gy was allowed in the experimental arm for questionable nodes (read: summed long- and short-axis diameter ≥1.7 cm and SUV ≥1.5 to <2 x background).The primary outcome was physician-scoring of the ability to eat 10 different food categories at one year after treatment, and it was virtually identical–and pretty great–either way at a mean of 92-93 out of 100. The secondary outcome of recurrence within the elective nodal volume within 2 years was 4-5% either way, and, interestingly, 10/13 (77%) of these were synchronous with a primary site recurrence suggesting post-radiation nodal seeding. With no differences found above, the authors performed post-hoc analyses to point to improvements in acute grade 3+ dysphagia and xerostomia-related quality-of-life with dose de-escalation. One has to wonder whether 50 Gy in 34 fractions could also be considered a de-escalation from the more typical 50 Gy in 25 fractions or 56 Gy in 35 fractions. Might there have been a more significant difference in swallowing outcomes had there been a larger difference in standard and de-escalated ENI doses? Finally, could the use of an intermediate dose level in the de-escalated arm have partially negated the benefit of dose de-escalation?
TBL: In UPGRADE-RT, reducing the dose for elective nodal irradiation from 50 Gy o 43 Gy in 34 fractions did not significantly improve swallowing but also didn’t increase the risk of failure in the elective volume. | van den Bosch, J Clin Oncol 2025