Dose-escalated stereotactic body radiotherapy re-irradiation in patients with recurrent head and neck cancer: a prospective phase 2 study using automated non-coplanar volumetric modulated arc therapy

John Nikitas; Ting Martin Ma; Kiri Cook; Kaley Woods; Amar U Kishan; Vishruth K Reddy; John V Hegde; Maie St John; Wanxing Chai-Ho; Deborah Wong; Fang-I Chu; Carol Felix; Stephen Tenn; Ke Sheng; Michael L Steinberg; Jennifer Y Kadowaki; Jonathan Pham; Dylan P O'Connell; Minsong Cao; Robert K Chin

doi:10.1016/j.radonc.2025.111283

Dose-escalated stereotactic body radiotherapy re-irradiation in patients with recurrent head and neck cancer: a prospective phase 2 study using automated non-coplanar volumetric modulated arc therapy

Radiother Oncol. 2026 Jan:214:111283. doi: 10.1016/j.radonc.2025.111283. Epub 2025 Nov 14.

Authors

John Nikitas¹, Ting Martin Ma², Kiri Cook³, Kaley Woods⁴, Amar U Kishan⁵, Vishruth K Reddy⁵, John V Hegde⁵, Maie St John⁶, Wanxing Chai-Ho⁷, Deborah Wong⁷, Fang-I Chu⁸, Carol Felix⁵, Stephen Tenn⁵, Ke Sheng⁹, Michael L Steinberg⁵, Jennifer Y Kadowaki⁵, Jonathan Pham⁵, Dylan P O'Connell⁵, Minsong Cao⁹, Robert K Chin¹⁰

Affiliations

¹ Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: John.Nikitas@pennmedicine.upenn.edu.
² Department of Radiation Oncology, University of Washington, Seattle, WA, USA.
³ Compass Oncology, Portland, OR, USA.
⁴ Department of Radiation Oncology, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: FChu@mednet.ucla.edu.
⁹ Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA.
¹⁰ Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: RKChin@mednet.ucla.edu.

PMID: 41242408
DOI: 10.1016/j.radonc.2025.111283

Abstract

Background and purpose: Re-irradiation for recurrent head and neck cancer is associated with poor local control and significant treatment-related toxicity. We hypothesized that automated non-coplanar volumetric modulated arc therapy (VMAT) can deliver more conformal, dose-escalated stereotactic body radiotherapy (SBRT) plans than conventional VMAT, which may improve local control without increasing toxicity.

Materials and methods: This was a single-arm, phase II trial that enrolled patients with histologically-confirmed, recurrent head and neck cancer (diameter < 5 cm) with prior head and neck radiotherapy. Patients were planned for treatment using both conventional VMAT (≤40 Gy) and automated non-coplanar VMAT (≤55 Gy) in 5 every-other-day fractions. Non-coplanar VMAT plans were selected if they could deliver higher planning target volume doses without higher organ-at-risk doses. The primary endpoints were one-year local control (compared to the historical rate of 60 % with SBRT using conventional VMAT) and one-year grade ≥ 3 treatment-related toxicity (compared to the historical rate of 20 %). Local control was estimated via Kaplan-Meier method. Toxicities were graded using Common Terminology Criteria for Adverse Events, v5.0.

Results: Twenty-nine patients were enrolled between February 2020-November 2023. Median follow-up was 18.1 months (interquartile range, 10.9-36.3). Non-coplanar VMAT plans were selected over conventional VMAT for all patients. One-year local control was 83.8 % (95 % confidence interval [CI], 62.4-93.6 %). One-year grade ≥ 3 toxicity was 17.4 %.

Conclusion: Automated non-coplanar VMAT achieved superior one-year local control compared to the historical local control rate without higher grade ≥ 3 toxicity. This represents one of the highest local control rates reported in a prospective trial of head and neck re-irradiation and a new approach to head and neck SBRT.

Publication types

Clinical Trial, Phase II

MeSH terms

Adult
Aged
Aged, 80 and over
Female
Head and Neck Neoplasms* / mortality
Head and Neck Neoplasms* / pathology
Head and Neck Neoplasms* / radiotherapy
Humans
Male
Middle Aged
Neoplasm Recurrence, Local* / pathology
Neoplasm Recurrence, Local* / radiotherapy
Prospective Studies
Radiosurgery* / adverse effects
Radiosurgery* / methods
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted / methods
Radiotherapy, Intensity-Modulated* / adverse effects
Radiotherapy, Intensity-Modulated* / methods
Re-Irradiation* / methods