Carbon ion reirradiation compared to intensity-modulated re-radiotherapy for recurrent head and neck cancer (CARE): a randomized controlled trial

Thomas Held, Kristin Lang, Sebastian Regnery, Katharina Weusthof, Adriane Hommertgen, Cornelia Jäkel, Eric Tonndorf-Martini, Johannes Krisam, Peter Plinkert, Karim Zaoui, Christian Freudlsperger, Julius Moratin, Jürgen Krauss, Semi B Harrabi, Klaus Herfarth, Jürgen Debus, Sebastian Adeberg, Thomas Held, Kristin Lang, Sebastian Regnery, Katharina Weusthof, Adriane Hommertgen, Cornelia Jäkel, Eric Tonndorf-Martini, Johannes Krisam, Peter Plinkert, Karim Zaoui, Christian Freudlsperger, Julius Moratin, Jürgen Krauss, Semi B Harrabi, Klaus Herfarth, Jürgen Debus, Sebastian Adeberg

Abstract

Background: Intensity-modulated re-radiotherapy (reIMRT) has been established as a standard local treatment option in patients with non-resectable, recurrent head and neck cancer (rHNC). However, the clinical outcome is unfavorable and severe toxicities (≥grade III) occurred in 30-40% of patients. The primary aim of the current trial is to investigate carbon ion reirradiation (reCIRT) compared to reIMRT in patients with rHNC regarding safety/toxicity as well as local control, overall survival (OS), and quality of life (QoL).

Methods: The present trial will be performed as a single center, two-armed, prospective phase II study. A maximum of 72 patients will be treated with either reIMRT or reCIRT to evaluate severe (≥grade III) treatment-related toxicities (randomization ratio 1:1). The primary target value is to generate less than 35% acute/subacute severe toxicity (≥grade III), according to the Common Terminology Criteria for Adverse Events v5.0, within 6 months after study treatment. The total dose of reirradiation will range between 51 and 60 Gy or Gy (RBE), depending primarily on the radiotherapy interval and the cumulative dose to organs at risk. Individual dose prescription will be at the discretion of the treating radiation oncologist. The local and distant progression-free survival 12 months after reirradiation, the OS, and the QoL are the secondary endpoints of the trial. Explorative trial objectives are the longitudinal investigation of clinical patient-related parameters, tumor parameters on radiological imaging, and blood-based tumor analytics.

Discussion: Recent retrospective studies suggested that reCIRT could represent a feasible and effective treatment modality for rHNC. This current randomized prospective trial is the first to investigate the toxicity and clinical outcome of reCIRT compared to reIMRT in patients with rHNC.

Trial registration: ClinicalTrials.gov ; NCT04185974 ; December 4th 2019.

Keywords: Head and neck cancer; Heavy ions; Intensity-modulated radiotherapy; Local control; Particle therapy; Reirradiation; Squamous cell carcinoma; Toxicity.

Conflict of interest statement

S.A. received grants from Accuray International Sàrl and Merck Serono GmbH outside the submitted work. J.D. received grants from CRI – The Clinical Research Institue GmbH, View Ray Inc., Accuray International Sàrl, Accuray Incorporated, RaySearch Laboratories AB, Vision RT limited, Merck Serono GmbH, Astellas Pharma GmbH, Astra Zeneca GmbH, Solution Akademie GmbH, Ergomed PLC Surrey Research Park, Siemens Healthcare GmbH, Quintiles GmbH, Pharmaceutecal Research Associates GmbH, Boehringer Ingelheim Pharma GmbH Co, PTW-Freiburg Dr. Pychlau GmbH, Nanobiotix A.A. outside the submitted work. The other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Study flow chart for trial subjects. A total of 72 patients will be randomized (1:1) to the experimental arm A (carbon ions) or the control arm B (photons)
Fig. 2
Fig. 2
Schedule of enrolment, interventions, and assessments for the prospective randomized controlled CARE trial (SPIRIT figure)

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