Personalized neck irradiation guided by sentinel lymph node biopsy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx with a clinically negative neck: (Chemo)radiotherapy to the PRIMary tumor only. Protocol of the PRIMO study

S van den Bosch, R P Takes, M de Ridder, R de Bree, A Al-Mamgani, W H Schreuder, F J P Hoebers, S van Weert, J B W Elbers, J A Hardillo, T W H Meijer, B E C Plaat, M A de Jong, J C Jansen, D J Wellenstein, G B van den Broek, W V Vogel, A I J Arens, J H A M Kaanders, S van den Bosch, R P Takes, M de Ridder, R de Bree, A Al-Mamgani, W H Schreuder, F J P Hoebers, S van Weert, J B W Elbers, J A Hardillo, T W H Meijer, B E C Plaat, M A de Jong, J C Jansen, D J Wellenstein, G B van den Broek, W V Vogel, A I J Arens, J H A M Kaanders

Abstract

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life.

Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment.

Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.

Keywords: Elective neck irradiation; Head and neck cancer; Radiotherapy; Sentinel lymph node biopsy.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2023 The Author(s).

Figures

Fig. 1
Fig. 1
Overview of the trial design.
Fig. 2
Fig. 2
Overview of neck irradiation in the experimental-arm.
Fig. 3
Fig. 3
Radiation dose planning in the experimental-arm. Transverse and coronal views of radiation dose planning with bilateral (A-B), unilateral (C-D) and no neck irradiation (E-F) for a case with cT3N0 laryngeal cancer, illustrating the major dosimetric gains to uninvolved tissues with sentinel lymph node biopsy guided neck irradiation.

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