Personalized Elective Neck Irradiation Guided by Sentinel Lymph Node Biopsy in Larynx and Pharynx Cancer. The PRIMO Study.

Summary

Rationale \| Elective neck irradiation 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. It is expected that elective neck irradiation can be omitted to one or both sides of the neck in 9 out of 10 patients with a clinically negative neck (cN0). For patients with clinically positive ipsilateral nodes (cN1-2b), it is expected that elective irradiation of the contralateral neck can be omitted in 7 out of 10 patients. This will enable better sparing of normal tissues from radiation and result in less permanent long-term 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 sentinel lymph node biopsy guided neck irradiation versus standard bilateral elective neck irradiation in 242 patients with cN0-N2b squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral elective neck irradiation is indicated. Patients randomized to the experimental-arm will undergo sentinel lymph node biopsy. Based on the histopathologic status of the sentinel lymph nodes, patients will receive no elective neck irradiation (if no nodal metastases found at both sides of the neck), unilateral neck irradiation only (if no nodal metastases found at contralateral side of the neck only) or bilateral neck irradiation (if nodal metastases found at both sides of the neck). Patients randomized to the control arm will not undergo sentinel lymph node biopsy but will receive standard bilateral elective neck irradiation. 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.

Conditions

• Laryngeal Squamous Cell Carcinoma
• Hypopharynx Squamous Cell Carcinoma
• Oropharyngeal Squamous Cell Carcinoma

Interventions

RADIATION

Sentinel lymph node biopsy guided selective elective neck irradiation

Patients will undergo sentinel lymph node biopsy. Based on the histopathologic status of the sentinel lymph node(s), selective elective neck irradiation is performed with standard radiation treatment of the primary tumor. There are 3 possible treatment scenarios. 1. Bilateral elective neck irradiation is indicated when lymph nodes at both sides of the neck contain metastases or when sentinel lymph node detection fails. 2. Unilateral elective neck irradiation is indicated when lymph nodes at one side of the neck only contain metastases. 3. Full omission of elective neck irradiation is indicated when lymph nodes at both sides of the neck are free of metastases.

RADIATION

Standard elective neck irradiation

Patients randomized to the control arm will receive the standard of care, according to (inter)national clinical practice guidelines. This will consist of (chemo)radiotherapy to the primary tumor with standard elective neck irradiation in all patients. No sentinel lymph node biopsy will be performed.

Sponsors & Collaborators

• UMC Utrecht

  collaborator OTHER

• The Netherlands Cancer Institute

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Maastro Clinic, The Netherlands

  collaborator OTHER

• Maastricht University Medical Center

  collaborator OTHER

• University Medical Center Groningen

  collaborator OTHER

• Radiotherapiegroep

  collaborator OTHER

• Rijnstate Hospital

  collaborator OTHER

• Medisch Spectrum Twente

  collaborator OTHER

• Radboud University Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-06

Primary Completion

2029-12-01

Completion

2029-12-01

Countries

• Netherlands

Study Locations