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

NCT05333523 | Recruiting Phase 3 DMC

• 1 other identifier: PRIMO v2.0 dd20250401
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 9

Brief 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

Keywords

Head and neck cancer; Squamous cell carcinoma; Sentinel lymph node biopsy; Elective neck irradiation; FDG-PET

Outcome Measures

Primary Outcomes (2)

• Number of patients with regional recurrence

  Only recurrence in regional lymph nodes in the absence of synchronous recurrence of the primary tumor or initially clinically positive nodes, or second primary head and neck tumors are considered as events

  24 months

• Patiënt reported xerostomia related quality of life as assessed by EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35)

  6 months

Study Arms (2)

Sentinel lymph node biopsy guided selective elective neck irradiation

EXPERIMENTAL

* Sentinel lymph node biopsy * Radiotherapy (IMRT/VMAT with SIB) to the primary tumor with selective elective neck irradiation guided by histopathologic status of the sentinel lymph node(s)

Radiation: Sentinel lymph node biopsy guided selective elective neck irradiation

Standard elective neck irradiation

ACTIVE COMPARATOR

\- Radiotherapy (IMRT/VMAT with SIB) to the primary tumor with standard bilateral elective neck irradiation

Radiation: Standard elective neck irradiation

Interventions

Sentinel lymph node biopsy guided selective elective neck irradiation RADIATION

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.

Sentinel lymph node biopsy guided selective elective neck irradiation

Standard elective neck irradiation RADIATION

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.

Standard elective neck irradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥18 years) with newly diagnosed cT1-4N0-2bM0 squamous cell carcinoma of the oropharynx (HPV-), larynx or hypopharynx, or cT1-4N0-1M0 oropharynx (HPV+) (AJCC TNM 8)
• Histopathological diagnosis of squamous cell carcinoma.
• Adequate staging of the neck including CT or MRI, and 18F-FDG-PET demonstrating no contralateral lymph node metastases.
• Recommendation for curative intent external beam (chemo)radiotherapy made by a multidisciplinary head and neck oncology team (in case of chemoradiotherapy, only patients receiving concomitant platinum-based regimen are eligible).
• Bilateral ENI is indicated according to Dutch consensus guidelines (LPHHRT) (see Appendix 13.1).
• Procedures for SLNB (i.e. tumor accessible for tracer injection, imaging and surgery under general anesthesia) are deemed feasible by the head and neck surgeon.

You may not qualify if:

• Recurrent disease or previous anticancer treatment to the head and neck area (e.g. radical attempt or tumor reductive surgery, neck dissection, neo-adjuvant chemotherapy or radiotherapy) except for endoscopic glottic laser micro surgery.
• Well lateralized oropharyngeal cancers and early stage laryngeal cancers requiring no or unilateral ENI according to Dutch consensus guidelines (LPHHRT)
• Patients receiving concomitant non-platinum-based systemic agents (e.g. cetuximab).
• Patients that qualify for proton therapy and want to be treated accordingly.
• Compromised airway or tracheostomy.
• Any active invasive malignancy within the last 3 years except for early stage basal/squamous cell carcinoma of the skin and incidental finding of stage T1N0M0 prostate cancer.
• Any somatic, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• UMC Utrecht: collaborator
• The Netherlands Cancer Institute: collaborator
• Erasmus Medical Center: collaborator
• Leiden University Medical Center: collaborator
• Maastro Clinic, The Netherlands: collaborator
• Maastricht University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Radiotherapiegroep: collaborator
• Rijnstate Hospital: collaborator
• Medisch Spectrum Twente: collaborator

Study Sites (9)

The Netherlands Cancer Institute

Amsterdam, Netherlands

RECRUITING

Radiotherapiegroep / Rijnstate Ziekenhuis

Arnhem, Netherlands

NOT YET RECRUITING

Medisch Spectrum Twente (MST)

Enschede, Netherlands

NOT YET RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

MAASTRO Clinic / Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, Netherlands

RECRUITING

Related Publications (2)

• van den Bosch S, Takes RP, de Ridder M, de Bree R, Al-Mamgani A, Schreuder WH, Hoebers FJP, van Weert S, Elbers JBW, Hardillo JA, Meijer TWH, Plaat BEC, de Jong MA, Jansen JC, Wellenstein DJ, van den Broek GB, Vogel WV, Arens AIJ, Kaanders JHAM. 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. Clin Transl Radiat Oncol. 2023 Oct 26;44:100696. doi: 10.1016/j.ctro.2023.100696. eCollection 2024 Jan.

  PMID: 37965060 BACKGROUND

• van den Bosch S, Czerwinski M, Govers T, Takes RP, de Bree R, Al-Mamgani A, Hannink G, Kaanders JHAM. Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta-analysis. Head Neck. 2022 Nov;44(11):2621-2632. doi: 10.1002/hed.27175. Epub 2022 Sep 1.

  PMID: 36047597 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinoma, Squamous Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Central Study Contacts

Dr. S. van den Bosch, MD, PhD

CONTACT

+31 (0) 24 361 45 15; sven.vandenbosch@radboudumc.nl

Prof. Dr. J.H.A.M. Kaanders, MD, PhD

CONTACT

+31 (0) 24 361 45 15; j.kaanders@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2022
• First Posted: April 19, 2022
• Study Start: December 6, 2023
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

NL (9)