Brachytherapy (Interventional Radiotherapy) for Squamous Cell Carcinomas of the Nasal Vestibule: Optimization of Dose and Technique (BRAVO)

Brachytherapy (Interventional Radiotherapy) for Squamous Cell Carcinomas of the Nasal Vestibule: Optimization of Dose and Technique A Multicenter Prospective Registration Study Endorsed by HNS GEC-ESTRO WG

Rationale: Primary brachytherapy (also known as Interventional Radiotherapy, IRT) achieves high cure rates in cancer of the nasal vestibule (CNV) while preserving nasal aesthetics and function. In our recently published nationwide multicenter study, brachytherapy (BT) increased nose preservation probability from 61 to 82 % compared to external beam radiotherapy (EBRT). Although late toxicity was more common following BT, it was predominantly CTCAE grade 1-2 and deemed acceptable given the substantial benefit in local control and nose preservation.

However, a notable finding of our study was the substantial variation in BT practice, including implantation techniques, dose prescriptions, and treatment planning. Although this analysis covers one of the largest series of CNV patients to date, patient numbers were insufficient to reliably compare the efficacy of the different application/implantation techniques and doses. The retrospective design of the study proved inappropriate for a detailed analysis of the dose-volume data, which is necessary to correlate implantation and dose data to outcome. As the integral brachytherapy dose, as well as the dose inhomogeneity in tissue may vary widely depending on how the dose is prescribed, simple prescription doses are insufficient to characterize a brachytherapy plan comprehensively.

Given the excellent disease control achieved with BT, optimizing aesthetic and functional outcomes while minimizing toxicity becomes increasingly important. Therefore, to optimize BT treatment for CNV and facilitate its wider adoption, detailed prospective data collection on treatment parameters, dose plans, toxicity (both physician-reported and patient-reported), oncological outcomes, and functional results is necessary. This study is designed as a non-comparative, descriptive prospective registry aimed at systematically documenting current international practice in brachytherapy for cancer of the nasal vestibule.

Objective: To prospectively describe BT treatment techniques, parameters, oncological outcomes, acute and late toxicity and patient satisfaction; and to correlate these outcomes with treatment parameters. Specifically, to establish dose-response relationships for oncological control, toxicity, and functional outcomes.

Study design: Prospective observational multicentre registration study. Study population: Adults with a squamous cell squamous cell carcinoma of the nasal vestibule, considered suitable for primary brachytherapy.

Main study parameters/endpoints: To describe treatment techniques, dose prescriptions and brachytherapy dose plans in terms of dose-volume parameters. Oncological outcomes include details on recurrence and cancer-specific survival. Toxicity, patient satisfaction, and QoL will be assessed with validated patient questionnaires as through applicable CTCAE (physician based).

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoma Nasal Vestibule

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Casper Reijnen, MD, PhD; Phone Number: 0031243614505; Email: casper.reijnen@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • Radboud University Medical Center
    • Contact: Casper Reijnen, MD, PhD; Phone Number: 0031243614505; Email: casper.reijnen@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients referred for primary brachytherapy for cancer of the nasal vestibule in the participating institutes will be asked to participate.

Description

Inclusion criteria:

• Aged 18 years or older
• Rome stage 1-4 / Wang Stage T1 -T3
• Staging of the neck by ultrasound/FNAC and/or (FDG-PET)CT and/or MRI is performed
• Brachytherapy with curative intent as sole treatment for the primary tumor
• Suitable to undergo brachy procedure, based on clinical judgment

Exclusion criteria

• Other primary tumor, except bcc skin or curatively treated cancer > 3 years before inclusion
• Previous radiotherapy to the treated area
• Distant metastasis
• Inability to comply with study procedures, including filling out treatment related questionnaires and to comply with scheduled follow-up visits
• Non-squamous cell histology
• Combinations with systemic therapy
• Combination to EBRT and brachytherapy to primary tumor

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

ll patients referred for primary brachytherapy for cancer of the nasal vestibule; Newly diagnosed CNV patients, eligible according to the study in- and exclusion criteria. Patients will receive the same treatment and have the same follow-up as patients who do not participate in the study. Eligible patients will be asked to consent to the use of their tumor- and treatment data for the purpose of the study and to fill out QoL- and functional and cosmetic evaluation questionnaires at pre-specified timepoints at start of, during, and after treatment. Recruitment will be organized through the treating physician, who will obtain written informed consent, given according to standard research procedures. Patients will be accrued from participating institutions, recruited from the Dutch Head& Neck Cancer Working Party and the GEC-ESTRO H&N brachy workgroup (Groupe Européen de Curiethérapie and the European Society for Radiation Therapy and Oncology)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year local disease control	The primary endpoint is 3-year local disease control, defined as absence of histologically or radiologically confirmed local recurrence within the treated nasal vestibule region, measured from start of brachytherapy until recurrence or last follow-up.	3 years
3-year freedom from (partial) nose amputation	The second primary endpoint is 3-year freedom from (partial) nose amputation, defined as absence of histologically or radiologically confirmed local recurrence requiring (partial) removal of the nose, measured from start of brachytherapy until recurrence or last follow-up	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CTCAE toxicity scoring	CTCAE 5.0 toxicity scoring for skin, mucosa, septum (cartilage) assessed at baseline, end of treatment, 3 months, 6 months and annually up to three years after treatment. These will be assessed by the treating physician during clinical follow-up visits.	3 years
Toxicity scoring by patients	Pain, dryness/mucous secretion , nasal bleeding , nasal occlusion, synechiae, loss of smell/taste (applicable PRO-CTCAE components: anosmia, dysgeusia, pain, rhinorrhea, skin hyper/hypopigmentation).	3 years
Patient satisfaction	Patient satisfaction measured using validated questionnaires filled in by the patients at baseline, 3 months, 12, 24 and 36 months (NAFEQ questionnaire).	3 years
3-year regional and distant control	Defined as absence of histologically or radiologically confirmed regional recurrence (regional lymph node metastasis) or distant recurrence within the treated nasal vestibule region, measured from start of brachytherapy until recurrence or last follow-up.	3 years
Overall survival	measured from start of brachytherapy until recurrence or last follow-up	3 years
Patient satisfaction (2)	Patient satisfaction measured using validated questionnaires filled in by the patients at baseline, 3 months, 12, 24 and 36 months (ROE questionnaire).	3 years

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Erasmus Medical Center; Institut Català d'Oncologia; University of Luebeck; University Hospital, Zürich; Institut de Cancérologie de Lorraine; University of Navarra; University Hospital Erlangen; The Greater Poland Cancer Centre; San Giovanni Addolorata Hospital; Maastro Clinic, The Netherlands; UMC Utrecht, Utrecht, the Netherlands; Atrys Health; Hospital Clínica Benidorm; Amsterdam UMC; Saint John's Cancer Center of Lublin

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2034

Study Registration Dates

• First Submitted: August 26, 2026
• First Submitted That Met QC Criteria: August 31, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: brachytherapy; interventional radiotherapy; carcinoma nasal vestibule
• Other Study ID Numbers: 2026-19203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No