Personalized Volume-deescalated Elective Nodal Irradiation in Oropharyngeal Head and Neck Squamous Cell Carcinoma

NCT ID: NCT06563362

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-04

Study Completion Date

2030-02-28

Brief Summary

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Multicentric prospective model-based de-escalation of the elective clinical target volumes (CTV) in radiotherapy of oropharyngeal carcinoma of all stages with the goal to reduce toxicity.

The study investigates the feasibility of this approach as measured by the number of expected out-of-field recurrencies based on the individual patient's state of disease progression and risk factors

Detailed Description

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Local treatment of squamous cell carcinoma (SCC) of the oropharynx can consist of surgery, radiotherapy, or a combination of both. When treated with radiation, the target volume contains not only the primary tumor and clinically detected lymph node metastases. In addition, a large part of the lymph drainage system of the neck which is at risk of harboring occult metastases is irradiated, the so called "elective clinical target volume (CTV)". This elective CTV is currently based on clinical recommendations, but there is limited data and evidence on (occult) lymphatic spread and the required size of the elective CTV. This standard radiotherapy approach is associated with early and late toxicity. Toxicities such as pain, dermatitis, mucositis, but also long-term sequela like swallowing dysfunction, lymphedema and dysgeusia are commonly described, which can even lead to hospitalization or long-term symptoms with subsequent life-quality impairment.

A de-escalation of the treatment could result in less toxicity. Multiple studies have evaluated potential ways to de-escalate treatment and reduce toxicity, such as dose reduction or change of chemotherapeutic agent. Another possible de-escalation strategy, which is pursued here, is to reduce the elective clinical target volume.

A multi-institutional dataset of 598 oropharyngeal SCC patients in whom the detailed patterns of lymph node involvement are reported was collected. The publicly available online platform www.LyProX.org was developed to share and visualize the data. Based on this data, a statistical model of lymphatic tumor progression to perform a statistical analysis to estimate the probability of occult metastases in the clinically negative lymph node levels was developed. The patient's state of metastatic lymphatic progression is described via a hidden Markov model. The state of tumor progression is described by a collection of hidden binary random variables that indicate the involvement of lymph node levels. The model parameters are the probabilities for the tumor to spread to and between lymph node levels and are learned from the dataset. Supporting clinical experience, these statistical calculations can subsequently be used as a basis, to personalize the risk estimation of occult lymph node metastases in newly diagnosed patients based on their distribution of macroscopic metastases, T-stage, and lateralization of the primary tumor. A table with the possible different combinations of clinically observed lymph node involvement and the associated risk of occult lymph node involvement in the remaining, clinically negative lymph node levels (LNL) was created. By interpreting the results from both the statistical analysis and clinical experience, the elective clinical target volume (CTV) was personalized based on a patient's individualized risk profile. As a final measure of quality assurance, the elective CTVs (CTV-3s) constructed in this way have been discussed individually by the investigators, to ensure consistency with data and clinical judgement and experience. This leads to a reduction of irradiated volume and, potentially, to a reduction in early and late toxicity.

The aim of this clinical trial is to determine the safety of the use of a personalized de-escalated elective nodal CTV in oropharynx SCC patients treated with primary (chemo)radiotherapy.

Conditions

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Oropharynx Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Elective target volume de-escalation arm

Target volume de-escalation

Group Type EXPERIMENTAL

De-escalation of irradiated volume

Intervention Type RADIATION

De-escalation of elective clinical target volumes as recommended by a model-based approach

Interventions

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De-escalation of irradiated volume

De-escalation of elective clinical target volumes as recommended by a model-based approach

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Patients with a newly diagnosed (no pre-treatment) squamous cell carcinoma of the oropharynx (i.e. tonsils, base of tongue, oropharyngeal walls, oropharyngeal surface of epiglottis; ICD-10 codes C01, C09, C10), T1-4, N0-3.
* Treatment with definitive (chemo) radiotherapy planned, with elective irradiation of the lymph nodes.
* Age ≥ 18 years, no upper age limit.
* ECOG performance score \< 3.
* History/physical examination within 30 days prior to study inclusion by head and neck surgeon and/or radiation oncologist.
* FDG-PET scan prior to study inclusion. In case of inability to perform or contra-indication, at least contrast enhanced MRI scan obligatory.
* Participants need to provide informed consent.


* Patients with a newly diagnosed (no pre-treatment) squamous cell carcinoma of the oropharynx (i.e. tonsils, base of tongue, oropharyngeal walls, oropharyngeal surface of epiglottis; ICD-10 codes C01, C09, C10), T1-4, N0-3.
* Treatment with definitive (chemo) radiotherapy planned, with elective irradiation of the lymph nodes.
* Age ≥ 18 years, no upper age limit.
* ECOG performance score \< 3.
* History/physical examination within 30 days prior to study inclusion by head and neck surgeon and/or radiation oncologist.
* FDG-PET scan prior to study inclusion. In case of inability to perform or contra-indication, at least contrast enhanced MRI scan obligatory.
* Participants need to provide informed consent.

Exclusion Criteria

* Multilevel primary tumors extending unambiguously beyond the oropharynx into the oral cavity, naso- or hypopharynx
* Distant metastases detected.
* Previous surgery, chemotherapy or radiotherapy treatment for other head and neck cancers.
* Previous surgery in head and neck region affecting the cervical lymphatic system. Dissection of singular lymph nodes for diagnostic purposes before treatment start is allowed.
* Synchronous or previous malignancies. Exceptions are curatively treated basal cell carcinoma or SCC of the skin, or in situ carcinoma of the cervix uteri, low- or intermediate- risk prostate cancer or breast with a progression-free follow-up time of at least 3 years without any remaining disease burden, or other previous malignancy with a progression-free interval of at least 5 years without any remaining active/progressive disease burden regardless whether the treatment is completed or ongoing as a maintenance treatment (e.g. androgen deprivation therapy for prostate cancer).
* Pregnancy or breast feeding
* Any severe mental or psychic disorder affecting decision making and ability to provide informed consent.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role collaborator

University Hospital, Geneva

OTHER

Sponsor Role collaborator

Ospedale Regionale Bellinzona e Valli

OTHER

Sponsor Role collaborator

Réseau Hospitalier Neuchâtelois

OTHER

Sponsor Role collaborator

Kantonsspital Aarau

OTHER

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Panagiotis Balermpas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

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Zurich University Hospital

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Cantonal Hospital Aarau

Aarau, , Switzerland

Site Status RECRUITING

Ospedale Regionale di Bellinzona

Bellinzona, , Switzerland

Site Status RECRUITING

Inselspital Bern

Bern, , Switzerland

Site Status RECRUITING

Hôpitaux universitaires de Genève

Geneva, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Panagiotis Balermpas, MD

Role: CONTACT

+41 44 255 35 67

Debra Lauer, MSc

Role: CONTACT

+41 43 253 28 17

Facility Contacts

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Panagiotis Balermpas

Role: primary

Oliver Riesterer, Prof. Dr. med.

Role: primary

+41 62 838 42 49

Francesco Martucci

Role: primary

Olgun Elicin

Role: primary

+41 31 632 26 32

Sébastien Tran, Dr. med.

Role: primary

+41 22 372 70 90

Other Identifiers

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DeEscO

Identifier Type: -

Identifier Source: org_study_id

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