Dose De-escalation and Sentinel LN Mapping Driven Radiotherapy of Contralateral Neck in Ipsilateral Node Positive HNSCC

NCT04688528 | Recruiting

• 2 other identifiers: S63909FAF-C/2018/1266
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 10

Brief Summary

The study involves head and neck squamous cell carcinomas (HNSCC) of the oral cavity, oropharynx, larynx or hypopharynx with positive nodes on only one side of the neck and no distant metastasis treated by primary (chemo)radiotherapy. The elective node irradiation on the contralateral side is not always mandatory and the dose may be too high. In this study, we evaluate two strategies: the impact of sentinel lymph node mapping to tailor the volumes to irradiate and the dose reduction.

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

HNSCC; Dose and Volume de-escalation in radiotherapy; sentinel lymph nodes mapping

Outcome Measures

Primary Outcomes (1)

• Contralateral regional control (cRC) rate at 2 years

  The rate of tumor control in the draining nodal regions of the neck.

  From baseline to 2 years after radiotherapy

Secondary Outcomes (7)

• Questionnaire assessing the quality of life of patients with head and neck cancer

  From baseline to every 2 months in the first year and every 3 months in the second year after radiotherapy.

• Questionnaire assessing the quality of life of cancer patients.

  From baseline to every 2 months in the first year and every 3 months in the second year after radiotherapy.

• Normal tissue complication probability (NTCP) gain estimation

  Time from RT up to 2 years after RT.

• Local Control

  Time from RT until local progression or death whichever comes first, up to 2 years after RT.

• Survival

  Time from RT until the occurrence of a new tumor or death whichever comes first, up to 2 years after RT.

Study Arms (3)

Arm A: Unilateral RT

EXPERIMENTAL

If SPECT/CT shows ipsilateral drainage and the tumor does not cross the midline, the subject will automatically be assigned to Arm A, and will receive ipsilateral Radiotherapy with reduced prophylactic dose outside of the macroscopically involved nodes. The contralateral side of the neck will be spared according to the absence of sentinel lymph node drainage.

Radiation: Dose de-escalation and / or Volume de-escalation

Arm B: Whole level

EXPERIMENTAL

If SPECT/CT shows contralateral drainage, the subject will be randomized between 'Whole level' and 'SLN alone'. Arm B 'Whole Level': on the contralateral side of the neck, the whole level(s) containing the draining sentinel lymph node(s) will be irradiated at the reduced prophylactic dose. The ipsilateral side of the neck will be irradiated conform to arm A.

Radiation: Dose de-escalation and / or Volume de-escalation

Arm C: SLN alone

EXPERIMENTAL

If SPECT/CT shows contralateral drainage, the subject will be randomized between 'Whole level' and 'SLN alone'. Arm C 'SLN alone': on the contralateral side of the neck, only the sentinel node(s) will be irradiated at the reduced prophylactic dose. The ipsilateral side of the neck will be irradiated conform to arm A.

Radiation: Dose de-escalation and / or Volume de-escalation

Interventions

Dose de-escalation and / or Volume de-escalation RADIATION

The dose de-escalation and/or volume de-escalation strategy will be individually adapted in function of the draining pattern of sentinel lymph nodes on the contralateral side of the neck.

Arm A: Unilateral RT; Arm B: Whole level; Arm C: SLN alone

Eligibility Criteria

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

You may qualify if:

• Written informed consent given according to ICH/GCP and national/local regulations must be obtained prior to any screening procedures.
• World Health Organization (WHO) performance status 0-1.
• Age ≥ 18 years.
• Patients with a pathologically proven invasive HNSCC, including oral cavity, oropharynx (independently of HPV status), larynx or hypopharynx.
• Decision by Multidisciplinary Tumor Board of primary treatment with radical radiotherapy with or without concurrent chemotherapy (according to the local guidelines).
• Baseline imaging of the neck:
• ≤ 2.5 mm slices CT with iodine injection (independently or during the FDG-PET/CT examination IF acquired in normal diagnostic conditions, i.e. arms along the thorax with diagnostic quality);
• MRI not mandatory but allowed, performed according to centres guidelines;
• FDG-PET/CT.
• Tumor characteristics:
• cT-classification (8th TNM staging): T1(except T1 of glottis)-T4a (or, for p16+ oropharyngeal tumors classified cT4, if criteria are compatible with cT4a-stage of p16- tumors).
• cN-classification (8th TNM staging), as assessed by iodine contrasted CT (or MRI) and FDG-PET:
• i. mandatorily cN0 contralaterally to the primary tumor (or on one side of the neck for midline primary tumors):
• \. smallest diameter \< 5 mm in retropharyngeal level (VIIa);
• \. smallest diameter of Küttner node (level IIa) \< 12 mm;

You may not qualify if:

• Patient has history of:
• radiotherapy or surgery in the neck with potential impact on lymphatic drainage ("violated neck");
• cancer in the last five years (excluding skin basal cell carcinoma, in situ cervix carcinoma and T1 of glottis or lip, completely chirurgically resected (R0) without intervention disturbing cervical lymph drainage);
• Absolute contra-indication to iodine contrast injection, even after proper cortisone and cetirizine pre-medication.
• HNSCC from nose, sinuses, oesophagus, salivary glands or nasopharynx.
• Non-HNSCC histology.
• Positive contralateral neck by node size or positive US-FNAC in dubious nodes.
• Synchronous second malignancy.
• Distant metastasis.
• Tumor crossing the midline without contralateral mapping after 99mTc-nanocolloïd injection.
• Tumor too large to be safely injected, as deemed by the surgeon. In case of doubt, contact may always be taken with the national coordinating investigator to discuss the situation and take a final decision.
• Any psychological disorder or familial, sociological or geographical condition which, in the investigator's opinion, might jeopardise participant's safety or compliance with the protocol.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method.
• Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatments) or vasectomised partner.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Stichting tegen Kanker: collaborator
• KU Leuven: collaborator

Study Sites (10)

ZOL

Genk, Limburg, 3600, Belgium

RECRUITING

Jessa Ziekenhuis

Hasselt, Limburg, 3500, Belgium

RECRUITING

OLV Aalst

Aalst, 9300, Belgium

RECRUITING

UCL Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Institute Jules Bordet

Brussels, Belgium

RECRUITING

University Hospital Gent

Ghent, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

RECRUITING

AZ Sint-Maarten

Mechelen, 2800, Belgium

RECRUITING

CHU-UCL Namur

Namur, Belgium

RECRUITING

AZ Turnhout

Turnhout, 2300, Belgium

RECRUITING

Related Publications (2)

• Daisne JF, Installe J, Bihin B, Laloux M, Vander Borght T, Mathieu I, Lawson G. SPECT/CT lymphoscintigraphy of sentinel node(s) for superselective prophylactic irradiation of the neck in cN0 head and neck cancer patients: a prospective phase I feasibility study. Radiat Oncol. 2014 May 28;9:121. doi: 10.1186/1748-717X-9-121.

  PMID: 24885222 BACKGROUND

• Longton E, Lawson G, Bihin B, Mathieu I, Hanin FX, Deheneffe S, Vander Borght T, Laloux M, Daisne JF. Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):652-661. doi: 10.1016/j.ijrobp.2020.03.021. Epub 2020 Apr 12.

  PMID: 32294522 RESULT

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

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

Study Officials

• Jean-François Daisne, Prof. Dr.

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-François Daisne, MD, PhD

CONTACT

+32-16-34-76-00; jean-francois.daisne@uzleuven.be

Chris Bruyninckx, BA

CONTACT

+32-16-34-76-00; chris.bruyninckx@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 30, 2020
• Study Start: June 10, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (10)