Reducing radiation for head and neck cancer treatment

A Prospective Randomized Phase 2 Study of Dose and Volume De-escalation Radiotherapy With Sentinel Lymph Nodes Mapping for Contralateral Irradiation in Unilaterally Node Positive Head and Neck Squamous Cell Carcinomas (SEMIRAHN)

This study is testing if using a special mapping technique can help reduce the amount of radiation needed for patients with head and neck cancer while still effectively treating their disease.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 147 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (other)
• Drugs / interventions: chemotherapy
• Locations: 10 sites (Genk, Limburg and 9 other locations)
• Trial ID: NCT04688528 on ClinicalTrials.gov

What this trial studies

This study focuses on patients with head and neck squamous cell carcinoma (HNSCC) who have positive lymph nodes on one side of the neck. It evaluates the use of sentinel lymph node mapping to tailor radiation treatment, potentially reducing the volume and dose of radiation delivered to the contralateral neck. By identifying which nodes require irradiation, the study aims to minimize the risk of severe side effects associated with excessive radiation. The approach is based on previous findings that suggest individualized treatment can lead to better outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with pathologically confirmed invasive HNSCC and a performance status of 0-1.

Not a fit: Patients with distant metastasis or those not eligible for radical radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to safer radiation treatment protocols that reduce side effects for patients with HNSCC.

How similar studies have performed: Previous studies have shown success with similar approaches in individualizing radiation treatment for HNSCC patients.

Eligibility criteria

Inclusion criteria

1. Written informed consent given according to ICH/GCP and national/local regulations must be obtained prior to any screening procedures.
2. World Health Organization (WHO) performance status 0-1.
3. Age ≥ 18 years.
4. Patients with a pathologically proven invasive HNSCC, including oral cavity, oropharynx (independently of HPV status), larynx or hypopharynx.
5. Decision by Multidisciplinary Tumor Board of primary treatment with radical radiotherapy with or without concurrent chemotherapy (according to the local guidelines).
6. Baseline imaging of the neck:

   1. ≤ 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);
   2. MRI not mandatory but allowed, performed according to centres guidelines;
   3. FDG-PET/CT.
7. Tumor characteristics:

   1. 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).
   2. 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):

        * 1\. smallest diameter \< 5 mm in retropharyngeal level (VIIa);
        * 2\. smallest diameter of Küttner node (level IIa) \< 12 mm;
        * 3\. smallest diameter \< 10 mm or sum of smallest and largest diameters \< 17 mm in any other level;
        * 4\. no central necrosis ;
        * 5\. maximal standardized uptake value (SUVmax) ≤ 2.2;
        * 6\. in dubious cases (typically 2.2 \< SUVmax \< 4.5 and inconclusive CT or MRI), US-guided FNAC may be required to exclude positive node contralaterally.
      * ii. ipsilaterally positive (if any of the above mentioned criteria is met), i.e. cN1, cN2a, cN2b, ipsilateral cN3b; or cN1 for oropharyngeal p16+ tumors.
   3. No distant metastasis.

Exclusion criteria

1. Patient has history of:

   1. radiotherapy or surgery in the neck with potential impact on lymphatic drainage ("violated neck");
   2. 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);
   3. Absolute contra-indication to iodine contrast injection, even after proper cortisone and cetirizine pre-medication.
2. HNSCC from nose, sinuses, oesophagus, salivary glands or nasopharynx.
3. Non-HNSCC histology.
4. Positive contralateral neck by node size or positive US-FNAC in dubious nodes.
5. Synchronous second malignancy.
6. Distant metastasis.
7. Tumor crossing the midline without contralateral mapping after 99mTc-nanocolloïd injection.
8. 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.
9. 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.
10. 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.

Where this trial is running

Genk, Limburg and 9 other locations

• ZOL — Genk, Limburg, Belgium (RECRUITING)
• Jessa Ziekenhuis — Hasselt, Limburg, Belgium (RECRUITING)
• OLV Aalst — Aalst, Belgium (RECRUITING)
• UCL Saint-Luc — Brussels, Belgium (RECRUITING)
• Institute Jules Bordet — Brussels, Belgium (RECRUITING)
• University Hospital Gent — Ghent, Belgium (RECRUITING)
• Universitaire Ziekenhuizen Leuven — Leuven, Belgium (RECRUITING)
• AZ Sint-Maarten — Mechelen, Belgium (RECRUITING)
• CHU-UCL Namur — Namur, Belgium (RECRUITING)
• AZ Turnhout — Turnhout, Belgium (RECRUITING)

Study contacts

• Principal investigator: Jean-François Daisne, Prof. Dr. — Universitaire Ziekenhuizen KU Leuven
• Study coordinator: Jean-François Daisne, MD, PhD

Conditions: Squamous Cell Carcinoma of Head and Neck, HNSCC, Dose and Volume de-escalation in radiotherapy, sentinel lymph nodes mapping