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ClinicalTrials.gov ID

NCT04688528

Lead Sponsor

Universitaire Ziekenhuizen KU LeuvenOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

147Estimated

Last Update Posted

Jul 1, 2024Actual

Start Date

Jun 10, 2021Actual

Primary Completion Date

Jan 2027Estimated

Completion Date

Jan 2027Estimated

Official Title

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)

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.

Detailed Description

The risk of lymph drainage to the contralateral side of the neck is limited to maximum 50% of the patients. Moreover, the risk of occult metastases lies between 20 and 40%. As a consequence, the rule of irradiating the contralateral neck with a prophylactic intent ("elective nodal irradiation") in nearly all HNSCC patients roughly doubles the irradiated volume and, hence, increases the risk of developing more frequent and more severe acute and late side effects. The use of sentinel lymph node mapping to assess the contralateral side of the neck should help to determine the individual drainage to the contralateral side of the neck and, in case of drainage, determine which nodes need to be irradiated. The ultimate goal is to reduce the volume irradiated at prophylactic dose to decrease the risk of severe late side effects (volume de-escalation strategy). This strategy is proposed based on the recent completion of a similar study led by the coordinating investigator, together with the head and neck team of the CHU-UCL-Namur, in HNSCC patients without macroscopic nodes in the neck and treated with (chemo)radiotherapy. It was shown that sentinel lymph node mapping helped to safely individualize and de-escalate the elective nodal irradiation volume and significantly reduce the risk of severe late side effects. Anyway, it is unknown if the whole sub-region of the neck containing the sentinel lymph node(s) or the node(s) only should be defined as target volume.

Moreover, the dose used nowadays for elective nodal irradiation, i.e. 50 Gy in fractions of 2 Gy or biologically equivalent, dates back from the 70's. Many arguments (a.o. our better capacity to stage the neck with 3D imaging and the use of concomitant chemotherapy in the majority of node-positive HNSCC) are in favour of dose de-escalation. A multicentric randomized study performed in 100 HNSCC recently showed that the elective dose could be reduced to 40 Gy in fractions of 2 Gy or biologically equivalent, helping to reduce the risk of late dysphagia at 6 months post-radiotherapy. Confirmatory studies need to be performed on larger groups of patients.

The primary aim is to evaluate contralateral regional control (cRC) rate at 2 years in 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 (chemo)radiotherapy applying a dose- and/or volume de-escalation.

• Squamous Cell Carcinoma of Head and Neck

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

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

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.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Universitaire Ziekenhuizen KU LeuvenOTHER

Collaborators

Stichting tegen KankerOTHER

KU LeuvenOTHER

laurien.de.waele@olvz-aalst.be

monique.gilsoul@chuuclnamur.uclouvain.be