De-Intensification Radiotherapy Postoperative Head Neck

Last updated: March 13, 2026
Sponsor: University of Erlangen-Nürnberg Medical School
Overall Status: Completed

Phase

2

Condition

N/A

Treatment

A: De-Intensification RT primary tumor region

C. De-Intensification RT primary tumor region AND contralateral lymph nodes

B: De-Intensification RT contralateral lymph nodes

Clinical Study ID

NCT02528955
DIREKHT
  • Ages > 18
  • All Genders

Study Summary

In patients with squamous cell carcinoma of the oral cavity, the oropharynx and larynx with >= pT3 and or pN+ postoperative radio - or radiochemotherapy is the standard of care. Postoperative radiochemotherapy is indicated in patients with multiple lymph node metastasis, lymph node metastasis with extracapsular spread and or R1/2 resection.

Locoregional control rates are over 80% after surgery and radio(chemo)therapy. But many patients suffer from therapy-related long-term side-effects, like xerostomia, dysphagia, fibrosis, trismus etc.

The aim of this study is to investigate if depending on primary tumor stage, quality of resection ( resection margin) and number of lymph node metastasis and performed neck dissection an adapted de-intensified dose- and target volume concept may be performed without reducing locoregional-control but with reducing radiotherapy-related side-effects.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Histologic proven squamous cell carcinoma of the oral cavity/larynx/oro- orhypopharynx

  2. Postoperative tumor status:

  • Oral cavity, oropharynx or larynx: pT1-3, pN0-pN2b

  • Hypopharynx: pT1-2; pN1

  1. Patients that fulfill one or both of the following criteria:

  • ≤ pT2, R ≥ 5 mm, L0, Pn0

  • ≤ 3 ipsilateral lymph node metastases (if a contralateral adequate neckdissection is performed, no contralateral neck dissection is recommended inpatients with strictly ipsilateral localised tumors of the oropharynx or oralcavity)

  1. R0-Resection (resection margin ≥ 1mm)

  2. No distant metastasis cM0

  3. age ≥ 18 years, no upper age limit

  4. ECOG ≤ 2

  5. Patients that understood protocol contents and are able to behave according toprotocol

  6. Signed study-specific consent form prior to therapy

  7. In case of indicated simultaneous chemotherapy:

  • adequate bone marrow function (leucocytes > 3,5x10^3, platelets > 100x 10^3,hemoglobin > 10g/dl

  • sufficient liver function: bilirubin < 2,0mg/dl, ALT, AST < less than 3 timesupper limit of normal

  • sufficient renal function: normal serum creatinine, glomerular filtration rate > 60ml/min

Exclusion

Exclusion Criteria:

  1. pregnant or lactating/nursing women

  2. fertile patients that are not willing to use highly effective methods ofcontraception (per institutional standards) during treatment

  3. Any condition potentially hampering compliance with the study protocol and follow-upschedule

  4. On-treatment participation on other trials

  5. R1 or R2 resection status

  6. pN2c and pN3

  7. cM1

  8. prior radiotherapy in the head and neck region , prior chemo- or immunotherapy (neoadjuvant/induction)

  9. time between surgery and beginning of radio(chemo)therapy > 6 weeks

  10. Prior (> 4 months before beginning of radio(chemo)therapy) neck dissection

  11. In case of indicated simultaneous chemotherapy:

  • reduced hearing ability (especially upper frequency range)

  • known dihydropyrimidindehydrogenase (DPD) deficiency

  • simultaneous therapy with brivudin or other DPD-inhibitors

  • uncontrolled serious disease, including physical and mental diseases, forexample within last 6 months:instable angina pectoris, heart attack, seriouscardiac dysrhythmias, stroke, serious carotid stenosis, neurologic orpsychiatric disorders including epilepsy, dementia, psychosis; uncontrolledinfection; liver cirrhosis Child B or C, severe hepatic impairment; severeblood count changes; severe renal impairment, HIV

Study Design

Total Participants: 200
Treatment Group(s): 3
Primary Treatment: A: De-Intensification RT primary tumor region
Phase: 2
Study Start date:
October 01, 2014
Estimated Completion Date:
September 30, 2025

Study Description

The study is a non-randomized phase-II trial. In total there are 3 therapy arms.

Patients are assigned to one of these therapy arms according to the tumor status and the quality and kind of surgery. The aim of this study is to investigate if a risk-adapted dose- and target-volume concept in clearly defined patient groups is possible to individualize postoperative radiotherapy without reducing locoregional-control but with reducing radiotherapy-related side-effects.

There are two main issues to investigate:

  1. Dose prescription in primary tumor region:

    In this study it should be investigated if a dose reduction to 56 Gy in the primary tumor region is possible, if the resection margin is >= 5mm, tumor stage is <=pT2 and if there are no other risk factors like perineural spread or peritumoral lymphangiosis.

  2. Target volume definition in elective lymph node levels

    It should be investigated if ipsilateral cervical lymph irradiation alone allows adequate locoregional control in selected patients:

    ipsilateral lymph node metastasis <=3 and contralateral pN0 (adequate contralateral selective neck dissection performed) or contralateral cN0 (in patients with strictly ipsilateral localized tumors of the oral cavity or oropharynx)

    Considering these facts 3 therapy groups are possible:

    A:

    Criteria:

    • pT2, R ≥ 5 mm, L0, Pn0

      • 3 lymph node metastasis or patients with < 3 ipsilateral lymph node metastasis and a bilateral primary tumor without adequate contralateral neck dissection

    Intervention:

    • Reduction of radiation dose in the primary tumor region to 56 Gy,

    • Elective Radiotherapy of both neck sides

    B:

    Criteria:

    •> pT2 and/or R < 5mm and/or L1 and/or Pn1

    •≤ 3 ipsilateral lymph node metastasis (and contralateral pN0 (>= 6 resected lymph nodes) or contralateral cN0 in patients wih strictly ipsilateral localised ( >= 5 mm distance from midline) cancer of the oral cavity or oropharynx

    Intervention

    •No dose reduction in primary tumor region (prescribed dose in primary tumor region: 64 Gy)

    •Reduction of target volume: only elective radiotherapy of the ipsilateral neck, no contralateral neck irradiation

    C:

    Criteria

    • pT2, R ≥ 5 mm, L0, Pn0

    • 3 ipsilateral lymph node metastasis (and contralateral pN0 (>= 6 resected lymph nodes) or contralateral cN0 in patients wih strictly ipsilateral localised ( >= 5 mm distance from midline) cancer of the oral cavity or oropharynx

    Intervention

    •Reduction of radiation dose in the primary tumor region to 56 Gy, AND

    •Reduction of target volume: only elective radiotherapy of the ipsilateral neck, no contralateral neck irradiation

    In all arms the dose prescription for the lymph node regions is as follows:

    •elective lymph node level (either ipsi- or bilateral): 50 Gy

    •lymph node level with lymph node metastasis without extracapsular extension: 56Gy

    • lymph node level with lymph node metastasis with extracapsular extension: 64 Gy

    In all arms simultaneously chemotherapy is recommended in the following cases:

    • lymph node metastasis with extracapsular extension •>= 3 lymph node metastasis

    All patients are stratified according to HPV status.

    Additional investigations:

    • swallowing endoscopy (before, 6 and 24 months after radiotherapy)

    • translational research (especially individual radiosensitivity, immunologic parameters in peripheral blood during treatment)

    • QoL

Connect with a study center

  • Dept. of Radiooncology, University Hospital

    Erlangen, 91054
    Germany

    Site Not Available

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