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:
1. Histologic proven squamous cell carcinoma of the oral cavity/larynx/oro- or
hypopharynx
2. Postoperative tumor status:
- Oral cavity, oropharynx or larynx: pT1-3, pN0-pN2b
- Hypopharynx: pT1-2; pN1
3. 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 neck
dissection is performed, no contralateral neck dissection is recommended in
patients with strictly ipsilateral localised tumors of the oropharynx or oral
cavity)
4. R0-Resection (resection margin ≥ 1mm)
5. No distant metastasis cM0
6. age ≥ 18 years, no upper age limit
7. ECOG ≤ 2
8. Patients that understood protocol contents and are able to behave according to
protocol
9. Signed study-specific consent form prior to therapy
10. 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 times
upper limit of normal
2. fertile patients that are not willing to use highly effective methods of contraception
(per institutional standards) during treatment
3. Any condition potentially hampering compliance with the study protocol and follow-up
schedule
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, for example
within last 6 months:instable angina pectoris, heart attack, serious cardiac
dysrhythmias, stroke, serious carotid stenosis, neurologic or psychiatric
disorders including epilepsy, dementia, psychosis; uncontrolled infection; liver
cirrhosis Child B or C, severe hepatic impairment; severe blood count changes;
severe renal impairment, HIV
1. locoregional recurrence rate after 2 years (Time Frame - after 2 years): (recurrence in-radiation field, radiation field margin, outside radiation field for example contralateral)
Secondary outcome:
1. Overall Survival (Time Frame - after 2 and 5 years)
2. disease-free survival (Time Frame - after 2 and 5 years)
3. distant-metastasis-free survival (Time Frame - after 2 and 5 years)
4. acute toxicity according to ctc-ae v.4.0 (Time Frame - during therapy and up to 8 weeks after therapy)
5. late toxicity according to ctc-ae v.4.0 (Time Frame - follow-up period (5years))
6. Quality of Life as measured by questionaires (Time Frame - before and during treatment and in the follow-up for 5 years): questionaires: EORTC QLQ-C30 and QLQ-H&N35 and EAT-10
Active Comparator: A:De-Intensification Radiotherapy (RT) primary tumor region A:De-Intensification Radiotherapy (RT) primary tumor region
≤ 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
Active Comparator: B:De-Intensification Radiotherapy contralateral lymph nodes > 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
Active Comparator: C:De-Intensification RT primary tumor region /contralateral LN ≤ 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
A: De-Intensification RT primary tumor region: A:
Reduction of radiation dose in the primary tumor region to 56 Gy,
Elective Radiotherapy of both neck sides
B: De-Intensification RT contralateral lymph nodes: B:
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. De-Intensification RT primary tumor region AND contralateral lymph nodes: C:
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
Quelle: ClinicalTrials.gov
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