De-intensification of Postoperative Radiotherapy in Selected Patients With Head and Neck Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- locoregional recurrence rate after 2 years
Study Overview
Brief 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.
Detailed 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:
- 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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologic proven squamous cell carcinoma of the oral cavity/larynx/oro- or hypopharynx
- •Postoperative tumor status:
- •Oral cavity, oropharynx or larynx: pT1-3, pN0-pN2b
- •Hypopharynx: pT1-2; pN1
- •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)
- •R0-Resection (resection margin ≥ 1mm)
- •No distant metastasis cM0
- •age ≥ 18 years, no upper age limit
- •Patients that understood protocol contents and are able to behave according to protocol
- •Signed study-specific consent form prior to therapy
- •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
- •sufficient renal function: normal serum creatinine, glomerular filtration rate > 60ml/min
Exclusion Criteria
- •pregnant or lactating/nursing women
- •fertile patients that are not willing to use highly effective methods of contraception (per institutional standards) during treatment
- •Any condition potentially hampering compliance with the study protocol and follow-up schedule
- •On-treatment participation on other trials
- •R1 or R2 resection status
- •pN2c and pN3
- •prior radiotherapy in the head and neck region , prior chemo- or immunotherapy (neoadjuvant/induction)
- •time between surgery and beginning of radio(chemo)therapy > 6 weeks
- •Prior (> 4 months before beginning of radio(chemo)therapy) neck dissection
- •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
Arms & Interventions
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
Intervention: A: De-Intensification RT primary tumor region (Radiation)
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
Intervention: B: De-Intensification RT contralateral lymph nodes (Radiation)
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
Intervention: C. De-Intensification RT primary tumor region AND contralateral lymph nodes (Radiation)
Outcomes
Primary Outcomes
locoregional recurrence rate after 2 years
Time Frame: 2 years
(recurrence in-radiation field, radiation field margin, outside radiation field for example contralateral)
Secondary Outcomes
- acute toxicity according to ctc-ae v.4.0(during therapy and up to 8 weeks after therapy)
- Quality of Life as measured by questionaires(before and during treatment and in the follow-up for 5 years)
- disease-free survival(after 2 and 5 years)
- late toxicity according to ctc-ae v.4.0(follow-up period (5years))
- Overall Survival(after 2 and 5 years)
- distant-metastasis-free survival(after 2 and 5 years)