Study Investigating Reduced-Dose Radiation Therapy Following Surgery in Patients with Squamous Cell Carcinoma of the Head and Neck (DIREKHT2)

Squamous cell carcinomas of the head and neck (HNSCC) are malignant tumors that develop in the mucous membranes of the mouth, pharynx, or larynx. The main risk factors are long-term tobacco and alcohol use, as well as infection with human papillomaviruses (HPV). The standard treatment for locally advanced HNSCC involves surgery, followed by radiation therapy and, frequently, cisplatin-based chemotherapy (radiochemotherapy). While this combination can improve the chances of cure, a problem with radiation therapy is that not only the actual tumor area but also the surrounding healthy tissue is irradiated as a precaution to treat any possible, invisible tumor remnants. While this increases the likelihood of completely removing the tumor, it often leads to significant long-term effects such as difficulty swallowing and speaking, or the need for long-term nutritional support via a feeding tube (percutaneous endoscopic gastrostomy, PEG). These side effects can have a severe and lasting impact on patients’ quality of life.

The goal of the DIREKHT2 study is to investigate whether reducing the radiation field—that is, avoiding radiation to healthy lymph node regions—is just as effective but better tolerated than the current treatment. To this end, patients will be randomly assigned to two groups. In one group (the control group), radiation is administered as has been standard practice—that is, to the area of the original tumor, to the lymph node regions with metastases, and additionally to adjacent, healthy neck regions. In the other group (treatment group), this preventive radiation to the healthy neck regions is deliberately omitted in order to reduce the patients’ radiation exposure.

The study is divided into two phases. In the first phase (Phase 2), the study will examine whether patients in the treatment group are less likely to require a feeding tube (PEG tube) after one year. This would be an indication of a better quality of life after treatment. If this goal is achieved without an increase in recurrences in the irradiated area (locoregional recurrence), the study will move on to the next phase (Phase 3). In this phase, the main focus will be on determining whether the reduced radiation dose provides the same long-term protection against tumor regrowth in the treated region as standard radiation therapy. Patients will be followed up for approximately 2 years as part of the study.

Men and women aged 18 and older who have already undergone surgery for squamous cell carcinoma of the oral cavity, pharynx, or larynx and who require postoperative radiation therapy are eligible to participate. No more than three lymph node regions may be affected, and there must be no tumor metastases. Previous radiation or chemotherapy in the head and neck region excludes participants, as does participation in other studies or an existing pregnancy or breastfeeding.