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The latest developments in head and neck cancer treatment using advanced radiation therapy were reviewed during the 95th Annual Meeting of the German Society for Otorhinolaryngology, Head and Neck Surgery on May 9 in Essen. New approaches and technologies aim to maximize efficacy while minimizing toxicity, Sonja Buske reports.

An interesting approach is the use of hadron-based therapies such as proton and carbon radiation, according to Prof. Heath Skinner, Chair of the Department of Radiation Oncology at the University of Pittsburgh, USA. “There are obvious dosimetric advantages over classical radiotherapy, as a significant dose reduction is possible for organs at risk,” he told the audience. “On the other hand, protons are less ‘robust’. This means that a millimeter change in the tumor can dramatically affect how much radiation the surrounding organs receive.”

In addition, while several positive retrospective studies show potential benefits in reducing radiation exposure to surrounding healthy tissue, they are ‘‘biased by patient population and some show worse late effects,” Skinner noted. Further randomized studies are necessary to be able to make a clear statement about the effectiveness of hadron-based therapy.

Heath Skinner, MD, PhD, Radiation Oncology Clinical Networks at UPMC Hillman Cancer. © UPMC

Adaptive therapy

Another way to reduce toxicity is adaptive therapy, which means changing the radiation field based on tumor response. The classic approach is to reduce the area treated when the radiotherapist recognizes from the daily diagnostic images that the tumor has become smaller or there has been some anatomy change in the patient. One study tested how toxicity changes when the area treated is regularly adjusted every week. “The result was sobering, as there were no improvements in toxicity,” he concluded.


Instead of reducing toxicity by changing the radiation directly, many studies have used a variety of drugs in combination with radiation to improve tumor response. “Unfortunately, most radiosensitizers have failed,” he said. “More recently, immunotherapy delivered in combination with radiation or chemoradiation has been studied, however, this combination has also underperformed. Regrettably, in the clinical trial setting, the combination of immunotherapy and radiation or chemoradiation delivered concurrently in head and neck cancer.”

Biologically guided radiotherapy

One potential explanation for these failures is treating all patients with the same types of treatment. Biologically guided radiotherapy, on the other hand, is a promising approach to improving treatment results. Here, biomarkers are used to adapt the radiotherapy to the individual biology of the tumor.

“As an example, head and neck tumors associated with human papillomavirus or HPV are known to respond very well to radiation, and several studies of these tumors in which the radiation dose is reduced show promising results,’’ he said. ‘‘Additionally, other tumor biomarkers are being studied to guide radiation dosing with the hope that personalized treatment approaches can improve the effectiveness of radiotherapy.”

Linear accelerator with integrated PET/CT

Another focus is on the development of advanced technologies such as the Reflexion X1, a linear accelerator with integrated PET/CT, which enables precise and biologically guided radiotherapy. The so-called SCINTIX® technology is used at only a few centers in the world and is a new type of therapy for patients with tumors attributable to primary and metastatic cancer. This technology uses continuously updated live data throughout the treatment session to determine where to deliver radiotherapy.

A study conducted in 2024 investigated the application of this system and its impact on treatment outcomes in patients with head and neck squamous cell carcinomas (HNSCC). The study shows promising results and highlights the potential of this advanced technology to improve patient care, according to Skinner. “While it’s early days, this technology could represent a paradigm shift in the treatment of HNSCC and further improve patient outcomes,” he said enthusiastically.

The Reflexion X1 enables precise and biologically guided radiotherapy. The system uses tumor radiotracer uptake to guide radiation therapy. © UPMC

Further randomized studies are lacking

In summary, it can be said that modern radiotherapy approaches are becoming increasingly important in the treatment of HNSCC. However, most of the approaches discussed lack validation in large, randomized trials and clinical studies.

“Our understanding of the relationship between the biology of head and neck cancer and the radiation response is still suboptimal,” admitted Skinner, who  believes it is possible to maximize the efficacy of radiotherapy while minimizing toxicity, by integrating advanced technologies, adaptive treatment strategies, and biology-guided approaches.

‘‘This opens new opportunities to improve patient outcomes and develop personalized treatment approaches for head and neck cancer patients. With the increasing understanding of tumor biology and the development of new technologies, we may be at the beginning of a new era in the treatment of head and neck cancer,” he concluded.


Heath Skinner, MD, PhD, is medical director of Radiation Oncology Clinical Networks at UPMC Hillman Cancer Center and Chair of the Department of Radiation Oncology at the University of Pittsburgh, USA. He specializes in the study and treatment of head, neck and lung cancers. Skinner completed a combined MD/PhD program at West Virginia University and subsequently a combined internship and residency in radiation oncology at the University of Texas MD Anderson Cancer Center (MDACC). He maintains an active translational research laboratory focused on identifying novel, clinically applicable biomarkers for radioresistance. (© UPMC)