Altered fractionaton - HypoARC
Standard Fractionation applies 2Gy of radiaton dose, every day for 30-35 fractions. This means that the whole radiotherapy schedule lasts 6-7 weeks, which is the most common applied schedule worldwide. Why 2Gy and not 4Gy? This was a result of unacceptable late radiotherapy toxicity, including fibrosis and necrosis of tissues. At least, this was what we believed...but this has now changed. Novel radiotherapy technology allows he administration of higher dose of radiation to the tumor, at the same time keeping low the dose to the surrounding normal organs. Not all tumors are sensitive to 2Gy and, in fact, many tumors, due to hypoxia or intrinsic radioresistance, demand larger daily doses to suffer a good damage. Moreover, by applying large daily doses daily, the total treatment time is reduced to 3-4 weeks, which consists the so called 'accelerated radiotherapy'. In this way, cancer cells cannot proliferate during radiotherapy and, treatment becomes more effective. We, therefore, proposed the concept of Hypofractionatd and Accelerated Radiotherapy' or HypoAR or, when supported with cytoprotective drugs, HypoARC. During the past 15 years, we obtained a strong experience by applying such regimens for the treatement of hundreds patients with breast, lung, prostate, bladder and head-neck cancer, confirming high efficacy and low toxicity.
Chemotherapy and Molecular Targeting Radiosensitization
Immunotherapy and Super-Hypofractionation for recurrent tumors
Simultaneous radiotherapy and cisplatin or cetuximab chemotherapy provide cure rates of less than 50%, in locally advanced SqHNC. About 20-30% of tumors will not respond to radiotherapy and 30-40% of responders will relapse after months or years since radiotherapy. The results of chemotherapy are rather poor, and immunotherapy with anti-PD-1 agents provides overall response rates of 15% and disease stabilization in 45%, for a median of 3-4 months. Re-irradiation is an option provided that recurrence occurs at least 1 year after the first irradiation. Ultra-Hypofractionated (UH-RT) radiotherapy has been postulated to induce radio-vaccination, enhancing the vulnerability of tumors to immune response. The efficacy and tolerance of anti-PD-1 immunotherapy in combination with UH-RT is under investigation in a large scale phase II trial.