Neurofibromatosis (NF1, NF2)- radiation sensitivity

• Neurofibromatosis (NF) is one of the most common autosomal dominant hereditary diseases and is divided into two subtypes, both of which are two different diseases but have many similarities in addition to their inheritance. Both types are characterized by a high de novo mutation rate.
• Neurofibromatosis 1 (NF1), also known as Recklinghausen's disease, manifests itself in particular with typical café-au-lait spots, numerous benign neurofibromas of nerves.
• Neurofibromatosis 2 (NF2) is characterized by the development of unilateral or bilateral vestibular schwannomas, as well as frequent meningiomas or gliomas of the CNS. (Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspectiveNeurofibromatosis).

• Six patients with neurofibromatosis have already been examined. The patients with NF1 had borderline to very high radiosensitivity on examination, while the patient with NF of unknown type had radiosensitivity within the normal range.

• In fibroblast strains from the skin of NF 1 and 2 patients, seven out of nine patients were found to have significantly increased radiation sensitivity compared to healthy volunteers in patients chronically exposed to ionizing radiation. This is evidence of a link between increased sensitivity at the cellular level during chronic irradiation and NF, regardless of the type of NF. Cellular radiosensitivity of patients with different types of neurofibromatosis
• Studies of NF1 fibroblasts showed an increased sensitivity to radiation. The DNA repair mechanisms in NF1 fibroblasts are severely restricted, and after ten minutes of irradiation, remarkably few double-strand breaks were detected in these cells. The ATM-dependent signaling and repair pathways are restricted in NF1 patients. Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates
• It has been found that there is a possibility that fibroblast cultures from patients with neurofibromatosis show an early onset of senescence, sometimes associated with an inability to respond to DNA-damaging agents (ionizing radiation and actinomycin D have been studied). Sensitivity of Cultured Skin Fibroblasts from Patients with Neurofibromatosis to DNA-Damaging Agents
• The cultivation of in-vitro colonies of fibroblasts from NF fibromas did not differ significantly from the cultivation of healthy skin fibroblasts from healthy volunteers; in particular, there was no significant difference in the dose-dependent reduction in the ability to form colonies in fibroblasts irradiated with different doses. Cell-culture studies on neurofibromatosis (von Recklinghausen's disease)
• In stimulated blood lymphocytes, a significantly increased incidence of breaks, dicentric chromosomes and translocations was found in NF lymphocytes compared to non-NF lymphocytes. Evidence of chromosomal instability in neurofibromatosis
• The stochastic risk of secondary carcinomas as a result of chemotherapy or radiotherapy is significantly increased in NF-1. A threefold increased risk has been described in children with NF-1 compared to children with NF-1 with only surgical therapy. (Second primary tumors in neurofibromatosis 1 patients...;Subsequent Neoplasms After a Primary Tumor in Individuals With Neurofibromatosis Type 1). In adults with malignant peripheral nerve sheath tumors classified as either radiation-induced in non-NF-1 or radiation-associated in NF-1 patients, the latent period until the appearance of secondary tumors was slightly shorter in NF-1 patients (11.8 months) than in non-NF-1 patients (13.3 months).

• Clinically, young NF1 and NF2 patients with cerebral irradiation show an increased rate of cerebral arterial disease in the area of irradiation compared to non-NF patients. Risks of Radiation Therapy in Patients With Neurofibromatosis

In NF, the high secondary malignancy risk is in the foreground. Patients usually have a borderline or slightly increased radiation sensitivity with regard to deterministic risks. Radiotherapy is feasible with regard to undesirable treatment consequences after adjustment of the fraction dose.

On the other hand, there is a high risk of secondary carcinoma. The indication should therefore be limited to cases where no alternative therapy is possible.
We are happy to test these patients in order to make a treatment decision or therapy possible. With our test, however, we can only test the deterministic risk of neurofibromatosis, but not the stochastic risk.