Fanconi anaemia (FA) - radiation sensitivity

Fanconi anemia (FA) is a rare genetic recessive syndrome that leads to bone marrow degeneration and an increased risk of cancer. The cause is a deficit in the repair of crosslinks between the two DNA strands. At least 13 repair proteins are involved in the complex repair process.

Five patients have been studied so far, three of whom showed significantly increased radiation sensitivity.

In mainly homozygous carriers of FA mutations, a significantly increased chromosomal radiation sensitivity and genomic instability could be detected, even in the parents of the patients to a certain extent. Diagnosis of Fanconi anaemia by ionizing radiation- or mitomycin C-induced micronuclei

• Some of the literature describes that the results of measurements of individual radiation sensitivity are often not related to clinical radiation sensitivity. This is described in more detail in the "Case reports" section.

• Most of the non-transplanted FA patients with various cancer entities died within the three months following radiotherapy due to their advanced tumor diseases, among other causes. Some of the patients developed severe adverse side effects from radiotherapy. One patient with a carcinoma of the upper esophagus died of laryngeal edema and pneumonia after receiving a dose of 70Gy. It is probably advisable to perform surgical interventions as frequently as possible and to be cautious when using chemotherapeutic agents or radiotherapy in the presence of DNA repair disorders. Radiosensitivity in Fanconi's anemia patients
• No association with increased cellular radiation sensitivity was found in a patient with clinical radiosensitivity and no evidence that chromosomal testing should be standard in patients with Fanconi's anemia. Clinical and Cellular Radiosensitivity in Inherited Human Syndromes
• In einem Bericht von zwölf Tumorpatienten (besonders im Kopf-Hals-Bereich) mit FA wurde von diesen bei neun Patienten eine Mukositis, bei 8 Patienten Schluckbeschwerden und bei der Hälfte der Patienten eine Panzytopenie festgestellt. Zudem sei es zu Ösophagusstenosen, Larynxödemen und Wundzerfällen gekommen, bei fast der Hälfte der Patienten musste die Strahlentherapie vorzeitig beendet werden. Vier Patienten starben während der Strahlentherapie. Die postoperative krankheitsfreie Überlebenszeit betrug 0-55 Monate. Es solle das Ansprechen von FA-Patienten weiter untersucht werden, um das Risiko des Auftretens unerwünschter Folgen der Radiotherapie zu minimieren. Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma
• Another FA patient showed a pronounced clinical radiation sensitivity in the form of confluent ulcerative oropharyngeal mucositis following treatment for tonsillar carcinoma. This patient also showed a discrepancy between cellular predictive radiosensitivity tests and the observed clinical radiosensitivity. Normal cellular radiosensitivity in an adult Fanconi anaemia patient with marked clinical radiosensitivity
• In a case report, an FA patient with a head and neck tumor was reported to have increased acute toxicity but no severe late effects of radiotherapy, while another FA patient with a head and neck tumor experienced acute hematotoxicity leading to death after only 8 Gy. It was suggested that radiotherapy or radiochemotherapy may be possible and useful for FA patients in individual therapy. Fanconi's Anemia and Clinical Radiosensitivity
• Conventional radiation doses could be dangerous for patients with DNA repair defects, such as FA. Radiation sensitive patients should be identified in order to avoid radiation therapy or to adjust the radiation dose. Clinical Radiation Sensitivity With DNA Repair Disorders: An Overview

• At present, it is not possible to say with certainty whether certain in vitro tests are justified for predicting the radiation reaction. Especially in view of the partial discrepancy between the clinical radiation sensitivity and the common in vitro radiation sensitivity measurements, it is probably difficult to justify a decision for or against radiation therapy on this basis. Clinical and Cellular Radiosensitivity in Inherited Human Syndromes
• Many case reports suggest that there is an increased risk of serious acute and late toxicities in FA patients - however, FA patients cannot generally be denied radiotherapy.
• Radiotherapy or radiochemotherapy for FA patients may be possible and useful in individual therapy. Fanconi's anemia and clinical radiosensitivity report on two adult patients with locally advanced solid tumors treated by radiotherapy
• In our opinion, patients with FA should be tested as early as possible, even without a tumor, in order to know the radiation sensitivity of the individual patient. Due to the often necessary bone marrow transplantation, the radiosensitivity measurement can no longer be carried out on the lymphocytes. It is therefore advisable to carry out the radiosensitivity measurement at an early stage. In the case of increased radiation sensitivity, this would mean that attempts could be made to minimize the dose used during diagnostic measures. Should a tumor disease occur, the fraction doses of the therapy could be adjusted according to the radiation sensitivity.