Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disease, characterized by the formation of heterotopic ossification (HO) in muscles, ligaments, and tendons. Flare-ups, an inflammatory process that often precedes the formation of HO, can occur spontaneously, but trauma is also a common trigger. It is not known whether radiotherapy, especially in higher doses, might cause sufficient trauma or inflammation to trigger a flare-up and subsequent HO in FOP patients. We report the case of a patient undergoing radiotherapy for the treatment of a 1-cm-wide basal cell carcinoma (BCC) of the lower lip. In addition, we present a systematic review of the available literature. Our patient received 54 Gy in 18 fractions with orthovoltage therapy, resulting in a clinical complete response of the tumor. Six months after treatment, there were no signs of HO either clinically or on [ 18 F]NaF PET/CT. The systematic review identified 11 publications describing either radiation treatment in FOP or radiation therapy as a cause of HO in non-FOP patients. Six case reports described the use of radiation in FOP patients for various reasons, including one with a high-dose treatment of a lip BCC using superficial X-ray therapy. The remaining five studies described the use of low-dose radiotherapy to prevent or treat either an FOP flare-up or HO formation. None of these cases showed worsening of disease that could be attributed to the use of radiation therapy. Radiation induced HO in non-FOP patients was rare and occurred in five studies. The largest of these studies suggested that HO was induced after treatment with high doses, resulting in more widespread evidence of tissue damage, potentially being the end result of this damage. In conclusion, available reports suggest no contraindication to radiotherapy in FOP patients; although the number of cases was small, systematic toxicity reports often were not available, and none of the reports described high-dose, high-energy radiation treatment at locations such as muscle and joint regions.

18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications

“…These results suggest that 18 F-NaF-PET is capable of identifying heterotopic ossification lesions without any preceding flare-ups, demonstrating superiority over MRI [ 101 , 102 ]. In fact, 18 F-NaF is currently the only in vivo biomarker recognized and available for detecting and monitoring the progression of FOP [ 103 ].…”

Fibrodysplasia Ossificans Progressiva: A Case Series and Literature Review

“…Only 700 cases have been reported so far throughout the world. The disease has a predilection towards female sex [1,5]. It occurs mostly sporadically but it has got an autosomal dominant inheritance.…”

“…This disease occurs due to mutation in the FOP gene located on chromosome 4. These results increase in Bone morphogenic Protein 4 (BMP 4) [1,2,8]. This increase in BMP 4 leads to ossification in connective tissues of voluntary muscles, tendons and fascia.…”

“…Fibrodysplasia Ossificans Progressiva is rare congenital disorder which occurs most commonly as result of new mutation [1][2][3][4][5]. It is inherited as autosomal dominant disease [1,2,6,7].This disease is manifested by extra skeletal bone formation in axial musculature, which start developing in first decade of life, apart from this bilateral hallux valgus deformity is present since birth. This disease occurs due to mutation in the FOP gene located on chromosome 4.…”

“…With growing age, ribbons and sheaths of extra skeletal bone is formed which functionally lock the spine to skull, skull to jaw, and spine to limbs. Patient gradually lose mobility [1][2][3][4]. Patient become wheelchair bound by 20 years of age, bedridden by 30 years and usually leads to death by 40 years of age.…”