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

Esmée Botman,Jan Coen Netelenbos,Max Dahele,Adriaan A Lammertsma,Marelise Eekhoff,Pieter Raijmakers,Marieke Visser,Bernd P Teunissen,Thomas Rustemeyer,Jakko A Nieuwenhuijzen,Linda J Schoonmade

doi:10.3389/fendo.2020.00006

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 [18F]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.

Highlights

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disorder, which is characterized by heterotopic ossification (HO) in muscle, ligaments, and tendons [1, 2]
To the best of our knowledge, this is the first systematic review of literature relating to the use of radiotherapy in patients with FOP
The available reports suggest that radiotherapy in FOP patients does not lead to the formation of HO at the irradiated site

Summary

INTRODUCTION

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disorder, which is characterized by heterotopic ossification (HO) in muscle, ligaments, and tendons [1, 2]. If radiotherapy does lead to HO formation, it should be detectable by either increased [18F]NaF uptake on PET or the presence of HO at the irradiated site on a follow-up CT. In combination with pre-existing jaw ankyloses, the loss of lip mobility increased the difficulty of eating and drinking To assess whether these problems were caused by formation of HO in the irradiated area, [18F]NaF PET/CT (Gemini TF-64; Philips Medical Systems, Best, Netherlands) was performed. Based on a limited sample of seven patients with FOP (including ours), a range of radiotherapy doses appear to have been well-tolerated, with no reports of excessive or unexpected HO formation and no reports to suggest that the intended outcomes (primarily prevention, treatment of HO, and treatment of BCC) were any worse than expected. The authors stated that HO in the ankylosed mandible might have been caused by a combination of factors, including chemotherapy,

Design

DISCUSSION

ETHICS STATEMENT