Gemcitabine-Induced Myonecrosis Following Hypofractionated Radiation

Abstract

Palliative radiation is often used to abate pain and prevent bone fractures in patients with metastatic cancer. Hypofractionation, meaning delivery of larger doses of radiation in each treatment session (fraction), has become the standard of care in most cases. It not only reduces the burden on the medical system and facilitates the relief of symptoms but also enables the maintenance of the continuity of systemic therapy. Radiation recall phenomenon (RRP) is an acute inflammatory reaction in previously irradiated tissues that is provoked by chemotherapeutic drug administration. The incidence, severity, and prognosis of RRP following hypofractionated radiation therapy have not been studied. The symptoms of RRP depend on the radiation field, with the greatest concern associated with mucosal and dermal damage, though other symptoms have also been reported. Here, we describe a case of a 41-year-old woman with metastatic breast cancer (hormone receptor-positive, HER2/neu negative), who received palliative radiation to four other fields along the course of her disease, before her presentation with isolated myonecrosis of the thigh muscles. This RRP occurred four months following the last of two fractions of 8 Gy radiation to this region, given three months apart, and after six courses of cisplatin + gemcitabine. The symptoms improved with cessation of gemcitabine and prolonged administration of non-steroidal anti-inflammatory medications.

Keywords: gemcitabine; hypofractionation; myositis; radiation recall phenomenon; radiation-induced myonecrosis.

Figure 1. Radiation fields to the left femur 95% isodose: (A) axial view, recent treatment; (B) sagittal view, recent treatment; (C) axial view, previous treatment; and (D) sagittal view, previous treatment.

Figure 2. Hematoxylin and eosin slide of semitendinosus muscle biopsy.

The biopsy indicates acute inflammation, characterized by infiltration of neutrophils, lymphocytes, and macrophages (black markers), and diffuse prominent interstitial edema (white arrows), indicated by fluid within the extracellular spaces of muscle tissue disrupting the arrangement of muscle fibers.

Figure 3. Magnetic resonance imaging of the thigh.

(A) Axial T2-W with fat suppression and (B) T1-W with fat suppression after intravenous (IV) gadolinium injection MRI images of the thighs. Massive muscle edema involving the majority of the muscles of the left thigh is observed. Following contrast injection, multiple round myonecrotic lesions (arrows) are seen along the tract of the radiation beam.