Bone Cancer Case Highlights Need for Long-term Monitoring After Radiotherapy for Cushing’s

Bone Cancer Case Highlights Need for Long-term Monitoring After Radiotherapy for Cushing’s
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A 67-year-old woman developed bone cancer 30 years after receiving radiation therapy to treat Cushing’s disease, according to a case report. 

Although the risk of bone cancer after radiation therapy is very low, this case highlights the need for long-term follow-up of Cushing’s patients treated with radiation. 

The case study, “Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing’s disease,” was published in the journal Endocrinology, Diabetes & Metabolism Case Reports

Cushing’s disease is caused by a tumor or excess growth of the pituitary gland, a pea-size gland located at the base of the brain. 

The most common pituitary tumor is called an adenoma, which is non-cancerous and leads to the release of excess adrenocorticotropic hormone (ACTH) stimulating the adrenal glands — located above both kidneys — to make too much cortisol, a condition called hypercortisolism.

Surgery is the standard first-line treatment for pituitary tumors, which can be followed by radiation therapy, also called radiotherapy, in cases of incomplete tumor removal or persistent ACTH secretion, occurring in up to 30% of patients. The combination of surgery and radiation leads to hormone and tumor control in most cases. 

Despite these advances, radiotherapy may result in complications, including the pituitary gland not producing enough hormones, or hypopituitarism, vision problems, and in some cases, secondary cancers.

According to researchers at Blacktown Hospital in Australia, such was the case of a 67-year-old woman, who had been treated for Cushing’s disease, including radiotherapy, and then developed bone cancer 30 years later. 

She was brought to her local emergency department following a tonic-clonic seizure, which is characterized by muscle stiffening and twitching, as well as a prolonged post-seizure state of disorientation, known as a postictal state. 

According to her medical records, she was diagnosed with presumed Cushing’s disease at 37 years old based on clinical and biochemical hypercortisolism. Although imaging tests did not show a pituitary tumor, she underwent surgery, which also failed to find a tumor. Due to persistent hypercortisolism, she received radiotherapy.

Her hypercortisolism was only resolved upon surgical removal of the adrenal glands after medication failed to control her hormones. She was maintained on hormone replacement therapy with prednisolone and fludrocortisone.

Her records showed various other issues including high blood pressure, treated heart disease, chronic pain, depression, a long smoking history, and fractures in her spine caused by hormone therapy. There was no history of seizures.

An MRI found a soft-tissue mass in the skull bones that had spread into the brain, consistent with  a diagnosis of osteosarcoma — the most common form of bone cancer, which mostly occurs in children and young adults. CT scans of the abdomen and pelvis did not find evidence of additional cancer as the source of her skull and brain cancer. 

Despite being treated with medications to control seizures, she continued to experience seizures while in the hospital, which required sedation and intubation with ventilation. Repeat CT scans of her brain found bleeding, and as such, she underwent surgery five days after admission to remove the tumor in her brain and skull bones. 

She was removed from ventilation on day nine, showing mild improvements in neurological status and delirium. However, on day 12, she went into cardiac arrest and died, despite attempts at resuscitation. Further examination of tumor tissue confirmed osteosarcoma that started in the skull bones and spread to the surrounding areas. 

The authors proposed that previous radiation therapy for Cushing’s disease led to her skull bone cancer based on factors such as the development of the cancer within or close to the path of the radiation beam, the presence of a different tumor type before radiation, a long period between radiation and cancer diagnosis (at least three years), and a confirmed diagnosis of secondary cancer. 

Furthermore, osteosarcoma is the most common form of radiation-induced cancer of the bone.

“The prevalence of radiation-induced osteosarcoma and other [cancers] of the skull in patients with prior radiotherapy for pituitary tumors has not been established and is largely described through case reports,” the researchers wrote. However, “the risk of radiation-induced osteosarcoma following radiotherapy is exceedingly rare, occurring in 0.01–0.03% of all irradiated patients.”

Additionally, the researchers noted that the risk of radiation-induced sarcomas increases with higher radiotherapy dose and field size.

In nine case reports presented in the study, the mean age at diagnosis of a secondary tumor was 50 years, ranging from 16 to 75 years, with a mean latency period between radiation and cancer diagnosis of 13 years. 

“At 30 years, this is the longest reported duration between radiotherapy for a pituitary tumor and development of a radiation-induced osteosarcoma in the literature,” they wrote. “Long-term follow-up studies on patients receiving [radiation] are warranted to examine the risk of development of such tumors.” 

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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