Read more

March 06, 2020
2 min read
Save

Morphology of bone metastases should guide treatment in medullary thyroid cancer

Matthias Kroiss

Adults with medullary thyroid cancer who develop osteolytic bone metastases are more likely to experience skeletal-related adverse events compared with similar patients who develop osteoblastic bone metastases, suggesting that antiresorptive therapies should be considered based on the morphology of disease, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

“The impact of bone metastases in metastatic medullary thyroid carcinoma (MTC) on patient morbidity and prognosis has not been studied in detail previously,” Matthias Kroiss, MD, PhD, senior physician and researcher at University Hospital Würzburg, Germany, told Healio. “In this large multicenter, retrospective study, we found bone metastases to be present in 29% of patients with metastatic MTC. We found that the type, ie, the morphology of bone metastasis on imaging, is important and may guide treatment. Osteolytic metastases cause complications more frequently than osteoblastic metastases and are associated with poor prognosis.”

Kroiss and colleagues analyzed data from 114 adults diagnosed with MTC and evidence of bone metastases between 1973 and 2016 from four German tertiary care centers participating in a study group for rare, malignant thyroid tumors. The median age at primary diagnosis of sporadic MTC was 45 years; median age at diagnosis of hereditary MTC was 27 years. Median follow-up from time of diagnosis of MTC was 5.8 years; median follow-up after a diagnosis of bone metastases was 26.6 months. Primary endpoint was skeletal-related events and all-cause mortality. Researchers used Kaplan-Meier analyses to estimate survival.

Thyroid ultrasound female 2 2019.  
Adults with medullary thyroid cancer who develop osteolytic bone metastases are more likely to experience skeletal-related adverse events compared with similar patients who develop osteoblastic bone metastases.
Source: Adobe Stock

Within the cohort, 43 patients died during follow-up. Median overall survival after a diagnosis of bone metastases, which occurred on average 2.1 years after the initial diagnosis, was 1.8 years. Bone metastases were multifocal for 79% of the patients and located preferentially in the spine (86%) and pelvis (60%). Morphology of bone metastases was osteolytic, osteoblastic and mixed in 32%, 25% and 22% of cases, respectively, with 21% of cases of unknown morphology.

During follow-up after primary diagnosis of bone metastases, 47% of adults developed at least one skeletal-related event, including bone radiation (50%), pathological fracture (32%) and bone surgery (12%). First skeletal-related events occurred a median of 8 months after primary diagnosis of bone metastases; a first skeletal-related event led to a diagnosis of bone metastases for 34% of adults.

Adults with osteolytic metastases were more likely to develop a skeletal-related event (42%; P = .047); only 17% of skeletal related events occurred among adults with osteoblastic metastases, according to researchers.

PAGE BREAK

Researchers found that the presence of osteolytic metastases (HR = 3.85; 95% CI, 1.52-9.77), but not the occurrence of skeletal-related events, was associated with impaired overall survival.

Among 36 adults in the cohort treated with antiresorptive therapy (bisphosphonate or denosumab [Prolia, Amgen] therapy), researchers observed fewer skeletal-related events vs. untreated patients (P = .04).

“In patients with metastatic MTC, the detection of bone metastases requires particular attentiveness,” Kroiss said. “When osteolytic metastases are present, antiresorptive treatment with bisphosphonates or denosumab should be considered. It appears advisable to focus on potential skeletal-related clinical symptoms and to perform close follow-up investigations by imaging.”

Kroiss said the researchers could not clarify whether tyrosine kinase inhibitor treatment is beneficial and whether a particular drug is a better choice for patients with bone metastases in the setting of MTC.

“Skeletal-related adverse events should become an endpoint in clinical trials for MTC,” Kroiss said. “In this rare disease, accrual of a larger number of patients in prospective clinical registries may close the gap of knowledge in this particular area.” – by Regina Schaffer

For more information:

Matthias Kroiss, MD, PhD, can be reached at University Hospital Würzburg, Department of Internal Medicine, Division of Endocrinology and Diabetology, Oberdurrbacher Str. 6, 97080 Würzburg; email: kroiss_m@ukw.de; Twitter: @matthiaskroiss.

Disclosures: The authors report no relevant financial disclosures.