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Thymomas and thymic carcinomas are rare diseases in which malignant tumors form on the outside of the thymus.

However, while linked together, they are different, said James Stevenson, MD, of the Cleveland Clinic.

"They are both rare -- maybe less than 2,000 cases a year in this country -- so there's not a lot of familiarity with treating these tumors," said Stevenson. "Thymomas have a better overall prognosis than thymic carcinomas, and tend to be smaller and more resectable than thymic carcinomas, which have more of a tendency to be aggressive and metastatic."

Another factor that distinguishes thymomas from thymic carcinoma is that thymomas often present with autoimmune diseases, particularly myasthenia gravis, the chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles. According to a approximately half of patients with cortical thymoma develop myasthenia gravis, while 15% of myasthenia gravis patients have thymomas.

Therefore, said Stevenson, when a patient presents with symptoms associated with autoimmunity, clinicians should consider the possibility of an underlying thymoma.

Other patients may have symptoms related to the tumor itself, said Stevenson. "The [tumors] could be large and cause chest pressure, pain, and shortness of breath. And then there are patients who are probably asymptomatic and [whose tumors] are found incidentally on a CT scan done for other reasons."

Whether or not a tumor is considered resectable will be key in determining treatment options, said Stevenson. For patients with resectable cancers, surgical removal of the tumor is the primary treatment for thymoma and thymic carcinoma, and offers the best chances for longer-term survival.

On the other hand, Stevenson noted, if a surgeon looks at the tumor and sees it has spread to nearby tissues and organs, "we can do things to make it resectable, and in most cases that would be chemotherapy."

Thymomas and thymic carcinomas have different prognoses, he continued: Thymomas are associated with 5-year survival rates of 60% or higher. "With earlier and more localized ones, most of those are curable with surgery alone. Even patients with thymoma who have more extensive disease at presentation can live for years, because [thymoma] can be a more indolent type of malignancy."

"One thing we have to keep in mind when treating thymomas if they are more advanced is understanding that these people can have more prolonged survival," Stevenson added. "We want treatments that aren't going to be too toxic and have too many long-term side effects that can readily affect quality of life for someone who is going to be living for more than 5 years with an incurable malignancy. We want to treat these thymomas, but we want to keep prognosis and quality of life in mind."

Thymic carcinoma, however, is not associated with the long-term survival seen with thymoma, Stevenson said, noting that immunotherapy has recently become an option for the disease.

While at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., Giuseppe Giaccone, MD, PhD, led a .

"We found pembrolizumab is active in thymic carcinoma," said Giaccone, now associate director for clinical research at the Sandra and Edward Meyer Cancer Center of Weill-Cornell Medicine in New York City. The response rate among the 40 patients in the study was 22.5%.

A , he noted. "We also looked at ways of selecting patients. Patients with high PD-L1 expression – more than 50% -- had a higher chance of responding. But PD-L1 is not a precise marker. Although it is quite good, you can't completely rely on it to select patients."

Giaccone said that while pembrolizumab was well tolerated in general, 15% of patients had serious immune-related adverse events.

"The immune-related adverse events are much higher than in other tumor types, and this is probably due to the fact that the thymus is really where immunity is formed," he said. "And thymic tumors are often associated with autoimmune disorders, so even though we excluded patients with a history of autoimmune disorders we had six patients develop them."

"So the drug is active, the treatment is definitely a good option, and the duration of response is much longer than anything else I've seen before," said Giaccone. "However, patients just have to be monitored very carefully, because of the potential to develop autoimmune disorders."

As for other immunotherapies, Giaccone pointed to a . This phase II trial failed to show any tumor shrinkage in 15 patients treated with nivolumab, leading the researchers to terminate patient accrual and conclude that "further development of nivolumab is not recommended in previously treated unresectable or recurrent [thymic carcinoma]."

Those results seem to suggest that there are differences between these drugs, "even though they have the same target," Giaccone said. "We have seen similar findings also in lung cancer where pembrolizumab appears to be better than nivolumab."

As for immunotherapy and thymomas, Giaccone noted that the South Korean study included seven patients with thymomas, five of whom developed severe autoimmune disorders.

"Thymomas have a much higher risk of developing autoimmune disorders than thymic carcinomas do, and I think they should not be treated with these drugs because the risk is too high," he said. "Fifteen percent is high enough, but when it comes to 50% or more, then the risk is bigger than the potential benefit."