Study Finds Radiation Before Surgery Can Make Immunotherapy More Effective for Mesothelioma

Mesothelioma is often treated with a multimodal therapy of surgery, chemotherapy, and radiation therapy. Though these treatments are considered the standards of care, as curative and palliative options, researchers have debated the exact role of radiation for mesothelioma over the years. Some studies have suggested the therapy is not effective and mesothelioma tumors may be resistant to the treatment overall. Others have claimed that the treatment is best used palliatively to shrink tumors and help alleviate symptoms.

Recent studies, however, are exploring the role of radiation therapy for mesothelioma when combined with immunotherapy. Research suggests radiation can help immunotherapy be more effective and prolong survival, with some even suggesting the combination could one day be a new standard of care.

Radiation and Immunotherapy for Mesothelioma

In recent years, many clinical trials have focused around improving the potential and efficacy of immunotherapy for mesothelioma, a treatment that works by boosting the immune system to fight cancer. Numerous studies have tested the treatment in combination with other traditional therapies, like surgery and chemotherapy, and have shown success in extending life expectancy. Other clinical trials are now testing different forms of radiation in combination with immunotherapy drugs.

In early-phase clinical trials, researchers found non-ablative hypofractionated radiation can impact the immune system in mesothelioma patients. Hypofractionated radiation therapy refers to the total dosage being divided into large doses, typically given once daily. With this type of dosage, treatment is generally given over a course of several days compared to normal radiation, which may be applied over several weeks.

In these studies, researchers found applying hypofractionated radiation seven days before surgery led to an antitumor effect driven by specific T cells known as CD8+ T cells and CD4+ T cells, which are responsible for the body’s immune responses to any pathogens and foreign cells. When compared to surgery alone or surgery with radiation completed 24 hours before the procedure, researchers did not see a positive immune response. As such, researchers believe the combination treatment paves the way for a targeted immunotherapy treatment, such as a CTLA-4 blockade or immune checkpoint, to destroy any remaining mesothelioma cells after surgery and promote antitumor activity in the body.

This research is still in the early phases, but shows promise for a future treatment combination that could help lead to a cure for mesothelioma. In next phase studies, the research team hopes to explore the optimal dosage and fractionation of radiation for this treatment combination, as well as test different immunotherapy drugs to monitor which has the best response.

More Research for Radiation Therapy and Mesothelioma

The clinical trial testing radiation with immunotherapy is not the first time the treatment has shown success when applied before or after surgery. One technique known as Surgery for Mesothelioma After Radiation Therapy or SMART has proven in various clinical trials to extend life expectancy from months to even years for some patients.

In various SMART studies for pleural mesothelioma, doctors apply a high dose of intensity-modulated radiation therapy (IMRT) over the course of several days about one week before surgery, including an extrapleural pneumonectomy (EPP). One study found the treatment combination could extend survival to 51 months on average, with patients experiencing 47 months disease-free. In comparison, average life expectancy for pleural mesothelioma patients is six months to one year.

Though the approach has shown promise, some doctors have still called into question the treatment’s efficacy and reliability. At the World Conference on Lung Cancer in fall 2018, one panel discussion reasoned that the application of radiation therapy before surgery could make surgical resection more difficult and increase the risk of fatal pneumonitis. Radiation pneumonitis occurs when the lung becomes inflamed from the therapy and commonly develops one or several months after treatment. In severe cases, the condition can lead to permanent scarring of the lungs or pulmonary fibrosis.

Some researchers argue adjuvant radiation, or radiation applied after surgery, may be more beneficial for more patients and help prevent tumor recurrence, which is highly common in mesothelioma patients. The lead researchers of the SMART approach are still working to enhance the efficacy of the multimodal treatment, and more studies around other applications and types of radiation for mesothelioma are expected.

Overall, though radiation’s past role in the treatment of mesothelioma has been debated, researchers continue to strive to find new ways to apply the therapy and improve efficacy. With continued research, they hope one day the treatment can be better utilized and possibly even lead to a cure.