A novel treatment combination for lung cancer studied in Tartu

Medical researchers of the University of Tartu and doctors of Tartu University Hospital have an ambitious plan to take their novel combination of stereotactic body radiotherapy and immunotherapy to treatment guidelines and thus reach suitable patients suffering from lung cancer. Up to 20 lung cancer patients will be included in the study SynAct Lung to assess the safety and efficiency of the new combination.

According to Jana Jaal, the organiser of the study and Associate Professor in Oncology of the University of Tartu and Senior Physician-Lecturer of the Haematology and Oncology Clinic of Tartu University Hospital, it has been a long-held opinion that a person cannot recover from final-stage (stage 4) lung cancer. The recent years, however, have shown that a third of lung cancer patients who had three to five secondary tumours (metastases) at the moment of diagnosis and who, in addition to systemic therapy, have also received local radiotherapy are alive five years later and even longer.

In current medical practice, only systemic drugs are used to treat metastatic non-small cell lung cancer of stage 4. In the SynAct Lung study, systemic therapy is supplemented by local radiotherapy. “Radiotherapy will address all sites of the tumour – the primary site in the lungs and up to five metastases in different organs. In addition to local radiotherapy, we will use immunotherapy as systemic therapy in the study. The recent years have shown high anti-cancer efficiency of immunotherapy in case of lung cancer,” Jaal explained.

By now we have a considerable amount of evidence-based information saying that ionising radiation has its role in the induction of anti-cancer immunity. “There is proof that in addition to the local effect, radiotherapy can stimulate anti-tumour immunity and thus boost the efficiency of immunotherapy. Radiotherapy brings about changes in the tumour microenvironment, making the cancer cells more immunogenic, further increasing the anti-tumour immune activation,” said Jaal.

The immune activation effect of radiotherapy is mainly described in the case of the so-called stereotactic body radiotherapy, which has emerged thanks to the continuous development of radiotherapy devices and software solutions. With this method, single high-radiation doses are used and only three to five therapy sessions take place. There are few side effects, as the irradiated area is minimised thanks to precise localisation (e.g. the metastasis and the surrounding 4–5 mm).

Jaal says that stereotactic body radiotherapy has been used in the world a bit longer than in Estonia. In Estonia, the first stereotactic body radiotherapy of metastasis took place in 2017 at the Department of Radio and Oncotherapy of Tartu University Hospital. “Immunotherapy has been used in oncology for only a few years. By joining the two methods, we can say that it is a novel treatment combination in both Estonia and abroad,” said Jaal.

The course of the study

To assess the efficiency of the novel treatment combination – stereotactic body radiotherapy and immunotherapy, 20 patients will be involved in the SynAct Lung study over the next 18 months. 

Patients who 

• have been diagnosed with non-small cell lung cancer of stage 4,
• are at least 18 years old,
• have up to five metastases in other organs, and
• have not received prior treatment to the metastatic disease 

are expected to participate in the study.

Patients eligible for the study will first receive radiotherapy for the primary site in the lungs, followed by stereotactic body radiotherapy of up to five metastases. During the radiotherapy of the primary site, the systemic immunotherapy starts, including treatments with Durvalumab every four weeks. “Naturally, the study involves a more systematic control of safety and anti-cancer efficiency,” emphasised Jaal.

“If we manage to prove the efficiency of the combination of stereotactic body radiotherapy and immunotherapy in Estonia, it is likely to be followed by wider-scale studies elsewhere in Europe. We are hoping that a wider proof of its efficiency will lead to including the scheme to all treatment guidelines, so it can reach all suitable patients,” said Jaal.

Clinical and laboratory research

The researchers want to include patients across Estonia in the study carried out at Tartu University Hospital. “We are conducting the study in Tartu, as in addition to the clinical aspect, the project requires wide-range laboratory research to describe the immune activation effect of the treatment combination in more detail. We also aim to find new biomarkers related to treatment efficiency,” described Jaal, adding that for the safe and fast transport of the samples, direct proximity of the laboratory is highly important. 

The laboratory research of the study will be done by the Molecular Pathology Research Group of the Institute of Biomedicine and Translational Medicine of the University of Tartu in cooperation with Professor of Molecular Immunology Pärt Peterson and Research Professor of Cellular Immunology Kai Kisand.