CLINICAL RESEARCH. Six Swedish university hospitals are now accepting patients in a unique randomized study that will hopefully improve the prognosis for patients with metastasized melanoma. The study is being led by the University of Gothenburg and Sahlgrenska University Hospital and is examining whether survival after immunotherapy can be improved by removing remaining metastases.
“Today, we do not know whether survival can be improved by removing metastases surgically. Unfortunately, metastatic surgery is rarely of value for patients since new metastases begin growing again shortly after surgery. However, our hypothesis is that patients with metastatic melanoma responding to immunotherapy can be an interesting and hopeful exception,” says Carl Jacob Holmberg, a surgeon at Sahlgrenska University Hospital and a PhD student at the University of Gothenburg in a group associated with the Wallenberg Centre for Molecular and Translational Medicine (WCMTM).
The project plans to include patients in the study during the coming 18 months and hopes to be able to present results in 2024.
Nobel discovery
Malignant melanoma is a very aggressive disease that easily spreads, and its metastases can appear in all organs of the body. Previously, the prognosis was very bad if the disease had spread systemically, and about 70 percent of the patients died within one year of having received their diagnosis. By introducing immunotherapy, considerably more patients now survive longer and are even potentially cured. This discovery that cancer can be treated by mobilizing the body’s own immune defenses resulted in the 2018 Nobel Prize for James P. Allison and Tasuku Honjo.
Today, most patients with metastasized melanoma are offered immunotherapy. In 10–20 percent of the patients, the metastases disappear completely and the patients are declared free of cancer, but in about 50 percent of the patients the metastases only partially respond and the disease stabilizes. Holmberg feels that the results are amazing even though up to half of the patients will have remaining tumors in their bodies even with effective treatment. This is the group of patients that will be included in the study. They will be randomized for metastasis surgery with continued immunotherapy, or only continued immunotherapy, which is the current standard of care.
“Regardless of the results we achieve, the study will contribute with clinically important knowledge that we currently lack. If surgery of systemic metastasis proves to increase survival, this will likely change treatment strategies both in Sweden and internationally. If the study, on the other hand, shows no effect at all, we will be able to focus on identifying patients where surgery can improve symptoms, such as bleeding from metastases in the intestines.”
Give T-cells an advantage
The unique study that now begins at six Swedish university hospitals means that patients being treated with immunotherapy for metastasized melanoma will be randomized into an intervention group, where the metastases are surgically removed and immunotherapy continued, or a control group without surgical intervention but with continued immunotherapy.
Holmberg feels that the theory behind the study is very appealing:
“Immunotherapy works by mobilizing the body’s own T-cells, but we have only a limited number of these immune cells. If we remove tumors and the metastases that have proven to be more resistant to treatment, we can hopefully give the T-cells an advantage in the battle of keeping the cancer in check. We will carefully study in our lab the effect of the immunotherapy on the removed metastases to try to understand more about why certain metastases respond to treatment while other do not.”
Close cooperation between the academia and the medical care system
The study is called SUMMIST trial (Surgery of Metastatic Melanoma After Systemic Immunotherapy) and is being led from Gothenburg, where Sahlgrenska Academy and Sahlgrenska University Hospital have become an important center for clinical treatment and research on malignant melanoma.
“Our research group can pride itself on high-quality patient-centered translational research, close contacts between the hospital and the University, and collaboration with leading international institutions,” says Roger Bagge Olofsson, an associate professor at Sahlgrenska Academy and surgeon at Sahlgrenska University Hospital, whose research team is associated with both the Wallenberg Centre for Molecular and Translational Medicine and Sahlgrenska Center for Cancer Research at the University of Gothenburg.
“At Sahlgrenska, we also have a fantastic collaboration between surgery and oncology, which allows us not only to give patients individualized care but also to be innovative with new studies that can bridge previous barriers,” says Lars Ny, a senior lecturer at Sahlgrenska Academy and oncologist at Sahlgrenska University Hospital.
In the last decade, the incidence in Sweden has increased by about 5 percent annually, and compared to the rest of the world melanoma is much more common in Sweden, with an incidence of nearly 25 per 100,000 residents.
BY: ELIN LINDSTRÖM
