Unlocking the Potential of Localized Treatments By Better Understanding Treatment Response

It’s easy to think of melanoma – or any cancer – in black and white terms. You have it or you don’t, it responds or it’s resistant to treatment, or it grows or it shrinks. However, like most things, the reality is far more complex. Reid Thompson, MD, PhD, a 2021 recipient of the ASTRO-MRA Young Investigator Award, is working to disrupt this simplistic black and white understanding of cancer and is unleashing the full potential of localized treatment approaches, in combination with systemic therapy such as checkpoint immunotherapy, at the same time.

“Melanoma treatments are fast evolving and as we get more effective treatment options, the picture becomes even more complex,” says Dr. Thompson. “Measuring tumor burden and treatment response across [all the metastatic lesions across] the body is increasingly important as we incorporate additional treatment modalities into our armamentarium. Getting a better picture of what’s happening, that’s what my research is hoping to address.”

Dr. Thompson is an assistant professor of radiation medicine at Oregon Health & Science University. In addition to his research, he exclusively treats patients facing skin cancers. 

“Broadly speaking, radiation oncology is one of the three [historical] pillars in cancer therapy,” says Dr. Thompson. Today, oncology care has expanded to encompass four broad treatment pillars – surgery, radiation, chemotherapy, and immunotherapy. As the newest pillar, immunotherapy has been a game changer in the treatment of melanoma and other cancers.

About half of all patients facing cancer will receive radiation during the course of their treatment.¹ While this figure is lower among melanoma patients, a growing subset of melanoma patients will receive care from a radiation oncologist during their journey. “In melanoma, radiation can be used in place of surgery in select cases, following surgery to reduce the likelihood of recurrence, to target lesions on specific organs including the brain, or even as supportive therapy to ease pain. Increasingly, radiation is being combined with other treatments such as checkpoint immunotherapies.” 

In addition to his work in radiation oncology, Dr. Thompson is also interested in the field of computational biology. Put simply, computational biology is the development and application of theories, mathematical models, and computer simulation in the study of biology. It’s this combined specialization, of radiation medicine and computational biology, that fuels his research. 

“The picture for metastatic melanoma patients is mixed,” says Dr. Thompson. “To really understand what is happening, we need to convert our thinking away from looking at the whole and instead think of cancer as a mixture of individual processes each of which may have a unique path.”

Using the RECIST 1.1 guidelines – the current way doctors measure treatment response – a patient treated with multiple lines of therapy who has progressive tumors all over their body, and a second patient with the same tumor burden who has a complete response with the exception of a single new lesion – are the same.

“Under our current guidelines, these two hypothetical patients both have progressive disease,” says Dr. Thompson. “But clearly this isn’t giving us a good sense of what is happening to each patient. We need a more nuanced picture of what is happening with each metastatic lesion across the entire body so that we can create intelligent plans that blend in focal, localized treatments into a complex treatment plan.”

To do this, Dr. Thompson is enrolling patients with metastatic melanoma into a clinical trial to better assess how their treatments are working using a combination of imaging, circulating tumor DNA (ctDNA) tests, immune correlates, and many other translational biomarkers. Among a cohort of 20 patients, he will monitor tumor response to a combination of local therapy – radiation or surgery – combined with systemic checkpoint immunotherapy. Taken together, he hopes this data will allow him to construct a framework that can track response on a lesion, organ, treatment, and at an individual level. 

Dr. Thompson hopes that with a better understanding of how a given treatment is working throughout the body, we can be more strategic in our response. This would allow doctors to be more precise and individualized in their treatment planning. 

“If we know that immunotherapy is working for a given patient, except for a few stubborn lesions, this type of framework would allow us to pinpoint those areas with additional therapies,” says Dr. Thompson. “By being more precise, we may be able to avoid the side effects or risks that a second systemic therapy could bring with it.”

Dr. Thompson’s work is supported by a joint grant from the Melanoma Research Alliance (MRA) and the American Society for Radiation Oncology (ASTRO). Joint funding mechanisms like this are a win for organizations like ASTRO and MRA because it allows both organizations to leverage additional money to fund more significant research, and a win for patients because it incentivizes additional interdisciplinary research that is increasingly required to move the needle.

”In addition to the benefit of offering more funding to top-notch researchers,” says H. Timothy Hsiao, PhD, Director of Scientific Affairs at ASTRO, “the MRA-ASTRO collaboration is especially strategic for the advancement of medicine because it promotes dialogue among leading experts from both fields to nurture new ideas for the next generation of interdisciplinary innovation.”

“Interdisciplinary research is so critically important today,” says Dr. Thompson. “I would not be able to do this work without this award from ASTRO and MRA. This funding has gotten me started working on a topic that is important to patients facing melanoma and one that I believe has implications for the radiation oncology community at large.”