Navigating the Intersection of Radiation Therapy and Immunotherapy in Endometrial Cancer

Further investigation is needed regarding the integration of radiation therapy with immunotherapy, particularly in patients with recurrent or persistent endometrial cancer receiving chemoimmunotherapy, according to Idalid Franco, MD, MPH, who noted that there remains minimal guidance in this area.

Franco also emphasized that although the paradigm is changing one thing that remains is the importance of personalized treatment decisions that account for disease stage, histology, and patient comorbidities in addition to in-depth discussions with patients to align treatment priorities.

“The theme for [the conference] this year is ‘Waves of Change,’” Franco reported in an interview with OncLive at The Radiation Oncology Summit: ACRO 2024. “[Therefore], I am thinking about how endometrial cancer has evolved, especially over the past few years, and about the impact on our communities and our patients. I really wanted to discuss the different treatment paradigms for the physicians who are here as well as the residents and medical students.”

In the interview, Franco delved into the evolving landscape of endometrial cancer, emphasizing the integration of immunotherapy, molecular biomarkers, and risk factors for recurrence, as well as highlighted the importance of biomarker testing in personalizing care.

Franco is the director of Equity Access and Inclusion in the Department of Radiation Oncology at Brigham and Women’s Hospital and an instructor at Harvard Medical School, both in Boston, Massachusetts.

OncLive: Please expand on what you discussed during your presentation on immunotherapy in gynecologic cancers.

Franco: We [spoke] about the integration of immunotherapy and molecular biomarkers and which patients are, based on risk factors have a higher risk of recurrence, particularly within the first 5 years [following diagnosis]. Therefore, it’s important to think about the new immunotherapy trials that have come out for endometrial cancer, particularly [in] the higher stages.

How has the field of endometrial cancer shifted in recent years?

There has been a lot of changes. Over the past year there’s been a new staging system that’s been proposed [that is] really thinking about what is being integrated within these new staging systems. Although we’re still using the older staging system, we need to think about risk factors like lymphovascular space invasion, molecular markers, and the tumor environment.

[We also need to think] about the intersectionality of patient risk factors and not just the molecular size of the tumor itself, but the social determinants of health, about whether there’s access to standard of care treatment, and how those intersecting [items] might affect patient outcomes overall.

What is the importance of biomarker testing for these patients?

We know that in recent years, there have been different outcomes [for patients] in terms of whether a patient is POLE-mutated or has mismatch repair–deficient or –proficient disease. We know that some of these patients respond differently to things like systemic therapy, immunotherapy, or even radiation therapy, so thinking about how we can integrate these [markers] to better personalize care [is critical].

How is radiation therapy being integrated with immunotherapy in the realm of gynecologic cancer?

Currently, [radiation therapy] is not [being integrated] and that is an area that we really need to think about and investigate. Currently there isn’t a lot of guidance, especially for radiation oncologists.

For example, if there’s a patient who comes in with International Federation of Gynecology and Obstetrics grade 3 or grade 2 persistent endometrial cancer, or recurrent endometrial cancer, if they’re getting chemotherapy and immunotherapy with pembrolizumab [Keytruda] for example, [it is unknown] at what point we would integrate radiation. This is because the studies that have been done have not looked at radiation in particular. That is a perfect area for the field to start moving into.

How do you navigate treatment decisions for these patients considering factors such as disease stage, histology, or comorbidities?

As we’ve heard throughout the conference, radiation oncology is personalized medicine. This is because we’re thinking about treatment fields, doses, and about constraints for organs at risk. Having an in-depth discussion with the patient in terms of risk for recurrence, as well as risk for comorbidities may affect whether we’re concerned about the toxicities from radiation.

What I love to do is to really understand the patient needs, the patient priorities, and then to integrate the standard of care treatment based on that.

Looking to the future, how would you like to see this treatment landscape evolve?

One of the trends that we’re seeing with endometrial cancer is an increase in incidence for Latina patients. Thinking about what is adding to this [is important]. Is it comorbidities such as obesity or diabetes? Or are there other risk factors? Thinking about how we’re considering all our at-risk populations [remains important].

Similarly, Black women have worse outcomes [compared with others]. Most of the time these patients are presenting either at a more advanced stage or with more high-risk histology. Thinking about why these patient populations are coming in with these differences and how we can better [improve] care [will be a focus].