Silvia Formenti

5 Questions With Dr. Silvia Formenti

Shifting paradigms in radiation oncology with breakthrough research

Silvia Formenti

Dr. Silvia Formenti never imagined she’d become a world-renowned researcher when she started her medical career. But while she was a resident in Italy, three cancer patients she had grown close to all died within the same month. “To learn that these patients whom I had really cared for had passed away made me rethink how I could make an impact,” says Dr. Formenti, who is Radiation Oncologist-in-Chief at NewYork-Presbyterian/Weill Cornell Medicine and Chair of the Department of Radiation Oncology at Weill Cornell Medicine. “It led me to write my first immunology research proposal, even though I had never worked in a lab before.”

That proposal received funding and brought her to the University of Southern California to study human monoclonal antibodies, marking the start of a four-decade career as a physician-scientist. Dr. Formenti’s work has helped introduce a new role for radiation therapy in cancer treatment: as a tool that stimulates the immune system to recognize a tumor and reject it. Her research has shown that by combining immune checkpoint inhibitors with focal radiation, the immune system could be activated to fight cancer, with the irradiated tumor acting much like a vaccine — unlocking a potentially game-changing cancer treatment.

While radiation-based immunotherapy is still far from broad clinical implementation, Dr. Formenti recognizes that every trial of this novel application is a step toward bringing hope to people with few treatment options. One of her most gratifying moments is the yearly visit she gets from a former patient who went into remission from advanced metastatic non-small cell lung cancer after undergoing this experimental treatment. “It was clearly an exceptional case, but the pleasure I derive from seeing this patient every year is much greater than any publication or award,” she says.

Dr. Formenti spoke to NYP Advances to discuss what she’s learned along her path as a physician-scientist and why research is such a critical component of patient care.

What made you choose oncology as your specialty?

When I started doing my clinical rotations in Italy, I noticed there was a difference in how doctors interacted with cancer patients compared with patients who had more treatable diseases like cardiovascular disease, kidney dysfunction, and even neurological dysfunction. When cancer was the diagnosis, there seemed to be a lack of communication and less attention given to the patient. That helped me decide on oncology because, at least back then, cancer patients seemed to me to be the most underserved.

What has compelled you to continue pursuing research throughout your career?

It’s about empathy. Feeling the pain of others doesn't drain me or take away from me, it makes me work harder. It reminds me of the pressing need for the research we do: to improve outcomes in patients.

Feeling the pain of others doesn't drain me or take away from me, it makes me work harder. It reminds me of the pressing need for the research we do: to improve outcomes in patients.

One of my early role models, Dr. Alexandra Levine, former division chief of hematology at USC, taught me the importance of clinical research and how it can be applied practically to individual patients. She was equally dedicated to academic research and being an exceptionally compassionate doctor, and her model of caring for patients has stayed with me throughout my career.

I also recognize that doing clinical translational research is an incredible privilege because the patients who consent to our trials put their lives in our hands. Being honored with their trust and confidence is a huge responsibility, but it is also what compels us to succeed and make progress.

It’s been widely noted that a gender gap remains among physician-scientists. What advice do you have for women doctors interested in this career path?

Never give up. Stick to your vision and accept that it may not necessarily get easier as you progress in your career. Establish a network of support, especially with other women, because there can be a lot of rejection in research, and it takes resilience to bounce back and restart. It’s so much easier to overcome obstacles as a team; I have been lucky to have an exceptional one, from the lab to the clinic and including research administration. But the gender gap persists. I consistently see incredible potential in women that, for various reasons, isn’t leveraged enough. I take it seriously to identify and enable their potential, no matter what their role is.

I also think that women are often under multiple stressors. If you’re trying to balance career with a family, accept that not everything is going to be perfect. I had three kids in four years when I was in California, and I had to juggle that with volunteering in the classroom, lab work, and seeing patients. While my children were always my priority, they adapted to my career and my passion for cancer research. For instance, I learned that they stopped telling me when they had a sore throat because the rumor in the house was, “If you don’t have cancer, mom isn’t much interested.” They became confident that any minor sickness would soon pass.

Personally, I feel like having competing priorities helps train you to multitask and become more tolerant, to accept imperfection and prioritize what is important. I was lucky that everything came together.

What drives you to continue expanding the boundaries of your field?

Since medical school I’ve been fascinated with how the body builds a history of interaction with different conditions and diseases. The immune system is such an important component of human homeostasis, and there’s still a lot to learn about how it individually fights inflammation, infection, and cancer.

What’s also been immensely motivating is seeing gifted people around me succeed and grow into clinical investigators and translational scientists.

What’s also been immensely motivating is seeing gifted people around me succeed and grow into clinical investigators and translational scientists. In 2016, we created an international congress of medical professionals studying radiation immunotherapy called ImmunoRad that meets every year, with contributors from all over the world. To see this line of research grow exponentially is incredibly satisfying.

Combining radiation and immunotherapy is still a relatively young field. How do you hope to see it evolve?

What we’re learning is that generally there is a proportion of patients whose tumors shrink or even disappear with radiation and immunotherapy, but in the majority of cases it either doesn’t work or works briefly and then stops. There could be many reasons. Maybe we were targeting the wrong immune checkpoint block, maybe we need to target more than one block, or maybe the patient doesn’t have the immune fitness it takes to reject a tumor. For each patient there is a signature that needs to be identified to help design treatments for them. We are rapidly learning how to match individual patterns of immune evasion with the correct therapies in a much more personalized way.

We have a lot more work to do, but I’m very confident there will be more and more happening in immunotherapy. That’s why I’m privileged to be at NewYork-Presbyterian and Weill Cornell Medicine, because I’ve found fantastic collaborators, not only in our department but across departments, who have joined in trying to answer all the questions we have.

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Silvia Formenti: Shifting paradigms in radiation oncology with breakthrough research

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