Proton Therapy Shows Promise in Reducing Toxicity and Improving Outcomes for Gynecologic Cancer Patients

Over the past few decades, oncologists have made significant gains in reducing morbidity and mortality in many forms of cancer. Unfortunately, these advances haven't extended to some gynecologic cancers. For endometrial cancer, the most common gynecologic cancer in the U.S, the number of patients diagnosed and killed by this cancer have continued to rise, fueled by an aging population and an increase in obesity, two of its most common risk factors. This year, the American Cancer Society estimates that more than 69,000 will be diagnosed with endometrial cancer and nearly 14,000 will die from it, with Black women disproportionately affected compared to other racial groups. While cervical cancer has seen a decrease in incidence due to HPV vaccination and improved screening, the cancers that are now diagnosed tend to be more aggressive. These factors have led to no significant improvements in survival from endometrial and cervical cancers in the last 5 decades. 

Like most cancers, endometrial, cervical and other gynecological cancers are typically treated with surgery, chemotherapy, and radiation. The most significant limiting factor in completing appropriate treatment and achieving better outcomes for these patients is the toxicity of the treatment itself.  Research suggests that the type of radiation can make a difference in gynecologic cancer outcomes, with proton therapy having significant benefits over photon therapy. 

Dr. P. Reed McDonagh, III
Assistant Professor of Radiation Oncology, University of Maryland School of Medicine

Avoiding Acute Toxicity

In a study published in November 2025 in the International Journal of Radiation Oncology, Biology, and Physics, a team led by researchers from the Maryland Proton Treatment Center (MPTC) compared outcomes from 155 patients treated within our center for their cervical, endometrial, or vaginal cancers. 106 received the most advanced type of photon therapy available, known as volume modulated arc therapy (VMAT), and 49 received the most advanced form of proton therapy, known as intensity modulated proton therapy (IMPT).  

A retrospective analysis showed that only 27% of patients receiving IMPT had moderate or severe non-blood-related side effects, compared with 43% of those treated with VMAT. Looking specifically at acute grade 2 gastrointestinal toxicities, they were experienced by 1 in 4 of the VMAT group, but only 1 in 10 of the IMPT group. This benefit almost certainly stems from the ability of proton therapy to specifically target tumors while sparing healthy tissue – a difficult feat in the crowded environment of the pelvis, where reproductive organs sit in close proximity to the bowel. 

These advantages helped the IMPT patients avoid treatment breaks and prematurely discontinued treatment courses, which affected 4% of this group compared to 13% of the VMAT group. This result is particularly important for those with cervical cancer, for whom studies have shown a sharp uptick in recurrence with pauses in treatment. 

Further Benefits 

Other studies have shown even more benefits for proton therapy in gynecologic cancers: This modality's targeted nature can help prevent further damage to the bowel, bladder, and other tissues in patients who must undergo reirradiation after photon therapy. It can also better protect healthy tissue in patients when proton radiation is combined with hyperthermia, a relatively unique way to enhance the effects of radiation offered at our center and a few others across the country. By boosting the effects of radiation, hyperthermia along with proton therapy allows patients to get similar effects to higher dose radiation while avoiding the side effects. Proton therapy can also help patients preserve healthy blood counts by avoiding irradiating bone marrow in the pelvis and vertebrae and help younger patients reduce the risk of second radiation-induced cancers. 

Together, these benefits showcase the wealth of advantages for proton therapy in patients with gynecologic malignancies.