Esophageal cancer is one of the most complex cancers to treat, often requiring a combination of strategies. In Wisconsin, where the incidence rate remains higher than the national average, there is an urgent need to improve how care is delivered and experienced by patients.
At the MCW Cancer Center, investigators across disciplines are aligning clinical care and research to better understand the disease and refine treatment approaches. One approach is the phase 2 PULSO trial, led by Lindsay Puckett, MD, Associate Professor of Radiation Oncology, that evaluates whether a new method of delivering radiation can improve the patient experience without compromising effectiveness. The study is testing Pulsed Low-Dose-Rate (PLDR) radiation, which is designed to maintain cancer-killing effects while reducing harm to healthy tissue.
“PULSO is one of the first trials to explore PLDR in esophageal cancer. This technique has already shown promise in treating brain cancer at MCW and other centers. We’re hopeful it could improve outcomes and reduce treatment toxicity for our patients,” said Dr. Puckett.
If successful, PULSO could inform larger studies and future standards for delivering radiotherapy in esophageal cancer. It also reflects the Cancer Center’s broader commitment to advancing care through more precise treatments, deeper biological insight, and coordinated, patient-centered care.
Understanding What Drives Better Treatment
PULSO compares standard chemoradiation with PLDR, which delivers the same total dose in a slower, pulsed pattern with brief pauses between exposures. These pauses are designed to allow healthy tissue time to recover between doses, reducing treatment-related toxicity while maintaining effectiveness against cancer cells. During the study, researchers are evaluating whether patients experience fewer side effects during and after treatment, as well as how well they tolerate therapy overall.
“We’ve screened more than 40 patients for the PULSO trial, and we’re hopeful that number will continue to grow,” said Dr. Puckett. “There’s been a lot of interest and we’re starting to see supporting data emerge that reinforces what we’re studying.”
The trial includes a translational research component in collaboration with Heather Himburg, PhD, Professor of Radiation Oncology. Her lab is analyzing RNA sequencing from patient samples to determine whether there are measurable molecular differences between this approach and standard radiation and to better understand how tumors respond at a biological level.
“Clinically, we’re asking whether patients experience less toxicity with this approach,” said Dr. Puckett. “But we’re also really interested in what’s happening at the molecular level. Are there measurable differences? Can we show that something biologically distinct is occurring?”
This focus on both clinical outcomes and tumor biology builds on a broader body of work from Dr. Puckett’s research team aimed at understanding how patients respond to treatment and where current approaches fall short.
In a recent study published in Cancers, the team analyzed real-world outcomes in patients with esophageal adenocarcinoma who received induction chemotherapy prior to chemoradiation compared to those who did not. The study found no clear improvement in survival, treatment response, or surgical outcomes, pointing to the limitations of existing approaches.
In an abstract presented at the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting, the team identified gene expression differences between tumors that showed a strong response to treatment, shrinking significantly after chemoradiation, and those that did not. These findings point to underlying biological factors that may help explain why some patients respond better than others. Additional research presented at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting offered insight into more aggressive forms of the disease, including differences observed in tumors from patients with brain metastases. Both of these abstracts were supported by a research grant from the Ryan M. Schaller Foundation.
Together, this work is helping define how esophageal cancer responds to treatment, why outcomes vary across patients, and how new approaches like PULSO can be designed to improve both effectiveness and tolerability.
Care Built Around Each Unique Case
This work is embedded in Froedtert & MCW’s Gastroesophageal Cancer Program, launched in early 2025 to bring together clinical care and research in a more coordinated way. The program connects specialists across surgery, medical oncology, radiation oncology, radiology, pathology, and supportive care, creating a more aligned approach to treating these complex cancers.
At the center of that approach is a weekly multidisciplinary tumor board, where each patient case is reviewed in real time. Treatment decisions are shaped by input from across specialties, ensuring that all options, including clinical trials like PULSO, are considered early and thoughtfully.
“The tumor board gives us a consistent opportunity to review cases together, identify trial eligibility, and make sure we’re thinking through all available options,” said Dr. Puckett.
That level of coordination has led to more patients being considered for clinical trials and improved alignment across care teams as treatment strategies continue to evolve. It has also helped the team better understand the patient population they are seeing, including an increase in squamous cell carcinoma cases, which may open up new opportunities for future research.
“As treatment approaches have changed, it can be challenging to keep everyone aligned across specialties. Having a dedicated multidisciplinary program has made a big difference,” Dr. Puckett said. “Overall, it’s helped us identify where the needs are and how we can continue to refine our approach to better support patients.”