Sylvester Researchers Deliver Multiple Oral Presentations and More at ASTRO 2022

Researchers representing Sylvester Comprehensive Cancer Center, part of the University of Miami Health System and University of Miami Miller School of Medicine, presented multiple studies and participated in several panel discussions at the leading meeting in radiation oncology, the 2022 ASTRO Annual Meeting, in San Antonio, Texas.

The American Society for Radiation Oncology (ASTRO) is the largest radiation oncology society in the world, with nearly 10,000 members. This year’s annual meeting featured more than 1,700 research presentations on advances in cancer care.
Twelve of the cancer center’s researchers presented on oncology topics related to prostate, brain, genitourinary, and breast cancers, as well as diversity and other issues in the specialty and how to overcome them.

“Sylvester had an impressive presence, showcasing not only our impactful research but also attention to important issues in oncology, such as diversity, at one of today’s most prestigious radiation oncology meetings,” said Alan Pollack, M.D., Ph.D., professor and chair of radiation oncology at the Miller School.

Dr. Pollack presented “Challenging Cases in Genitourinary (GU) Malignancies: Incorporating Imaging Findings into Personalized Treatment Recommendations,” and was the presenting author during a meeting discussion on GU cancers. He also was part of panel and discussed the “State of the Art Selection and Treatment of Localized Prostate Cancer.”

“These presentations and my role, overall, at ASTRO reflect our commitment to effectively incorporating imaging to optimize the treatment of GU cancers, including prostate, bladder, and kidney cancers,” Dr. Pollack said.

Novel Imaging Approaches for Glioblastoma

Eric A. Mellon, M.D., Ph.D., co-leader of Sylvester’s Neurologic Cancer Site Disease Group and associate professor of radiation oncology and biomedical engineering at the Miller School, was principal investigator on three studies presented on glioblastoma, the most common cancer originating in the brain, with an average survival of only 18 to 24 months.

Dr. Mellon presented “Glioblastoma Response during Chemoradiation by Daily Quantitative Multiparametric MRI.” William Jin, M.D., a resident in radiation oncology, presented “Can Spectroscopic Magnetic Resonance Imaging be Used to Delineate Recurrent Glioblastoma?”

Miller School M.D./Ph.D. student Kaylie Cullison presented “Interfractional Dynamics of Glioblastoma Treated on MRI-Linac,” research for which she received ASTRO’s Annual Meeting Travel Award in the Physics category. Only 30 of nearly 2,000 abstract submissions for the Annual Meeting Travel Award were selected. Cullison received a $1,000 honorarium, a certificate of recognition, and complimentary ASTRO registration.

“Winning this award has been incredible because this is the first oral presentation that I will have presented at a professional conference. It has been encouraging that the work we’re doing really matters. And I’m an aspiring radiation oncologist, so it has been exciting to have my work recognized,” said Cullison, whose Ph.D. research goal is to develop an algorithm that predicts outcome in glioblastoma patients treated with radiation therapy on MRI-Linac.

Sylvester’s glioblastoma research stands out because the cancer center uses unique imaging techniques to measure early response of glioblastoma and uncover more disease than is possible at many cancer centers.

“Dr. Jin is presenting on a new technique called spectroscopic MRI which allows us to probe into the brain where it is often unclear if there is disease. The imaging tells us whether there is disease allowing us to focus radiation on areas. His presentation is based on a clinical trial that we helped to run a few years ago,” Dr. Mellon said. “Based on that data, we have an ongoing clinical trial that I am heading here at Sylvester based on that technique.”

Cullison’s work on using the MRI-Linac for glioblastoma is based on Sylvester’s experience as the fourth center worldwide to acquire the MRI-guided radiation therapy machine.

“We were the first to treat glioblastoma on this device and have been optimizing the technology for brain application. It’s a hybrid that allows us to deliver radiation therapy while acquiring MRI. Getting an MRI every day gives us a unique window into seeing how that tumor responds to treatment,” Dr. Mellon said.

Dr. Mellon’s presentation looks at different MRI based parameters to see how patients are responding to treatment.

“We have a $5 million, seven-year grant from the National Cancer Institute to study how advanced imaging during treatment may be used to improve radiation therapy for patients with glioblastoma. This is the first towards that grant and a large focus of our lab,” Dr. Mellon said.

Radiation Therapy and Prostate Cancer

Alan Dal Pra, M.D., director of the Radiation Oncology Clinical Research Program at Sylvester and medical director of radiation oncology at Lennar Coral Gables, delivered oral and poster presentations at the ASTRO meeting.

His oral presentation “Prognostic and Predictive Performance of a 24-Gene Post-Operative Radiation Therapy Outcomes Score (PORTOS) in a Phase 3 Randomized Trial of Dose-Intensified Salvage Radiotherapy after Radical Prostatectomy (SAKK 09/10),” reflected Sylvester’s work on PORTOS, a genomic signature that measures important pathways related to cancer’s response to radiation treatment.

“This work is groundbreaking, as it may represent the first predictive biomarker to help personalize dose prescription in patients receiving salvage radiotherapy for prostate cancer,” Dr. Dal Pra said. “Predictive biomarkers are essential tools to help identify the right treatment for the right patient. In prostate cancer, there is a lack of predictive biomarkers measured before treatment to inform and identify who is likely or unlikely to benefit from a specific treatment,” he said.

Dr. Dal Pra and colleagues studied PORTOS in prostate cancer patients treated in a randomized clinical trial performed in Europe and showed that those patients with a high PORTOS score had significantly improved outcomes when higher radiotherapy doses were used.

Co-first author of the oral session study “PSMA PET mapping of postoperative local recurrence and impact on prostate fossa contouring guidelines for salvage radiation therapy,” Dr. Dal Pra said this collaboration between Sylvester and UCLA suggests that current contouring guidelines used to plan salvage radiation treatments in prostate cancer patients with local recurrence need updating.

“It’s important that we consider information from novel imaging modalities, such as PSMA PET, which in our study identified recurrences that fell partially or fully outside of the clinical target volume determined by current guidelines,” Dr. Dal Pra said.

In the poster presentation “An Analysis of PTV Margins for Postoperative Prostate Radiotherapy Using a Dose Accumulation Workflow,” Sylvester researchers studied planning target margins (PTV) used to ensure appropriate radiotherapy target coverage.

“The larger the PTV, the higher the dose to normal tissues that do not need to be treated, leading to more side effects,” Dr. Dal Pra said. “This is the work of Sylvester’s medical physicist, Dr. Elizabeth Bossart and Miguel Noy, a medical student at Albany Medical College. We reassessed the PTV margins currently used in many centers, including Sylvester. Our study suggests that, in the context of contemporary radiotherapy imaging technologies, PTV margins could possibly be reduced. A PTV margin reduction is an important step towards further decrease of side effects from treatment.”

Dr. Dal Pra and Brandon Mahal, M.D., are co-mentoring Miller School medical student Karthik Meiyappan, who gave an oral presentation at ASTRO on a study by Sylvester researchers using whole transcriptome assays to assess 5,780 radical prostatectomy samples for ataxia telangiectasia mutated (ATM) expression. They found prostate cancer patients with high ATM expression had poorer survival outcomes and significantly higher metastasis risk.

Next, they assessed whether radiation treatment differentially affects outcomes in patients with high versus low ATM expression. Using data from a matched cohort, the authors found no significant differences in outcomes in patients not receiving radiotherapy. However, in patients receiving radiotherapy, there were significant differences by ATM expression levels, with patients with the highest quartile of ATM expression having significantly worse outcomes. Therefore, a high ATM expression may be predictive of poor radiotherapy response in prostate cancer patients.

“This is the first clinical investigation in prostate cancer to focus on RNA transcriptomic expression of ATM rather than ATM mutations, meaning we gain insight into effects of the actual activity of the gene and not just its genetic code,” Meiyappan said. “There are very few biomarkers we know of which can predict prostate cancer response to a specific treatment, and with further investigation, ATM expression could be one of the first.”

Novel Prostate Cancer Treatment

Benjamin J. Rich, M.D., resident physician in radiation oncology at the Miller School, presented “Para-aortic Radiation Therapy for Oligorecurrent Prostate Cancer,” which he said is a novel treatment.

“We are the first institution to do this treatment for prostate cancer that has spread to the para-aortic lymph nodes,” Dr. Rich said. “The idea is that it could help men with oligorecurrent prostate cancer avoid life-long hormonal therapy.” This work is the background of a phase 2 clinical trial that has been developed by Dr. Rich and Dr. Dal Pra.

Assessing Prostate Cancer SBRT Toxicity

Mayank Patel, M.D., a radiation oncology resident at the Miller School, presented “Dose to the Bladder Trigone and Acute Urinary Toxicity after Prostate SBRT in a Randomized Phase 3 Trial.”

Dr. Patel’s presentation looked at the association between the dose to the bladder trigone and acute genitourinary toxicity in patients treated with prostate stereotactic body radiation therapy (SBRT). The bladder trigone is the most innervated sub-volume of the bladder and the most adjacent to the prostate. Dr. Patel and colleagues found a trend between the radiation dose to the bladder trigone and acute GU toxicity, suggesting that special attention should be made to the dosimetry of this sub-volume to reduce incidences of acute toxicity.

“This is an extremely hot topic right now in the radiation oncology community as there is a new push to treat these patients with SBRT as opposed to conventional fractionation over several weeks. Our project is especially interesting to many people in the prostate community,” Dr. Patel said.

Dr. Patel said that attending ASTRO is an excellent experience for any young radiation oncologist.

“There is no better way to meet so many experts and leaders in the field all in one place,” Dr. Patel said.

Studying the Tumor Microenvironment

Scott M. Welford, Ph.D., Tumor Biology Program co-leader at Sylvester and professor and Biology Division chief in the Department of Radiation Oncology at the Miller School, presented “Hypoxia and Tumor Microenvironment,” a topic he said is fundamental to how patients respond to radiation.

“It has been appreciated for decades that tumors create hypoxia by consuming all the of oxygen around them and then adapt to the deprived conditions, which makes them more aggressive and harder to treat,” Dr. Welford said. “A prime example occurs at the molecular level. Radiation requires oxygen, albeit a low level, to deliver its lethal blow to a cancer cell by causing toxic DNA damage. Additionally, though, tumors change their behavior to survive in the absence of oxygen by using alternative means of energy production. Blocking the immune system is a consequence of those alternative approaches.”

As a result, the microenvironment is a strong prognostic indicator for patient stratification and an important focus of potential therapeutic opportunities, he said.

More Diverse Clinical Trial Enrollment

Crystal Seldon Taswell, M.D., radiation oncology resident at the Miller School and Jackson Memorial Hospital and chair of Society for Women in Radiation Oncology, presented “Data-driven Approaches to Promoting Enrollment of Women, Racial, Ethnic, Sexual and Gender Minorities and Elderly Patients in Clinical Trials: Pathways for Future Success, and “Migrating Financial Toxicity Related to Study Enrollment.”

“Financial toxicity is a real concern for patients with cancer and can present a specific obstacle to enrollment on clinical trials,” Dr. Taswell said. “My ASTRO presentation revolved around methods to mitigate financial toxicity for our cancer patients. This reflects on Sylvester as an institution because Sylvester actively works to improve clinical trial enrollment for those facing financial toxicity in order to create more equitable outcomes for all.”

Improving Breast Cancer Treatment

Sylvester researcher Laura Freedman, M.D., associate professor of Radiation Oncology, moderated the breast cancer session “Fractionation and Toxicity.”

“Experts on the panel presented exciting research on shortening treatment courses, which is much more convenient for patients. One presentation looked at as few as three treatments,” Dr. Freedman said. “Another presentation looked at helping patients with radiation-related fatigue, and another at decreasing arm swelling. While these presentations are not practice-changing at this time, they provide thoughts that lead to future research that could ultimately help patients with these side effects of treatment.”

Tags: American Society for Radiation Oncology, ASTRO, breast cancer, Dr. Alan Pollack, glioblastoma research, Miller School of Medicine, prostate cancer, Radiation oncology, Sylvester Comprehensive Cancer Center