The Clinical Trials session focused on promising advances in radiation therapy that helped extend progression-free survival and reduced or delayed the need for hormone therapy in patients with recurring prostate cancer, identified the first biomarker to guide hormone therapy to patients most likely to benefit from it and explored the use of low-dose radiation therapy to improve quality of life for people with conditions other than cancer. Two studies also investigated how lowering radiation doses would affect disease control for patients with lymphoma and brain cancer.
The session was moderated by Kenneth Rosenzweig, MD, FASTRO, of the Icahn School of Medicine at Mount Sinai in New York and by Farzan Siddiqui, MD, PhD, CPE, FASTRO, of Henry Ford Hospital and Wayne State University in Detroit.
The session’s first presentation was from Daniel Spratt, MD, of University Hospitals Seidman Cancer Center, Case Western Reserve University, in Cleveland, “A Double-Blinded Placebo-Controlled Biomarker Stratified Randomized Trial of Apalutamide (APA) and Radiotherapy for Recurrent Prostate Cancer (NRG GU006, BALANCE trial).”
This randomized, placebo-controlled study provided the first prospectively validated predictive biomarker to guide the use of hormone therapy for patients with recurring prostate cancer following radical prostatectomy. Aided by a gene expression test (PAM50) adapted from a test used to classify breast tumors into subtypes, researchers classified patients with recurring prostate cancer as either those with luminal B tumors or those with non-luminal B tumors and treated both subtypes with either placebo or 240 daily mg of apalutamide, a next-generation hormone therapy that blocks androgen receptors to prevent testosterone from getting to the prostate. The study found significant improvements in biochemical progression-free survival for patients with luminal B tumors (compared to those treated with placebo) but no differences for patients with non-luminal B tumors.
“Until now, we’ve been doing a one-size-fits-all treatment,” Dr. Spratt said. “This will allow us to only treat those patients for whom the treatment will offer a benefit.”
Dr. Spratt was followed by Amar Kishan, MD, PhD, of the University of California, Los Angeles, recipient of the 2025 Leibel Memorial Award. The award is given to early- to mid-career American Board of Radiology-certified or board-eligible principal investigators chosen each year by the Annual Meeting Steering Committee based on their abstract’s peer-reviewed scores.
Dr. Kishan presented “177Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer: Primary Endpoint Analysis of the Phase II LUNAR Randomized Trial.” The study found progression-free survival could be significantly extended for patients whose prostate cancer had recurred in a limited number of areas outside the prostate (five or fewer on an advanced PSMA-based PET/CT scan) by adding PSMA-targeting radioligand therapy with 177Lu-PNT2002 to metastasis-directed stereotactic body radiation therapy (SBRT). The addition of 177Lu-PSMA to SBRT more than doubled progression-free survival, without significantly increasing toxicity, from 7.4 months with SBRT alone to 17.6 months with the combination approach.
“The LUNAR trial is the first study to combine these therapies,” Dr. Kishan said. “Patients were able to avoid hormonal therapy — and all the associated side effects — for longer, with hormonal-therapy free survival improved from 14.1 months with SBRT alone to 24.3 months with the combination.”
Mack Roach, MD, PhD, FASTRO, of the University of California, San Francisco, then presented “Androgen Deprivation Therapy (ADT) and High Dose Definitive Radiotherapy (RT) +/- Whole Pelvic RT in Patients with Unfavorable Intermediate or Favorable High-Risk Prostate Cancer: Early Results of a Phase III Randomized Controlled Trial.”
This study, the largest study completed in localized prostate cancer with the primary endpoint of overall survival, compared prophylactic whole pelvic radiation therapy (WPRT) to prostate-only, dose-escalated radiation therapy (PORT) in 2,590 patients with unfavorable intermediate or high-risk prostate cancer and found it did not improve overall survival or prostate cancer specific survival after 10 years, with a median follow-up of 7.3 years. However, Dr. Roach noted that these were early results and that 80% of prostate cancer deaths typically occur beyond 10 years of follow-up, and therefore these results will need additional follow-up to draw conclusions about the primary endpoint.
“Some people might think this is a negative study,” Dr. Roach said. “I don’t happen to be one of them.” He added that there was a 4-point difference between the two arms in biochemical failure, the secondary endpoint, with 17% failure rate for the PORT arm and 13% in the WPRT arm.
“Most importantly for our patients, the high prostate cancer specific survival rate of 98% and relatively low morbidity confirms that ADT plus PORT appears to represent an excellent treatment option for these patients.”
Discussant Karen Hoffman, MD, FASTRO, of the University of Texas MD Anderson Cancer Center in Houston, shared her perspective on the three trials, noting that she refers to Drs. Spratt, Kishan and Roach as “the three musketeers, given their innovative ways of fighting prostate cancer.”
Next, Jarad Martin, MD, MB, ChB, PhD, of Calvary Mater Newcastle Hospital in New South Wales, Australia presented, “Toxicities and Quality of Life Following Observation or Radiation Therapy for Dupuytren’s Disease in the International DEPART Randomized Trial.” The study was the first of two trials in the session exploring the use of low-dose radiation for conditions other than cancer.
“Dupuytren’s disease is a common health problem affecting the hands that can cause the fingers to curl up, or contract, affecting day-to-day activities,” Dr. Martin said. “The DEPART randomized trial accrued over 400 people to test whether giving low dose radiotherapy in the early phases of Dupuytren’s disease can reduce the risk of developing contractures. While waiting for that main outcome, our preliminary results report the promising findings that low dose radiotherapy is safe, and people who receive it have better quality of life after three years of follow-up.”
Byoung Hyuck Kim, MD, PhD, of SMG-SNU Boramae Medical Center in Seoul, Korea, presented the second non-cancer related radiation therapy study, “Clinical Effectiveness of Single Course Low-Dose Radiation Therapy in Knee Osteoarthritis: Short-term Results from the Randomized, Sham-Controlled Trial.” Using a novel, sham-controlled design, this randomized trial showed a single course of low-dose radiation could provide significant pain relief and improve physical function for people with mild to moderate knee osteoarthritis.
“People with painful knee osteoarthritis often face a difficult choice between the risks of side effects from pain medications and the risks of joint replacement surgery,” Dr. Kim said. “There’s a clinical need for moderate interventions between weak pain medications and aggressive surgery, and we think radiation may be a suitable option for those patients especially when drugs and injections are poorly tolerated.” One of the limitations of the study is the lack of generalizability to other groups because of the overall low BMI of the patients who were enrolled.
Discussant Gopal Bajaj, MD, FASTRO, of Inova Schar Cancer Institute in Fairfax, Virginia, noted that there has been “resurging global interest” in the use of functional radiation therapy and that Dr. Martin’s and Dr. Kim’s studies would provide much-needed “rigorous data to validate its use, though the results are still early.” Dr. Bajaj added of Dr. Kim’s study, “When patients seek care, they already have contractures, so we need to understand the potential benefit of radiation for patients who have undergone surgical fixation.”
The final two studies investigated how lowering radiation doses would affect disease control in two types of cancer. Christopher Kelsey, MD, FASTRO, of Duke University Medical Center in Durham, North Carolina, presented “Decreasing the Dose of Consolidation Radiation Therapy in DLBCL/HGBL: A Phase II Trial by the International Lymphoma Radiation Oncology Group.” The study, which enrolled a diverse group of 243 patients from 16 institutions in Asia, Europe and the U.S., found high rates of local control could be achieved when lowering the dose of consolidation radiation from the currently recommended 30 Gy to 20 Gy.
“As outcomes for patients with diffuse large B-cell lymphoma have improved and long-term remissions are now achieved in most cases, optimizing treatment intensity has become increasingly important to minimize unnecessary acute and long-term risks,” Dr. Kelsey said. “This study demonstrated that lowering the dose of consolidation radiation therapy did not compromise efficacy. Given that many patients are young and face potential long-term complications from both chemotherapy and radiation, the findings of this international study represent an important step forward in refining treatment approaches.”
To close out the session, Feng Liu, MD, of Hunan Cancer Hospital in Changsha, China, presented “Efficacy of Hypofractionated Stereotactic Radiotherapy with Different Dose Fractionation Regimens Combined with Concurrent Bevacizumab in Recurrent High-Grade Gliomas: A Randomized Controlled Trial.”
The study compared three hypofractionated stereotactic radiation therapy regimens, each combined with concurrent bevacizumab, and found that regimens with higher doses per fraction (27 Gy in 3 fractions or 30 Gy in 5 fractions) achieved better objective response rates and progression-free survival than a more protracted regimen with lower dose per fraction (35 Gy in 10 fractions).
“This study addresses a critical gap in the management of recurrent high-grade gliomas, an aggressive condition with limited treatment options,” Dr. Liu said. “The findings offer clinically relevant insights into balancing efficacy and toxicity, thereby supporting more informed treatment personalization and potentially improving outcomes for patients with this challenging disease.”
