E-News Exclusives
Deep Radiomics Boost Chemotherapy Prediction in Breast Cancer
In an era where precision medicine is rapidly transforming cancer treatment paradigms, innovative approaches that harness the power of advanced imaging and AI are at the forefront of oncological research. A recent breakthrough study spearheaded by Jiang, Low, Huang, and their team has demonstrated the potential of 18F-FDG PET/CT-based deep radiomic models to significantly enhance the prediction accuracy of chemotherapy responses in breast cancer patients. This pioneering work, reported in Medical Oncology in 2025, marks a significant stride toward personalized therapeutic strategies, promising to refine clinical decision-making and improve patient outcomes.
The challenge of predicting how breast cancer will respond to chemotherapy remains a critical bottleneck in oncology. Traditional biopsy methods, though informative, offer limited insights and suffer from spatial sampling bias due to the heterogeneous nature of tumors. Radiomics, an emerging discipline that extracts high-dimensional quantitative features from medical images, offers an unprecedented window into tumor biology beyond what is visible to the naked eye. By integrating 18F-FDG PET/CT imaging with deep learning algorithms, the new approach captures complex tumor phenotypes and metabolic patterns associated with treatment efficacy.
At the heart of this research lies 18F-FDG PET/CT, a hybrid imaging modality that combines metabolic and anatomical information. 18F-FDG, a radiolabeled glucose analog, is preferentially taken up by highly metabolic tumor cells, enabling visualization of active malignancies and their aggressive phenotypes. The CT component, on the other hand, provides structural information that complements metabolic data. By employing deep radiomic modeling on this multidimensional dataset, the researchers developed algorithms capable of discerning subtle variations in tumor texture, intensity, and shape that correlate with chemotherapy responsiveness.
Source: Bioengineer.org
Radiation Therapy Overcomes Immunotherapy Resistance in Some Cancers
By sparking the immune system into action, radiation therapy makes certain tumors that resist immunotherapy susceptible to the treatment, leading to positive outcomes for patients, according to new research by investigators at the Johns Hopkins Kimmel Cancer Center Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the Netherlands Cancer Institute. The work was supported by the National Institutes of Health.
In the study, published July 22 in Nature Cancer, investigators dove deep into the molecular biology of nonsmall cell lung cancer to pinpoint what happens on a cellular and molecular level over time when the cancer is treated with either radiation therapy followed by immunotherapy or immunotherapy alone. They found that radiation plus immunotherapy induced a systemic antitumor immune response in lung cancers that do not typically respond to immunotherapy. The combination therapy also yielded improved clinical response in patients whose tumors harbor features of immunotherapy resistance. Clinically, the results suggest that radiation therapy can help overcome immunotherapy resistance in certain patients.
“For a fraction of lung cancers where we aren’t expecting therapy responses, radiation may be particularly effective to help circumvent primary resistance to immunotherapy; this could potentially be applicable to acquired resistance, too,” says senior study author Valsamo “Elsa” Anagnostou, MD, PhD, codirector of the Upper Aerodigestive Malignancies Program, director of the Thoracic Oncology Biorepository, leader of Precision Oncology Analytics, coleader of the Johns Hopkins Molecular Tumor Board, and codirector of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins.
Researchers have long sought to better understand why some tumors grow resistant to immunotherapy—a treatment strategy that leverages the body’s own immune system to fight cancer cells—and how to intercept that resistance. Radiation therapy has been proposed as one possible way to induce a systemic immune response because of a unique phenomenon called the abscopal effect. Radiation at the site of a primary tumor typically causes tumor cells to die and release their contents into the local microenvironment. Sometimes, the immune system discovers those contents, learns the tumor’s molecular footprint, then activates immune cells around the body to attack cancer cells at tumor sites that were not the targets of the radiation, including some far away from the primary cancer in the body.
Because of this effect, radiation therapy could potentially improve how well an immunotherapy works against a cancer, even far from the original radiation site. Yet little is known about the molecular biology behind the abscopal effect, or how to predict when and in which patients it will occur. To study this phenomenon, Anagnostou and colleagues obtained samples from patients with lung cancer at different times throughout their treatment journey and from various locations in the body, not just at the primary tumor site. They collaborated with Willemijn Theelen and Paul Baas at the Netherlands Cancer Institute, who were running a phase II clinical trial on the effect of radiation therapy followed by immunotherapy, specifically the PD-1 inhibitor pembrolizumab.
With help from Theelen and Baas, Anagnostou’s team analyzed 293 blood and tumor samples from 72 patients, obtained at baseline and after three to six weeks of treatment. Patients in the control group received immunotherapy alone, while the experimental group received radiation followed by immunotherapy. The team then performed multiomic analyses on the samples—combining different “omics” tools, including genomics, transcriptomics, and various cell assays—to deeply characterize what was happening to the immune system systemically and in the local microenvironment at tumor sites that were not directly exposed to radiation. In particular, the team focused on immunologically “cold” tumors—tumors that typically do not respond to immunotherapy. These tumors can be recognized by particular biomarkers: a low mutation burden, no expression of a protein called PD-L1, or the presence of mutations in a signaling pathway called Wnt.
Following radiation and immunotherapy, the team found that “cold” tumors far from the site of radiation experienced a prominent reshaping of the tumor microenvironment. Anagnostou describes this shift as the tumors “warming up,” transitioning from little or no immune activity to inflamed sites with strong immune activity, including the expansion of new and preexisting T cells.
“Our findings highlight how radiation can bolster the systemic antitumor immune response in lung cancers unlikely to respond to immunotherapy alone,” says lead study author Justin Huang, who led the multiomic analyses. “Our work underscores the value of international, interdisciplinary collaboration in translating cancer biology insights to clinical relevance.”
With Kellie Smith, PhD, an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and a Bloomberg~Kimmel Institute for Cancer Immunotherapy researcher, Anagnostou’s team focused on patients who attained long-term survival with combination radiotherapy and immunotherapy, and performed a functional test to find out what the patients’ own T cells were doing in the body. In cell cultures, they confirmed that the T cells expanding in patients who received radiation and immunotherapy were indeed recognizing specific mutation-associated neoantigens from the patients’ tumors. Finally, by tracking patient outcomes from the clinical trial, the team observed that patients with immunologically cold tumors that “warmed up” due to radiation therapy had better outcomes than those who did not receive radiation therapy.
“It was super exciting and truly made everything come full circle,” Anagnostou says. “We not only captured the abscopal effect, but we linked the immune response with clinical outcomes in tumors where one would not expect to see immunotherapy responses.”
Using specimens from the same cohorts of patients, the team has recently been working to capture the body’s response to immunotherapy by detecting circulating tumor DNA in the blood. That work was presented April 28 at the annual meeting of the American Association for Cancer Research in Chicago.
Source: Johns Hopkins Medicine
