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Hormone Therapy of Little Benefit with Radiotherapy after Prostate Surgery

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Findings could help patients avoid side significant effects and improve quality of life

Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

A new study led by UCLA Health investigators suggests that adding hormone therapy to post-operative radiotherapy may provide little survival benefit for most men with prostate cancer, especially for those with very low PSA levels before treatment. 

The researchers found that for men with low PSA levels prior to radiotherapy, adding hormone therapy, whether short-term or long-term, did not improve overall survival. Men with higher PSA levels before radiation may see modest improvements in survival and metastasis-free survival, suggesting hormone therapy may be beneficial primarily for this higher-risk group.

The results were published today in The Lancet and presented by Dr Amar Kishan, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA, during the plenary session of the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco. 

“Hormone therapy, which impacts the ability of testosterone to stimulate prostate cancer growth and repair, has been shown to improve outcomes when combined with radiotherapy in men whose prostates are still intact. However, whether it has a similar benefit for men receiving radiotherapy after prior surgery has remained unclear,” said Kishan, first author of the study and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center. “At the same time, hormone therapy carries significant side effects, including severe fatigue, hot flashes, sexual dysfunction, weight gain, bone loss and metabolic changes that can increase cardiovascular risk. Our findings show that for most men with detectable but low PSA levels (<0.5 ng/mL), after surgery to remove the prostate, post-operative radiotherapy is highly effective on its own. By safely omitting hormone therapy in these patients, we can potentially spare them months of treatment that may substantially affect their quality of life without extending survival.”

To better understand the impact of hormone therapy in this setting, the researchers conducted a large-scale, individual patient-level meta-analysis through the MARCAP Consortium, an international collaboration co-led by Kishan that is designed to evaluate long-term outcomes across randomized clinical trials.

The team analysed data from 6057 men enrolled in six randomised trials comparing post-operative radiotherapy alone to radiotherapy combined with either short-term (4-6 months) or long-term (24 months) hormone therapy. By pooling individual patient data rather than relying on summary trial results, investigators were able to examine outcomes in greater detail, including how pre-radiation PSA levels influenced treatment benefit.

Patients were followed for a median of nine years, allowing researchers to assess long-term overall survival, metastasis-free survival and recurrence outcomes. The analysis also enabled direct comparisons between short-term and long-term hormone therapy to determine whether extending treatment duration improved outcomes.

The researchers found that overall, 83.6% of men who received post-operative radiotherapy alone were alive after 10 years, compared with 84.3% for those who received post-operative radiotherapy plus hormone therapy.

Researchers found that pre-radiotherapy PSA levels, a measure of prostate-specific antigen in the blood after prostatectomy, played a crucial role. Men with low PSA levels before radiotherapy (≤0.5 ng/mL) saw no benefit from hormone therapy. In contrast, men with higher PSA levels showed modest improvements in survival, suggesting that hormone therapy may only be worthwhile for those with elevated PSA. 

The study also examined the duration of hormone therapy. Short-term therapy did not improve overall survival, though it slightly reduced the risk of cancer spreading. Long-term therapy showed a small survival benefit, particularly for men with higher PSA levels after prostatectomy. However, the team’s statistical analysis demonstrated that extending short-term therapy to long-term therapy did not further improve survival, although it did modestly lower the risk of metastasis.

“Our goal is always to treat the cancer while minimizing harm,” said Kishan. “This study helps us move toward more personalised care for men with prostate cancer. By better identifying who truly benefits from hormone therapy, we can make treatment smarter, reduce unnecessary interventions and focus on improving patients’ overall well-being.”

Building on those findings, ongoing research is working to further refine that approach. Trials such as the BALANCE Trial aim to pinpoint biomarkers that can identify which men are most likely to benefit from hormone therapy after surgery, helping tailor treatment decisions even more precisely.

Source: UCLA Health

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Improving Understanding of Female Sexual Anatomy for Better Pelvic Radiotherapy

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Female reproductive system. Credit: Scientific Animations CC4.0 BY-SA

Researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with other leading institutions across the country, have published an innovative study that provides radiation oncologists with practical guidance to identify and protect female sexual organs during pelvic cancer treatment.  

Published in the latest issue of Practical Radiation Oncology, this study addresses a long-standing gap in cancer care by bringing key female sexual anatomy into consideration during routine radiotherapy planning and survivorship research. 

The study, “Getting c-literate: Bulboclitoris functional anatomy and its implications for radiotherapy,” synthesises current scientific knowledge and pairs it with original anatomic dissection, histology, and advanced imaging analysis. The work focuses on the bulboclitoris, a female erectile organ (consisting of the clitoris and the vestibular bulbs) that plays a central role in sexual arousal and orgasm and can be exposed to radiation during treatment for pelvic cancers. 

“Pelvic radiotherapy can be life-saving, but it can also affect sexual function and quality of life,” said Deborah Marshall, MD, MAS, Assistant Professor, Departments of Radiation Oncology and Population Health Science and Policy at the Icahn School of Medicine at Mount Sinai; Division Chief of Women’s Health, Department of Population Health Science and Policy; and senior author of the study. “Compared to male sexual anatomy, female erectile structures have been largely invisible in standard radiation workflows. Our goal was to provide clinicians with a practical anatomy-grounded way to change that.” 

Using detailed anatomic and radiologic correlation, the research team demonstrates how the bulboclitoris and related neurovascular structures can be identified on standard CT and MRI scans and consistently outlined (or “contoured”) for radiotherapy planning. This step-by-step guidance makes it feasible for clinicians to measure radiation dose to these tissues and begin linking exposure to patient-reported outcomes related to arousal and orgasm. 

“This work builds upon our previous knowledge that the clitoris is not just an external structure,” Dr. Marshall said. “It includes an entire internal organ comprised of erectile tissues located just outside the pelvis, and those tissues matter for sexual health and, in particular, for female sexual pleasure. Once clinicians can reliably see and measure them, we can begin to ask better questions, have better conversations with patients, and ultimately deliver better care.” 

Sexual function outcomes after pelvic radiotherapy have historically been understudied in women, limiting counselling, toxicity prevention strategies, and equitable survivorship care. By establishing a shared, standardised approach to identifying the bulboclitoris, the study lays the groundwork for future research to develop dose-volume constraints and mitigation strategies, as other organs at risk are managed in radiation oncology. 

For clinicians, the framework enables routine contouring and dose reporting using CT alone when necessary, with MRI improving soft-tissue visualization when available. In the absence of prospective dose-response data, the authors recommend minimising radiation dose to the bulboclitoris when oncologically appropriate, using an “as low as reasonably achievable” approach. 

For patients, the work supports more informed conversations about potential sexual side effects of pelvic radiotherapy, including changes in arousal, sensation, orgasm, lubrication, or pain. This research also promotes more personalized treatment planning that considers female sexual health and pleasure as a legitimate and important component of cancer survivorship. 

Next steps include prospective research through Mount Sinai’s STAR program, deeper mapping of neurovascular anatomy relevant to sexual function, expanded educational resources for oncology and radiology teams, and improved patient-reported outcome measures that reflect diverse sexual practices and experiences. 

Source: Mount Sinai

Categories : CancerTags :

Strong Evidence for Effectiveness of Metastasis-directed Radiotherapy in Prostate Cancer

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Photo by Jo McNamara

Metastasis-directed therapy (MDT) significantly improved outcomes in patients with oligometastatic prostate cancer, according to a new study from researchers at The University of Texas MD Anderson Cancer Center published today in Lancet Oncology.

The study is a first-of-its-kind meta-analysis of individual patients across all available randomised clinical trials evaluating the addition of metastasis-directed radiation therapy to standard-of-care treatment.

According to corresponding author Chad Tang, MD, associate professor of Genitourinary Radiation Oncology, gathering level one evidence of the benefits of MDT in this cancer type has been a challenge due to several factors. Most significant among them are that only a small number of patients have oligometastatic cancer – meaning they have multiple metastases but not enough to be considered widely metastatic – and the relative indolence of oligometastatic disease.

“If we can identify and treat this disease in the narrow window before it spreads too far, we know that patient outcomes are significantly better. But gathering this data is difficult,” Tang said. “By bringing together all available patient data from randomized clinical trials, we have provided the best evidence to date that MDT improves patient outcomes.”

What is MDT and what is the significance of this study on oligometastatic prostate cancer?

Broadly, MDT can include multiple treatment approaches. In this setting, the most common form of MDT is radiation therapy, which targets metastases at a stage when cancer has begun to spread but hasn’t yet spread widely. This approach potentially brings several benefits to patients, such as delaying the time to progression and limiting the need for more aggressive therapies that will further impact quality of life.

The most common form of MDT is stereotactic body radiation therapy (SBRT), a type of very precise radiation therapy. In previous studies, like the Phase II EXTEND trial presented in 2024, MDT significantly improved progression-free survival (PFS). 

These and similar findings have led to widespread adoption of MDT in the oligometastatic setting, despite the lack of level one evidence.

To try and address that lack of data, researchers from several institutions created a global consortium, known as X-MET, to gather the data from all randomized trials for analysis at MD Anderson. Individual patient data from seven trials were ultimately included in this meta-analysis, known as WOLVERINE.

What were the results of the study?

This study, which included 574 men, showed a significant benefit for the patients receiving the MDT arm in PFS, radiographic PFS, and castration resistance-free survival.

Patients in the MDT arm gained a median of 7.6 months before disease progression, 4.9 months before radiographic disease progression, and 2.5 months before developing castration-resistance disease, compared to patients receiving standard of care alone. These findings were consistent across the individual trials and in the aggregated data.

Additionally, there were no significant differences in safety between the treatment arms. No grade five toxicities were observed in either arm, and any adverse effects above grade two were similar between the two arms.

“We hope that this dataset will lay the groundwork for future Phase III trials, which hopefully will show an overall survival benefit for these patients,” Tang said. “However, what this data does already show is the best evidence to date that MDT significantly benefits patients without adding any notable safety risks.”

Source: The University of Texas MD Anderson Cancer Center

Categories : Cancer DermatologyTags :

Research Finds Protein Behind Radiotherapy-induced Skin Damage

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The protein Dickkopf 3 plays a key role in the development of radiation-induced fibroses – and could be a promising target for novel therapies

Picture by Macrovector on Freepik

Radiotherapy is one of the main treatment forms for cancer. Among its most common side effects is skin damage, right up to chronic inflammations and fibroses. At present, such long-term damage can only be treated symptomatically and leads to thickened, painful, or sensitive skin for months to years after the radiation treatment. A team led by LMU immunologist Professor Peter Nelson (LMU University Hospital) and Roger Sandhoff and Peter E. Huber from the German Cancer Research Center (DKFZ) has identified a protein called Dickkopf 3 (DKK3) as a main cause of long-term skin damage after radiotherapy – a decisive step for the development of novel, more targeted therapy options.

The results were published in Signal Transduction and Targeted Therapy.

By investigating mouse models and human cells and tissue samples, the researchers demonstrated that DKK3 is activated after radiotherapy in a certain group of skin cells that are responsible for skin renewal. This activity triggers a chain reaction which promotes inflammations and the formation of scar-like tissue and leads to chronic skin damage. The key findings were driven by the work of LMU students, Li Li and Khuram Shehzad. Their efforts were essential in identifying DKK3 as the critical molecular mediator and in establishing the mechanistic framework presented in the paper. “We also observed similar processes in the kidney,” says Nelson. “This indicates that the activation of DKK3 is a fundamental mechanism that promotes fibrosis in various tissues.”

According to the researchers, these findings underscore that DKK3 represents a promising new treatment target. “Drugs that block DKK3 could one day help prevent or reduce long-term skin damage after radiotherapy and thus improve the quality of life of cancer patients and survivors,” says Nelson. The researchers are currently investigating, moreover, whether this approach could also contribute to the prevention of scar formation in other organs.

Source: Ludwig Maximilian University of Munich

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Targeted Radiation During Surgery Reduces Pancreatic Cancer Recurrence

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Image of a what is targeted with radiation. Red represents the pancreatic tumor, which is contacting with a major nearby artery. Yellow represents the Baltimore Triangle, which is now targeted in all patients, in addition to red volume. Credit: Amol Narang, M.D.

Using targeted radiation during surgery – referred to as intraoperative radiation – to eliminate pancreatic cancer cells that have spread to areas around the pancreas, investigators at Johns Hopkins have been able to reduce the recurrence rate around the pancreas to 5%. This is believed to be the lowest ever reported for this population of patients, according to a preliminary study by the team from the Johns Hopkins Kimmel Cancer Center.

The study was presented at the American Society for Radiation Oncology annual meeting in September 2025.

The study enrolled 20 patients with borderline resectable or locally advanced pancreatic cancer. Patients received presurgical chemotherapy and radiation targeted to shrink the tumours away from the blood vessels. Then, during surgery to remove their tumours, patients received another dose of precisely targeted radiation using a robotic device that carries small radioactive beads inserted through catheters. The device enabled the team to pinpoint a triangular area near the pancreas, where recurrences commonly occur. Only one of the 20 patients experienced a recurrence around the pancreas at the 24-month mark – a major achievement for a cancer that, until recently, had lagged behind other cancers in treatment success.

By the time most pancreatic cancers are diagnosed, the tumours have spread to affect important blood vessels around the pancreas. Historically, patients with pancreatic cancers whose blood vessels were affected could not undergo surgical removal of their tumours. But in the past decade, clinicians at the Johns Hopkins Kimmel Cancer Center’s Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care have pioneered new approaches that use chemotherapy and radiation to shrink the tumours away from blood vessels, enabling more patients to undergo surgical removal of their tumours.

However, many of these patients continued to experience tumor recurrences, and Amol Narang, M.D., associate professor of radiation oncology and molecular radiation sciences, and his colleagues sought to determine why.

The team learned that the pancreatic cancer cells were spreading along nerves near the pancreas to a fatty, nerve-dense triangular area just above the pancreas, which Narang calls the “Baltimore triangle.” When he and his colleagues started targeting the Baltimore triangle with radiation before surgery to kill these stray cancer cells, pancreatic cancer recurrence rates in their patients dropped from 47% to 12% at two years post-surgery. Yet, in the 12% who experienced recurrences around the pancreas, the recurrences continued to occur in the Baltimore triangle.

To further lower recurrence rates, Narang and his colleagues decided to deliver an additional round of Baltimore triangle-targeted radiation to patients during surgery after removal of the pancreatic tumour. He explained that, during the surgery, surgeons remove a part of the duodenum, next to the pancreas, making it easier to access the Baltimore triangle without risking harm to surrounding organs. The combination of radiation targeted to the Baltimore Triangle prior to surgery as well as intraoperative radiation to the triangle during surgery allowed Narang to deliver ablative doses of radiation to this region.

“The combination of intraoperative radiation and targeting the Baltimore triangle has gotten us to a 5% recurrence rate, which is the lowest-ever reported recurrence rate around the pancreas for this population of patients to our knowledge. But I think we can drop to 0% in our next study,” Narang says. “We must do whatever we can to prevent recurrences from happening, because when pancreatic cancer comes back, it is often incurable. These results give us hope, though, that this can be done for a cancer where even decade ago, most thought this wasn’t possible.”

The only recurrence in the study occurred in the part of the Baltimore triangle that the team had difficulty reaching during the intraoperative treatment. Currently, the team is developing strategies to target this hard-to-reach part of the triangle, with the hopes of reducing recurrences to zero. Once they’ve mastered that refined approach, they would like to team up with other cancer centres across the US to run a larger clinical trial to confirm their results. 

Source: Johns Hopkins Medicine

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Single-dose Radiation Before Surgery Can Eradicate Breast Cancer

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These two magnetic resonance imaging (MRI) scans were taken 10 months apart. On the left, the blue arrow points to the edge of a breast tumour, and the red arrow locates a biopsy clip, which appears as a black dot. The MRI on the right, which includes the biopsy clip, shows the tumour is gone after a single, targeted dose of radiation and antihormone therapy.

A single, targeted high dose of radiation delivered before other treatments could completely eradicate tumours in most women with early-stage, operable hormone-positive breast cancer, according to a study led by UT Southwestern Medical Center researchers. The findings, published in JAMA Network Open, could shift the paradigm for patients with the most common form of breast cancer, who typically undergo surgery before a regimen of radiation therapy.

“This is a major advance in the field,” said study leader Asal Rahimi, MD, Professor of Radiation Oncology. “This treatment protocol provides patients a significant time savings, spares a lot of their tissue from irradiation, and allows them to still undergo any type of oncoplastic surgery they may choose, all while very effectively treating their disease.”

Like patients with other forms of cancer, those with breast cancer are typically treated with a combination of surgery to remove tumours, medications such as hormone blockers, chemotherapy, and radiation, often in that order. In addition, many patients choose to have breast reconstructive surgeries before radiation treatment.

Having targeted radiation prior to surgery has several benefits, including a more than 100-fold smaller volume of tissue being irradiated compared with whole breast radiation; one day of radiation compared with up to 6.5 weeks of radiation, creating a huge time savings for patients; and more options for patients seeking reconstructive surgery, explained Dr Rahimi.

Early-stage, hormone-positive breast cancer accounts for 60–75% of all breast cancers. Seeking a more time-efficient way to treat these patients, Dr Rahimi and her colleagues tested a strategy in which 44 patients started treatment with a single dose of targeted radiation. While typical radiation therapy protocols call for 1.8–2.67Gy per day for 16 to 33 days, the researchers divided the study participants into three groups and gave each patient a single dose of 30, 34, or 38Gy. The volunteers then went on hormone-blocking drugs and waited a median of 9.8 months until they underwent surgery to remove any residual tumour tissue.

In 72% of study participants, the surgeons found no residual tumor left, indicating that patients had a “pathological complete response.” An additional 21% of patients had a “near complete response,” meaning that their cancer was more than 90% eliminated.

Further analysis showed that time to surgery was the best predictor of response. The longer patients waited to undergo surgery, the more likely their tumours were to disappear, regardless of the radiation dose or tumour size. These results were probably due to the time it takes cells to die or be removed by the immune system after radiation therapy, Dr Rahimi explained.

This new treatment protocol could hold significant advantages over the current gold standard, said Marilyn Leitch, MD, Professor of Surgery. For example, being able to wait to schedule surgery will allow patients to plan for the disruption it brings to their lives. The radiation course lasts a single day rather than weeks. Plus, in the future, this new approach may eliminate the need for surgery in some patients.

“Much of the current research in breast cancer is looking at ways to reduce the extent of surgery, radiation, and/or medical therapy that is required to completely treat early-stage breast cancer. It is very exciting to be part of innovative research that can improve the quality of life of our cancer patients and minimize the extent of treatment they require,” Dr Leitch said.

The research team is currently enrolling patients in a phase two clinical trial. “If the results mirror the ones from this study, an initial targeted dose of radiation could become a new treatment option for patients with small, early-stage, hormone-positive breast cancer,” Dr Leitch said.

Source: UT Southwestern Medical Center

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Radiotherapy After Mastectomy Can Be Avoided

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Photo by Jo McNamara

Radiotherapy can be safely omitted as a treatment for many breast cancer patients who have had a mastectomy and are taking anti-cancer drugs, as shown in a study published in the New England Journal of Medicine. An international trial found that patients with early-stage breast cancer who underwent a mastectomy had similar 10-year survival rates whether or not they received radiotherapy.

Experts say the findings should help guide treatment discussions, as many patients who currently qualify for radiotherapy after mastectomy under existing guidelines may not actually need it.

Outdated practice

For many patients with early-stage breast cancer treated by mastectomy and anti-cancer drugs, chest wall radiotherapy has long been standard to kill any remaining cancer cells and lower the risk of recurrence. 

The practice is based on trials from the 1980s, now considered outdated, leaving uncertainty about its benefit and leading to variation in use worldwide.

The SUPREMO trial (Selective Use of Postoperative Radiotherapy after Mastectomy), led by the University of Edinburgh, studied the impact of chest wall radiotherapy in patients at intermediate risk of breast cancer returning. 

International trial

The group included women from 17 countries with one to three affected lymph nodes, as well as those with none but who had other tumour features of aggressive behaviour that increase the chance of recurrence.

All 1607 patients in the study underwent mastectomy, axillary surgery – removing lymph nodes from the armpit – and modern anti-cancer therapy. They were randomly assigned to chest wall radiotherapy (808 women) or no radiotherapy (799).

Little benefit

There was no difference in overall survival of patients after ten years of follow up – 81.4% of those who received radiotherapy were still alive, compared with 81.9% of those who did not.

Radiotherapy also had no impact on disease-free survival – the length of time without any cancer returning – or on the cancer spreading from the breast around the body, the study found.

Radiotherapy had minimal impact on cancer recurring at the site of mastectomy. Nine patients who received the treatment saw their breast cancer return on the chest wall, compared with 20 who did not. Side effects from radiotherapy were mild with no excess deaths reported from cardiac causes.

Improved drugs

Experts attribute radiotherapy providing less benefit than previously thought to progressive improvements in treatment, particularly better drug treatments, which continue to reduce the chances of the cancer returning, and boost survival rates.

The research team caution that the study only looked at those with intermediate-risk breast cancer. Patients with a higher risk of their cancer returning could possibly benefit from chest wall radiotherapy, they add.

The SUPREMO trial provides no evidence to support the continued use of radiotherapy to the area of the chest wall in most patients with intermediate-risk breast cancer who have undergone a mastectomy if they are also treated with modern anti-cancer drug treatment.

 Professor Ian Kunkler Institute of Genetics and Cancer, University of Edinburgh

Although reported toxicity in the trial was mild, we know that almost all patients experience some side effects of radiotherapy, that can even develop even some years after treatment. Avoiding unnecessary irradiation will reduce both treatment burden and, for example, the detrimental effects on breast reconstruction for these mastectomy patients.

 Dr Nicola Russell Netherlands Cancer Institute and study coordinator on behalf of the EORTC

The international research team included scientists from the UK, Netherlands, Australia and China.

Source: University of Edinburgh

Categories : CancerTags :

Radiotherapy Overcomes Resistance to Immunotherapy in Some Cancers

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By sparking the immune system into action, radiation therapy makes certain tumours that resist immunotherapy susceptible to the treatment, leading to positive outcomes for patients, according to new research published July 22 in Nature Cancer. Investigators dove deep into the molecular biology of non-small 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 anti-tumour immune response in lung cancers that do not typically respond to immunotherapy. The combination therapy also yielded improved clinical response in patients whose tumours harbour features of immunotherapy resistance. 

Clinically, the results suggest that radiation therapy can help overcome immunotherapy resistance in certain patients. Researchers at the Johns Hopkins Kimmel Cancer Center Bloomberg~Kimmel Institute for Cancer Immunotherapy and the Netherlands Cancer Institute conducted the study, which was supported by the National Institutes of Health. 

“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, co-director of the Upper Aerodigestive Malignancies Program, director of the Thoracic Oncology Biorepository, leader of Precision Oncology Analytics, co-leader of the Johns Hopkins Molecular Tumor Board and co-director of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins. 

Researchers have long sought to better understand why some tumours grow resistant to immunotherapy 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 tumour typically causes tumour cells to die and release their contents into the local microenvironment. Sometimes, the immune system discovers those contents, learns the tumour’s molecular footprint, then activates immune cells around the body to attack cancer cells at tumour 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 has been 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 tumour 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 analysed 293 blood and tumour 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 characterise what was happening to the immune system systemically and in the local microenvironment at tumour sites that were not directly exposed to radiation. 

In particular, the team focused on immunologically “cold” tumours — those that typically do not respond to immunotherapy. These tumours can be recognised by particular biomarkers: a low mutation burden, no expression of a protein called PD-L1, or the presence of mutations in a signalling 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 pre-existing T cells. 

“Our findings highlight how radiation can bolster the systemic anti-tumor 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.” Huang was awarded the 2025 Paul Ehrlich Research Award in recognition of groundbreaking discoveries by young investigators and their faculty mentors at the Johns Hopkins University School of Medicine.     

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’ tumours. 

Finally, by tracking patient outcomes from the clinical trial, the team observed that patients with immunologically cold tumours 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,” says Anagnostou. “We not only captured the abscopal effect, but we linked the immune response with clinical outcomes in tumours 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 tumour DNA (ctDNA) 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

Categories : Cancer Neurodegenerative DiseasesTags :

Breast Cancer Treatment Linked to a Reduction in Alzheimer’s Disease Risk

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Photo by National Cancer Institute on Unsplash

A Korean population-based cohort study investigated the risk of Alzheimer’s disease (AD) among breast cancer survivors compared to age-matched controls without cancer. The study, published in JAMA Network Open, found that breast cancer survivors had an 8% lower risk of AD than controls, with a significant association in survivors over 65 years old – though the effect did not persist past five years. Radiotherapy was associated with a lower risk of AD among breast cancer survivors – but not other treatments.

Breast cancer survivors may experience long-term health consequences, including cognitive function and risk of dementia. The risk of AD among breast cancer survivors is still unclear and may vary depending on age at diagnosis, treatment received, and time since treatment.

Previous studies reported mixed results on the risk of AD among breast cancer survivors, with some finding no increase in risk and others finding a 35% increased risk for those diagnosed at age 65 or older. These studies have been hampered by a number of methodological issues, including not accounting for risk factors.

Cytotoxic chemotherapy can cause cognitive decline termed ‘chemobrain’. Other chemotherapy drugs such as anthracycline may reduced AD risk by reducing the formation of amyloid deposits. Endocrine therapy may increase the risk of dementia by lowering oestrogen, but studies suggest that the use of tamoxifen and aromatase inhibitors is associated with a lower risk of AD. An increase in dementia is seen in radiotherapy for head and neck cancers.

To investigate the risk of AD among breast cancer survivors, researchers used the Korean National Health Insurance Service (K-NHIS) database, exploring whether there is an association with cancer treatment and various confounding factors.

Among 70 701 breast cancer survivors (mean age, 53.1 years), 1229 cases of AD were detected, with an incidence rate of 2.45 per 1000 person-years. Survivors exhibited a slightly lower risk of AD compared with cancer-free controls, especially among individuals 65 years or older (SHR, 0.92; 95% CI, 0.85-0.99). But landmark analyses found that this lower risk did not persist beyond five years of survival. Radiotherapy was associated with reduced risk of AD among survivors, while chemotherapy and endocrine therapy had no significant impact. Anthracycline use, however, did show a non-significant decrease in risk.

Differences in doses and timing of radiotherapy may influence the effects. The incident exposure to the brain is estimated to be 0.2Gy from a breast cancer radiotherapy dose of 50Gy. A pilot study found that patients with AD who received low-dose whole-brain radiotherapy at 3Gy showed a temporary improvement in cognitive function. This improvement is believed to be due to a neuroprotective effect on microglia. Other studies have noted a transient risk reduction for AD in breast cancer radiotherapy; however, patients receiving radiotherapy usually do so in conjunction with breast-conserving surgery – those opting for this procedure are younger, with fewer comorbidities and smaller tumours.

The study suggests that cancer treatment may have benefits against AD development, but the risk of AD may differ depending on the duration of survival.

The findings indicate that breast cancer treatment may not directly lead to AD, and that managing modifiable risk factors for AD, such as smoking and diabetes, is a feasible option to lower AD risk among breast cancer survivors.

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Hyperbaric Oxygen for Radiation-induced Injuries Provides Lasting Relief

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Photo by National Cancer Institute on Unsplash

Hyperbaric oxygen treatment provides long-term relief for patients suffering from late radiation-induced injuries after treatment of cancer in the lower abdominal area. Five years after hyperbaric oxygen therapy, the positive effects remain. This has been shown in a study conducted at the University of Gothenburg, published in eClinicalMedicine.

Radiation therapy is a component of many cancer treatments in organs such as the prostate, colon, ovaries and cervix. While tumour cells are destroyed, 5-10% of patients experience severe side effects due to healthy tissue being affected by the radiation therapy.

Symptoms may include urinary incontinence, bleeding and severe pain from the lower abdomen that becomes both physically and socially disabling. These problems can occur several years after radiation therapy and cause chronic and increasing discomfort.

Researchers have previously shown that patients experience significantly less discomfort after hyperbaric oxygen treatment. The question in the current study was whether the relief would last over several years. The time aspect is important for future decisions on broader use of the method.

From severe problems to a normal life 

Initially, all participants had severe symptoms. The group that was randomly assigned to hyperbaric oxygen treatment fared significantly better than the control group in terms of incontinence, bleeding and pain. The positive effects were sustained over the five year follow-up period. 

Nicklas Oscarsson, senior consultant in anaesthesiology and intensive care, and researcher at the University of Gothenburg and Sahlgrenska University Hospital was the principle investigator of the study:

“Patients who respond to treatment go from being very distressed by their symptoms and restricted by their need to have quick access to a toilet, to being able to live a fully normal life. Now we know that this pronounced improvement last for at least five years. The treatment can therefore lead to the healing of an otherwise chronic injury,” he states.

The effects achieved are due to cells sensing and adapting to high oxygen levels. The increased levels of oxygen provided in a hyperbaric chamber increases vascular growth and stops chronic inflammation, reducing severe side effects.

For the oxygen treatments, participants spent 90 minutes a day in a hyperbaric chamber on 30-40 occasions, at a pressure of 1.4 atmospheres (equivalent to 14m underwater). The control group received the usual treatment, which normally includes medication and physiotherapy, for example.

The capacity already exists today

“We have reason to believe that there are many patients with severe symptoms who are never referred to hyperbaric oxygen therapy. Today we already have the capacity to treat more patients, but we need to be better at sharing our knowledge with our colleagues and with patient associations,” says Nicklas Oscarsson.

Severe side effects after radiation therapy are one of the main limitations on the dose of radiation that can be given in cancer treatment. The availability of a treatment that can reduce the number of people affected by these side effects opens the door to increased radiation doses and thus more curable tumours. One area for further investigation, according to the researchers, is whether early treatment with hyperbaric oxygen can prevent the occurrence of severe side effects.

The results are based on surveys and analyses of the participants who have been involved all the way, 70 adults. The treatments were conducted at five university hospitals in the Nordic countries: Rigshospitalet in Denmark, Turku in Finland, Haukeland in Norway, and Karolinska and Sahlgrenska in Sweden.

Source: University of Gothenburg