Tag: radiotherapy

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.

Categories : Cancer New Compounds and TreatmentsTags :

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

Categories : Cancer Ethics and LawTags :

Court Orders Gauteng Health Department to Treat Cancer Patients

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Judge rules failure to deal with backlog of patients needing radiation treatment is unconstitutional

By Liezl Human

Photo by Bill Oxford on Unsplash

The Gauteng Department of Health is appealing against a judgment by the Johannesburg High Court ordering it to provide radiation oncology treatment to a backlog of nearly 3000 cancer patients at Charlotte Maxeke Hospital and Steve Biko Hospital.

In April last year, activists from SECTION27, Cancer Alliance and the Treatment Action Campaign (TAC) joined cancer patients to march to the department’s provincial office, demanding that millions of rands set aside for radiation treatment be used.

The matter was then taken to court by the Cancer Alliance, represented by SECTION27, after years of attempts to engage with the department about radiation services. They said in a statement they wanted the court to compel the department to provide treatment to the backlog of cancer patients still waiting.

Some patients have been on the list for nearly three years, while others have died while waiting, according to the judgment by Acting Judge Stephen van Nieuwenhuizen. He noted that “irreparable harm” has occurred and continues to occur in the absence of treatment.

He said the backlog, of mostly Charlotte Maxeke patients, had grown due to a lack of radiation equipment at the hospital and a shortage of staff. This was in spite of an allocation of R784-million over three years, specifically ring-fenced for radiology oncology services. The allocation was also meant to help clear the backlog of patients.

Delays in finalising a tender for these services meant that R250-million was returned to National Treasury at the end of the fiscal year, he said.

The judge found that the provincial department had infringed on the rights of these cancer patients in that a high standard of professional ethics had not been maintained. “Efficient and effective use of resources were not promoted. Services were not provided impartially, fairly, equitably and without bias.”

Judge van Nieuwenhuizen said the provincial health department had done “nothing meaningful” since the money was allocated in March 2023 to actually provide radiation oncology treatment to the cancer patients. “On the other hand, the health and general well-being of cancer patients has significantly deteriorated. There is a clear, imminent and ongoing irreparable harm that cancer patients who are on the backlog list are suffering.”

The judge ruled that the department’s failure to provide radiation services to cancer patients on the backlog list was unconstitutional and unlawful.

He added that the provincial health officials “have conducted themselves as a law unto themselves” and ordered that measures be put in place to ensure officials are “held to account for their constitutionally imposed obligation to provide healthcare services … to cancer patients who are on the backlog list”.

He also ordered that the list of cancer patients still awaiting radiation treatment must be updated within 45 days and that a progress report and long-term plan must be submitted to the court within three months.

Salomé Meyer, director of the Cancer Alliance, told GroundUp the ruling would allow the court to get accurate information on the circumstances of each patient still waiting for treatment.

She said the judgment “confirms that civil society has a role to play to hold the government responsible for what it is supposed to do”.

In a statement on 2 April, the department confirmed that it had filed an application for leave to appeal against the ruling. The department said “there are several substantive grounds of appeal, which if left unchallenged will be greatly prejudicial to the patients undergoing radiation oncology services at the hospitals” and might set an “undesirable” precedent.

Republished from Groundup under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article.

Categories : Cancer PaediatricsTags :

Radiopharmaceuticals Being Tested for Brain Tumours in Children

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Credit: National Cancer Institute

Neuroblastoma is a rare disease that affects children, often before the age of two. Some are born with the disease. Paediatric surgeon Jakob Stenman is investigating whether targeted radioactive drugs can slow down the disease in those with the most severe form.

Neuroblastoma is a complicated disease, with the most aggressive variant called high-risk neuroblastoma. Children with this disease are treated very intensively. They may undergo surgery, chemotherapy, high-dose chemotherapy with stem cell transplantation, radiotherapy and antibody treatment. Treatment often lasts up to a year and a half.

Despite this, the survival rate is around 60%, according to the Swedish Childhood Cancer Foundation.

“Some relapse in their disease, and we currently lack curative treatment for them,” says Jakob Stenman, a researcher at the Department of Women’s and Children’s Health at Karolinska Institutet.

It is these children, those who have relapsed, that he is treating in a study with targeted radioactive drugs. These are molecules that attach to the surface of cancer cells. These molecules have an appendage: the radioactive substance lutetium-177. The drug first moves through the bloodstream but then attaches to the cancer cells. The emitted radiation damages the cancer cells but unfortunately also the neighbouring healthy cells.

“We have treated ten children so far. Unfortunately, the disease has not disappeared in any of these cases, but it seems to be slowing down, and some benefit more than others from the treatment. When it comes to side effects, the children have tolerated the treatment well,” says Jakob Stenman.

The hope is to be able to prevent relapse

He reports that the interest has been great from clinics in other countries where these children are treated. Hospitals from Lithuania, the Netherlands, the United Kingdom and are now involved.

In neuroblastoma, cancer cells often look very different, even in the same patient. In some metastases, there may be many cells with a surface where the drug attaches, while in other metastases there may be fewer such cells. This means that the targeted drug attaches to fewer cells in some of the metastases. As a result, the local radiation dose is too low in these metastases, which can then continue to grow and spread further.

Jakob Stenman therefore believes that the treatment could be more effective if the radioactive substance used is even more potent, which in this context means that it emits even more energy (ie, radiation). If it then attaches to fewer cells in a metastasis, it might still be able to eliminate all the cancer cells there. But it must act even more locally to protect other tissues from the higher radiation dose.

The researchers have identified several substances they believe could work in this way. These include actinium-225, astatine-211 or lead-212. The effects and side effects of actinium-225 are now being investigated in cell studies and animal experiments. The goal is to start a clinical trial with actinium in three to five years.

“If what we believe turns out to be true, we hope to be able to prevent relapse and thereby enable a cure for a larger proportion of children who have developed high-risk neuroblastoma,” says Jakob Stenman.

Text: Annika Lund for Medicinsk Vetenskap nr 4 2024 

Source: Karolinska Institutet

Categories : CancerTags :

Shorter, Higher-dose Radiotherapy for Prostate Cancer Delivers Promising Results

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Photo by Jo McNamara

A new large-scale study co-led by UCLA Health Jonsson Comprehensive Cancer Center investigators provides the strongest evidence yet that a shorter, standard-dose course radiation treatment is just as effective as conventional radiotherapy for early-stage prostate cancer, without compromising the safety of patients.

The shorter approach, known as isodose moderately hypofractionated radiotherapy (MHFRT), delivers slightly higher doses of radiation per session, allowing the total treatment duration to be over four to five weeks instead of seven to eight weeks.

According to the study, patients who received this type of MHFRT had the same cancer control rates as those who received conventional radiotherapy. Additionally, the risk of long-term side effects affecting the bladder and intestines was no higher with MHFRT, confirming its safety. 

The findings were published in the Lancet Oncology.

“We believe these data strongly support that isodose MHFRT should become the preferred standard of care MHFRT regimen for prostate cancer,” said Dr Amar Kishan, executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA and co-first author of the study. “More broadly, there appears to be little reason to consider conventional radiotherapy over MHFRT for the types of patients enrolled in these trials given these results.”

While MHFRT is now the most commonly used radiotherapy regimen for prostate cancer, concerns remain about whether delivering a higher daily dose increases the risk of urinary and bowel issues, such urinary incontinence, chronic diarrhoea and rectal bleeding.

MHFRT: isodose versus dose-escalated

To better understand whether there might be an increased risk of toxicity with the delivery of a higher dose per day of radiation, Kishan and the team of researchers examined data from more than 5800 patients across seven randomised clinical trials comparing standard therapy with two different MHFRT approaches: isodose MHFRT, which maintains the total radiation dose at a level similar to standard therapy, and dose-escalated MHFRT, which increases the total dose in hopes of enhancing tumour control.

The analysis found patients who received isodose MHFRT (60Gy in 20 fractions) had similar cancer control and side effects compared to those receiving conventional radiation therapy, with no significant difference in the five-year progression-free survival (77.0% for MHFRT vs 75.6% for conventional).

Patients who received higher dose-escalated MHFRT did not improve cancer control when compared to those receiving standard doses, with five-year progression-free survival rates being identical to conventional therapy (82.7% in both groups). Patient-reported outcomes also showed significantly higher gastrointestinal side effects (7.2% vs 4.9%), particularly bowel issues. 

While dose-escalated MHFRT was expected to improve outcomes, the data showed no additional benefit in cancer control and a higher risk of gastrointestinal side effects, noted Kishan. This underscores the advantage of isodose MHFRT, which provides the same effectiveness as conventional therapy without increasing toxicity.

“These findings reinforce isodose MHFRT as the standard of care, offering the same cancer control as conventional treatment but with fewer side effects than dose-escalated MHFRT,” said Kishan, who is also a researcher in the UCLA Health Jonsson Comprehensive Cancer Center. “Patients can safely opt for a shorter treatment schedule without compromising their outcomes, ensuring they receive effective care with fewer visits and minimal added risk. Less time in treatment can still mean the best possible results.”

Source: University of California – Los Angeles Health Sciences

Categories : CancerTags :

A Citrus Remedy Quenches Dry Mouth in Cancer Patients

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Photo by Diana Polekhina on Unsplash

A natural citrus oil from oranges, lemons, and limes is proving highly effective in relieving dry mouth, and when combined with a new lipid formulation, new research suggests it may be effective without significant side effects.

Developed by the University of South Australia in collaboration with the Medical School at Stanford University, this world first formulation uniquely combines limonene (a citrus essential oil) with a lipid-based drug delivery system to treat dry mouth (xerostomia), a common side effect of radiotherapy.

The new formula demonstrated 180-fold better solubility than pure limonene in lab experiments and boosted relative bioavailability by over 4000% compared to pure limonene in pre-clinical trials.

Dry mouth is the most reported side effect following radiotherapy for the treatment of head and neck cancer, affecting up to 70% of patients due to salivary gland damage. It can lead to difficulty speaking and swallowing, significantly reducing quality of life.

Limonene has protective effects on saliva production during radiotherapy, but its poor solubility means high doses are needed to take effect, and these cause indigestion, abdominal discomfort and unpleasant ‘citrus burps’.

Lead researcher, Professor Clive Prestidge says UniSA’s new limonene-lipid combination creates a ‘super-solubilising’ treatment that reduces dry mouth at lower dose and without uncomfortable side effects.

“The therapeutic benefits of limonene are well known. It’s used as an anti-inflammatory, antioxidant, and mood-enhancing agent, and can also improve digestion and gut function. But despite its widespread use, its volatility and poor solubility have limited its development as an oral therapy,” Prof Prestidge says.

“As limonene is an oil, it forms a film on the top of the stomach contents, causing significant stomach pain and discomfort.

“Our novel formulation combines limonene with healthy fats and oils – called lipids – to create a super-solubilising compound that the body can easily absorb with reduced uncomfortable side effects.

“This increases the dispersion of limonene in the stomach, boosts absorption, and controls biodistribution – all while increasing a patient’s saliva production and reducing dry mouth.”

Co-researcher Dr Leah Wright says the formulation has the potential to significantly improve the quality of life for cancer patients and others suffering dry mouth conditions.

“Cancer patients undergoing radiotherapy and other medical treatments regularly experience dry mouth, which not only prevents them from comfortably swallowing, but can also have other negative and potentially life-threatening outcomes,” Dr Wright says. 

“While limonene can be ingested directly, it’s not well tolerated, especially by those with dry mouth. Plus, its poor absorption prevents it from effectively reaching the salivary glands – the target site.

“This inventive and highly impactful limonene-lipid formulation could provide a simple, effective oral solution for dry mouth, offering cancer patients long-lasting relief and comfort, improved oral health, and a higher quality of life during a difficult time.”

Clinical trials for the new formula are ongoing, with next steps to be announced soon.

Source: University of South Australia

Categories : Cancer Neurology New Compounds and TreatmentsTags :

Drug More than Doubles Survival Time for Glioblastoma Patients

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

A drug developed at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has been shown to extend survival for patients with glioblastoma, the most common primary brain tumour in adults.

Results of a trial led by the university and reported in Nature Communications revealed that a unique investigational drug formulation called Rhenium Obisbemeda (186RNL) more than doubled median survival and progression-free time, compared with standard median survival and progression rates, and with no dose-limiting toxic effects.

“As a disease with a pattern of recurrence, resistance to chemotherapies and difficulty to treat, glioblastoma has needed durable treatments that can directly target the tumour while sparing healthy tissue,” said lead author Andrew J. Brenner, MD, PhD, professor and chair of neuro-oncology research with Mays Cancer Center at UT Health San Antonio. “This trial provides hope, with a second trial under way and planned for completion by the end of this year.”

Brenner said that the median overall survival time for patients with glioblastoma after standard treatment fails with surgery, radiation and chemotherapy is only about 8 months. More than 90% of patients have a recurrence of the disease at its original location.

Rhenium Obisbemeda enables very high levels of a specific activity of rhenium-186 (186Re), a beta-emitting radioisotope, to be delivered by tiny liposomes, referring to artificial vesicles or sacs having at least one lipid bilayer. The researchers used a custom molecule known as BMEDA to chelate or attach 186Re and transport it into the interior of a liposome where it is irreversibly trapped.

In this trial, known as the phase 1 ReSPECT-GBM trial, scientists set out to determine the maximum tolerated dose of the drug, as well as safety, overall response rate, disease progression-free survival and overall survival.

After failing one to three therapies, 21 patients who were enrolled in the study between March 5, 2015, and April 22, 2021, were treated with the drug administered directly to the tumours using neuronavigation and convection catheters.

The researchers observed a significant improvement in survival compared with historical controls, especially in patients with the highest absorbed doses, with a median survival and progression-free time of 17 months and 6 months, respectively, for doses greater than 100Gy.

Importantly, they did not observe any dose-limiting toxic effects, with most adverse effects deemed unrelated to the study treatment.

“The combination of a novel nanoliposome radiotherapeutic delivered by convection-enhanced delivery, facilitated by neuronavigational tools, catheter design and imaging solutions, can successfully and safely provide high absorbed radiation doses to tumours with minimal toxicity and potential survival benefit,” Brenner concluded.

Source: University of Texas Health Science Center at San Antonio

Categories : Cancer New Compounds and TreatmentsTags :

A Protein from Tardigrades may Blunt the Effects of Radiotherapy

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A tardigrade, otherwise known as a “water bear”. Credit: NIH

Drawing inspiration from a tiny organism that can withstand huge amounts of radiation, researchers have developed a new strategy that may protect patients from this kind of damage. Their approach makes use of a protein from tardigrades, often also called “water bears,” which are usually less than a millimetre in length. 

When the researchers injected messenger RNA encoding this protein into mice, they found that it generated enough protein to protect cells’ DNA from radiation-induced damage. If developed for use in humans, this approach could benefit many cancer patients, the researchers say.

“Radiation can be very helpful for many tumours, but we also recognise that the side effects can be limiting. There’s an unmet need with respect to helping patients mitigate the risk of damaging adjacent tissue,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.

Traverso and James Byrne, an assistant professor of radiation oncology at the University of Iowa, are the senior authors of the study, which appears in Nature Biomedical Engineering. The paper’s lead authors are Ameya Kirtane, an instructor in medicine at Harvard Medical School and a visiting scientist at MIT’s Koch Institute for Integrative Cancer Research, and Jianling Bi, a research scientist at the University of Iowa.

Extreme survival

Radiation is often used to treat cancers of the head and neck, where it can damage the mouth or throat, making it very painful to eat or drink. It is also commonly used for gastrointestinal cancers, which can lead to rectal bleeding. Many patients end up delaying treatments or stopping them altogether.

“This affects a huge number of patients, and it can manifest as something as simple as mouth sores, which can limit a person’s ability to eat because it’s so painful, to requiring hospitalization because people are suffering so terribly from the pain, weight loss, or bleeding. It can be pretty dangerous, and it’s something that we really wanted to try and address,” Byrne says.

Currently, there are very few ways to prevent radiation damage in cancer patients. There are a handful of drugs that can be given to try to reduce the damage, and for prostate cancer patients, a hydrogel can be used to create a physical barrier between the prostate and the rectum during radiation treatment.

For several years, Traverso and Byrne have been working on developing new ways to prevent radiation damage. In the new study, they were inspired by the extraordinary survival ability of tardigrades. Found all over the world, usually in aquatic environments, these organisms are well known for their resilience to extreme conditions. Scientists have even sent them into space, where they were shown to survive extreme dehydration and cosmic radiation.

One key component of tardigrades’ defence systems is a unique damage suppressor protein called Dsup, which binds to DNA and helps protect it from radiation-induced damage. This protein plays a major role in tardigrades’ ability to survive radiation doses 2000 to 3000 times higher than what a human being can tolerate.

When brainstorming ideas for novel ways to protect cancer patients from radiation, the researchers wondered if they might be able to deliver messenger RNA encoding Dsup to patient tissues before radiation treatment. This mRNA would trigger cells to transiently express the protein, protecting DNA during the treatment. After a few hours, the mRNA and protein would disappear.

For this to work, the researchers needed a way to deliver mRNA that would generate large amounts of protein in the target tissues. They screened libraries of delivery particles containing both polymer and lipid components, which have been used separately to achieve efficient mRNA delivery. From these screens, they identified one polymer-lipid particle that was best-suited for delivery to the colon, and another that was optimized to deliver mRNA to mouth tissue.

“We thought that perhaps by combining these two systems – polymers and lipids – we may be able to get the best of both worlds and get highly potent RNA delivery. And that’s essentially what we saw,” Kirtane says. “One of the strengths of our approach is that we are using a messenger RNA, which just temporarily expresses the protein, so it’s considered far safer than something like DNA, which may be incorporated into the cells’ genome.”

Protection from radiation

After showing that these particles could successfully deliver mRNA to cells grown in the lab, the researchers tested whether this approach could effectively protect tissue from radiation in a mouse model.

They injected the particles into either the cheek or the rectum several hours before giving a dose of radiation similar to what cancer patients would receive. In these mice, the researchers saw a 50 percent reduction in the amount of double-stranded DNA breaks caused by radiation.

The researchers also showed that the protective effect of the Dsup protein did not spread beyond the injection site, which is important because they don’t want to protect the tumour itself from the effects of radiation. To make this treatment more feasible for potential use in humans, the researchers now plan to work on developing a version of the Dsup protein that would not provoke an immune response, as the original tardigrade protein likely would.

If developed for use in humans, this protein could also potentially be used to protect against DNA damage caused by chemotherapy drugs, the researchers say. Another possible application would be to help prevent radiation damage in astronauts in space.

Source: MIT

Categories : Cancer Obstetrics & GynaecologyTags :

A Short Course of Radiation Therapy for Endometrial Cancer Patients is Effective

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

In a randomised clinical trial, researchers from Huntsman Cancer Institute at the University of Utah (the U) have found that short-course, higher dose vaginal brachytherapy for endometrial cancer had similar effectiveness to more frequent, lower dose sessions.

Gita Suneja, MD, MS, physician-scientist at Huntsman Cancer Institute and professor of radiation oncology at the U, is the first author of the SAVE trial report – which stands for, Short-Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared with Standard of Care.

“There isn’t high quality-data on optimal dose and schedule for brachytherapy treatments. Because of this, practice patterns really vary,” says Suneja. “The SAVE trial sought to try to lower the number of treatments that patients were receiving but maintain short-term quality of life and disease control.”

Endometrial cancer is a disease that begins in the lining of the uterus. The primary treatment for endometrial cancer is surgery, including the removal of the uterus, cervix, and upper vagina. Brachytherapy, a form of internal radiation, is used as a secondary treatment to prevent the cancer’s return. Patients receiving vaginal cuff brachytherapy are treated with internal radiation by way of an applicator in the vaginal cavity.

The SAVE trial compared two groups who received different treatment doses over a varying number of sessions. The control group received the standard treatment – between three to five appointments with lower doses. The experimental group received higher doses of radiation in just two sessions.

“The study outcomes will help improve cancer care for Huntsman Cancer Institute patients across the five states of the Mountain West.”

Gita Suneja, MD, MS

The researchers found similarly effective short-term outcomes and few acute toxicities for the patients in the experimental group.

David Gaffney, MD, PhD, FACR, FABS, FASTRO, physician-scientist at Huntsman Cancer Institute and professor of radiation oncology at the U, developed the idea for the SAVE study after seeing patient need. According to the American Cancer Society, endometrial cancer is the most common cancer of the female reproductive organs. Incidence is on the rise, as is the mortality rate.

“It is a big win when we can preserve good outcomes and make cancer care easier,” says Gaffney.

The results of the SAVE trial were published in JCO Oncology Advances.

Source: Huntsman Cancer Institute