Tag: radiotherapy

Categories : Cancer Ethics and LawTags : Leave a comment

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

Categories : CancerTags :

Link between Early and Long-term Side Effects from Prostate Cancer Radiotherapy

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

Men undergoing radiation therapy for prostate cancer who experience side effects early in treatment may face a higher risk of developing more serious long-term urinary and bowel health issues, according to a new study led by investigators from the UCLA Health Jonsson Comprehensive Cancer Center.

The study found that patients who experienced moderate acute urinary side effects in the first three months after radiation were nearly twice as likely to develop late urinary complications years later compared to those without early symptoms. Similarly, patients with early bowel side effects had nearly double the risk of chronic bowel issues.

The findings, published in The Lancet Oncology, highlight the importance of developing strategies to better manage acute toxicities to help improve long-term outcomes and quality of life for patients.

“Men with prostate cancer are living longer than ever, and our goal is to reduce the risk of late toxicities, such as difficulty urinating or rectal bleeding, that can impact a patient’s quality of life for years,” said Dr Amar Kishan, executive vice chair of radiation oncology and senior author of the study. “This study highlights innovations we’re developing, such as using smaller treatment margins in prostate radiation to minimize early side effects, that can lead to lasting benefits by also reducing the risk of long-term complications for patients.”

Radiation therapy is often a key treatment for localised prostate cancer, often involving higher doses to better control the disease. While this approach effectively controls cancer, it can also harm nearby healthy tissues, causing acute and late-term side effects.

Acute toxicity refers to side effects that occur during treatment or within the first three months after it ends, and they are typically temporary. Common urinary side effects include increased frequency of urination, difficulty urinating and discomfort during urination. Bowel-related side effects may include softer stools or diarrhea, as well as rectal discomfort during bowel movements.

Late toxicity, on the other hand, can appear months or even years later and can last for years. Late urinary toxicities include narrowing of the urethra and having blood in the urine. Late bowel toxicities include having blood in the stool or having an ulcer in the wall of the rectum. These issues often can have a bigger impact on a person’s quality of life compared to acute side effects.

While both acute and late toxicities are caused by radiation’s effect on healthy tissues, the connection between the two hasn’t been well-studied, particularly using large-scale data. 

To better understand this relationship, the researchers analysed data from over 6500 patients from six randomised phase 3 clinical trials that shared detailed, individual-level data on short-term and long-term side effects affecting the urinary and bowel systems.

The researchers found patients with moderate or worse early side effects were more likely to experience severe late effects, even years after treatment. Men with early urinary or bowel issues were also more likely to report significant drops in their ability to manage daily activities and overall quality of life.

For urinary toxicity, experiencing acute toxicity increased the rate of late toxicity from 7.5% to 12.5%, and for bowel toxicity, experiencing acute toxicity increased the rate of late toxicity from 12.7% to 22.5%.

The odds of having a clinically-significant decline in urinary quality of life were 1.4 times as high for men who had moderate acute urinary toxicity. The odds of having a clinically-significant decline in bowel quality of life were 1.5 times as high for men who had moderate acute bowel toxicity.

“These results show that acute toxicities following prostate radiotherapy are associated with late toxicities months and years later,” said first author Dr John Nikitas, oncology resident at UCLA Health. “This underscores the importance of measures that reduce the risk of acute toxicities because they may also potentially improve long-term outcomes and quality of life for patients.”

Kishan emphasised the potential impact of newer techniques to reduce both acute and late toxicities:

“Reducing early side effects through advanced techniques like MRI-guided radiation, which allows for more precise targeting of tumours, and urethral-sparing methods, which uses spacers between the prostate to protect surrounding tissues and rectum could potentially help lower the risk of lasting side effects.”

However, more studies are needed to determine if specific strategies to reduce early side effects will improve long-term outcomes and whether treating short-term side effects early can help prevent long-term complications.

Source: University of California – Los Angeles Health Sciences

Categories : CancerTags :

Drug Enhances Radiotherapy for Lung Cancer Metastases in the Brain

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Lung cancer metastasis. Credit: National Cancer Institute

In new research, a team led by University of Cincinnati researchers has identified a potential new way to make radiation more effective and improve outcomes for patients with lung cancer that has spread to the brain. The study, led by first author Debanjan Bhattacharya, PhD, appears in the journal Cancers, and uses a benzodiazepine analogue.

According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States, accounting for about one in five cancer deaths. Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, making up approximately 80% to 85% of all lung cancer cases.

Up to 40% of lung cancer patients develop brain metastases during the course of the disease, and these patients on average survive between eight and 10 months following diagnosis.

Current standard of care treatments for lung cancer that spreads to the brain include surgical removal and stereotactic brain radiosurgery (using precisely focused radiation beams to treat tumours) as well as whole brain irradiation in patients with more than 10 metastatic brain lesions.

“Lung cancer brain metastasis is usually incurable, and whole brain radiation treatment is palliative, as radiation limits therapy due to toxicity,” said Bhattacharya, research instructor in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine. “Managing potential side effects and overcoming resistance to radiation are major challenges when treating brain metastases from lung cancer. This highlights the importance of new treatments which are less toxic and can improve the efficacy of radiation therapy, are less expensive, and can improve the quality of life in patients.”

Research focus

Bhattacharya and his colleagues at UC focused on AM-101, a synthetic analogue, meaning it has a close resemblance to the original compound, in the class of benzodiazepine drugs. It was first developed by James Cook, a medicinal chemist at the University of Wisconsin-Milwaukee. Prior to this study, AM-101’s effect in non-small cell lung cancer was unknown. 

AM-101 is a particularly useful drug in the context of brain metastases in NSCLC, Bhattacharya said, as benzodiazepines are known to be able to pass through the blood-brain barrier that protects the brain from potential harmful invaders that can also block some drugs from reaching their target in the brain.

Research results

The team found that AM-101 activated GABA(A) receptors located in the NSCLC cells and lung cancer brain metastatic cells. This activation triggers the “self-eating” process of autophagy where the cell recycles and degrades unwanted cellular parts.

Specifically, the study showed that activating GABA(A) receptors increases the expression and clustering of GABARAP and Nix (an autophagy receptor), which boosts the autophagy process in lung cancer cells. This enhanced “self-eating” process of autophagy makes lung cancer cells more sensitive to radiation treatment.

Using animal models of lung cancer brain metastases, the team found AM-101 makes radiation treatment more effective and significantly improves survival. Additionally, the drug was found to slow down the growth of the primary NSCLC cells and brain metastases.

In addition to making radiation more effective, adding AM-101 to radiation treatments could allow for lower radiation doses, which could reduce side effects and toxicity for patients, Bhattacharya said. The team is now working toward opening Phase 1 clinical trials testing the combination of AM-101 and radiation both in lung cancer within the lungs and lung cancer that has spread to the brain.

Source: Aalto University

Categories : Cancer DermatologyTags :

Treating Radiation-induced Skin Injuries with Aspirin Hydrogels

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Photo by National Cancer Institute on Unsplash

Radiation is a powerful tool for treating cancer, but prolonged exposure can damage the skin. Radiation-induced skin injuries are painful and increase a person’s chances of infection and long-term inflammation. Now, researchers in ACS Biomaterials Science & Engineering report an aspirin-containing hydrogel that mimics the nutrient-rich fluid between cells and accelerates healing of skin damaged by radiation in animals. With further development, the new salve could provide effective and rapid wound healing for humans. 

Most people undergoing radiotherapy for cancer will experience radiation-induced skin injury that can include redness, pain, ulcers, necrosis and infection. There are few treatments for these wounds, with the most common methods being debridement and hyperbaric oxygenation. Wound dressings made from hydrogels are gaining popularity because they are easy to apply and provide a wet environment for healing that is similar to the inside of the body. Glycopeptide-based hydrogels are especially promising: In laboratory and animal studies, the nanofibre structures have promoted cellular growth and regulated cell adhesion and migration. A research team led by Jiamin Zhang, Wei Wang, Yumin Zhang and Jianfeng Liu proposed loading aspirin, a common anti-inflammatory drug, into a glycopeptide-based hydrogel to create a multifunctional wound dressing for radiation-induced skin injuries.       

In lab tests with cultured cells, the researchers found that the aspirin-contained hydrogel scavenged reactive oxygen species, repaired DNA double-strand breaks and inhibited inflammation caused by radiation exposure without affecting cellular growth. In mouse models of radiation-induced skin injury, the researchers found that dressing wounds for three weeks with the salve reduced acute injuries and accelerated healing – results that the team says point to its potential as an easy-to-administer, on-demand treatment option for reducing radiation damage and promoting healing in humans.

Source: American Chemical Society