Tag: radiotherapy

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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 : Leave a comment

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

Categories : Cancer Medical IndustryTags :

Life Healthcare Concludes Agreement to Sub-License “RM2”

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Photo by Khwanchai Phanthong on Pexels

Life Healthcare through its wholly owned subsidiary Life Molecular Imaging Limited (LMI), has entered into a contract with Lantheus Holdings Inc. (“Lantheus”), to sub-license one of LMI’s early-stage novel radiotherapeutic and radio diagnostic products (RM2).

“As part of Life Healthcare’s strategy to monetise LMI’s product development portfolio, we are delighted to have found a partner for our RM2 product”, said Pete Wharton-Hood, Life Healthcare, CEO.  “Through this agreement, LMI has secured a partnership for the development of this early-stage diagnostic and therapeutic product through to commercialisation. This exciting opportunity unlocks some of the value in LMI’”, continued Wharton-Hood.

Lantheus will make an upfront payment of $35 million for the sub-licensing rights to RM2, as per the agreement. In addition, several payments will potentially be paid to LMI on the achievement of development and regulatory milestones as well as royalty payments when the product is sold commercially.

The sub-licensing agreement secures Lantheus’ rights to develop the product and complete the early development in collaboration with LMI. “LMI is uniquely positioned to assist in this area, says Wharton -Hood and we are pleased by this development as it showcases and harnesses the specialised, dedicated and focused talent within LMI”. “With Lantheus’ experience in developing and providing access to radiotheranostics in cancer, we are confident in our decision to hand them the reins for this promising theranostic pair and are honored to work with them toward improving the future of people with prostate and breast cancer,” said Ludger Dinkelborg, CEO, Life Molecular Imaging.

Lantheus Holdings, Inc. is listed on NASDAQ in the United States of America and is the leading radiopharmaceutical-focused company committed to delivering life-changing science to enable clinicians to Find, Fight and Follow disease to deliver better patient outcomes. Lantheus has been providing radiopharmaceutical solutions for more than 65 years and has identified value and commercial opportunity in continuing the development of RM2.

LMI is a wholly owned subsidiary in Life Healthcare and is registered in the United Kingdom. The company has a product Neuraceq® which has been approved in many countries and is used to detect amyloid plaque in the brain through a PET-CT Scan and has multiple products in early clinical development. LMI also provides clinical research services for pharmaceutical companies.

Life Healthcare has retained R1bn to provide for funding requirements of LMI as part of the Alliance Medical Group disposal which was concluded earlier this year “This transaction will reduce the quantum required and Life Healthcare will consider distributing a portion of the surplus to shareholders as part of the full year dividend,” stated Wharton-Hood.

About RM2

RM2 is a 9 amino acid peptide that binds to Gastrin Releasing Peptide receptor (GRPr); and can be used to treat multiple malignant tumors like prostate, breast, lung, glioma, and ovarian tumors.

About Life Molecular Imaging

LMI is a wholly owned subsidiary in Life Healthcare and is registered in the United Kingdom. The company has one globally approved product Neuraceq ® that is used to detect amyloid plaque in the brain through a PET-CT scan and has multiple products in early clinical development as well as providing clinical research services for pharmaceutical companies.

Categories : CancerTags :

Activists and Patients March on Gauteng Health Department Demanding Radiation Treatment

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Nearly R800-million set aside for radiation treatment outsourcing has not been spent

Activists and patients marched on Tuesday in Johannesburg demanding radiation treatment for cancer. Photo: Silver Sibiya

By Silver Sibiya for GroundUp

Activists and cancer patients marched to the offices of the Gauteng department of health on Tuesday demanding that millions of rands allocated for radiation treatment for cancer patients be used.

SECTION27, Cancer Alliance and Treatment Action Campaign (TAC) called for the department to use R784-million set aside by the provincial treasury in March 2023 to outsource radiation treatment. They say not a single patient has received treatment through this intervention a year later.

In an open letter to health MEC Nomantu Nkomo-Ralehoko last week, Khanyisa Mapipa from SECTION27, Salomé Meyer from the Cancer Alliance and Ngqabutho Mpofu from TAC said that in March 2022, Cancer Alliance had compiled a detailed list of approximately 3000 patients who were awaiting radiation oncology treatment.

They said there were shortages of staff in the two radiation oncology centres in Gauteng, Steve Biko Academic Hospital and Charlotte Maxeke Johannesburg Academic Hospital. Charlotte Maxeke Hospital had only two operational machines compared to seven in 2020. Tenders for new equipment had been delayed and the backlog of patients was increasing, they said.

As a result, SECTION27 and Cancer Alliance had asked the provincial treasury to set aside R784-million to outsource radiation treatment. The money had been allocated in March 2023, but a year later, no service provider had been appointed.

“It has actually been four years since the matter was brought to the Department of Health,” said Mapipa on Tuesday. She said cancer patients were not getting the treatment they needed.

“We as Cancer Alliance and SECTION27 ran to Gauteng Treasury to ask them to allocate these funds. Gauteng Treasury responded and they gave this money, but this money is still sitting.”

Thato Moncho, who was diagnosed with breast cancer in September 2020, is one of the patients on the waiting list. She said she had faced many delays in her treatment. “I’ve had three recurrences of cancer and I need to have radiation six weeks after my surgery, which they failed to give me. I have pleaded with the MEC of Health and the Chief Executive Officer at Charlotte Maxeke to speed up the process so I can get my radiation but they failed.”

“I’m pleading: help us so we can get radiation to live a normal life with our family.”

Gauteng Department of Health spokesperson Motalatale Modiba said the department had received the memorandum and would respond to it. He acknowledged that there had been delays which he said were caused by tender processes.

“It is in our interest to ensure that we get to address the backlog of those that require treatment, and the department will formally respond to the concerns that have been raised.” He said a tender had been awarded.

“In May the process to treat patients will start in both hospitals.”

“The respective heads of oncology in Charlotte Maxeke and Steve Biko hospitals are busy with that process of onboarding.”

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

Source: GroundUp

Categories : Cancer NeurologyTags :

A New Way to Prevent Cognitive Decline from Radiotherapy

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Photo by National Cancer Institute on Unsplash

Microglia, the brain’s immune cells, can trigger cognitive deficits after radiation exposure and may be a key target for preventing these symptoms, University of Rochester researchers have found. Their work, published in the International Journal of Radiation Oncology Biology Biophysics, builds on previous research showing that after radiation exposure microglia damage synapses, the connections between neurons that are important for cognitive behaviour and memory.

“Cognitive deficits after radiation treatment are a major problem for cancer survivors,” M. Kerry O’Banion, MD, PhD, professor of Neuroscience, member of the Wilmot Cancer Institute, and senior author of the study said.

“This research gives us a possible target to develop therapies to prevent or mitigate against such deficits in people who need brain radiotherapy.”

Using several behavioural tests, researchers investigated the cognitive function of mice before and after radiation exposure.

Female mice performed the same throughout, indicating a resistance to radiation injury but Male mice could not remember or perform certain tasks after radiation exposure.

This cognitive decline correlates with the loss of synapses and evidence of potentially damaging microglial over-reactivity following the treatment.

Researchers then targeted the pathway in microglia important to synapse removal. Mice with these mutant microglia had no cognitive decline following radiation. And others that were given the drug, Leukadherin-1, which is known to block this same pathway, during radiation treatment, also had no cognitive decline.

“This could be the first step in substantially improving a patient’s quality of life and need for greater care,” said O’Banion. “Moving forward, we are particularly interested in understanding the signals that target synapses for removal and the fundamental signaling mechanisms that drive microglia to remove these synapses. We believe that both avenues of research offer additional targets for developing therapies to help individuals receiving brain radiotherapy.”

O’Banion also believes this work may have broader implications because some of these mechanisms are connected to Alzheimer’s and other neurodegenerative diseases.

Source: University of Rochester Medical Center

Categories : CancerTags :

Combining Diagnosis and Treatment into One to Treat Pancreatic Cancer

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Pancreatic cancer cells. Credit: NIH

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. Many PDAC tumours go undetected in early stages since they go undetected by conventional imaging methods such as fluorodeoxyglucose positron emission tomography (PET) scans. To tackle this problem, researchers in Japan are combining diagnostic and therapeutic procedures into a single integrated process: ‘theranostics’.

In an article recently published in the Journal of Nuclear Medicine, the Osaka University-led team has developed a ‘radio-theranostics’ strategy that uses a new radioactive antibody to target glypican-1 (GPC1), a protein highly expressed in PDAC tumours. Theranostics, particularly radio-theranostics, has been receiving increasing attention because, by radio-labelling the compounds used to target certain molecules in cancer cells, diagnosis and treatment can be carried out sequentially.

“We decided to target GPC1 because it is overexpressed in PDAC but is only present in low levels in normal tissues,” explains Tadashi Watabe, lead author of the study.

The team used a monoclonal antibody (mAb) designed to target GPC1. The mAb could be labelled with isotopes of zirconium (89Zr) or astatine (211At). First, they injected the 89Zr-GPC1 mAb into a xenograft mouse model, which has a human pancreatic cancer tumour.

“We monitored 89Zr-GPC1 mAb internalisation over seven days with PET scanning,” explains Kazuya Kabayama, the second author of the article. “There was strong uptake of the mAb into the tumours, suggesting that this method could support tumour visualisation. We confirmed that this was mediated by its binding to GPC1, as the xenograft model that had GPC1 expression knocked out showed significantly less uptake.”

The researchers next tested this model with alpha therapy using 211At-GPC1 mAb, a method that could support radioactive label-based delivery of a therapeutic molecule to its target. Administration of 211At-GPC1 mAb resulted in DNA double-strand break induction in the cancer cells, as well as significantly reduced tumour growth. Control experiments showed that these antitumor effects did not occur when mAb internalisation was blocked. Additionally, non-radiolabelled GPC1 mAb did not induce these effects.

“Both radiolabeled versions of the GPC1 mAb we examined showed promising results in PDAC,” says Watabe. “89Zr-GPC1 mAb showed high humoral uptake, while 211At-GPC1 mAb could be used for targeted alpha therapy to support suppression of PDAC tumour growth.”

These highly impactful data demonstrate the potential for using a theranostics approach in PDAC, a disease in dire need of new diagnostic and therapeutic options. In the future, this could lead to early detection of PDAC with PET imaging and systemic treatment with alpha therapy.

Source: Osaka University

Categories : CancerTags :

High-accuracy, High-dose Radiotherapy Proves Effective against Prostate Cancer

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

Patients with intermediate risk, localised prostate cancer can be treated as effectively using fewer and higher doses of radiation therapy delivered over five treatment sessions as they can with lower doses delivered over several weeks, according to researchers from The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

Significant reduction in treatment time

Results from the PACE B (Prostate Advances in Comparative Evidence) phase III randomised trial showed that stereotactic body radiotherapy (SBRT) performed as well as standard radiotherapy treatment for people whose prostate cancer had not spread, demonstrating a 96% chance of no disease progression within five years, compared to 95% for conventional radiotherapy.

SBRT, which can be delivered on a CyberKnife or standard radiotherapy machines, allows clinicians to target tumours to sub-millimetre precision. This approach uses advanced imaging and treatment planning techniques to deliver radiation with pinpoint accuracy, minimising damage to surrounding healthy tissue. It delivers five high doses of radiation to patients over one to two weeks, compared to standard radiotherapy, which delivers more moderate doses over a much longer period of time – usually around 20 sessions for patients in the UK, which can take up to one month.

Drawing from 38 centres across the UK, Ireland and Canada, researchers enrolled 874 people who preferred radiation treatment or were unsuitable for surgery. Patients were randomly assigned to receive either SBRT, consisting of five doses over one to two weeks, or standard radiation consisting of 20 doses over four weeks or 39 doses over 7.5 weeks. None of the patients received hormonal therapy.

“For something as serious as a cancer diagnosis, the treatment was incredibly easy”

The trial investigated whether SBRT was non-inferior to conventional radiation for treating people with intermediate risk, localised prostate cancer. Non-inferiority was measured by whether patients remained free of biochemical clinical failure (BCF), defined as an increase in prostate-specific antigen (PSA) levels, distant metastases or other evidence the cancer was returning, or death from prostate cancer.

Five years after treatment, people treated with SBRT had a BCF-event free rate of 95.7% compared to 94.6% for those treated with conventional radiotherapy, demonstrating that SBRT was non-inferior to conventional radiation.

Side effects were low in both groups and at five years not significantly different between treatment arms.

One patient who benefited from the treatment was 64-year-old Alistair Kennedy-Rose, who was diagnosed with prostate cancer in 2014 at his local hospital following a blood test which revealed his prostate-specific antigen levels were raised. Alistair was referred to The Royal Marsden and, after being recruited to the PACE-B trial, was treated with SBRT via CyberKnife.

He said: “When I was diagnosed I had no symptoms at all, so it came as quite a shock. There can be a lot of anxiety following a cancer diagnosis, but just ten days after I was referred to the Royal Marsden, I started SBRT. I still find it unbelievable that five days later I finished my treatment, for something as serious as a cancer diagnosis it was incredibly easy. I haven’t had any side effects and I’ve been able to live my life to the full. I can’t thank The Royal Marsden enough for what they have done for me.”

Source: The Royal Marsden