Category: Cancer

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GLP-1 Agonists may Reduce Colorectal Cancer Risk

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By HualinXMN – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=133759262

A groundbreaking study by researchers at Case Western Reserve University suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), normally used to treat diabees, may also reduce the risk of colorectal cancer (CRC). The findings, published in the journal JAMA Oncology, support the need for clinical trials to determine whether these medications could prevent one of the deadliest types of cancers.

Eventually, the medications may also show promise in warding off other types of cancer associated with obesity and diabetes.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at the Case Western Reserve School of Medicine and the study’s co-lead researcher.

Glucagon-like peptide-1 receptor agonists, or GLP-1 RAs can lower blood-sugar levels, improve insulin sensitivity and help manage weight. They’ve also been shown to reduce the rates of major cardiovascular ailments. Importantly the protective effect of GLP-1 RAs are noted in patients with or without overweight/obesity.

“To our knowledge,” said co-lead researcher Rong Xu, a professor at the School of Medicine, “this is the first indication this popular weight-loss and anti-diabetic class of drugs reduces incidence of CRC, relative to other anti-diabetic agents.”

Berger and Xu are members of the Case Comprehensive Cancer Center.

In the US, the American Cancer Society estimates CRC is the third-leading type of cancer in both sexes, with 153 000 new cases per year. It is also the second-leading cause of cancer mortality with 52 550 deaths per year.

Since GLP-1 RAs have been shown to be effective anti-diabetic and weight-loss agents, the researchers hypothesized they might reduce incidence of CRC.

Using a national database of more than 100 million electronic health records, the researchers conducted a population-based study of more than 1.2 million patients.

These individuals had been treated with anti-diabetic agents from 2005-19; the CWRU team examined the effects of GLP-1 RAs on their incidence of CRC, as compared to those prescribed other anti-diabetic drugs.

Population-based research means matching as many people as possible with the same characteristics, such as sex, race, age, socio-economic determinants of health and other medical conditions, to accurately compare the drug’s effects.

Among 22 572 patients with diabetes treated with insulin, there were 167 cases of CRC. Another 22 572 matched patients treated with GLP-1 RAs saw 94 cases of CRC. Those treated with GLP-1 RAs had a 44% reduction in incidence of CRC.

In a similar comparison of 18 518 patients with diabetes treated with Metformin, compared to 18 518 patients with diabetes treated with GLP-1 RAs, had a 25% reduction in CRC.

“The research is critically important for reducing incidence of CRC in patients with diabetes, with or without overweight and obesity,” Berger said.

Source: Case Western Reserve University

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Existing Allergy Medication Unleashes Antitumour Immunity against Lung Cancer

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Photo by Anna Shvets

Researchers from Mount Sinai report in Nature that they have identified an allergy pathway that, when blocked, unleashes antitumour immunity in mouse models of non-small cell lung cancer (NSCLC).

And in an early parallel study in humans, combining immunotherapy with dupilumab – an Interleukin-4 (IL-4) receptor-blocking antibody widely used for treating allergies and asthma – boosted patients’ immune systems, with one out of the six experiencing significant tumour reduction.

“Immunotherapy using checkpoint blockade has revolutionised treatment for non-small cell lung cancer, the most common form of lung cancer, but currently only about a third of patients respond to it alone, and in most patients, the benefit is temporary,” says senior study author Miriam Merad, MD, PhD, at the Icahn School of Medicine at Mount Sinai.

“A big focus of our program TARGET is to use single cell technology and artificial intelligence to identify molecular immune programs that can dampen tumour immune response to checkpoint blockade.”

Also known as a PD1 inhibitor, checkpoint blockade is a type of cancer immunotherapy that can unleash the cancer-killing activity of T cells.

“Using single cell technologies, we discovered that the immune cells infiltrating lung cancers, as well as other cancers we studied, exhibited characteristics of a ‘type 2’ immune response, which is commonly associated with allergic conditions like eczema and asthma,” says first study author Nelson LaMarche, PhD, a postdoctoral research fellow in the lab of Dr Merad.

“These results led us to explore whether we could repurpose a medication typically used for allergic conditions to ‘rescue’ or enhance tutor response to checkpoint blockade,” says Thomas Marron, MD, PhD, co-senior author of the study.

“Strikingly, we found that IL-4 blockade enhanced lung cancer response to checkpoint blockade in mice and in six lung cancer patients with treatment-resistant disease. In fact, one patient whose lung cancer was growing despite checkpoint blockade had nearly all their cancer disappear after receiving just three doses of the allergy medication, and his cancer remains controlled today, over 17 months later.”

The researchers are encouraged by the initial results but emphasise the need for larger clinical trials to validate the drug’s efficacy in treating NSCLC.

Beyond the clinical trial findings reported in the current Nature paper, the investigators have now expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients, and are starting to investigate its use in early-stage lung cancer as well. Through these trials, they are searching for biomarkers to identify those cancer patients who might benefit from dupilumab treatment.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

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The Quest to Repurpose Existing Drugs for Lung Cancer that Metastasised to the Brain

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Lung cancer metastasis. Credit: National Cancer Institute

The largest review of papers for brain metastases of lung cancer has found abnormalities in their genetic mutations and for which licensed drugs could be clinically trialled to find out if they could treat the disease. The research led by the University of Bristol and published in Neuro-Oncology Advances also uncovered differences in those mutations between smokers and non-smokers.

Brain metastases most commonly occur from lung and breast cancer, and in the majority of cases are fatal. The genetic mutations in primary lung cancers have been widely studied, but less is known about the changes in the cancer once it has metastasised to the brain.

The research team wanted to find out the genetic changes in brain metastasis from non-small cell lung cancer (NSCLC) and whether there are drugs already available that could potentially be offered to these patients.

The researchers carried out a review from 72 papers of genetic mutations in brain metastasis of NSCLC from 2346 patients’ data on demographics, smoking status, genomic data, matched primary NSCLC, and PD-L1 – a protein found on cancer cells.

The study found the most commonly mutated genes were EGFR, TP53, KRAS, CDKN2A, and STK11.

Common missense mutations – mutations that lead to a single amino acid change in the protein coded by the gene – included EGFR L858R and KRAS G12C

In certain cases the genetic mutations were different in the brain metastasis from the primary lung cancer.

There were also differences in the genetic mutations in smokers versus patients who had never smoked. Brain metastases of smokers versus non-smokers had different missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups.

The research team found from the top ten commonly mutated genes which had primary NSCLC data, 37% of the specific mutations assessed were different between primary NSCLC and brain metastases.

The researchers suggest Medicines and Healthcare products Regulatory Agency-approved drugs already licensed could potentially be tested to treat the disease in clinical trials.

The genetic landscape of the different subtypes of NSCLC is well known. TP53 and LRP1B mutations are common to all NSCLC subtypes, but certain subtypes also have specific alterations.

Lung adenocarcinoma is the most common type of lung cancer and has higher frequencies of KRAS, EGFR, KEAP1, STK11, MET, and BRAF somatic mutations – changes that have accumulated in the cancer genome.

Some studies suggested that the genomic landscape of NSCLC in smokers vs non-smokers differ independent of subtype.

One study found EGFR mutations, ROS1 and ALK fusions to be more prevalent in non-smokers, whereas KRAS, TP53, BRAF, JAK2, JAK3 and mismatch repair gene mutations were more commonly mutated in smokers.

Kathreena Kurian, Professor of Neuropathology and Honorary Consultant at North Bristol NHS Trust, Head of the Brain Tumour Research Centre at the University of Bristol and co-author of the paper, said: “Our research recommends that all patients should have their brain metastasis examined for mutations in addition to their primary lung cancer because they may be different.

“This evidence could form the backbone for new clinical trials for patients with brain metastasis in non-small cell lung cancer using drugs that are already available.”

The team suggest the next steps for the research would be to consider whole genome sequencing on brain metastasis to look for other types of mutations, such as, common insertions/deletions for which drugs are already available.

Source: University of Bristol

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New Study Finds that Fatty Acid in Beef, Lamb and Dairy Boosts Cancer-fighting T Cells

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Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumours and kill cancer cells, according to a new study by researchers from the University of Chicago.

The research, published in Nature, also shows that cancer patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting potential as a nutritional complement to conventional cancer therapy. Although trans fatty acids that are industrially produced are known to be harmful to health, natural ones such as TVA are linked to health benefits. But the researchers don’t envision prescribing diets packed with red meat and cheese – rather, TVA would be a supplement.

“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, professor of medicine at UChicago and one of the senior authors. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumour immunity by activating an important immune pathway.”

Searching for nutrients that activate immune cells

Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, they started with a database of around 700 known metabolites that come from food and assembled a ‘blood nutrient’ compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumour immunity by activating CD8+ T cells, which are critical for killing cancerous or virally infected cells.

After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.

Feeding mice a diet enriched with TVA significantly reduced the tumour growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumours.

The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, professor of chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumour fighting ability.

Finally, working with other researchers, the team analysed blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested leukaemia cell lines and saw that TVA enhanced the ability of an immunotherapy drug to kill leukaemia cells.

TVA as a supplement

The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimised amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.

“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.

‘The new research also highlights the promise of this ‘metabolomic’ approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level — I find that really amazing and intriguing.”

Source: University of Chicago

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Ultra-processed Foods Linked to Mouth, Throat and Oesophagus Cancer Risk

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Eating more ultra-processed foods (UPFs) may be associated with a higher risk of developing cancers of the upper aerodigestive tract (ie, the mouth, throat and oesophagus), according to a new study in the European Journal of Nutrition. The authors of this study, led by the University of Bristol and the International Agency for Research on Cancer (IARC), say that obesity associated with the consumption of UPFs may not be the only factor to blame.

Several studies have identified an association between UPF consumption and cancer, including a recent study which looked at the association between UPFs and 34 different cancers in the largest cohort study in Europe, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which followed 450 111 adults who for approximately 14 years.

As more evidence emerges about the associations between eating UPFs and adverse health outcomes, researchers from the Bristol Medical School and IARC wanted to explore this further.

Since many UPFs have an unhealthy nutritional profile, the team sought to establish whether the association between UPF consumption and head and neck cancer and oesophageal adenocarcinoma in EPIC could be explained by an increase in body fat.

Results from the team’s analyses showed that eating 10% more UPFs is associated with a 23% higher risk of head and neck cancer and a 24% higher risk of oesophageal adenocarcinoma in EPIC.

Increased body fat only explained a small proportion of the statistical association between UPF consumption and the risk of these upper-aerodigestive tract cancers.

Fernanda Morales-Berstein, a Wellcome Trust PhD student at the University of Bristol and the study’s lead author, explained: “UPFs have been associated with excess weight and increased body fat in several observational studies. This makes sense, as they are generally tasty, convenient and cheap, favouring the consumption of large portions and an excessive number of calories. However, it was interesting that in our study the link between eating UPFs and upper-aerodigestive tract cancer didn’t seem to be greatly explained by body mass index and waist-to-hip ratio.”

The authors suggest that other mechanisms could explain the association.

For example, additives including emulsifiers and artificial sweeteners which have been previously associated with disease risk, and contaminants from food packaging and the manufacturing process, may partly explain the link between UPF consumption and upper-aerodigestive tract cancer in this study.

Fernanda Morales-Berstein and colleagues did caution that the associations between UPF consumption and upper-aerodigestive tract cancers found in the study could be affected by certain types of bias.

This would explain why they found evidence of an association between higher UPF consumption and increased risk of accidental deaths, which is highly unlikely to be causal.

Inge Huybrechts, Team head of the Lifestyle exposures and interventions team at IARC, added: “Cohorts with long-term dietary follow-up intake assessments, considering also contemporary consumption habits, are needed to replicate these study’s findings, as the EPIC dietary data were collected in the 1990s, when the consumption of UPFs was still relatively low. As such associations may potentially be stronger in cohorts including recent dietary follow-up assessments.”

Further research is needed to identify other mechanisms, such as food additives and contaminants, which may explain the links observed.

However, based on the finding that body fat did not greatly explain the link between UPF consumption and upper-aerodigestive tract cancer risk in this study, Fernanda Morales-Berstein, suggested: “Focussing solely on weight loss treatment, such as semaglutide, is unlikely to greatly contribute to the prevention of upper-aerodigestive tract cancers related to eating UPFs.”

Source: University of Bristol

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Copper and Ozone are the Secret Ingredients for Cheaper Cancer Drug Production

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Photo by National Cancer Institute on Unsplash

Part of the reason cancer is such a devastatingly costly disease to treat is because cancer drugs are often require very expensive, specialised ingredients to produce. But thanks to pathbreaking research by UCLA chemists, led by organic chemistry professor Ohyun Kwon, the price of drug treatments for cancer and other serious illnesses may soon plummet.  

For example, one chemical used in making some anti-cancer drugs costs US$3200 per gram – 50 times more than a gram of gold. The UCLA researchers devised an inexpensive way to produce this drug molecule from a chemical costing just US$3 per gram. They were also able to apply the process to produce many other chemicals used in medicine and agriculture for a fraction of the usual cost.

Their breakthrough, published in the journal Science, involves a process known as “aminodealkenylation.” Using oxygen as a reagent and copper as a catalyst to break the carbon-carbon bonds of many different organic molecules, the researchers replaced these bonds with carbon-nitrogen bonds, converting the molecules into derivatives of ammonia called amines.

Amines interact strongly with molecules in living plants and animals, so they are widely used in pharmaceuticals, as well as in agricultural chemicals. Familiar amines include nicotine, cocaine, morphine and amphetamine, and neurotransmitters like dopamine. Fertilisers, herbicides and pesticides also contain amines.

Industrial production of amines is therefore of great interest, but the raw materials and reagents are often expensive, and the processes can require many complicated steps to complete. Using fewer steps and no expensive ingredients, the process developed at UCLA can produce valuable chemicals at a much lower cost than current methods.

“This has never been done before,” Kwon said. “Traditional metal catalysis uses expensive metals such as platinum, silver, gold and palladium, and other precious metals such as rhodium, ruthenium and iridium. But we are using oxygen and copper, one of the world’s most abundant base metals.”

The new method uses ozone to break the carbon-carbon bond in alkenes (a form of hydrocarbon with double carbon-carbon bonds) and a copper catalyst to couple the broken bond with nitrogen, turning the molecule into an amine. In one example, the researchers produced a c-Jun N-terminal kinase inhibitor – an anti-cancer drug – in just three chemical steps, instead of the 12 or 13 steps previously needed. The cost per gram can thus be reduced from thousands of dollars to just a few dollars.

In another example, the protocol took just one step to convert adenosine – a neurotransmitter and DNA building block that costs less than 10 US cents per gram – into the amine N6-methyladenosine. The amine plays crucial roles in controlling gene expression in cellular, developmental and disease processes, and its production cost has previously been US$103 per gram.

Kwon’s research group was able to modify hormones, pharmaceutical reagents, peptides and nucleosides into other useful amines, showing the new method’s potential to become a standard production technique in drug manufacturing and many other industries.

Source: University of California – Los Angeles

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When it Comes to Personalised Cancer Treatments, AI is no Match for Human Doctors

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Cancer treatment is growing more complex, but so too are the possibilities. After all, the better a tumour’s biology and genetic features are understood, the more treatment approaches there are. To be able to offer patients personalised therapies tailored to their disease, laborious and time-consuming analysis and interpretation of various data is required. In one of many artificial intelligence (AI)projects at Charité – Universitätsmedizin Berlin and Humboldt-Universität zu Berlin, researchers studied whether generative AI tools such as ChatGPT can help with this step.

The crucial factor in the phenomenon of tumour growth is an imbalance of growth-inducing and growth-inhibiting factors, which can result, for example, from changes in oncogenes.

Precision oncology, a specialised field of personalised medicine, leverages this knowledge by using specific treatments such as low-molecular weight inhibitors and antibodies to target and disable hyperactive oncogenes.

The first step in identifying which genetic mutations are potential targets for treatment is to analyse the genetic makeup of the tumour tissue. The molecular variants of the tumour DNA that are necessary for precision diagnosis and treatment are determined. Then the doctors use this information to craft individual treatment recommendations. In especially complex cases, this requires knowledge from various fields of medicine.

At Charité, this is when the “molecular tumour board” (MTB) meets: Experts from the fields of pathology, molecular pathology, oncology, human genetics, and bioinformatics work together to analyse which treatments seem most promising based on the latest studies.

It is a very involved process, ultimately culminating in a personalised treatment recommendation.

Can artificial intelligence help with treatment decisions?

Dr Damian Rieke, a doctor at Charité, and his colleagues wondered whether AI might be able to help at this juncture.

In a study just recently published in the journal JAMA Network Open, they worked with other researchers to examine the possibilities and limitations of large language models such as ChatGPT in automatically scanning scientific literature with an eye to selecting personalised treatments.

AI ‘not even close’

“We prompted the models to identify personalised treatment options for fictitious cancer patients and then compared the results with the recommendations made by experts,” Rieke explains.

His conclusion: “AI models were able to identify personalised treatment options in principle – but they weren’t even close to the abilities of human experts.”

The team created ten molecular tumour profiles of fictitious patients for the experiment.

A human physician specialist and four large language models were then tasked with identifying a personalised treatment option.

These results were presented to the members of the MTB for assessment, without them knowing where which recommendation came from.

Improved AI models hold promise for future uses

Dr. Manuela Benary, a bioinformatics specialist reported: “There were some surprisingly good treatment options identified by AI in isolated cases. “But large language models perform much worse than human experts.”

Beyond that, data protection, privacy, and reproducibility pose particular challenges in relation to the use of artificial intelligence with real-world patients, she notes.

Still, Rieke is fundamentally optimistic about the potential uses of AI in medicine: “In the study, we also showed that the performance of AI models is continuing to improve as the models advance. This could mean that AI can provide more support for even complex diagnostic and treatment processes in the future – as long as humans are the ones to check the results generated by AI and have the final say about treatment.”

Source: Charité – Universitätsmedizin Berlin

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CRISPR-Cas9 Gene Editing may Unleash Cancer Cell Resistance

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CRISPR-Cas9 is a customisable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way. Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH

Researchers from the Karolinska Institutet in Sweden have identified potential pitfalls in the use of the gene editing technique CRISPR-Cas9, a gene scissors that is used for cancer treatments. Their findings are published in Life Science Alliance.

The study has identified that a cancer cell line, derived from leukaemia, removes a region that encodes a tumour-suppressing gene and genes that control cell growth.

“We found that this elimination often occurs when cancer cells are exposed to stress, such as when using CRISPR, gene scissors, or other treatments such as antibiotics. The elimination changes gene regulation in a unique way, which in turn affects basic biological processes such as DNA replication, cell cycle regulation, and DNA repair,” says Claudia Kutter, research group leader at the Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet.

This knowledge is important for researchers, clinicians, and biotechnologists to correctly interpret and apply gene editing results. The study also has clinical relevance, as the observed eliminations are in genes associated with cancer, which has implications for cancer research and treatment.

“Shockingly, this elimination has been unintentionally overlooked by many researchers who modify genes in cancer cells by CRISPR screenings. The elimination also occurred more frequently in patients who have undergone cancer treatment. The treated cancer cells had, due to the elimination, a selective advantage, which is bad for the patient’s long-term survival as these cells remained after the treatment,” says Claudia.

“The study mainly serves as a warning signal, but also opens doors for further research aimed at harnessing the potential of gene editing while minimising unintended consequences,” Claudia concludes.

Source: Karolinska Institutet

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Redispensing Unused Cancer Pills could Save Millions

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Redispensing cancer drugs reduces both medical costs and environmental impact, according to research from Radboudumc pharmacy published in JAMA Oncology. The annual savings could amount to tens of millions.

Cancer drugs as pills are not always used up by patients. The drugs are mostly expensive and environmentally damaging, both in production and (waste) disposal. In her PhD research, Lisa-Marie Smale of Radboudumc investigated whether these unused drugs can be collected and reissued. Does such an approach ultimately lead to lower environmental impact and costs?

Redispense medication

When redispensing medications, the quality must be guaranteed. Therefore, in this study the medications were packaged separately and fitted with a sensor, which registers whether returned medications were kept within the required temperature. Smale: “If packaging, temperature and expiration date are in order, the returned medications can be redispensed. For two years we investigated this procedure in cooperation with the pharmacies of four Dutch hospitals; Radboudumc, UMC Utrecht, Jeroen Bosch hospital and St Antonius hospital. Over a thousand patients who were taking oral cancer medications at home participated in the study during that period.”

Saving tens of millions

The results look promising. The investment in the method, such as packaging with a temperature sensor, amounts up to 37 euros per patient per year. This is offset by savings of 613 euros. Annually, this results in a net saving per patient of 576 euros. Smale: “In the Netherlands, we can save between 20 and 50 million euros annually with this redispensing of medication. Meanwhile, we have further optimised the process, making a net saving of 655 euros per patient possible. In the Netherlands, we have relatively low drug prices. If you look at the US, where the price of new drugs is over 300 percent higher, in principle much more money can be saved there.”

Large-scale consequence

Of all wasted medicine packaging, two-thirds could be reissued. Project leader Charlotte Bekker of Radboudumc says, “Based on the results, the study will be expanded to 14 hospitals. Again, we are looking at cancer pills. Reissue is only allowed in the context of a scientific study because of European rules. We hope that the approach can eventually be used nationwide, as well as for other drugs.”

Sustainability and social impact also benefit

“This approach is cost-effective for expensive drugs,” Smale says, “but ultimately there are other factors you want to consider, such as sustainability or social impact. Think of the environmental impact you can reduce by not destroying drugs but redispensing them; this can also be beneficial for drugs that are in short supply.”

Broad interest

To the researcher’s knowledge, this study the first to examine drug redispensing with guaranteed quality. The topic is attracting strong interest, not only in the medical community but also beyond. Several parties are committed to make further expansion possible. In addition to the participating hospitals, the Dutch Association of Hospital Pharmacists (NVZA) is also closely involved. And it is part of the Green Deal objectives to make healthcare more sustainable. Smale: “We are happy to work with all parties to address and reduce the cost and environmental impact of wasted medicines.”

Source: Radboud University Medical Center

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Study Confirms Link between CT Scans in Young People and Increased Risk of Cancer

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A multinational study of almost one million individuals confirms a strong and clear association between radiation exposure from CT scans in young people and an increased risk of blood cancers. These results, published in Nature Medicine, highlight the importance of continuing to apply strict radiological protection measures, particularly in paediatric populations. 

The benefits of computed tomography (CT) for imaging in patient management (including diagnostic efficacy, treatment planning and disease follow-up) are undisputed. But in recent decades the extensive use of this procedure has raised concerns about the potential cancer risks associated with exposure to ionising radiation, particularly in young patients.

“The exposure associated with CT scans is considered low (less than 100mGy), but it is still higher than for other diagnostic procedures,” says Elisabeth Cardis, Head of the Radiation Group at ISGlobal and senior author of the study. Previous studies have suggested an increased risk of cancer in in children exposed to CT scans, but they had several methodological limitations.

To address these limitations, clinicians, epidemiologists and dosimetrists from nine European countries (Belgium, Denmark, France, Germany, Netherlands, Norway, Spain, Sweden, and UK) came together to conduct a multinational, European-funded study, EPI-CT, coordinated by the International Agency for Research on Cancer (IARC).

“Implementing this large, multinational study was challenging – it involved extracting data from radiology records of 276 hospitals and linking them to population-based registries in nine countries, all while maintaining the confidentiality of the individuals’ data,” says Cardis.

A dose-dependent association

The study analysed data from almost one million people, who underwent at least one CT scan before the age of 22. The dose of radiation delivered to the bone marrow, where blood cells are produced, was estimated for each person. By linking this information to national cancer registries, EPI-CT researchers were able to identify those who developed a blood cancer over time. Individuals were followed for an average of 7.8 years, although for those who had CT scans in the early years of the technology, researchers were able to monitor cancer incidence for more than 20 years after the first scan.

The results show a clear association between the total radiation doses to the bone marrow from CT scans and the risk of developing both myeloid and lymphoid malignancies. A dose of 100mGy approximately tripled the risk of developing a blood cancer. These results suggest that a typical scan today (with an average dose of about 8mGy) increases the risk of developing these malignancies by about 16%. “In terms of absolute risk, this means that, for every 10 000 children who have a CT scan, we can expect to see about 1–2 cases of cancer in the 12 years following the examination,” says first author Magda Bosch de Basea, ISGlobal researcher at the time of the study.

The authors point out that more work is needed to ensure that doses and technical parameters are systematically and adequately collected in the clinics in real time to further improve risk estimates in the future.

Public health implications

Today, more than one million children in Europe undergo CT scans every year. Although radiation doses from CT scans have decreased substantially in recent years, the findings of this study underline the need to raise awareness among the medical community and to continue to apply strict radiation protection measures, especially in the youngest patients. “The procedure must be properly justified – taking into account possible alternatives – and optimised to ensure that doses are kept as low as possible while maintaining good image quality for the diagnosis,” Cardis explains. 

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