Tag: childhood cancers

Categories : Cancer NeurologyTags :

Epigenetic Changes Drive this Rare Malignant Paediatric Brain Tumour

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A healthy neuron. Credit: NIH

A new study published in Life Science Alliance revealed how aberrant epigenetic regulation contributes to the development of atypical teratoid/rhabdoid (AT/RT) tumours, which mainly affect young children. There is an urgent need for more research in this area as current treatment options are ineffective against these highly malignant tumours.

Most tumours take a long time to develop as harmful mutations gradually accumulate in cells’ DNA over time. AT/RT tumours are a rare exception, because the inactivation of one gene gives rise to this highly aggressive form of brain cancer.

AT/RT tumours are rare central nervous system embryonic tumours that predominantly affect infants and young children.

On average, 73 people are diagnosed with AT/RT in the USA each year. However, AT/RT is the most common central nervous system tumour in children under one years old and accounts for 40-50% of diagnoses in this age group. The prognosis for AT/RT patients is grim, with a postoperative median survival of only 11-24 months.

The collaborative study conducted by Tampere University and Tampere University Hospital examined how aberrant DNA methylation distorts cellular developmental trajectories and thereby contributes to the formation of AT/RT. DNA methylation is a normal process of controlling expression whereby methyl groups are added to the DNA strand, adding epigenetic information.

The new study showed that DNA methylation interferes with the activity of multiple regulators, which usually regulate the differentiation and maturation of central nervous system cells during brain development. Disrupted cell differentiation promotes the abnormal, uncontrolled proliferation of cells that eventually form a tumour.

The study also found several genes that regulate cell differentiation or inhibit tumour development and are silenced in AT/RT together with increased DNA methylation.

“These results will provide deeper insights into the development of AT/RTs and their malignancy. In the future, the results will help to accelerate the discovery of new treatments for this aggressive brain tumour,” says senior author Docent Kirsi Rautajoki from Tampere University.

Source: Tampere University

Categories : Cancer PaediatricsTags :

Cannabis for Children’s Cancer Symptoms Lacks Hard Evidence

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Credit: National Cancer Institute

For the management of children’s cancer symptoms, cannabis products have increased in popularity, but questions remain over their efficacy and safety. A recent review of published studies to date shows a lack of evidence to determine the dosing, safety, and efficacy of medical marijuana or cannabis-containing products for managing symptoms experienced by children with cancer. The analysis is published online in CANCER, a peer-reviewed journal of the American Cancer Society.

Although great strides have been made in treatments for childhood cancer, even leading to cures for many patients, many children still suffer from symptoms such as pain, anxiety, and weight loss related to cancer and its treatment. Over the last decade, cannabis products, both synthetic cannabinoids and natural phytocannabinoids, have gained popularity with patients and families for managing such symptoms, but paediatric oncologists are cautious to authorise cannabis for their patients given the limited data to inform dosing, product selection, and safety monitoring.

To provide insights for clinicians and parents, and to inform an upcoming clinical trial, a team led by Lauren E. Kelly, PhD, associate professor of pharmacology and therapeutics in the Rady Faculty of Health Sciences at the University of Manitoba, searched the medical literature to summarise existing knowledge about the potential benefits and harms of cannabis products in children with cancer.

The investigators identified 19 unique studies with a total of 1927 participants with cancer: eight retrospective chart reviews, seven randomised controlled trials, two open‐label studies, and two case reports. The products studied included medical-grade cannabinoids (such as the prescription drug nabilone), synthetic cannabinoids, and unspecified cannabis herbal extracts. Products were most commonly used to manage chemotherapy‐induced nausea and vomiting.

In the randomised controlled trials, patients who used cannabinoids were more likely to experience drowsiness, feeling high, dizziness, and dry mouth. Also, trial participants who received cannabinoids were almost four times more likely to drop from the study due to adverse events, compared with the control group who received placebo. Across all included studies, no serious cannabis‐related adverse events were reported.

Dr Kelly and her colleagues noted that most studies did not adequately describe the types, dosing, frequencies, and routes of administration of cannabis products, and outcomes were mixed and were reported in different ways. Therefore, researchers should develop standards for reporting cannabis exposures, cannabis‐related effects, and patient outcomes.

“It was difficult to measure benefit across studies, given a range of different outcomes and study designs; however, in interventional studies with active control groups, cannabinoids performed better in managing nausea and vomiting. Data are lacking on cannabinoids’ effects on pain, mood, sleep, and health-related quality of life,” said Dr Kelly. “Given that some children report benefits and some children experience adverse events, it is critical that more rigorous studies evaluating the effects of cannabinoids on children with cancer are conducted and shared with parents, patients, and the health care community.”

This literature review informed the design of a three-arm tolerability trial later this year.

Source: Wiley

Categories : Cancer Cardiovascular Disease PaediatricsTags :

First Guideline for Heart Complications in Childhood Cancer Treatment

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Photo by National Cancer Institute on Unsplash

Experts led by researchers from the Murdoch Children’s Research Institute have created the world’s first international clinical guidelines to help prevent and treat heart complications in children undergoing cancer treatment.

Published in JACC:Advances, the guidelines cover cardiovascular disease assessment, screening and follow-up, for paediatric patients receiving cancer treatment with new molecular therapies, immunotherapy, chemotherapy and radiotherapy.

The expert consensus has defined the high-risk group of cancer patients who should undergo a heart check-up, standardised an approach to screening and surveillance during treatment and provided recommendations to protect vulnerable young hearts.

Murdoch Children’s Associate Professor Rachel Conyers said while international guidelines to monitor poor heart side effects during therapy exist for adult patients, none were specific to children.

Associate Professor Conyers said the success of new cancer drugs had increased the chances of cardiac side effects that occur early on during therapy, sometimes within days, which warranted closer heart health surveillance and earlier monitoring.

“Recent advances in treating childhood cancer have resulted in survival rates of more than 80 percent. However, improving serious health outcomes in survivors remains an important and essential focus and prevention is key,” she said.

“Heart complications are a leading cause of death for childhood cancer survivors, second only to cancer relapse. Modern treatments including precision medicine have broadened the agents that can cause heart problems.”

Childhood cancer survivors are 15 times more likely to have heart failure and eight times more likely to have heart disease than the general population.

Associate Professor Conyers said the guidelines would be an indispensable tool for clinicians to significantly reduce the harmful impact of cancer drugs on children’s hearts.

“The guidelines are a major advance for the cardio-oncology field as before this there was no defined approach for surveillance or follow up of pediatric patients during treatment despite new therapeutics having early heart complications such as high blood pressure, abnormal heart beats and heart failure,” she said.

The Australian and New Zealand expert group consisted of pediatric and adult cardiologists and pediatric oncologists who undertook a Delphi consensus approach across 11 areas of cardio-oncology care. The Australian New Zealand Children’s Oncology Group endorsed the study with the guidelines useful for any tertiary institutes treating pediatric oncology patients or initiating cardio-oncology clinics.

Source: Murdoch Children’s Research Institute

Categories : Cancer COVIDTags :

Vaccine Hesitancy Among Caregivers of Childhood Cancer Survivors

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Photo by Priscilla du Preez on Unsplash

In a study published in Pediatric Blood & Cancer, researchers reported that caregivers of childhood cancer survivors expressed high rates of vaccine hesitancy, especially if they lacked confidence in governmental COVID response.

The researchers conducted a survey of 130 caregivers of childhood cancer survivors, 21% of caregivers expressed hesitancy to vaccinate themselves and 29% expressed hesitancy to vaccinate their children who had survived cancer.  

Caregivers who expressed confidence in the US government’s response to COVID were six times more likely to express willingness to self-vaccinate and were three times more likely to express willingness to vaccinate their children.  

Caregivers who reported that they were hesitant to vaccinate cited concerns about the speed of COVID vaccine development and a lack of safety and efficacy data in children, particularly children with cancer.

“Results suggest that COVID vaccination outreach to hesitant caregivers might be more effective when delivered by non-governmental organisations, including paediatric oncology care teams,” said senior author Kyle Walsh, PhD, of the Duke Cancer Institute. “Such providers are well-positioned to discuss potential risks and benefits of vaccination and to update families as longer-term outcomes data emerge from vaccine trials and registries.”

Source: Wiley

Categories : Cancer GeneticsTags :

Comprehensive Genome Sequencing Can Improve Cancer Outcomes

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Image source: National Cancer Institute

Researchers from St Jude Children’s Research Hospital have demonstrated the feasibility of comprehensive genomic sequencing for all paediatric cancer patients, which maximises the lifesaving potential of precision medicine.

All 309 patients who enrolled in the study were offered whole genome and whole exome sequencing of germline DNA. For the 253 patients for whom adequate tumour samples were available, whole genome, whole exome and RNA sequencing of tumour DNA was carried out.

Overall, 86% of patients had at least one clinically significant variation in tumour or germline DNA. Those included variants related to diagnosis, prognosis, therapy or cancer predisposition. An estimated 1 in 5 patients had clinically relevant mutations that would not have been picked up with standard sequencing methods.

“Some of the most clinically relevant findings were only possible because the study combined whole genome sequencing with whole exome and RNA sequencing,” said Jinghui Zhang, PhD, St Jude Department of Computational Biology chair and co-corresponding author of the study.

While such comprehensive clinical sequencing is not widely available, as the technology becomes less expensive and accessible to more patients, comprehensive sequencing will become an important addition to paediatric cancer care.

“We want to change the thinking in the field,” said David Wheeler, PhD, St Jude Precision Genomics team director and a co-author of the study. “We showed the potential to use genomic data at the patient level. Even in common pediatric cancers, every tumor is unique, every patient is unique.

“This study showed the feasibility of identifying tumour vulnerabilities and learning to exploit them to improve patient care,” he said.

Tumour sequencing resulted in a change in treatment for 12 of the 78 study patients for whom standard of care was unsuccessful. In four of the 12 patients, the treatment changes stabilised disease and extended patient lives. Another patient, one with acute myeloid leukaemia, went into remission and was cured by blood stem cell transplantation.

“Through the comprehensive genomic testing in this study, we were able to clearly identify tumor variations that could be treated with targeted agents, opening doors for how oncologists manage their patients,” said co-corresponding author Kim Nichols, MD, St Jude Cancer Predisposition Division director.

The results of the study were published online in the journal Cancer Discovery.

Source: St. Jude Children’s Research Hospital

Journal information: Newman, S., et al (2021) Genomes for Kids: The scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discovery. doi.org/10.1158/2159-8290.CD-20-1631.