Children of cancer patients are too often excluded from the disease journey, research shows

The announcement of a cancer diagnosis abruptly and durably alters the course of daily life – not just for the person receiving it, but also for their family.

New research to be presented at the ESMO Congress 2021 suggests that adequate communication and support for children of cancer patients still represents a significant unmet need that parents require help to fulfil.

In 2020, an estimated 4.6 million individuals aged 20 to 54 years were diagnosed with the disease at a time of their lives when they are most likely to be raising children.

The impact of parental cancer on a child’s development varies according to the child’s age and the evolution of the illness, but also, crucially, depending on how the child has been included in the parent’s disease journey.

Giving bad news to their children and addressing the distress this may cause them is one of the most daunting tasks that parents face at a time when they must process their own emotions about the disease.

Yet according to Prof. Carlo Alfredo Clerici, a clinical and child psychology expert from University of Milan, Italy, not involved in the study, “Current psychological perspectives see a certain degree of information to children about their parents’ disease, and about the possibility of their death, as useful and protective against traumatic phenomena.”

Ignorance is not bliss when a parent has cancer.

The social and cultural resistance that often stands in the way of this type of dialogue with children is evident from the results of a survey of 103 patients in Tunisia, almost 90% of whom reported communication disorders on the subject of the parent’s illness and more than 40% choosing not to disclose the whole truth about their disease.

According to study author Dr. Sinen Korbi, Institute Salah Azaiez, Tunis, the idea is widespread among patients that they are protecting their children’s psychosocial equilibrium by shielding them from the reality of the illness.

“This was cited as a concern by seven of the 18 parents in our study who chose to conceal the truth from their children entirely,” he reported, adding that these represent missed opportunities to give hope to children at a time when, even in Tunisia where many cancers are diagnosed at an advanced stage, people do recover from the disease.

Almost all study participants (96%) observed behavioural changes in their children ranging from anxiety and depression, through academic difficulties all the way to violence and substance abuse – but only nine parents consulted a child psychiatrist.

“Many people think they can handle these issues on their own or with help from relatives, but they need to be encouraged to report these problems to us so we can refer them to specialists if needed: this can be as simple as asking patients how their children are doing every time we see them,” said Korbi.

“This study makes clear the need to increase knowledge about the role of psychological and emotional dimensions in people’s lives.Efforts should be made to better understand and take into account, in a way that is compatible with social >and cultural perspectives, the fact that children build their own interpretation of life and that they can suffer significantly when they do not have adults helping them to stay in contact with reality,” said Clerici. “Future research should also aim to capture traumatic phenomena that unfold over time and which are associated with more worrying long-term consequences than the individual symptoms of distress reported here.”

Trauma becomes particularly likely when a child is confronted with a parent’s death from cancer. Communication with children about the disease should be an ongoing process that, ideally, would begin shortly after the announcement of an incurable cancer diagnosis and include practical preparations for life after the parent has died.

These key conversations should be addressed in an age-appropriate way, but parents, who need guidance from professionals, mostly navigate the experience on their own, while health and social care professionals are often unaware of the challenges faced during this period.

Distinguishing between how much it is possible to prepare a child for the loss of a parent to reduce traumatic phenomena and the extent to which this loss constitutes a suffering that words can neither prevent nor mitigate, Clerici underlined the importance of recognising that the support needs of children are not limited to the terminal phase of the disease and early stages of bereavement.

“Their entire growth path will be shaped by the challenge of finding in the surviving parent, in new social and emotional relationships, opportunities to make up for their loss,” he said. “Activating care resources that ensure long-term psychological support and monitoring of the child could help these individuals face the challenges of existence without feeling emotional loneliness or abandonment and, while meeting modest reimbursements from health systems, has the potential to produce significant healthcare savings in the long term.”

FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations

The Food and Drug Administration has granted accelerated approval to mobocertinib for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to select patients with the above mutations for mobocertinib treatment.

Approval was based on Study 101, an international, non-randomised, open-label, multicohort clinical trial (NCT02716116) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Efficacy was evaluated in 114 patients whose disease had progressed on or after platinum-based chemotherapy. Patients received mobocertinib 160 mg orally daily until disease progression or intolerable toxicity.

The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review (BICR) and response duration. The ORR was 28% (95% CI: 20%, 37%) with a median response duration of 17.5 months (95% CI: 7.4, 20.3).

The most common adverse reactions (>20%) were diarrhoea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.

Product labelling includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhoea.

The recommended mobocertinib dose is 160 mg orally once daily until disease progression or unacceptable toxicity.

Story published courtesy of ecancer

Therapy using dual immune system cells effectively controls neuroblastoma

A newly developed immunotherapy that simultaneously uses modified immune-fighting cells to home in on and attack two antigens, or foreign substances, on cancer cells was highly effective in mice implanted with human neuroblastoma tissue, report researchers from the UNC Lineberger Comprehensive Cancer Center and the UNC School of Medicine.

The dual targeting restricted regrowth of the tumour as well as prevented the neuroblastoma cells from evading the attacking immune cells.

The research findings are published in Nature Cancer.

Neuroblastoma is a cancer of immature nerve cells and occurs mainly in children younger than six years of age. The tumours are typically found on top of adrenal glands but can also develop in the abdomen, chest, neck, pelvis, and bone. Approximately 500 to 1,000 cases are diagnosed annually in the United States.

“Tumour cells are characterised by a mixed expression of antigens, and we engineered dual immune-system T cells to maximise their capacity to prevent tumours from evading detection by the immune system,” said Hongwei Du, PhD, a postdoctoral fellow at UNC School of Medicine.

“Furthermore, the modified T cells were also able to receive important signals, which is somewhat unique as there have been many challenges in getting certain types of immunotherapies to overcome the unfriendly tumour environment found in solid tumours.”

The researchers utilised CAR-T cell (chimeric antigen receptor-T cell) immunotherapy, which involves harvesting immune-system T cells from a patient and genetically re-engineering them in the lab to recognise targets on the surface of cancer cells when they are re-infused into patients.

Specifically, the scientists coupled the recognition of two antigens expressed by the tumour cells with the combination of two key co-stimulatory molecules: CD28, a protein expressed on T cells after early activation, and 4-1BB, an important co-stimulatory protein that is involved in T-cell survival and memory formation.

Both CD28 and 4-1BB have been shown to be equally effective in clinical studies in patients with blood-borne cancers when used individually. However, the combination of CD28 and 4-1BB co-stimulation appears to be critical in solid tumours. Research efforts by Du resulted in ways to deliver both signals efficiently.

The scientists first looked at neuroblastoma cells in the laboratory to see how they responded to a combined immune cell attack. Given the positive results of the lab studies, the researchers then looked at mice implanted with neuroblastoma to see how they would respond to co-stimulation by CD28 and 4-1BB modified T cells.

Indeed, the co-stimulatory cells were very effective in reducing cancer in mice bearing large numbers of neuroblastoma tumours.

“We know that certain CAR-T therapies are safe for patients with solid tumours, but so far treatments have not led to the degree of tumour regression we would like to see,” said Gianpietro Dotti, MD, professor in the UNC School of Medicine Department of Microbiology and Immunology and co-leader of the Immunology Program at UNC Lineberger.

“We ultimately designed a strategy that simultaneously addresses the most challenging tasks in solid tumours, such as generating CAR-T cells that rapidly eliminate the tumour and persist in controlling tumour growth. Furthermore, our system prevents tumour recurrence.”

If this therapeutic approach is as promising in people as it has been in mice, the researchers said targeting three, four or more antigens expressed by tumour cells could be even more effective.

They will proceed with caution as over-stimulation could exponentially increase side-effects. To counter this, the researchers can use a ‘safety switch’ technology that Dotti, Barbara Savoldo, MD, PhD, professor of paediatrics and assistant director of the UNC Lineberger Immunotherapy Program, and others developed to regulate the level of CAR-T generated stimulation.

“We are currently implementing clinical studies to look at several potential single targets,” said Dotti.

“If these studies prove that the therapies are safe, we’ll then progress to the next logical step, which is looking to see if our therapy is effective against a combination of targets.”

Study sheds light on link between colorectal cancer and diet high in red meat

Diets high in red and processed meats have been linked with colorectal cancer, and a recent study helps explain why.

The study, designed by Kana Wu, principal research scientist at Harvard T.H. Chan School of Public Health, found that frequent consumption of red and processed meat is linked with a specific pattern of DNA damage, known as an “alkylating mutational signature,” in colorectal tumors. This “alkylating” damage was caused by specific compounds that are produced in the body after consuming red meat, according to a July 22, 2021, National Cancer Institute article.

The article noted that such mutational signatures are similar to crime scene fingerprints, allowing researchers to trace the origins of the mutations that led to a tumor’s formation, and that the new discovery may be useful in preventing, detecting, and treating colorectal cancer.

In a video interview on OncologyTube, Wu explained that the preservatives in processed meats may contain alkylating agents, which are responsible for the type of DNA damage found in the study. She added that high consumption of red and processed meat is also associated with higher risk of other chronic diseases, such as heart disease and diabetes, not just colorectal cancers—important considerations when making dietary choices.

International study of rare childhood cancer finds genetic clues, potential for tailored therapy

In children with rhabdomyosarcoma, or RMS, a rare cancer that affects the muscles and other soft tissues, the presence of mutations in several genes, including TP53, MYOD1, and CDKN2A, appears to be associated with a more aggressive form of the disease and a poorer chance of survival. This finding is from the largest-ever international study on RMS, led by scientists at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health. 

The study, published in the Journal of Clinical Oncology on June 24, provides an unprecedented look at data for a large cohort of patients with RMS, offering genetic clues that could lead to more widespread use of tumor genetic testing to predict how individual patients with this childhood cancer will respond to therapy, as well as to the development of targeted treatments for the disease. 

“These discoveries change what we do with these patients and trigger a lot of really important research into developing new therapies that target these mutations,” said Javed Khan, M.D., of NCI’s Genetics Branch, who led the study.

“The standard therapy for RMS is almost a year of chemotherapy, radiation therapy, and surgery. These children get a lot of toxic treatments,” said the study’s first author, Jack Shern, M.D., of NCI’s Pediatric Oncology Branch. “If we could predict who’s going to do well and who’s not, then we can really start to tailor our therapies or eliminate therapies that aren’t going to be effective in a particular patient. And for the children that aren’t going to do well, this allows us to think about new ways to treat them.” 

RMS is the most common type of soft tissue sarcoma in children. In patients whose cancer has remained localized, meaning that it has not spread, combination chemotherapies have led to a five-year survival rate of 70%-80%. But in patients whose cancer has spread or come back after treatment, the five-year survival rate remains poor at less than 30%, even with aggressive treatment. 

Doctors have typically used clinical features, such as the location of the tumor in the body, as well as its size and to what extent it has spread, to predict how patients will respond to treatment, but this approach is imprecise. More recently, scientists have discovered that the presence of the PAX-FOXO1 fusion gene that is found in some patients with RMS is associated with poorer survival. Patients are now being screened for this genetic risk factor to help determine how aggressive their treatment should be. 

Scientists have also begun using genetic analysis to dig more deeply into the molecular workings of RMS in search of other genetic markers of poorer survival. In this new study — the largest genomic profiling effort of RMS tumors to date — scientists from NCI and the Institute for Cancer Research in the United Kingdom analyzed DNA from tumor samples from 641 children with RMS enrolled over a two-decade period in several clinical trials. Scientists searched for genetic mutations and other aberrations in genes previously associated with RMS and linked that information with clinical outcomes. Among the patterns that emerged, patients with mutations in the tumor suppressor genes TP53, MYOD1, or CDKN2A had a poorer prognosis than patients without those mutations. 

Using next-generation sequencing, researchers found a median of one mutation per tumor. Patients with two or more mutations per tumor had even poorer survival outcomes. In patients without the PAX-FOXO1 fusion gene, more than 50% had mutations in the RAS pathway genes, although RAS mutations did not appear to be associated with survival outcomes in this study.  

The researchers believe that although they have identified the major mutations that may drive RMS development or provide information about prognosis, they have only scratched the surface in defining the genetics of this cancer, with many more mutations yet to be discovered. They note that more work is needed to identify targeted drugs for those mutations, and future clinical trials could incorporate genetic markers to more accurately classify patients into treatment groups. Two NCI-sponsored Children’s Oncology Group clinical trials are currently being developed using these markers, and all participants will have their tumors molecularly profiled. 

The researchers hope that routine tumor genetic testing for rare cancers, such as RMS, will soon be a standard part of the treatment plan, as it is for more common cancers, such as breast cancer. 

“Genetic testing is going to become the standard of care,” said Dr. Shern. “Instead of just the pathologists looking at these tumors, we’re now going to have molecular profiling, and that’s a leap forward.”  

This study was conducted by an international consortium comprised of scientists at NCI and the Children’s Oncology Group in the United States, and the Children’s Cancer and Leukaemia Group and the National Cancer Research Institute’s Young Onset Soft Tissue Sarcoma Subgroup in the United Kingdom. The data are available at clinomics.ccr.cancer.gov/clinomics/public. The research was supported by NCI and St. Baldrick’s Foundation in Monrovia, California.

Combination treatment for common glioma type shows promise in mice

Artist’s rendering of a glioma cell under attack from the immune system.Ella Marushchenko

In a study funded by the National Institutes of Health, researchers tested a novel combination treatment approach on mice with tumors with characteristics similar to human astrocytomas — a type of slow-growing glioma—and found tumor regression in 60 percent of the mice treated. These encouraging results, published in the Journal of Clinical Investigation, could be the first step toward developing a treatment for this type of brain cancer.

Gliomas are common brain tumors that comprise about one third of all cancers of the nervous system.

Led by senior authors Maria Castro, Ph.D. and Pedro Lowenstein, M.D., Ph.D. along with a team of researchers at the University of Michigan Rogel Cancer Center(link is external) in Ann Arbor specifically tested inhibitors of the compound D-2-Hydroxyglutarate (D-2-HG), which is produced by cancer cells, on a mouse version of astrocytoma carrying mutations in the genes IDH1 and ATRX, along with an inactivated form of the tumor suppressor protein 53 (TP53) gene.

When the implanted mice were treated with a drug to block the production of D-2-HG along with standard of care radiation and temozolomide (chemotherapy) treatments, their survival significantly improved. Looking more closely at tumor cells grown in dishes, the researchers saw that blocking D-2-HG caused the cells to become more susceptible to radiation treatment. However, the treatment also increased the amount of an “immune checkpoint” protein, which tumors use to turn off T cells and evade the immune system.

Inhibiting this immune checkpoint protein with an additional drug resulted in an even greater improvement in survival, because the mouse’s own immune system was able to attack the tumor. Importantly, this combination therapy also led to immunological memory against the glioma, meaning that the mouse now had T cells tailored to the specific tumor. Because gliomas almost always grow back after treatment, these T cells make the animal better prepared to fend off regrowth.

It must be emphasized that these experiments were performed in mice. Nonetheless the preclinical results produced by this combination therapy could represent a key advance in developing an improved treatment regimen, which combines D-2-HG and immune checkpoint inhibition, radiation, and temozolomide, for patients with astrocytomas.

Meet Zach Sobiech | My Last Days

Meet Zach, a forever 18 year old osteosarcoma warrior. Zach was a compassionate and loving soul with a passion for living life to the fullest.

In 2009, Zach went on a run with his sister after a lazy summer. When he came home, he was complaining of a sore hip. His mother, Laura said if it persisted, they’d go to the doctor. After a few weeks, the pain was still there so Zach and his mom went to the doctor. The doctor had an x-ray performed, ruled out anything major and sent him home. After the pain got worse, Laura decided to take him back to the doctor where an MRI was ordered. Zach’s parents, Laura and Rob both accompanied him to the MRI where they found out that he had a tumor. The doctor wasn’t completely sure what type of tumor and said it could be one of three possibilities – lymphoma, fibrous dysplasia or osteosarcoma. “Osteosarcoma is the worst of the three,” Rob said, in the book, “Clouds, a memoir.” 

Zach was officially diagnosed after a biopsy was performed. The doctor confirmed Laura and Rob’s worst fears, osteosarcoma. “The words hit me with the percussion of a bomb; I couldn’t breathe and my ears rang. As much as I had prepared myself to hear those words, I wasn’t ready for their impact” remembers Laura. 

Credit: American Childhood Cancer Organization