Category: Cancer

Categories : Cancer COVIDTags :

COVID Vaccination Boosts Nasopharyngeal Cancer Treatment Success

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Photo by Gustavo Fring at Pexels

Patients with nasopharyngeal cancer are often treated with immunotherapy. It was previously feared that, due to its immune response stimulation, COVID vaccination could reduce the success of cancer treatment or cause severe side effects. A recent study published as a “Letter to the editor” in the journal Annals of Oncology now gives the all-clear on this matter. What’s more, the study showed that cancer drugs actually worked better after vaccination with the Chinese vaccine SinoVac than in unvaccinated patients.

Many cancer cells are capable of subverting the body’s immune response. They do this by acting on the PD-1 receptor, they effectively shut down these endogenous defence forces. Drugs can be used to block PD-1 receptors. This enables the immune system to fight the tumour more effectively.

Vaccination against COVID also stimulates the immune response, involving the PD-1 receptor. “It was feared that the vaccine would not be compatible with anti-PD-1 therapy,” explains Dr Jian Li of the Institute of Molecular Medicine and Experimental Immunology (IMMEI) at the University Hospital Bonn. “This risk is especially true for nasopharyngeal cancer, which, like the SARS Cov-2 virus, affects the upper respiratory tract.”

Researchers from the Universities of Bonn and Shanxi in the People’s Republic of China investigated whether this concern is justified. More than 1500 patients treated in 23 hospitals from all over China participated in the analysis. Such multi-centre studies are considered to be particularly informative because the participants are very diverse and, moreover, the results are not distorted by regional characteristics.

Better response to cancer therapy

A subset of 373 affected individuals had been vaccinated with the Chinese COVID vaccine SinoVac. “Surprisingly, they responded significantly better to anti-PD-1 therapy than the unvaccinated patients,” explains Prof. Dr. Christian Kurts, Director of IMMEI. “Furthermore, they did not experience severe side effects more often.” The researchers cannot say why the treatment was more successful after vaccination. “We assume that vaccination activates certain immune cells, which then attack the tumor,” says Prof. Dr. Qi Mei of Shanxi University Hospital. “We will now investigate this hypothesis further.”

Nasopharyngeal cancer is quite rare in this country. In southern China and other countries in Southeast Asia, however, the disease is widespread. One of the suspected reasons for this is the frequent use of air conditioning in the hot and humid regions. Nutritional factors also appear to play an important role. In Taiwan, nasopharyngeal cancer is now considered one of the leading causes of death among young men.

Source: University of Bonn

Categories : CancerTags :

A Shot of Vitamin C Gives Dendritic Cells a Potent Cancer-fighting Boost

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Vitamin C pills and orange
Photo by Diana Polekhina on Unsplash

New research published in Nucleic Acids Research has shown that vitamin C improves the immunogenic properties of dendritic cells, activating genes involved in the immune response. This discovery could help the development of potent new dendritic cell-based immunotherapies.

Since the onset of anticancer cell therapies, many types of immune cells have been used. The best-known of these cell therapies use lymphocytes, as in the highly successful CAR-T therapies. Recently, researchers have to turned to dendritic cells, known as the ‘master regulators of the immune system‘, for their ability to uptake and present antigens to the T-lymphocytes and induce an antigen-specific potent immune activation. This approach entails loading dendritic cells with specific antigens to create immune memory to make dendritic cell (DC)-vaccines.

To study dendritic cells in the lab, researchers differentiate them from monocytes using a particular set of molecular signalling. This differentiation is accomplished through a complex set of gene activation processes in the nucleus, mostly thanks to the activity of the chromatin remodelling machinery spearheaded by the TET family of demethylases, proteins that act upon the DNA epigenetic marks.

Vitamin C was already known to interact with several TET proteins to enhance its activity, but the specific mechanism was still poorly understood in human cells. In this study, a team lead by Dr Esteban Ballestar hypothesised that treating monocytes in vitro while differentiating into dendritic cells, would help the resulting cells be more mature and active.

The results obtained show that vitamin C treatment triggers an extensive demethylation at NF- kB/p65 binding sites compared with non-treated cells, promoting the activity of genes involved in antigen presentation and immune response activation. Vitamin C was also found to increase the communication of the resulting dendritic cells with other components of the immune system and stimulates the proliferation of antigen-specific T cells.

The researchers proved that vitamin C-stimulated dendritic cells loaded with antigens specific for the SARS-CoV-2 virus were able to activate T cells in vitro more efficiently than non-treated cells.

Overall, these new findings support the hypothesis that treating monocyte-derived dendritic cells with vitamin C may help generate more effective DC-vaccines. After consolidating these results in preclinical models and, hopefully, in clinical trials, a new generation of cell therapies based on dendritic cells may be used in the clinic to fight cancer more efficiently.

Source: Josep Carreras Leukaemia Research Institute

Categories : CancerTags :

Stopping Prostate Tumours from Evading Androgen Suppression Therapy

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Credit: Darryl Leja / National-Human-Genome Research Institute / National Institutes of Health

Researchers have identified an investigational therapeutic approach that could be effective against treatment-resistant prostate cancer. Results of the Phase II clinical trial performed by Cedars-Sinai Cancer investigators and published in Molecular Therapy, have led to a larger, multicentre trial that will soon be underway.

Cancer of the prostate is the second-leading cause of cancer-related death in men. Many prostate tumours are not aggressive and may require no or minimal treatment. Aggressive tumours are initially treated with surgery or radiation therapy.

In roughly a third of patients, the cancer comes back after initial treatment, said Neil Bhowmick, PhD, research scientist at Cedars-Sinai Cancer, professor of Medicine and Biomedical Sciences and senior author of the study. Those patients are usually treated with medications that suppress the actions of testosterone and other androgens, which promote prostate tumour growth.

“Patients do really well until the tumour figures a way around the androgen-suppressing therapy,” Bhowmick said. “One way that it can do this is to cause cells to make only part of the protein that the drug binds to, rendering the drug useless. The partial proteins are called splice variants.”

Through research with human cells and laboratory mice, study first author Bethany Smith, PhD, figured out that the cancer cells were using a protein called CD105 to signal to the surrounding supportive cells to make these slice variant proteins. Investigators then conducted a trial in human patients to test a drug that they hoped would keep those partial proteins from forming by inhibiting CD105.

In the trial, 9 patients whose tumours were resistant to androgen-blocking therapy continued that therapy but were also given a CD105 inhibitor called carotuximab. Forty percent of those patients experienced progression-free survival, based on radiographic imaging.

“Every single one of the patients in our trial was totally resistant to at least one androgen suppressor, and the normal course of action would be to simply try a different one or chemotherapy, which research has shown generally doesn’t stop tumor growth for more than about three months,” Bhowmick said. “Carotuximab prevented the cancer’s workaround and made the tumor sensitive to androgen-suppressing therapy.”

Importantly, Bhowmick said, carotuximab also appears to prevent androgen receptor splice variants in the supporting cells surrounding tumours, further sensitising the tumour to the androgen suppressor.

“We found that this therapy may be able to, especially in early cancers, resensitize select patients to androgen suppression. This could allow patients to avoid or delay more toxic interventions such as cytotoxic chemotherapy,” said Edwin Posadas, MD, associate professor of Medicine at Cedars-Sinai and a co-author of the study. “We also hope to find ways of predicting which patients are most likely to benefit from this approach by testing blood and tissue samples using next-generation technologies housed at Cedars-Sinai Cancer.”

Study co-author Sungyong You, PhD, director of the Urologic Oncology Bioinformatics Group, pinpointed three biomarkers that could help indicate which patients will respond to this investigational therapy, and the team will validate those markers in a new clinical trial. This will allow future studies to target patients most likely to be helped by this intervention, Bhowmick said.

Source: Cedars-Sinai Medical Center

Categories : Cancer GastrointestinalTags :

Diverticular Disease Linked to Cancers outside the Gastrointestinal System

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Anatomy of the gut
Source: Pixabay CC0

In a large-scale study of cancer among 75 000 patients with a diagnosis of diverticular disease and colorectal histopathology, researchers have reported an elevated cancer risk in patients with diverticular disease. Their findings were published in the Journal of the National Cancer Institute.

The data comes from the ESPRESSO cohort, which covers all histopathology reports from Sweden’s 28 pathology departments. Through linkage with the Swedish national patient register, researchers identified patients with diverticular disease. Diverticular disease can present through gastrointestinal bleeding, but also through diverticulitis when patients may have fever, nausea and abdominal pain. Previous research has focused on colorectal cancer development in diverticular disease but less has been know about cancer development elsewhere. The researchers found a 33% increased risk of overall cancer in Swedish patients with diverticular disease.

“This is the first nationwide cohort study to demonstrate that diverticular disease is associated with an increased, long-term risk of overall cancer”, says first-author Wenjie Ma from Massachusetts General Hospital. “Diverticular disease is associated with an increased risk of specific cancers, including liver cancer and lung cancer.”

She also adds that “Given the high prevalence of diverticular disease, our results highlight the need for awareness for cancer, not only for colorectal cancer, in patients with diverticular disease.”

Patients with diverticular disease had significantly increased overall cancer incidence (24.5 vs 18.1 cancer cases per 1000 person-years). After adjusting for covariates, these rates corresponded to 1 extra cancer case in 16 individuals with diverticular disease followed for ten years.

“There has been a lot of research on extraintestinal cancer in other bowel disorders such as inflammatory bowel disease (IBD) and celiac disease, but less is known about diverticular disease”, says senior author Jonas F Ludvigsson, professor at Karolinska Institutet.

“These data suggest that patients with diverticular disease are at increased risk of other cancers than colorectal cancer, but it should also be emphasized that the absolute risk for cancer was moderate”, adds Ludvigsson. “I hope other researchers are inspired by our findings and explore the biological mechanisms underlying the association between diverticular disease and cancer”, he concludes.

Source: Karolinska Institutet

Categories : CancerTags :

Life Oncology Launches First AI-driven Ethos™ Radiotherapy Cancer Treatment in Sub-Saharan Africa

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The Life Oncology unit at Life Vincent Pallotti Hospital today launched the Ethos™  radiotherapy system, a revolutionary new technology, the first in Sub-Saharan Africa, which uses artificial intelligence (AI) and adaptive treatment to adjust cancer treatments in response to patients’ unique, changing needs.

The Ethos™ radiotherapy system allows radiotherapy specialists to treat cancer patients with the most accurate, precision techniques. “Adaptive therapy provides the ability to adapt the treatment plan based on tumour and anatomical changes. The goal is to better target the tumour, reduce radiation dose of healthy tissue, and potentially improve overall outcomes”, says Dr Louis Kathan, Life Healthcare’s Chief Medical Officer in South Africa.

Dr Kathan, who is also a radiation oncologist with close to 15 years of patient treatment experience, explains that the streamlined workflow of Ethos™ radiotherapy is enabled by its AI-driven planning and contouring capabilities. “The system allows us to use AI to adapt to a patient’s anatomy. This allows us to make decisions more efficiently on a daily basis based on each patient’s individual needs. The ability of the machine to deliver on-couch adaptive treatment puts the patient at the centre of care”, he added.

“Clinicians globally have waited for the day when they have the ability to adapt radiotherapy treatments to changes in patient anatomy. Typically changes to a patient’s treatment plan due to changes in anatomy require time-consuming re-scanning and re-planning between treatment sessions, which could take up to two days. The Ethos™ radiotherapy adaptive technology allows the treatment plan to be adjusted daily, in real-time and the treatment to be planned and administered, all within 20 to 30 minutes”, says Kulthum Ismail, unit manager: radiation therapy at the Life Oncology unit based at Life Vincent Pallotti Hospital.

The planning and treatment all happen in one session, making it a faster process compared to existing radiotherapy technology, although Kulthum added that there is still a big role to play for current systems being used.

Kulthum Ismail, unit manager: radiation therapy at the Life Oncology unit based at Life Vincent Pallotti Hospital

The Life Oncology unit at Life Vincent Pallotti Hospital is committed to delivering the very best oncology care with substantial investments made in recent years to technologies to place the hospital at the forefront of advanced treatments in surgical-, medical-, gynaecological- and radiation oncology. These include:

  • The Novalis Tx delivery system
  • Image guided radiosurgery for tumour motion monitoring
  • Respiratory gating (respiration triggered dose delivery)
  • Minimally invasive frameless radiosurgery for patient comfort
  • Radiofrequency ablation
  • Elements Multiple Brain Mets Stereotactic Radiosurgery System which delivers powerful treatment that targets multiple brain metastases (more than one cancer lesion in the brain) simultaneously, faster and more precisely

The Ethos™ radiotherapy system at Life Vincent Pallotti Hospital is already being used to treat patients with cervical, rectum, lung and prostate cancer. In time, other cancers are hoped to be included in the treatment programme. 

“The Ethos™ radiotherapy system offers a faster and more personalised, targeted approach to radiotherapy treatment which means we really are placing the patient at the centre of care,” said Adam Pyle, Life Healthcare’s CEO for South Africa. “It’s our way of navigating our patients into the future of oncology care as we continue to live our purpose of making life better.”

Pete Wharton-Hood, Group Chief Executive for Life Healthcare added that the Group’s aspiration to be a leading cancer care provider has taken a substantial step forward with the expansion at the Life Oncology unit at Life Vincent Pallotti Hospital in Cape Town. “As a people and patient-centric organisation, we continuously seek ways to build on our existing technological offerings and services to consistently improve patient outcomes, enhance our patient experience and drive accessible and affordable healthcare. This means we get to better support our specialists who we partner with, so that together we continue delivering improved patient quality, patient experience, efficiency, and clinical excellence.”

Categories : Cancer PaediatricsTags :

Blood Transfusion Increases Risks in Paediatric Cancer

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https://www.pexels.com/photo/a-close-up-shot-of-bags-of-blood-4531306/
Photo by Charlie-Helen Robinson on Pexels

A study published in the Journal of Pediatric Hematology/Oncology found that blood transfusion is associated with adverse outcomes, including infection and higher rates of tumour recurrence — in paediatric solid tumour oncology patients following surgical removal of the tumour.

“Blood transfusion is obviously hugely important when used in the appropriate clinical scenario, but there are some downsides,” said study author Shannon Acker, MD, an assistant professor of paediatric surgery in the University of Colorado School of Medicine. “It’s pro-inflammatory and suppresses the immune system because your body reacts to foreign tissue. It can be a vital intervention, but I think we’re starting to be a little more thoughtful about giving patients blood products.”

Understanding paediatric blood transfusion

Dr Acker and colleagues pursued this research, in part, because while the effects of packed red blood cell (PRBC) transfusion in adult populations have been widely studied, data are sparser for paediatric patients.

“It’s fairly well-documented that in adult patients, perioperative blood transfusion for solid tumour resection is associated with certain adverse outcomes,” Dr Acker explained. “But paediatric cancers are more rare, so they’re more challenging to study. We need more data to understand whether what we know to be true in adult cancers is also true in paediatric cancers.”

Using retrospective data on more than 260 paediatric patients over 11 years, the researchers included malignant solid tumours removed by surgeons across all surgical disciplines. Dr Acker acknowledges that grouping different types of cancer into one study lessens the validity of the research because different cancers have different outcomes, “but we needed a place to start so we can begin working toward more collaborative, multi-centre paediatric oncology research,” she said.

Higher rates of complications

Of the 360 paediatric patients who underwent tumour resection, 194 received a blood transfusion within 30 days of surgery.

Analysing the data, they saw that children who received a blood transfusion had higher rates of post-surgery infectious complications, a shorter disease-free interval, and higher rates of tumour recurrence. They also adjusted for receiving pre-operative chemotherapy and still found that blood transfusion was associated with higher rates of post-operative infectious complications and a shorter disease-free interval.

No relationship was seen between tumour type and rate of infectious complications or disease-free interval.

Providing the best patient care

An aim of the research and its findings is to continue supporting and facilitating conversations and practices about patient care. “Packed red blood cells carry oxygen to the body and help tissues get the oxygen that they need,” Acker says. “They’re essential. It used to be common practice that if a surgeon was taking out a tumour and the patient was losing blood, they would immediately get two units.”

She added that blood transfusion now is recognised as “not a totally benign intervention, so instead of immediately giving a patient two units, we start with one and see if that leads to an appropriate response. Our research shows that each additional unit increases risk of adverse outcomes, so we want to continue being thoughtful in using this intervention.”

Acker adds that a further goal of the research is to work with members of paediatric oncology surgical consortiums to draw data from national and international centres. “The data we have are good, but I don’t think they’re enough to convince people to change institutional protocols. If we can get more validated, multi-centre data, we can begin to look at a more granular level at timing of transfusions and types of cancers so we can continue providing the best patient care.”

Source: University of Colorado Anschutz Medical Campus

Categories : CancerTags :

Earlier Mammograms for Family History of Breast Cancer may be Unnecessary

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Woman receiving mammogram
Source: National Cancer Institute

A new study reported in the journal Cancer reconsiders guidelines for when to start screening with mammograms if a woman has a first degree relative who was diagnosed with breast cancer.

Women with a first-degree family relative diagnosed with breast cancer, who are otherwise at average risk, are often advised to get screened 10 years earlier than the relative’s diagnosis age. However, there is little evidence to support the long-standing recommendation.

UC Davis Comprehensive Cancer Center researcher Diana Miglioretti joined Danielle Durham, with the Department of Radiology at University of North Carolina at Chapel Hill, and five other researchers on the study. They analysed data from the Breast Cancer Surveillance Consortium on screening mammograms conducted from 1996–2016 to evaluate when screenings should begin for women with a family history of breast cancer.

More than 300 000 women were included in the national study. Researchers compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast cancer by relative’s age at diagnosis and screening age.

“The study concluded that a woman with a relative diagnosed at or before age 45 may wish to consider, in consultation with her doctor, initiating screening 5–8 years earlier than their relative’s diagnosis age, rather than a decade earlier. That puts them at a risk that is equal to that of an average-risk woman who is age 50, which is the most recommended age for starting mammograms,” said Durham.

BRCA gene mutation carriers may benefit from starting screenings earlier. Women ages 30–39 with more than one first-degree relative diagnosed with breast cancer may wish to consider genetic counselling.

Increasing the age for initiating screening could reduce the potential harms of starting breast cancer screenings too early. These include increased radiation exposure and false positive results that require women to return to the clinic for diagnostic imaging and possibly invasive procedures, but do not result in a breast cancer diagnosis. The earlier a woman starts receiving mammograms, the more screenings they will undergo over their lifetime – and that increases the chances of experiencing these harms.

“Mammography also may not perform as well in younger women because they are more likely to have dense breasts which increase the difficulty of finding cancer on the images and results in more false-positives,” Miglioretti said.

Source: University of California – Davis Health

Categories : Cancer ExerciseTags :

Trial to Investigate Exercise with Neodjuvant Chemotherapy for Breast Cancer

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Woman receiving mammogram
Source: National Cancer Institute

The prognosis for breast cancer has improved, allowing more and more women to be cured with a combination of surgery, radiotherapy and medical treatment. A new trial led by Karolinska Institutet will investigate whether combining neoadjuvant chemotherapy with exercise will improve the outcomes of breast cancer patients.

Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The main benefit of NACT is its ability to downstage large tumours with a view to treatment by breast-conserving surgery, although there is a non-significant increase in the local recurrence rate. The best proof of NACT efficacy is pathological complete response (pCR), ie the absence of invasive tumour on post-NACT on surgical histopathology.

“While it is known that physical exercise can help patients to better tolerate often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes”, explained Jana de Boniface, principal investigator of the trial and associate professor in the Breast Surgery Group, Department of Molecular Medicine and Surgery.

The Neo-ACT trial opened for recruitment in September 2022, and it is estimated that inclusion may be completed in December 2025.

Source: Karolinska Institutet

Categories : CancerTags :

Inflammatory Breast Cancer More Likely to Metastasise to the Brain

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Source: National Cancer Institute

Higher rates of brain metastases in patients with inflammatory breast cancer, a rare subtype of breast cancer, have been observed in studies, but detailed information is lacking. Now, a new study published in CANCER indicates that patients inflammatory breast cancer face a higher risk that their cancer will metastasise to the brain.

To provide insights into the incidence and risk factors for brain metastases in this patient population, Laura E.G. Warren, MD, and colleagues analysed data on 372 patients with stage III inflammatory breast cancer and 159 with stage IV inflammatory breast cancer. 

Over a median follow-up of five years, the incidence of brain metastases at one, two, and five years was 5%, 9%, and 18% among patients who presented with stage III disease, and 17%, 30%, and 42% among those with stage IV disease. Patients with triple-negative breast cancer faced a particularly high risk, and when they did experience brain metastases, their survival time was shorter than those with hormone receptor–positive or HER2-positive breast cancer who experienced brain metastases. Higher risks of brain metastases were also seen in patients whose cancer had metastasised to other parts of the body besides the brain, especially when this occurred at a young age. 

“The relatively high incidence of brain metastases seen in the study population highlights the need for future research on the potential role for surveillance brain imaging for high-risk patients. There is an open, phase II, single arm study at Dana-Farber Cancer Institute examining this question,” said Dr. Warren. “It also emphasises the need to obtain brain imaging in patients with inflammatory breast cancer presenting with neurologic symptoms given the high incidence of brain metastases in this population.” Most patients in this study who were diagnosed with brain metastases had neurologic symptoms, but because some patients may have undetected, asymptomatic brain metastases, the true incidence in patients with inflammatory breast cancer is likely even higher than what Dr Warren and her colleagues observed. 

An accompanying editorial notes that when considering whether to implement routine brain imaging tests in patients with inflammatory breast cancer, it will be important to determine whether earlier detection of brain metastases leads to improvements in both survival and quality of life.

Source: Wiley

Categories : CancerTags :

Mix-and-matching Old Drugs for Cheaper Bowel Cancer Treatment

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Female scientist in laboratory
Photo by Gustavo Fring on Pexels

Using old medicines in new combinations shows promise for treating bowel cancer, a group of University of Auckland researchers has found. They published their findings in Molecular Cancer Therapeutics.

“While there have been advances in treatments for this disease in recent years, the development of new medicines is expensive and time-consuming,” lead researcher Professor Peter Shepherd explained. “As a possible solution to this problem, our group has been investigating whether using old drugs in new ways could provide a faster and cheaper way of treating this disease.”

The scientists investigated several cancer drugs that are coming off patent soon. When they combined two such drugs, they found greatly enhanced overall effectiveness in treating bowel, or colorectal, cancer in their lab-based studies.

Developments in our understanding of how cancers function have paved the way for this research, Prof Shepherd said.

“In recent years, research has led to a rapid increase in our understanding of how colorectal cancer develops. In particular, some sub-types of the disease rely on the development of small blood vessels and on proteins called BRAF and beta-catenin.

“The research group identified existing drugs that target these and investigated the possibility that combining them could have powerful anti-cancer effects.”

Their studies have shown strong promise for two older drugs. One is an anticancer drug called axitinib. The other is pyrvinium, a low-cost drug that was developed in the 1960s to treat threadworm, which the researchers believe could be reformulated for use in cancer treatment. In one set of studies, the researchers found that the efficacy of another older drug targeting BRAF, called vemurafenib, could be greatly enhanced by adding axitinib. Axitinib works by reducing the growth of small blood vessels.

Both these drugs are used in other contexts to treat other types of cancer and will soon be off patent and so the cost of using them in treatment will drop greatly, Prof Shepherd said.

In a second set of studies, the group found evidence that pyrvinium, which targets beta-catenin, could also increase the efficacy of vemurafenib.

Dr Khanh Tran who performed most of the experiments said, “This work suggests that existing drugs might be able to be repurposed to treat this type of cancer which could significantly reduce the cost of such therapy.”

Dr Tran added, “Since the drugs we used are already in use for other purposes, it makes it much easier to develop clinical trials to see how the findings of our studies will actually translate to improved outcomes for patients with this disease.”

Source: University of Auckland