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Trust in scientists on the rise worldwide
Trust in scientists has seldom been more crucial than now.
Trust in scientists has seldom been more crucial than now, with people having to make large-scale lifestyle changes based on guidance from experts during the COVID-19 pandemic.
With scientists and those in the medical profession becoming increasingly visible in local and global media, this exposure appears to have had a positive effect.
The proportion of people expressing a high level of trust in scientists in their countries has increased in almost every region in the past two years, rising nine percentage points between 2018 and 2020 to 43 per cent globally.
This data is reported in the Wellcome Global Monitor for 2020 , which delves into the impact of COVID-19 on livelihoods, and people’s views on science. It follows Wellcome’s 2018 Monitor, its first on public attitudes to science and health worldwide.
Understanding how people around the world view science and scientists is critical to efforts to ensure widespread public attention to and compliance with scientific recommendations in future crises. — Wellcome Global Monitor 2020
With the pandemic emerging between the two surveys, the latest report provides insight into what impacts the situation has had on people’s attitudes, as well as on their lives.
Conducted as part of Gallup’s World Poll of attitudes and behaviours, the study was compiled via a survey of more than 119,000 people in 113 countries and territories in late 2020 and early 2021, at the same time as COVID-19 cases ramped up in many locations around the world.
This interactive visualisation explores the key outcomes from the study, evaluating findings in three focus areas – trust in science, the economic consequences of COVID-19, and levels of public support for global spending on preventing and curing diseases.
Building trust
East and South Asia, Australia and New Zealand, the Americas and Eastern Europe all saw rises of at least 10 percentage points between 2018 and 2020 in the proportion of people expressing a high level of trust in scientists in their countries.
And globally the number of people professing a high level of trust in science itself rose to 41 per cent, from 31 per cent in 2018.
“Trust is so important, both in science and in our health systems, and in governments, to ensure that public health can deliver,” says Beth Thompson, associate director of policy at Wellcome. “So, undoubtedly, it’s important that we develop that trust wherever we can around the world.”
The report findings also support the idea that growing trust is linked to scientists’ increased visibility in the media. “[It’s] particularly gone up among people who said they don’t know as much about science to start with,” says Thompson. “That could support the idea that it’s because people didn’t see a lot of science and didn’t have much access to it [before], and now, through the pandemic, they’ve had more exposure.”
But despite the positive picture overall in trust in scientists and science by region, there were two notable exceptions that upset the general trend in both categories – Sub-Saharan Africa and the Russia, Caucasus and Central Asia region. In both these regions, the figures fell between 2018 and 2020, dropping for scientists from 24 to 19 per cent and 34 to 28 per cent, respectively.
Meanwhile, figures ranged widely between countries: in Benin and Nigeria, just under 10 per cent of people surveyed expressed a high level of trust in scientists in their countries, compared to 72 per cent in Belgium, the highest globally.
Trust levels appear linked to perceptions of national government, says Wellcome, with those trusting their government 13 percentage points more likely to have high trust in scientists. In Nigeria, less than five per cent of people had high trust in government.
Trust is so important, both in science and in our health systems, and in governments, to ensure that public health can deliver. — Beth Thompson, associate director of policy, Wellcome
Worldwide, trust in scientists was almost as great as the 45 per cent figure for those expressing high levels of trust in doctors and nurses. This is noteworthy because, while doctors and nurses are still more trusted than scientists, the gap narrowed considerably from Wellcome’s 2018 report, even though trust in the medical profession also rose three percentage points between the two reports.
Trust in journalists and national governments also increased, though again, not as much as for scientists and science. However, trust for people in one’s neighbourhood fell, from 34 per cent to 29 per cent.
Broadening economic disparities
While COVID-19 seems to have had a positive impact on trust levels, the Global Monitor also shows the extent to which the pandemic has exacerbated economic disparities.
Almost half of workers in low- and lower-middle-income countries reported losing a job or business due to COVID-19, compared with a third globally and just a tenth in high-income countries.
Within countries, too, the economic gap widened. Globally, 41 per cent of those receiving the lowest 20 per cent of in-country incomes lost business, almost double the proportion among the richest fifth of people. In Latin America, the disparity was as much as triple.
Seven countries saw more than half of people losing a job or business, reaching two-thirds in the Philippines and Kenya. In Kenya in 2020, Wellcome highlights that almost three-quarters of people reported periods when they had insufficient money to buy food for their families.
Over half of people in seven countries reported losing a job or business due to COVID-19.
This backs up previous reports that have indicated how quickly such effects took hold in some countries, with 48 per cent of rural households in Kenya and 87 per cent in Sierra Leone facing missed meals or reduced portion sizes as early as April 2020 – just a month or so after COVID-19 was declared a pandemic.
The impacts of COVID-19 have been “deeply inequitable”, says Thompson. “We knew that those impacts were there, but I hope that by having more data it re-emphasises the importance of dealing with those inequities… We have to understand the inequities that people are facing and the situation that they’re living in to stand a real chance of tackling any of the big issues that are facing people.”00:00/01:30
Beth Thompson, associate director of policy at Wellcome, explains the issues behind the figures
At the same time, people in a number of low-income regions with large rural populations were among the likeliest to say their lives had not been affected by the pandemic, including Sub-Saharan Africa, Southeast Asia and Central Asia.
The figure was as high as 61 per cent in Laos, compared with just 19 per cent globally. Meanwhile, 45 per cent of people worldwide said their lives had been affected a lot by COVID-19.
Attitudes on disease prevention
One of the biggest questions is how countries should prepare together for the next pandemic, after COVID-19 put a spotlight on the vulnerability of today’s interlinked world. Key to this are attitudes on how spending on disease prevention should be directed globally.
With that in mind, Wellcome asked people how much they agreed with two separate statements – whether they thought their national government should spend on preventing diseases wherever they hit; and whether their government should spend only if their own country is at immediate risk.
However, there appeared to be some uncertainty over the statements, as at least 70 per cent of respondents strongly or somewhat agreed with both – including notable majorities in regions including South Asia, East Asia and Latin America.
Some countries saw big gaps between those who agreed with each statement. In Norway, 85 per cent agreed the government should spend wherever diseases hit, compared with 33 per cent saying this should only happen if it affected their own country. In Tunisia, meanwhile, it was the reverse, with figures of 38 and 87 per cent.
The need for international cooperation to prevent diseases will be an important consideration going forward, says Wellcome, citing the call by a G20 panel for new investments and mechanisms for international pandemic-focused financing, and analysts who argue for pandemic preparedness as a “global public good”.
But more progress is needed, says Thompson, with public attitudes set to be a crucial component of how this all shakes out in the future. “Global cooperation is the only way we’re going to solve huge challenges like COVID and, ultimately, politicians are accountable to their electorates in democracies,” says Thompson.
That means the need for public buy-in, with data like Wellcome’s helping evaluate this, she says, adding: “We hope this empowers the people in those different regions and within their countries to dig into the data to explore how it can be useful for them and what they might be able to take from it.”
Child asthma cases linked to cities’ dirty air
- Nitrogen dioxide (NO2) pollution is the cause of 1.85 million child asthma cases a year – study
- NO2 pollution is increasing in Sub-Saharan Africa, South Asia
- Air pollution reduction must be integrated into child health policies, say researchers.
A child in Cambodia getting asthma treatment using an inhaler. A study has highlighted rising nitrogen dioxide pollution levels as a leading cause of child asthma in urban areas in South Asia and Sub-Saharan Africa.
Reducing air pollution should be a crucial part of health strategies for children, as nitrogen dioxide (NO2) — a harmful pollutant emitted from burning fossil fuels — may lead to nearly 2 million new child asthma cases a year, research suggests.
The study, published this month in The Lancet Planetary Health, highlights rising NO2 pollution levels in urban areas in South Asia and Sub-Saharan Africa, where it suggests child asthma is a serious health concern.
Researchers from George Washington University in the US say it is the first study to estimate the global burden of asthma cases in children resulting from NO2 emissions in more than 13,000 cities.
“The findings suggest that clean air must be a critical part of strategies aimed at keeping children healthy.”
Susan Anenberg, professor of environmental and occupational health, George Washington University
“Our study found that nitrogen dioxide puts children at risk of developing asthma and the problem is especially acute in urban areas,” said Susan Anenberg, study co-author and a professor of environmental and occupational health at the university, in Washington DC.
Asthma affects around 262 million people worldwide, according to the 2019 Global Burden of Disease study, and is the most common chronic disease among children, causing inflammation of the lung’s airways.
However, reliable data is still lacking on the condition. Most asthma-related deaths occur in low- and middle-income countries where it is often under-diagnosed and under-treated, according to the World Health Organization.
NO2 is formed by the burning of fossil fuels such as oil and gas and is mainly emitted by vehicles, industry, agricultural machinery, and power plants.
By analysing ground concentration of NO2 and new cases of asthma in children from 2000 to 2019, researchers observed that, in 2019, an estimated 1.85 million new cases of childhood asthma were attributable to NO2 worldwide, and two thirds of these cases (1.22 million) were in urban areas.
NO2 pollution has been increasing in South Asia, Sub-Saharan Africa, and the Middle East, the researchers found, while air quality has shown improvements in Europe and the US.
Explaining the connection between NO2 and childhood asthma, the researchers said: “NO2 itself has been associated with adverse health outcomes including asthma exacerbation. Epidemiological studies have also found associations between transportation-related air pollutants [such as NO2] and new onset asthma in children.”
According to the researchers, some studies indicated that pollutants such as NO2 cause inflammation and changes in airways due to oxidative stress, sometimes resulting in asthma.
“The findings suggest that clean air must be a critical part of strategies aimed at keeping children healthy,” said Anenberg.
A review published in 2019 in the journal Environment International highlights possible measures to combat NO2 pollution, such as “a ventilation strategy with suitable filters…ventilating windows or intakes; traffic planning (location and density); and reducing the use of NO2-releasing indoor sources.”
Stanley Szefler, director of the Pediatric Asthma Research Program at the Breathing Institute of Children’s Hospital Colorado, US, who was not involved in the Washington DC study, told SciDev.Net: “The report by Anenberg and colleagues reinforces the role of air pollution on paediatric asthma incidence and supports the role of public health and environmental control stakeholders…to speak for clean air measures.
“Furthermore, the report suggests that monitoring environmental levels of nitric dioxide could serve as a surrogate marker [an indicator of a disease state] for regions of high risk for increased childhood asthma incidence as well as an indicator of the efficacy of mitigation measures for air pollution.”
Szefler was the lead author of a study published in 2020 in the journal Pediatric Pulmonology. It advocated for “a worldwide charter” on child asthma that would act as a roadmap for “better education and training”.
“The charter indicated that asthma guidelines alone are insufficient and need supplementing by government support, changes in policy, access to diagnosis and effective therapy for all children, with research to improve implementation,” Szefler added.
Sushmita Roychowdhury, director of pulmonology at Fortis Hospital, in Kolkata, India, says that paediatric asthma is becoming more common in highly populated cities.
“Children living in high-rises close to the main busy arterial roads are found to have more symptoms early on,” she said. “Most children in urban India waiting for school buses in the morning or those taking public transport are exposed to high concentrations of pollutants.”
DNA May Predict Side Effects from Radiation in Prostate Cancer Patients
A team from the UCLA Jonsson Comprehensive Cancer Center used prostate cancer patients’ DNA to create a model that appears to predict who will have side effects from radiation.
While radiation treatment is a very effective therapy for prostate cancer, around one in six men experiences more frequent or painful urination as a lingering side effect, otherwise known as genitourinary toxicity.
These disruptive side effects can occur no matter what type of radiation a patient receives: conventionally fractionated radiotherapy (lower daily doses given over the span of multiple weeks, i.e. long-course), or stereotactic body radiotherapy (higher daily doses given over the span of 10 days, i.e. short-course). In a new study, Dr. Amar Kishan of Jonsson Comprehensive Cancer Center and, lead author and vice chair of clinical and translational research in the Department of Radiation Oncology at UCLA, teamed up with Dr. Joanne Weidhaas, senior author and Head of Translational Research in the Department of Radiation Oncology, to determine if differences in a patient’s DNA would predict whether they would have genitourinary toxicity after receiving either type of radiation.
“One of the biggest goals of our research program is to try to minimize toxicity and improve quality of life after treatment,” Dr. Kishan said.
“The DNA “differences” we study are perfectly suited to help identify people who will respond differently to cancer therapies, like radiation. These different responses can result in toxicity,” Dr. Weidhaas said.
To conduct the study, published in Radiotherapy and Oncology, Dr. Kishan and colleagues analyzed DNA collected from 201 men who received either conventional fractionated radiotherapy or stereotactic body radiotherapy. Using unique differences in the patients’ DNA, the researchers then developed a model for both forms of radiation therapy to see if they could predict which patients would develop side effects.
The study found that the models were highly predictive in differentiating between those who would experience toxic side effects after radiation therapy and those who would not. Furthermore, the models were able to predict toxicity depending on which type of radiation the patient received, long-course or short-course, indicating they could potentially help with decision making in choosing one treatment course over the other.
In an ongoing clinical trial, Dr. Kishan is testing this model on a new set of patients to further confirm the study’s findings. In the trial, the results from the DNA analysis are shared with each patient, and the impact of the information on shared decision making, as well as decreasing toxicity in the group as a whole, is being evaluated.
“This research may ultimately guide a prostate cancer patient’s treatment plan,” said Dr. Kishan. “If we can know ahead of time who will tolerate radiation treatment and who may suffer these side effects, we can do a better job of assuring not only the best treatment but the one with least impact on quality of life.”
Early data indicate vaccines still protect against Omicron’s sister variant, BA.2
New data show that vaccines still protect against a spinoff of the Omicron variant, a welcome sign as the world keeps a close eye on the latest coronavirus iteration.
BA.2, as the sublineage is known, is part of the broader Omicron umbrella. Scientists are paying more attention to it as it begins to eat into the dominance of the more common Omicron strain, which is technically called BA.1.
BA.1 is what has driven massive spikes in cases around the world, but in countries including India, the Philippines, South Africa, and several countries in Europe, BA.2 has been picking up proportional steam and demonstrating a growth advantage over BA.1. The two lineages share many mutations, but have their own individual genetic twists as well.
As with any emerging variant, there are more questions than answers about BA.2’s transmissibility, severity, and ability to erode the immunity built by vaccination or prior infection. As the World Health Organization put it last week, “drivers of transmission and other properties of BA.2 are under investigation but remain unclear to date.”Trending Now:
But data this week from the U.K. Health Security Agency — which has done some of the leading work on new variants — offered a piece of reassuring news: There does not seem to be any loss of vaccine effectiveness against BA.2 compared to BA.1.
Vaccines already took a decent hit in the face of BA.1, particularly in their ability to prevent infection entirely, which is why so many immunized people have had breakthrough infections in recent weeks. But crucially, the vaccines’ protection against severe disease with Omicron has broadly stood up, and booster doses have helped shore up much of the protection that was lost.
This week, the U.K. agency estimated that, for people at least two weeks out from their booster shot, vaccine effectiveness against symptomatic disease was 63% against BA.1, versus 70% for BA.2. While that might suggest that BA.2 is less of a threat to vaccine protection than its Omicron sister, the full estimate ranges overlapped.
Jacob Lemieux, an infectious diseases physician at Massachusetts General Hospital who is helping lead a state program studying variants, said that in some countries, BA.2 is displacing BA.1, but that, “what we don’t know, and still have almost no information on, is what impact this will have on case counts, on hospitalizations, on death.”
Variants can behave differently in different places, depending on the levels and types of immunity people have there and what else is spreading. Different variants can co-circulate. And the composition of infections can change — with an emerging strain coming to take the lead in a given place — even as the total number of cases declines or stays flat. Put another way, even if BA.2 becomes dominant, it doesn’t have to cause another spike.Related: After Omicron, we could use a break. We may just get it
One factor that will help determine that is cross-protection: essentially, how well are the millions of people who’ve now been infected with BA.1 protected against infection from BA.2? Some variants offer better cross-protection against other forms of the virus than others. It appears that people who’ve been vaccinated and infected with Omicron have strong protection against Delta, for example.
Another possibility is that BA.2 — if it is more transmissible in our current landscape than BA.1 — could cause another uptick in cases, but whatever spike occurs could be broadly limited to infections because of the high levels of population immunity. That is, the link between cases and subsequent hospitalizations and deaths could become even more decoupled than it already is.
This week, for example, Danish authorities announced that they were ending most pandemic restrictions starting next week, because even with a high infection tally, there were few resulting hospitalizations.
Novel approaches to malignant brain tumor treatment aim to overcome familiar challenges
Although therapeutic advances during the past decade have dramatically improved cancer outcomes overall, the outlook for patients with malignant brain tumors has remained poor.
The 5-year relative survival rate for these patients increased only from 23% between 1975 and 1977 to 36% between 2009 and 2015, with rates in the single digits for those with particularly lethal brain tumor types, according to an analysis of population-based registry data by Miller and colleagues.
Source: University of California, Irvine.
One challenge to treatment of these aggressive tumors has been the inability of drugs to penetrate the blood-brain barrier. Use of treatments that can cross the barrier, such as chemotherapy and radiation therapy, often is limited because of toxicity. Other standard treatments, such as surgery, are not even an option for some patients because of the tumor location.
“Achieving effective treatment with minimal side effects is the biggest challenge in the field of malignant brain tumors right now,” Daniela A. Bota, MD, PhD, professor of neurology, vice dean for clinical research and medical director of the comprehensive brain tumor program at University of California, Irvine, told Healio | HemOnc Today. “Yet, we are making progress in glioblastoma. We are understanding more and more about what we need to do to develop more effective treatments, and it is my sincere belief that the next few years will bring us closer to a potential cure.”
Healio | HemOnc Today spoke with neuro-oncologists and radiation oncologists about novel treatment approaches for malignant brain tumors that have shown promise among adults and children, vaccines and other advances on the horizon, and efforts to address ongoing challenges facing this patient population.
Glioblastoma: ‘A complex disease’
Glioblastoma remains the most common and most lethal type of brain cancer in the United States, as well as one of the most difficult types to treat.
“Glioblastoma is a tumor that, until now, has been resistant to immunotherapy,” Bota said. “We have tried checkpoint inhibitors, which are revolutionizing the world of cancer for so many other malignancies, but unfortunately for both newly diagnosed and recurrent glioblastoma, the addition of checkpoint inhibitors to standard of care has not given us positive results.”
Some studies have suggested that administering checkpoint inhibitors before surgery for recurrent glioblastoma could improve survival outcomes.
Cloughesy and colleagues examined whether neoadjuvant vs. adjuvant-only treatment with the PD-1 inhibitor pembrolizumab (Keytruda, Merck) could alter the functional immune landscape and improve survival among 35 adults with recurrent, resectable glioblastoma.
Results of the study, published in 2019 in Nature Medicine, showed neoadjuvant pembrolizumab led to a significant increase in OS compared with adjuvant pembrolizumab (13.7 months vs. 7.5 months; HR = 0.39; 95% CI, 0.17-0.94). Neoadjuvant therapy also appeared associated with longer PFS (3.3 months vs. 2.4 months; HR = 0.43; 95% CI, 0.2-0.9). However, researchers noted the study’s small sample size and the need for larger trials to confirm their findings.
“We are still learning about which avenues will be our ‘success stories’ for patients with malignant brain tumors,” Rupesh R. Kotecha, MD, radiation oncologist and chief of radiosurgery and director of central nervous system metastasis at Miami Cancer Institute, part of Baptist Health South Florida, told Healio | HemOnc Today. “For immunotherapy, the studies so far have not recapitulated those in other disease sites where we have seen significant advances and improvements in survival. The studies performed to date have not been revealing and therefore we are not certain whether this is because of a failure of a particular treatment regimen, if the tumor biology is resistant to the type of immunotherapy approaches being tested, or if we are selecting the right patient population for testing of these therapies.”
One ongoing randomized clinical trial is examining the use of combination immunotherapy among an international cohort of patients with glioblastoma.
“This study includes patients with newly diagnosed MGMT-unmethylated glioblastoma and is testing two immunotherapy agents, nivolumab [Opdivo, Bristol Myers Squibb] plus ipilimumab [Yervoy, Bristol Myers Squibb], compared with standard-of-care temozolomide, which has been used in these patients for years but from which they do not benefit significantly with regard to survival,” Kotecha said.
Other research has shown administration of temozolomide at different times in a day may lead to different outcomes.
Results of a study published in 2021 in Neuro-Oncology Advances showed an association of morning administration of temozolomide with longer OS compared with evening administration among a cohort of patients with newly diagnosed glioblastoma. Of note, the benefit appeared more pronounced among patients with methylated MGMT disease.
“Glioblastoma is a complex disease and we simply need better treatments for these patients, which is why I devote all of my time and research to them,” Jian Li Campian, MD, PhD, associate professor of oncology in the department of oncology at Mayo Clinic in Rochester, Minnesota, and an author of the temozolomide study, told Healio | HemOnc Today. “But targeting one aspect is not enough to change the entire course of the disease — we need combination therapies. Finding a way to improve patients’ own immune status, such as correcting tumor- and treatment-related lymphopenia by cytokines, with combination therapies such as checkpoint inhibitors, vaccines or chimeric antigen receptor T-cell therapy, is something that should be tested. We are conducting this research now in [glioblastoma] animal models.”
Pediatric brain tumors
Pediatric brain tumors present their own set of challenges, depending on the type of tumor. Low-grade or benign tumors can be cured with surgery, whereas aggressive, inoperable malignant tumors typically result in short OS despite best treatments.
“Several advancements are on the horizon for pediatric patients with brain tumors and as we understand the molecular drivers of these tumors better, we will be able to uncover potential targets for those drivers,” Eric M. Thompson, MD, pediatric neurosurgeon at Duke University, told Healio | HemOnc Today.
“Essentially, we are entering a world of more personalized medicine as we obtain more data about what is causing and driving these pediatric brain tumors,” Thompson said. “Immunotherapy is a promising treatment avenue for pediatric brain tumors, and other studies are looking at personalizing therapy for certain pediatric patients.”
Vaccines also appear promising.
Thompson received a $1.8 million grant through FDA’s Orphan Products Grants Program to conduct a phase 2 study of a peptide vaccine targeting cytomegalovirus antigen for treatment of newly diagnosed pediatric high-grade glioma and diffuse intrinsic pontine glioma, as well as recurrent medulloblastoma.
“Cytomegalovirus is expressed in brain tumors, such as malignant gliomas, diffuse intrinsic pontine gliomas and in medulloblastomas, but not in normal brain tissue,” Thompson said. “We think this is an interesting target because it can attack these proteins in the tumors but leave normal brain tissue alone.”
The trial is being conducted through the CONNECT Consortium, which includes some of the busiest academic medical centers throughout North America and the world, according to Thompson.
“This is an exciting grant from the FDA and is important for these pediatric tumor types that are even rarer than adult brain tumors,” he said. “It is imperative for grants like this to fund interesting trials so that we can move the needle forward for patients who have rarer tumor types.”
‘Multiantigen targeting will be key’
Although some low-grade pediatric brain tumors have specific mutations that can be efficiently targeted with a single pathway drug, the same cannot be said of high-grade pediatric brain tumors, Nicholas A. Vitanza, MD, pediatric neuro-oncologist at Seattle Children’s Hospital, told Healio | HemOnc Today.
“Most of us in the field of pediatric neuro-oncology have seen the failures of molecularly targeted therapies for aggressive brain lesions,” Vitanza said. “Even as we learn more about the disease biologically, molecularly and epigenetically, no treatments have been a silver bullet. This was part of my interest in developing the brain tumor program at Seattle Children’s Hospital.”
Vitanza and colleagues are conducting three trials at Seattle Children’s including pediatric patients with mostly fatal disease that progressed after initial standard treatment. BrainChild-01 is examining the use of locoregionally administered, HER2-directed CAR T cells; BrainChild-02 is using EGFR-specific CAR T cells to treat children and young adults with relapsed or refractory EGFR-positive central nervous system tumors; and BrainChild-03 is using B7-H3-targeted CAR T cells for all patients with recurrent CNS tumors and those with the fatal brain tumor diffuse intrinsic pontine glioma.
“In the future, multiantigen targeting will be key when treating these patients. We hope to open a study of a multiantigen CAR T-cell therapy within the next year for pediatric patients with brain tumors,” Vitanza said. “We have more of an understanding of what cytokines are necessary to get CAR T cells to the tumor and once they get to the tumor, to not exhaust. In a few years, we will be living in a world where we give a CAR T cell that can express specific cytokines so that it ‘makes its own soup’ of cytokines around the CAR T cell that enhances its function and gives the cell the best chance to get where it needs to go.”
Bota also sees potential in a multiantigen-directed approach.
She and colleagues developed the clinical strategy for a personalized cancer vaccine, AV-GBM-1 (AIVITA Biomedical), that targets multiple antigens from autologous tumor-initiating cells that contribute to rapid disease growth.
Results of a phase 2 trial showed longer PFS with the vaccine compared with historical outcomes with standard-of-care treatment among a cohort of patients with newly diagnosed glioblastoma. Patients also tolerated the vaccine well.
“For vaccines, many clinical trials have shown great safety, but efficacy is not yet known. Much of the work on dendritic cell-based antitumor vaccines is now moving toward phase 3 clinical trials,” Bota said. “We are learning from the biology of glioblastoma that many times the problem is with the ability of the body to fight this cancer type because it is not localized at one level but at multiple levels.”
Other novel vaccines and oncolytic virus therapies developed at Duke University and at Universidad de Navarra in Spain also have begun to show promise, Vitanza added.
“However, we are in the first wave of understanding what these agents do in isolation from a safety and benefit perspective,” Vitanza said. “The promise is that for most aggressive brain tumor types, cures have all come from combined therapies and we haven’t even started to see the wave of combination immunotherapy treatment yet, but when we do, that is when we will have the ability to make a difference.”
Combination therapies, catheters
Another strategy being explored is immunotherapy combined with stereotactic radiation therapy.
“This is something that is currently being tested in the extracranial space and we are now exploring this in the brain, as well,” Kotecha said. “We have an ongoing trial here at Miami Cancer Institute that we are conducting along with Memorial Sloan Kettering Cancer Center in which patients with recurrent glioblastoma are receiving nivolumab in combination with stereotactic radiation therapy with the hope that we can achieve local disease control with radiation but also help to stimulate treatment response and an overall treatment effect with immunotherapy. There is another ongoing trial looking at a similar type of concept in a national setting for patients who have recurrent glioblastoma. That trial is examining the immunotherapy agent atezolizumab [Genentech, Roche] combined with the anti-IL-6-receptor inhibitor tocilizumab and stereotactic radiotherapy.”
For pediatric brain tumors, another novel treatment approach includes use of Ommaya reservoir catheters.
“With these catheters, we can deliver a CAR T-cell therapy either directly into the ventricular fluid of the brain or directly into the tumor cavity,” Vitanza said. “This is what we have been using in some of our trials, and preliminary data showed no patient has had cytokine release syndrome. By administering the cellular therapy directly into the brain, we are not only getting the cells to the area that we want them to go but we might be mitigating one of the most dangerous toxicities of CAR T-cell therapy.”
Continued challenges
Despite the promising research efforts underway, challenges remain — including access to clinical trials for certain patients.
In a cross-sectional survey conducted by the American Brain Tumor Association as part of its Metastatic Brain Tumor Initiative and published in NeuroOncology Practice, 72% of academic and 59% of private practice physicians reported that one or more of their patients with brain metastases had been denied participation in clinical trials.
Efforts have been made to improve clinical trial eligibility.
In November 2020, the Society for Neuro-Oncology organized a think tank to review the current landscape of and prioritize areas for improvement in glioblastoma clinical trials. Experts identified potential challenges related to clinical trial eligibility criteria and offered recommendations for design of future trials.
“Survival outcomes for our patients with glioblastoma have remained stagnant and we are not happy with this as clinicians,” Kotecha said. “We work every single day to design new trial concepts that have better patient selection. We are testing newer drugs, combining radiation with those drugs, and incorporating patient-centric outcomes to improve survival for our patients. When designing these clinical trials, we must think very carefully from the beginning about patient selection, such as the tumor profile for each individual patient and whether we choose specific therapies for that patient over another patient who has that same diagnosis.”
It is also important to keep in mind that some patients with metastatic brain tumors do not want the standard-of-care therapies that have been used for so long, Kotecha added.
“We should stop enrolling those patients onto those types of studies,” he said. “We know how our patients with glioblastoma do — they have done the same this year, last year and the year before that. We should take the well-captured historical data from prior clinical trials and use it as benchmarks so that we do not continue to randomly assign patients to a certain therapy and commit them to that standard of care.”
Vitanza said more clinical trials are needed for children with brain tumors.
“The biggest challenge we face with recurrent brain tumors is the life expectancy at the time of recurrence, which is usually on the scale of months — these children do not have a lot of time. We need more trial options so that children do not have to wait on lists to get on trials,” Vitanza said. “We need to develop our cellular products more quickly so that from the time the patient enrolls in a trial and we start developing this cellular therapy, we can get it to patients faster. We also need increased partnerships where patients don’t have to travel so far for treatment. We see so many children who have already gone through so much and then we have to take them away from home for significant parts of their lives, which is another layer of heartache on top of all of their other circumstances. Having more trials open at more sites and having more sites partner with other sites is important.”
Building clinical trials with complex designs in which multiple agents can be studied also remains a challenge, Bota said.
“One of the issues with this study design is that many times different immunotherapies are produced by different companies and many of them are still experimental even for other cancer types. Collaborations between multiple industry partners will be our next step.”
Regarding immunotherapy for malignant brain tumors, Campian said research must focus on overcoming immune resistance.
“This is where immunotherapy has hope to work in glioblastoma,” Campian said. “Looking at trials like CheckMate 143, CheckMate 498 and many others, these were all negative. However, during all these trials, no one checked lymphocytes, a critical component in our immune system. How could we miss something so simple? This is the low-hanging fruit. My colleagues and I are now conducting an early-phase trial in patients with newly diagnosed high-grade gliomas with a novel long-acting recombinant human interleukin-7 analog that we have so far found to be very safe. This long-acting IL-7 analog increases lymphocyte counts; in particular, it increases both CD4 and cytotoxic CD8 cell counts.”
Thompson expressed confidence in the many skilled researchers throughout the world currently conducting studies of pediatric brain tumors, Thompson said.
“The future is promising in a lot of ways for patients with brain tumors that have previously been incurable and have had poor results,” Thompson added. “Our ultimate hope is to improve survival and quality of life for our patients with challenging brain tumors.”
- References:
- Bagley SJ, et al. Clin Cancer Res. 2021;doi:10.1158/1078-0432.CCR-21-2750.
- Bota D, et al. Abstract 319. Presented at: Society for Immunotherapy of Cancer Annual Meeting (virtual); Nov. 9-14, 2020.
- Cloughesy TF, et al. Nat Med. 2019;doi:10.1038/s41591-018-0337-7.
- Damato AR, et al. Neurooncol Adv. 2021;doi:10.1093/noajnl/vdab041.
- Kim AE, et al. Neurooncol Pract. 2021;doi:10.1093/nop/npab042.
- Miller KD, et al. CA Cancer J Clin. 2021:doi:10.3322.caac.21693.
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