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A Cancer Trial’s Unexpected Result: Remission in Every Patient

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A Cancer Trial’s Unexpected Result: Remission in Every Patient

It was a small trial, simply 18 rectal most cancers sufferers, each one in every of whom took the identical drug.

However the outcomes have been astonishing. The most cancers vanished in each single affected person, undetectable by bodily examination, endoscopy, PET scans or M.R.I. scans.

Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Most cancers Middle, an writer of a paper printed Sunday within the New England Journal of Drugs describing the outcomes, which have been sponsored by the drug firm GlaxoSmithKline, stated he knew of no different examine by which a remedy utterly obliterated a most cancers in each affected person.

“I consider that is the primary time this has occurred within the historical past of most cancers,” Dr. Diaz stated.

Dr. Alan P. Venook, a colorectal most cancers specialist on the College of California, San Francisco, who was not concerned with the examine, stated he additionally thought this was a primary.

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A whole remission in each single affected person is “unheard-of,” he stated.

These rectal most cancers sufferers had confronted grueling therapies — chemotherapy, radiation and, probably, life-altering surgical procedure that would end in bowel, urinary and sexual dysfunction. Some would want colostomy baggage.

They entered the examine considering that, when it was over, they must bear these procedures as a result of nobody actually anticipated their tumors to vanish.

However they received a shock: No additional remedy was mandatory.

“There have been a number of pleased tears,” stated Dr. Andrea Cercek, an oncologist at Memorial Sloan Kettering Most cancers Middle and a co-author of the paper, which was offered Sunday on the annual assembly of the American Society of Scientific Oncology.

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One other shock, Dr. Venook added, was that not one of the sufferers had clinically important issues.

On common, one in 5 sufferers have some kind of hostile response to medicine just like the one the sufferers took, dostarlimab, often called checkpoint inhibitors. The remedy was given each three weeks for six months and value about $11,000 per dose. It unmasks most cancers cells, permitting the immune system to determine and destroy them.

Whereas most hostile reactions are simply managed, as many as 3 % to five % of sufferers who take checkpoint inhibitors have extra extreme issues that, in some instances, end in muscle weak point and issue swallowing and chewing.

The absence of great negative effects, Dr. Venook stated, means, “both they didn’t deal with sufficient sufferers or, in some way, these cancers are simply plain completely different.”

In an editorial accompanying the paper, Dr. Hanna Ok. Sanoff of the College of North Carolina’s Lineberger Complete Most cancers Middle, who was not concerned within the examine, referred to as it “small however compelling.” She added, although, that it isn’t clear if the sufferers are cured.

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“Little or no is understood concerning the length of time wanted to seek out out whether or not a medical full response to dostarlimab equates to treatment,” Dr. Sanoff stated within the editorial.

Dr. Kimmie Ng, a colorectal most cancers skilled at Harvard Medical Faculty, stated that whereas the outcomes have been “outstanding” and “unprecedented,” they might should be replicated.

The inspiration for the rectal most cancers examine got here from a medical trial Dr. Diaz led in 2017 that Merck, the drugmaker, funded. It concerned 86 folks with metastatic most cancers that originated in varied elements of their our bodies. However the cancers all shared a gene mutation that prevented cells from repairing injury to DNA. These mutations happen in 4 % of all most cancers sufferers.

Sufferers in that trial took a Merck checkpoint inhibitor, pembrolizumab, for as much as two years. Tumors shrank or stabilized in about one-third to one-half of the sufferers, they usually lived longer. Tumors vanished in 10 % of the trial’s members.

That led Dr. Cercek and Dr. Diaz to ask: What would occur if the drug have been used a lot earlier in the middle of illness, earlier than the most cancers had an opportunity to unfold?

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They settled on a examine of sufferers with regionally superior rectal most cancers — tumors that had unfold within the rectum and typically to the lymph nodes however to not different organs. Dr. Cercek had observed that chemotherapy was not serving to a portion of sufferers who had the identical mutations that affected the sufferers within the 2017 trial. As a substitute of shrinking throughout remedy, their rectal tumors grew.

Maybe, Dr. Cercek and Dr. Diaz reasoned, immunotherapy with a checkpoint inhibitor would permit such sufferers to keep away from chemotherapy, radiation and surgical procedure.

Dr. Diaz started asking firms that made checkpoint inhibitors if they might sponsor a small trial. They turned him down, saying the trial was too dangerous. He and Dr. Cercek needed to provide the drug to sufferers who might be cured with commonplace therapies. What the researchers have been proposing may find yourself permitting the cancers to develop past the purpose the place they might be cured.

“It is vitally laborious to change the usual of care,” Dr. Diaz stated. “The entire standard-of-care equipment needs to do the surgical procedure.”

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Lastly, a small biotechnology agency, Tesaro, agreed to sponsor the examine. Tesaro was purchased by GlaxoSmithKline, and Dr. Diaz stated he needed to remind the bigger firm that they have been doing the examine — firm executives had all however forgotten concerning the small trial.

Their first affected person was Sascha Roth, then 38. She first observed some rectal bleeding in 2018 however in any other case felt superb — she is a runner and helps handle a household furnishings retailer in Bethesda, Md.

Throughout a sigmoidoscopy, she recalled, her gastroenterologist stated, “Oh no. I used to be not anticipating this!”

The subsequent day, the physician referred to as Ms. Roth. He had had the tumor biopsied. “It’s undoubtedly most cancers,” he instructed her.

“I utterly melted down,” she stated.

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Quickly, she was scheduled to start out chemotherapy at Georgetown College, however a buddy had insisted she first see Dr. Philip Paty at Memorial Sloan Kettering. Dr. Paty instructed her he was virtually sure her most cancers included the mutation that made it unlikely to reply effectively to chemotherapy. It turned out, although, that Ms. Roth was eligible to enter the medical trial. If she had began chemotherapy, she wouldn’t have been.

Not anticipating a whole response to dostarlimab, Ms. Roth had deliberate to maneuver to New York for radiation, chemotherapy and, presumably surgical procedure after the trial ended. To protect her fertility after the anticipated radiation remedy, she had her ovaries eliminated and put again underneath her ribs.

After the trial, Dr. Cercek gave her the information.

“We checked out your scans,” she stated. “There may be completely no most cancers.” She didn’t want any additional remedy.

“I instructed my household,” Ms. Roth stated. “They didn’t consider me.”

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However two years later, she nonetheless doesn’t have a hint of most cancers.

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Pink Fire Retardant, a Dramatic Wildfire Weapon, Poses Its Own Dangers

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Pink Fire Retardant, a Dramatic Wildfire Weapon, Poses Its Own Dangers

From above the raging flames, these planes can unleash immense tankfuls of bright pink fire retardant in just 20 seconds. They have long been considered vital in the battle against wildfires.

But emerging research has shown that the millions of gallons of retardant sprayed on the landscape to tame wildfires each year come with a toxic burden, because they contain heavy metals and other chemicals that are harmful to human health and the environment.

The toxicity presents a stark dilemma. These tankers and their cargo are a powerful tool for taming deadly blazes. Yet as wildfires intensify and become more frequent in an era of climate change, firefighters are using them more often, and in the process releasing more harmful chemicals into the environment.

Some environmental groups have questioned the retardants’ effectiveness and potential for harm. The efficiency of fire retardant has been hard to measure, because it’s one of a barrage of firefighting tactics deployed in a major fire. After the flames are doused, it’s difficult to assign credit.

The frequency and severity of wildfires has grown in recent years, particularly in the western United States. Scientists have also found that fires across the region have become faster moving in recent decades.

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There are also the longer-term health effects of exposure to wildfire smoke, which can penetrate the lungs and heart, causing disease. A recent global survey of the health effects of air pollution caused by wildfires found that in the United States, exposure to wildfire smoke had increased by 77 percent since 2002. Globally, wildfire smoke has been estimated to be responsible for up to 675,000 premature deaths per year.

Fire retardants add to those health and environmental burdens because they present “a really, really thorny trade-off,” said Daniel McCurry, an assistant professor of civil and environmental engineering at the University of Southern California, who led the recent research on their heavy-metal content.

The United States Forest Service said on Thursday that nine large retardant-spraying planes, as well as 20 water-dropping helicopters, were being deployed to fight the Southern California fires, which have displaced tens of thousands of people. Several “water scooper” amphibious planes, capable of skimming the surface of the sea or other body of water to fill their tanks, are also being used.

Two large DC-10 aircraft, dubbed “Very Large Airtankers” and capable of delivering up to 9,400 gallons of retardant, were also set to join the fleet imminently, said Stanton Florea, a spokesman for the National Interagency Fire Center in Boise, Idaho, which coordinates national wildland firefighting efforts across the West.

Sprayed ahead of the fire, the retardants coat vegetation and prevent oxygen from allowing it to burn, Mr. Florea said. (Red dye is added so firefighters can see the retardant against the landscape.) And the retardant, typically made of salts like ammonium polyphosphate, “lasts longer. It doesn’t evaporate, like dropping water,” he said.

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The new research from Dr. McCurry and his colleagues found, however, that at least four different types of heavy metals in a common type of retardant used by firefighters exceeded California’s requirements for hazardous waste.

Federal data shows that more than 440 million gallons of retardant were applied to federal, state, and private land between 2009 and 2021. Using that figure, the researchers estimated that between 2009 and 2021, more than 400 tons of heavy metals were released into the environment from fire suppression, a third of that in Southern California.

Both the federal government and the retardant’s manufacturer, Perimeter Solutions, have disputed that analysis, saying the researchers had evaluated a different version of the retardant. Dan Green, a spokesman for Perimeter, said retardants used for aerial firefighting had passed “extensive testing to confirm they meet strict standards for aquatic and mammalian safety.”

Still, the findings help explain why concentrations of heavy metals tend to surge in rivers and streams after wildfires, sometimes by hundreds of times. And as scrutiny of fire suppressants has grown, the Forestry Service has set buffer zones surrounding lakes and rivers, though its own data shows retardant still inadvertently drifts into those waters.

In 2022, the environmental nonprofit Forest Service Employees for Environmental Ethics sued the government in federal court in Montana, demanding that the Forest Service obtain a permit under the Clean Water Act to cover accidental spraying into waterways.

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The judge ruled that the agency did indeed need to obtain a permit. But it allowed retardant use to continue to protect lives and property.

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2024 Brought the World to a Dangerous Warming Threshold. Now What?

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2024 Brought the World to a Dangerous Warming Threshold. Now What?

Source: Copernicus/ECMWF

Note: Temperature anomalies relative to 1850-1900 averages.

At the stroke of midnight on Dec. 31, Earth finished up its hottest year in recorded history, scientists said on Friday. The previous hottest year was 2023. And the next one will be upon us before long: By continuing to burn huge amounts of coal, oil and gas, humankind has all but guaranteed it.

The planet’s record-high average temperature last year reflected the weekslong, 104-degree-Fahrenheit spring heat waves that shuttered schools in Bangladesh and India. It reflected the effects of the bathtub-warm ocean waters that supercharged hurricanes in the Gulf of Mexico and cyclones in the Philippines. And it reflected the roasting summer and fall conditions that primed Los Angeles this week for the most destructive wildfires in its history.

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“We are facing a very new climate and new challenges, challenges that our society is not prepared for,” said Carlo Buontempo, director of the Copernicus Climate Change Service, the European Union monitoring agency.

But even within this progression of warmer years and ever-intensifying risks to homes, communities and the environment, 2024 stood out in another unwelcome way. According to Copernicus, it was the first year in which global temperatures averaged more than 1.5 degrees Celsius, or 2.7 degrees Fahrenheit, above those the planet experienced at the start of the industrial age.

For the past decade, the world has sought to avoid crossing this dangerous threshold. Nations enshrined the goal in the 2015 Paris agreement to fight climate change. “Keep 1.5 alive” was the mantra at United Nations summits.

Yet here we are. Global temperatures will fluctuate somewhat, as they always do, which is why scientists often look at warming averaged over longer periods, not just a single year.

But even by that standard, staying below 1.5 degrees looks increasingly unattainable, according to researchers who have run the numbers. Globally, despite hundreds of billions of dollars invested in clean-energy technologies, carbon dioxide emissions hit a record in 2024 and show no signs of dropping.

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One recent study published in the journal Nature concluded that the absolute best humanity can now hope for is around 1.6 degrees of warming. To achieve it, nations would need to start slashing emissions at a pace that would strain political, social and economic feasibility.

But what if we’d started earlier?

“It was guaranteed we’d get to this point where the gap between reality and the trajectory we needed for 1.5 degrees was so big it was ridiculous,” said David Victor, a professor of public policy at the University of California, San Diego.

The question now is what, if anything, should replace 1.5 as a lodestar for nations’ climate aspirations.

“These top-level goals are at best a compass,” Dr. Victor said. “They’re a reminder that if we don’t do more, we’re in for significant climate impacts.”

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The 1.5-degree threshold was never the difference between safety and ruin, between hope and despair. It was a number negotiated by governments trying to answer a big question: What’s the highest global temperature increase — and the associated level of dangers, whether heat waves or wildfires or melting glaciers — that our societies should strive to avoid?

The result, as codified in the Paris agreement, was that nations would aspire to hold warming to “well below” 2 degrees Celsius while “pursuing efforts” to limit it to 1.5 degrees.

Even at the time, some experts called the latter goal unrealistic, because it required such deep and rapid emissions cuts. Still, the United States, the European Union and other governments adopted it as a guidepost for climate policy.

Christoph Bertram, an associate research professor at the University of Maryland’s Center for Global Sustainability, said the urgency of the 1.5 target spurred companies of all kinds — automakers, cement manufacturers, electric utilities — to start thinking hard about what it would mean to zero out their emissions by midcentury. “I do think that has led to some serious action,” Dr. Bertram said.

But the high aspiration of the 1.5 target also exposed deep fault lines among nations.

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China and India never backed the goal, since it required them to curb their use of coal, gas and oil at a pace they said would hamstring their development. Rich countries that were struggling to cut their own emissions began choking off funding in the developing world for fossil-fuel projects that were economically beneficial. Some low-income countries felt it was deeply unfair to ask them to sacrifice for the climate given that it was wealthy nations — and not them — that had produced most of the greenhouse gases now warming the world.

“The 1.5-degree target has created a lot of tension between rich and poor countries,” said Vijaya Ramachandran, director for energy and development at the Breakthrough Institute, an environmental research organization.

Costa Samaras, an environmental-engineering professor at Carnegie Mellon University, compared the warming goals to health officials’ guidelines on, say, cholesterol. “We don’t set health targets on what’s realistic or what’s possible,” Dr. Samaras said. “We say, ‘This is what’s good for you. This is how you’re going to not get sick.’”

“If we were going to say, ‘Well, 1.5 is likely out of the question, let’s put it to 1.75,’ it gives people a false sense of assurance that 1.5 was not that important,” said Dr. Samaras, who helped shape U.S. climate policy from 2021 to 2024 in the White House Office of Science and Technology Policy. “It’s hugely important.”

Scientists convened by the United Nations have concluded that restricting warming to 1.5 degrees instead of 2 would spare tens of millions of people from being exposed to life-threatening heat waves, water shortages and coastal flooding. It might mean the difference between a world that has coral reefs and Arctic sea ice in the summer, and one that doesn’t.

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Each tiny increment of additional warming, whether it’s 1.6 degrees versus 1.5, or 1.7 versus 1.6, increases the risks. “Even if the world overshoots 1.5 degrees, and the chances of this happening are increasing every day, we must keep striving” to bring emissions to zero as soon as possible, said Inger Anderson, the executive director of the United Nations Environment Program.

Officially, the sun has not yet set on the 1.5 target. The Paris agreement remains in force, even as President-elect Donald J. Trump vows to withdraw the United States from it for a second time. At U.N. climate negotiations, talk of 1.5 has become more muted compared with years past. But it has hardly gone away.

“With appropriate measures, 1.5 Celsius is still achievable,” Cedric Schuster, the minister of natural resources and environment for the Pacific island nation of Samoa, said at last year’s summit in Azerbaijan. Countries should “rise to the occasion with new, highly ambitious” policies, he said.

To Dr. Victor of U.C. San Diego, it is strange but all too predictable that governments keep speaking this way about what appears to be an unachievable aim. “No major political leader who wants to be taken seriously on climate wants to stick their neck out and say, ‘1.5 degrees isn’t feasible. Let’s talk about more realistic goals,’” he said.

Still, the world will eventually need to have that discussion, Dr. Victor said. And it’s unclear how it will go.

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“It could be constructive, where we start asking, ‘How much warming are we really in for? And how do we deal with that?’” he said. “Or it could look very toxic, with a bunch of political finger pointing.”

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The second chart shows pathways for reducing carbon emissions that would have a 66 percent chance of limiting global warming this century to 1.5 degrees Celsius above the preindustrial average.

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U.S. Efforts to Cut Emissions Stalled in 2024 as Power Demand Surged

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U.S. Efforts to Cut Emissions Stalled in 2024 as Power Demand Surged

America’s efforts to cut its climate change pollution stalled in 2024, with greenhouse gas emissions dropping just a fraction, 0.2 percent, compared to the year before, according to estimates published Thursday by the Rhodium Group, a research firm.

Despite continued rapid growth in solar and wind power, emissions levels stayed relatively flat last year because demand for electricity surged nationwide, which led to a spike in the amount of natural gas burned by power plants.

The fact that emissions didn’t decline much means the United States is even further off-track from hitting President Biden’s goal of slashing greenhouse gases 50 percent below 2005 levels by 2030. Scientists say all major economies would have to cut their emissions deeply this decade to keep global warming at relatively low levels.

Since 2005, United States emissions have fallen roughly 20 percent, a significant drop at a time when the economy has also expanded. But to meet its climate goals, U.S. emissions would need to decline nearly 10 times as fast each year as they’ve fallen over the past decade. That seems increasingly unlikely, experts say, especially since President-elect Donald J. Trump has promised to dismantle Mr. Biden’s climate policies and promote the production of fossil fuels, the burning of which generates greenhouse gases.

“On the one hand, it is notable that we’ve now seen two years in a row where the U.S. economy grew but emissions went down,” said Ben King, an associate director at the Rhodium Group. “But it’s far from enough to achieve our climate targets.”

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The biggest reason that U.S. emissions have fallen in recent years is that electric utilities have been retiring their older, dirtier coal-fired power plants and replacing them with cheaper and less-polluting natural gas, wind and solar power. That trend mostly continued last year, with a few unexpected ups and downs.

The nation’s demand for electricity, which has stayed more or less flat for two decades, suddenly jumped by roughly 3 percent in 2024, in large part because scorching heat during the summer caused many Americans to crank up their air-conditioners. A smaller factor was that tech companies have been building more energy-hungry data centers in states like Virginia and Texas.

While power companies installed large numbers of wind turbines, solar panels and batteries last year to meet rising demand, natural gas use also rose to record highs, while coal use declined only slightly. The net result was that emissions from the power sector increased an estimated 0.2 percent, according to the Rhodium Group.

At the same time, transportation, the nation’s largest source of greenhouse gases, saw an 0.8 percent rise in emissions last year. Gasoline and jet fuel consumption both increased as Americans continued to drive and fly more after the pandemic. Nearly 10 percent of new car sales in 2024 were less-polluting electric vehicles, but those models still make up a small fraction of total cars on the road and have yet to put a major dent in transportation emissions.

On the flip side, emissions from America’s industrial sector — which includes steel, cement and chemicals — fell by 1.8 percent in 2024. Some of that may have been the result of lost output, as two hurricanes and a strike at the nation’s ports disrupted some factory activity in the fall, Mr. King said.

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“It’s a reminder that there’s always some bumpiness in emissions,” Mr. King said. “It’s not just a question of how many electric vehicles are on the road or how much solar we’ve installed. A big portion of our economy still relies on fossil fuels.”

One of the most striking findings in this year’s data was that emissions from oil and gas operations dropped roughly 3.7 percent in 2024. Even though the United States produced record amounts of oil and near-record amounts of natural gas last year, many companies appear to have curbed leaks of methane, which is the main ingredient in natural gas and which can seep into the atmosphere and contribute significantly to global warming.

Over the past few years, the Biden administration and several states have adopted new regulations that require oil and gas producers to detect and fix methane leaks. Many companies also have financial incentives to capture methane to sell rather than vent it into the air.

Between 2014 and 2024, U.S. companies appear to have reduced the amount of methane that escaped, per each cubic feet of gas they produced, by 40 percent, according to the Rhodium Group.

Several experts have estimated that greenhouse gases generated in the United States could start dropping sharply in the years ahead if many clean energy policies stay in place, particularly the 2022 Inflation Reduction Act that pumped hundreds of billions of dollars into low-carbon energy technologies such as electric vehicles, wind turbines, solar panels, nuclear reactors, green hydrogen and batteries.

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While Mr. Trump has pledged to scrap many of Mr. Biden’s subsidies and tax credits for electric vehicles and low-carbon energy, it remains to be seen whether Congress will agree.

That law has not yet had a major impact on the country’s emissions, said Mr. King, since it takes time for new factories to open and power plants to get built. But, he said, data shows that low-carbon energy and transportation now make up fully 5 percent of total U.S. private investment.

“That’s a leading indicator that things are changing quickly,” he said.

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