Cutting Edge Treatments

Exciting advances involve radiation, tumor surgery and new insights into the nervous system.

Karen WeintraubUSA TODAY 

Cutting-edge advances in cancer treatment are underway. 
 What if radiation treatments could be given in a handful of
seconds rather than weeks of treatments?
What if surgeons could actually see tumor cells rather than
simply hoping they got rid of them all?
What if scientists could come up with new ways to detect, treat and understand tumors?
These were among some of the ideas presented this week in Orlando, Florida, at the American Association for Cancer Research annual conference, where more than 6,500 scientists shared their work and their hopes for improving the lives of cancer patients.
Work against cancer has continued over the last three years, despite the pandemic, said Dr. Robert Vonderheide, the conference’s program committee chair. The thousands of presentations and 20,000-person turnout should convince people of that. 
Obviously, lots of the research is worth public attention. But with Vonderheide’s guidance, USA TODAY picked three ideas that seemed among the most surprising and hopeful, the kinds of approaches that have the potential to transform cancer treatment and patients’ lives.

The first is “flash” radiation, which concentrates weeks of treatments into a few days;
the second, an imaging technology that lights up cancer cells to help surgeons
track them down.

“Two of the most fundamental tools, cancer surgery and cancer radiation, are undergoing before our eyes fundamental changes in their technology,” said Vonderheide, who directs the Abramson Cancer Center at the University of Pennsylvania. “They are each promising better success.”

A third line of research is providing insights into the role of the nervous system in cancer, which could eventually be used to help patients sleep better, heal faster and live longer.

Researchers typically focus on a tumor, but there are “systemic signals that might tell us how best to treat a patient or that a patient actually has a lurking cancer,” Vonderheide said. Like the immune system, which has increasingly been manipulated to help fight  cancer over the last decade, the nervous system monitors the body and remembers
what it encounters. 

“The immune system is probably the first system to know that cancer exists. And probably the nervous system is the next one,” he said. “Maybe there’s new inroads in early detection if we focus on neurological health and immune health.” None of these new approaches is readily available yet, but Vonderheide thinks they’re among the advances worth watching. 

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Flash radiation could mean cancer treatment in seconds, not weeks
At least half of patients with solid tumors endure radiation at some point during their treatment. Radiation typically takes about 15 minutes, though sessions can last an hour
or more and are scheduled every weekday for three to nine weeks – requiring a total
of 15 to 40 visits.
Patients may suffer skin burns, dry mouth, difficulties eating and swallowing, and exhaustion. They must upend their lives and often a loved one’s to get to a clinic so many times.
Radiation therapy is traditionally delivered in small doses over weeks so it can efficiently kill tumor cells while being less toxic to surrounding healthy tissue, said Constantinos Koumenis, a professor of radiation biology at the University of Pennsylvania’s Perelman School of Medicine.
But as many radiation patients can attest, treatments still do plenty of damage to
normal tissue. Instead, Koumenis and dozens of other research teams have been testing
“flash radiation,” which uses ultra-high dose rate beams of energy to zap tumor cells.
Patients might get the same amount of radiation in just two to four sessions of less
than 1 second each. “The vulnerability of the tumor cells is essentially the same,” 
Koumenis said. “What’s different is the normal tissue is more resistant to the flash radiation.”

A therapist readies a proton therapy machine at the Roberts Proton Therapy Center at Perelman School of Medicine at the University of Pennsylvania.
Proton beam machines are gigantic, hugely expensive and not widely available,he said,

But they can also deliver flash radiation at 1,000 times the dose rate of conventional radiotherapy. While the X-rays used in conventional radiation damage normal tissue on the way to and from the tumor, proton beams are stopped by the tumor, so only affect healthy tissue in one direction, he said.
Koumenis and teams in Europe have been testing flash radiation in pets.
They’ve shown that they can efficiently and safely deliver these high-dose
rate beams in dogs and cats with sarcomas and head and neck cancers.
The first human trial, which started about two years ago, showed that the approach was safe and feasible in 10 patients whose cancer had spread to their bones. 

Additional human trials are ongoing or are being planned in the next two to three years.
Many more studies are needed, Koumenis said, but he hopes using flash radiation in head and neck cancer, for instance, might better preserve the taste buds and salivary glands, enabling the patient to maintain the ability to taste and swallow.
“We could keep the same dose, achieve the same control of the tumor,
but now spare these senses,” he said.
In other cases, when the radiation isn’t aimed at critical organs, patients might be able to tolerate higher doses “and perhaps achieve better control of the tumor and better survival because we’re not causing unacceptable side effects,” Koumenis said. “In my 25 years in radiobiology research, this is the most exciting we’ve been in this field.”

1.95M people may be diagnosed with cancer in 2023:

 What to know about the state of cancer
New imaging could helps surgeons remove more of the tumor
When surgeons go to take out a tumor, they use their instinct and years of experience to know when they’ve cut out enough. Then they send frozen slides to the pathology lab to quickly assess if they’ve gone safely beyond the tumor, creating a negative or clean margin.
But time and again, patients whose surgeons thought they got everything find out they didn’t.
“Positive margins kill people,” said Dr. Eben Rosenthal, chair of
the Department of Otolaryngology at Vanderbilt University in Nashville, Tennessee. 
“We do surgery the same way we did 30 years ago … It’s disappointing to me as a surgeon.” Rosenthal is at the forefront of an effort to literally highlight tumor cells,
offering surgeons an additional way to identify and eliminate cancer. 

Researcher Marisa Hom points to a nerve that has been colored with a fluorescent dye to make it easier for a surgeon to see.
By adding dyes to therapies that hone in on cancer cells,

A surgeon can get a better look at the tumor as it sits in the body, identifying tumors too small to be felt or seen with the naked eye.Once a tumor is removed, the dyed cells can help surgeons assess what part to send to pathology, avoiding the false sense of security that can come from sampling the wrong bit of tissue or cutting out more healthy cells than necessary – from, say, the nerves, tongue or brain, Rosenthal said.

“It tells you very quickly where to look,” he said.
But Rosenthal said the effort he started in 2010 has been mostly ad hoc, combining existing equipment and medication. “Literally, we’re just throwing things together that are not really intended for that purpose,” he said.
The approval process has been a challenge, he said,
because no one stands to make a lot of money from this procedure.
“I would love to see this developed in a way that would really help patients,” he said. “My goal is to show value, so that at some point when a company is able to get off the ground, we can know (it will work).” 

More: New cancer therapy takes personalized medicine to a new level
Study: Men with early prostate cancer can safely hold off on radiation or surgery

Manipulating the nervous system to fight cancer     
Growing a tumor is a lot like growing a new organ, according to Jeremy Borniger, an assistant professor at the Cold Spring Harbor Laboratory on New York’s Long Island.
It may look like a mass of cells, but a tumor is fed by blood vessels, communicates with the immune system, and like any other organ, connects to the body’s nervous system. 
For decades, scientists have explored ways to treat cancer by manipulating a tumor’s
blood supply and changing the way it interacts with the immune system.

Borniger is part of a burgeoning effort to focus on the role nerves play in cancer.
“They’re not just playing a passive role,” he said. “They’re important for all phases of cancer development from initiation all the way through to therapeutic resistance and responses to therapy.”
Many people with cancer suffer from chronic fatigue, sleep disruption, appetite changes and brain fog. These are all problems of the nervous system, said Borniger, who’s been working to figure out whether these symptoms stem from cancer therapy or cancer itself.
Studies in brain tumors have shown that cancercan affect brain circuits – and the tumors that tinker more are more dangerous. How common it is for nerves to directly talk to other types of cancer cells is one of the questions scientists are now asking, Borniger said. 

Nerves (in red) embedded in the breast tumor (white) of a mouse.
But it’s already clear that when treatments block the communication
between nerve and tumor cells, 

It “drastically alters” the tumor’s growth, cancer’s spread within the body and
its response to treatment. “It’s really exciting that we can mess with one tiny nucleus in
the brain and have such a strong effect on physiology and tumor growth,” Borniger said.
“The idea will be how linked are these things and what are the right knobs and dials to turn that we can restore this normal functioning so that we can block the bad signaling that promotes cancer.” 
So far, most of this work has been in animals, but early trials are beginning, particularly with already-approved medications like beta blockers that might affect the release of chemicals from the nervous system even in tumors like breast cancer.

Future treatments, Borniger said, might include electrical stimulation to better understand and directly affect the body’s wiring system, adding “good signals” to counteract the bad.
The bottom line, Borniger said, is that tumors are not floating in a vacuum, but integrated into the body’s systems.
“What’s becoming more evident is we need to start listening to how the body is responding to things and not just what’s happening in isolation,” he said. “One of the best ways we can listen to what’s going on is by tapping into the nervous system. Its function is to figure out what’s going on and to try and fix the problem.” This article was originally published in May 2022, and updated in February 2023.

Cancer is one of the world’s biggest killers, leading to 10 million deaths in 2020.
Scientists are using artificial intelligence, DNA sequencing, precision oncology
and other technologies to improve the treatment and diagnosis of the disease.
Breakthroughs include the DNA sequencing of more than 12,000 cancer tumours
and a new test for diagnosing pancreatic cancer – one of the deadliest cancers.
Cancer will kill nearly 10 million people in 2020 and is a leading cause of death globally, according to the World Health Organization.
Breast cancer, lung cancer and colon cancer are among the most common cancers.
Death rates from cancer were falling before the pandemic. Now COVID-19 has caused a big backlog in cancer diagnosis and treatment. But medical advances are continuing
to help the world fight cancer.

Here are some recent developments.

Precision oncology
Precision oncology is the “best new weapon to defeat cancer”, the chief executive of Genetron Health, Sizhen Wang, says in a blog for the World Economic Forum. This involves studying the genetic makeup and molecular characteristics of cancer tumours in individual patients. The precision oncology approach identifies changes in cells that might be causing the cancer to grow and spread. Personalized treatments can then be developed. Because precision oncology treatments are targeted – as opposed to general treatments like chemotherapy – it can mean less harm to healthy cells and fewer side effects as a result.

Artificial intelligence fights cancer
In India, World Economic Forum partners are using emerging technologies like artificial intelligence (AI) and machine learning to transform cancer care. For example, AI-based risk profiling can help screen for common cancers like breast cancer, leading to early diagnosis. AI technology can also be used to analyze X-rays to identify cancers in places where imaging experts might not be available.
These are two of 18 cancer interventions that The Centre for Fourth Industrial Revolution of the World Economic Forum India hopes to accelerate. Scientists at Cambridge University Hospitals have sequenced the DNA of more than 12,000 cancer tumors to reveal new clues about the disease. Image: Science/Cambridge University Hospitals.

Infographic of sequenced DNA of cancer tumours.

Greater prediction capabilities
Lung cancer kills more people in the US yearly than the next three deadliest cancers combined. It’s notoriously hard to detect the early stages of the disease with x-rays and scans alone. However, MIT scientists have developed an AI learning model to predict a person’s likelihood of developing lung cancer up to six years in advance via a low-dose CT scan. Trained using complex imaging data, ‘Sybil’ can forecast both short- and long-term lung cancer risk, according to a recent study. “We found that while we as humans couldn’t quite see where the cancer was, the model could still have some predictive power as to which lung would eventually develop cancer,” said co-author Jeremy Wohlwend.

Clues in the DNA of cancer
At Cambridge University Hospitals in England, the DNA of cancer tumours from
12,000 patients are revealing new clues about the causes of cancer, scientists say.
By analyzing genomic data, oncologists are identifying different mutations that
have contributed to each person’s cancer.
For example, exposure to smoking or UV light, or internal malfunctions in cells. These are like “fingerprints in a crime scene”, the scientists say – and more of them are being found. “We uncovered 58 new mutational signatures and broadened our knowledge of cancer,” says study author Dr Andrea Degasperi, from Cambridge’s Department of Oncology.

Liquid and synthetic biopsies
Biopsies are the main way doctors diagnose cancer – but the process is invasive and involves removing a section of tissue from the body, sometimes surgically, so it can be examined in a laboratory. Liquid biopsies are an easier and less invasive solution where blood samples can be tested for signs of cancer. Synthetic biopsies are another innovation that can force cancer cells to reveal themselves during the earliest stages of the disease.

DISCOVER How is the World Economic Forum bringing data-driven healthcare to life?

CAR-T-cell therapy
A treatment that makes immune cells hunt down and kill cancer cells was recently declared a success for leukaemia patients. The treatment, called CAR-T-cell therapy, involves removing and genetically altering immune cells, called T cells, from cancer patients. The altered cells then produce proteins called chimeric antigen receptors
(CARs). These recognize and can destroy cancer cells.
In the journal Nature, scientists at the University of Pennsylvania announced that
two of the first people treated with CAR-T-cell therapy were still in remission 12 years on.

Fighting pancreatic cancer
Pancreatic cancer is one of the deadliest cancers.
It is rarely diagnosed before it starts to spread and has a survival rate of less than
5% over five years. At the University of California San Diego School of Medicine,
scientists developed a test that identified 95% of early pancreatic cancers.
The research, published in Nature Communications Medicine, explains how
biomarkers in extracellular vesicles – particles that regulate communication
between cells – were used to detect pancreatic, ovarian and bladder cancer
at stages I and II. 

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Contact Karen Weintraub at kweintraub@usatoday.com.
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