Cancer Without Chemotherapy A Totally Different World

Dr. Seema Doshi was shocked and terrified when she found a lump in her breast that was eventually confirmed to be cancerous. “That rocked my world,” said Dr. Doshi, a dermatologist in private practice in the Boston suburb of Franklin who was 46 at the time of her diagnosis. “I thought, ‘That’s it. I will have to do chemotherapy.’”

She was wrong.

Dr. Doshi was the beneficiary of a quiet revolution in breast cancer treatment, a slow chipping away at the number of people for whom chemotherapy is recommended. Chemotherapy for decades was considered “the rule, the dogma,” for treating breast cancer and other cancers, said Dr. Gabriel Hortobagyi, a breast cancer specialist at MD Anderson Cancer Center in Houston. But data from a variety of sources offers some confirmation of what many oncologists say anecdotally — the method is on the wane for many cancer patients.

Genetic tests can now reveal whether chemotherapy would be beneficial. For many there are better options with an ever-expanding array of drugs, including estrogen blockers and drugs that destroy cancers by attacking specific proteins on the surface of tumors. And there is a growing willingness among oncologists to scale back unhelpful treatments.

The result spares thousands each year from the dreaded chemotherapy treatment, with its accompanying hair loss, nausea, fatigue, and potential to cause permanent damage to the heart and to nerves in the hands and feet.

The diminution of chemotherapy treatment is happening for some other cancers, too, including lung cancer, the most common cause of cancer deaths among men and women in the United States, killing about 132,000 Americans each year. Breast cancer is the second leading cause of cancer deaths among women, killing 43,000.

Still, the opportunity to avoid chemotherapy is not evenly distributed, and is often dependent on where the person is treated and by whom.

But for some patients who are lucky enough to visit certain cancer treatment centers, the course of therapy has changed. Now, even when chemotherapy is indicated, doctors often give fewer drugs for less time.

“It’s a totally different world,” said Dr. Lisa Carey, a breast cancer specialist at the University of North Carolina.

Dr. Robert Vonderheide, a lung cancer specialist who heads the University of Pennsylvania’s Abramson Cancer Center, remembers his early days on the job, about 20 years ago.

“The big discussion was, Do you give patients two different types of chemotherapy or three?” he said. There was even a clinical trial to see whether four types of chemotherapy would be better.

“Now we are walking in to see even patients with advanced lung cancer and telling them, ‘No chemo,’” Dr. Vonderheide said.

The breast cancer treatment guidelines issued by the National Cancer Institute 30 years ago were harsh: chemotherapy for about 95 percent of patients with breast cancer.

The change began 15 years ago, when the first targeted drug for breast cancer, Herceptin, was approved as an initial treatment for about 30 percent of patients who have a particular protein on their tumor surface. It was given with chemotherapy and reduced the chance of a recurrence by half and the risk of dying from breast cancer by a third, “almost regardless of how much and what type of chemotherapy was used,” Dr. Hortobagyi said.

In a few studies, Herceptin and another targeted drug were even given without chemotherapy, and provided substantial benefit, he added.

That, Dr. Hortobagyi said, “started to break the dogma” that chemotherapy was essential. But changing cancer therapies was not easy. “It is very scary,” to give fewer drugs, Dr. Hortobagyi said.

“It is so much easier to pile on treatment on top of treatment,” he continued, “with the promise that ‘if we add this it might improve your outcome.’”

But as years went by, more and more oncologists came around, encouraged by new research and new drugs.

The change in chemotherapy use is reflected in a variety of data collected over the years. A study of nearly 3,000 women treated from 2013 to 2015 found that in those years, chemotherapy use in early-stage breast cancer declined to 14 percent, from 26 percent. For those with evidence of cancer in their lymph nodes, chemotherapy was used in 64 percent of patients, down from 81 percent.

More recent data, compiled by Dr. Jeanne Mandelblatt, a professor of medicine and oncology at Georgetown, and her colleagues, but not yet published, included 572 women who were 60 or older and enrolled in a federal study at 13 medical centers. Overall, 35 percent of older women received chemotherapy in 2012. That number fell to 19 percent by the end of 2019.

Cheaper and faster genetic sequencing has played an important role in this change. The technology made it easier for doctors to test tumors to see if they would respond to targeted drugs. Genetic tests that looked at arrays of proteins on cancer cells accurately predicted who would benefit from chemotherapy and who would not.

There are now at least 14 new targeted breast cancer drugs on the market — three were approved just last year — with dozens more in clinical trials and hundreds in initial development.

Some patients have reaped benefits beyond avoiding chemotherapy. The median survival for women with metastatic breast cancer who are eligible for Herceptin went from 20 months in the early 1990s, to about 57 months now, with further improvements expected as new drugs become available. For women with tumors that are fed by estrogen, the median survival increased from about 24 months in the 1970s to almost 64 months today.

Now some are in remission 10 or even 15 years after their initial treatment, Dr. Hortobagyi said.

“At breast cancer meetings, a light bulb went off. ‘Hey, maybe we are curing these patients,’” Dr. Hortobagyi said.

Dr. Doshi’s oncologist, Dr. Eric Winer of the Dana-Farber Cancer Institute, gave her good news: A genetic test of her tumor indicated she would not get any significant benefit from chemotherapy. Hormonal therapy to deprive her cancer of the estrogen that fed it would suffice.

But as much as Dr. Doshi dreaded chemotherapy, she worried about forgoing it. What if her cancer recurred? Would chemotherapy, awful as it is, improve her outcome?

She got a second opinion.

The doctor she consulted advised a “very aggressive” treatment, Dr. Doshi said — a full lymph node dissection followed by chemotherapy.

She had multiple conversations with Dr. Winer, who ended up discussing her case with four other specialists, all of whom recommended against chemotherapy.

Finally, Dr. Doshi said, “my husband said I should just pick a horse and run with it.” She trusted Dr. Winer.

Her struggles mirror what oncologists themselves go through. It can take courage to back off from chemotherapy.

One of the most difficult situations, Dr. Winer said, is when a patient has far more advanced disease than Dr. Doshi did — hers had spread to three lymph nodes but no further — and is not a candidate for one of the targeted treatments. If such a patient has already had several types of chemotherapy, more is unlikely to help. That means there is no treatment.

It falls to Dr. Winer to tell the patient the devastating news.

Dr. Susan Domchek, a breast cancer specialist at the University of Pennsylvania, can relate to those struggles.

“It is the nature of being an oncologist to be perpetually worried that you are either overtreating or undertreating a patient,” she said.

“Some cases keep me up at night,” she said, “specifically the cases where the risks and benefits of chemotherapy are close, yet the stakes still feel so high.”

When Dr. Roy Herbst of Yale started in oncology about 25 years ago, nearly every lung cancer patient with advanced disease got chemotherapy.

With chemotherapy, he said, “patients would be sure to have one thing: side effects.” Yet despite treatment, most tumors continued to grow and spread. Less than half his patients would be alive a year later. The five-year survival rate was just 5 to 10 percent.

Those dismal statistics barely budged until 2010, when targeted therapies began to emerge. There are now nine such drugs for lung cancer patients, three of which were approved since May of this year. About a quarter of lung cancer patients can be treated with these drugs alone, and more than half who began treatment with a targeted drug five years ago are still alive. The five-year survival rate for patients with advanced lung cancer is now approaching 30 percent.

But the drugs eventually stop working for most, said Dr. Bruce Johnson, a lung cancer specialist at Dana-Farber. At that point many start on chemotherapy, the only option left.

Another type of lung cancer treatment was developed about five years ago — immunotherapy, which uses drugs to help the immune system attack cancer. Two-thirds of patients from an unpublished study at Dana-Farber were not eligible for targeted therapies but half of them were eligible for immunotherapy alone, and others get it along with chemotherapy.

Immunotherapy is given for two years. With it, life expectancy has almost doubled, said Dr. Charu Aggarwal, a lung cancer specialist at the University of Pennsylvania.

Now, said Dr. David Jackman of Dana-Farber, chemotherapy as the sole initial treatment for lung cancer, is shrinking, at least at that cancer treatment center, which is at the forefront of research. When he examined data from his medical center he found that, since 2019, only about 12 percent of patients at Dana-Farber got chemotherapy alone, Dr. Jackman said. Another 21 percent had a targeted therapy as their initial treatment, and among the remaining patients, 85 percent received immunotherapy alone or with chemotherapy.

In contrast, in 2015, only 39 out of 239 patients received a targeted therapy as their initial treatment. The rest got chemotherapy.

Dr. Aggarwal said she was starting to witness something surprising — some who had received immunotherapy are still alive, doing well, and have no sign of cancer five years or more after their initial treatment.

She said: “I started out saying to patients, ‘I will treat you with palliative intent. This is not curative.’”

Now some of those same patients are sitting in her clinic wondering if their disease is gone for good.

Chong H. Hammond’s symptoms were ambiguous — a loss of appetite and her weight had dropped to 92 pounds.

“I did not want to look at myself in the mirror,” she said.

It took from October 2020 until this March before doctors figured it out. She had metastatic lung cancer.

Then Dr. Timothy Burns, a lung cancer specialist at the University of Pittsburgh, discovered that Mrs. Hammond, who is 71 and lives in Gibsonia, Pa., had a tumor with two unusual mutations.

Although a drug for patients with Mrs. Hammond’s mutations has not been tested, Dr. Burns is an investigator in a clinical trial involving patients like her.

He offered her the drug osimertinib, which is given as a pill. This allowed her to avoid chemotherapy.

Ten days later she began feeling better and started eating again. She had energy to take walks. She was no longer out of breath.

Dr. Burns said her lung tumors are mostly gone and tumors elsewhere have shrunk.

If Mrs. Hammond had gotten chemotherapy, her life expectancy would be a year or a little more, Dr. Burns said. Now, with the drug, it is 38.6 months.

Dr. Burns is amazed by how lung cancer treatment has changed.

“It’s been remarkable,” he said. “We still quote the one-year survival but now we are talking about survival for two, three, four or even five years. I even have patients on the first targeted drugs that are on them for six or even seven years.”

Mark Catlin, who is being treated at Dana-Farber, is one of those patients.

On March 8, 2014, Mr. Catlin, who has never smoked, noticed a baseball-size lump under his arm. “The doctors told me to hope for anything but lung,” he said.

But lung it was. It had already spread under his arm and elsewhere.

Oncologists in Appleton, Wis., where he lives, wanted to start chemotherapy.

“I was not a fan,” Mr. Catlin said. His son, who lives in the Boston area, suggested he go to Dana-Farber.

There, he was told he could take a targeted therapy but that it would most likely stop working after a couple of years. He is 70 now, and still taking the therapy seven years later — two pills a day, with no side effects.

He rides a bike 15 to 25 miles every day or runs four to five miles. His drug, crizotinib, made by Pfizer, has a list price of $20,000 a month. Mr. Catlin’s co-payment is $1,000 a month. But, he says, “it’s keeping me alive.” “It’s almost surreal,” Mr. Catlin said.

Gina Kolata

By:

Source: Cancer Without Chemotherapy: ‘A Totally Different World’ – The New York Times

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Related Contents:

The Cancer Custodians Hidden Truths

woman-with-headscarf-getting-chemo-treatment-article

Part of Dennis Plenker’s daily job is growing cancer. And a variety of different ones, too. Depending on the day and the project, different tumors may burgeon in the petri dishes stocked in the Cold Spring Harbor Laboratory where Plenker works as a research investigator. They might be aggressive breast cancers.

They might be glioblastomas, one of the deadliest brain tumors that rob patients of their ability to speak or read as they crowd out normal cells. Or they might be pancreatic cancers, the fast and vicious slayers that can overtake a healthy person within weeks or even days.

These tiny tumor chunks are transparent and bland—they look like little droplets of hair gel that accidentally plopped into a plastic dish and took hold. But their unassuming appearance is deceptive. If they were still in the human bodies they came from, they would be sucking up nutrients, rapidly growing and dodging the immune system defenses.

But in Plenker’s hands—or rather in the CSHL’s unique facility—these notorious killers don’t kill anyone. Instead, scientists let them grow to devise the most potent ways to kill them. These tumor chunks are called organoids. They are three-dimensional assemblages of malignant growths used to study cancer behavior and vulnerability to chemotherapy and the so-called “targeted drugs”—the next generation therapies.

Scientists used to study tumors at a single-cell level, but because tumors grow as cell clusters in the body, it proved to be inefficient. The three-dimensional structures make a difference. For example, chemo might destroy the tumor’s outer cell layer, but the inner ones can develop resistance, so where single cells may die, a 3D mass will bounce back. Organoids can provide a window into these little-known mechanisms of drug resistance.

They can reveal how normal tissues turn malignant and where the cellular machinery goes off-track to allow that to happen. As their name suggests, organoids are scientists’ windows into organs, whether healthy or stricken with disease. You need to know your enemy to beat it, Plenker says, and cancer organoids offer that opportunity.

Taken from patients currently undergoing cancer treatments, these tumor chunks will reveal their weaknesses so scientists can find the cancers’ Achilles’ heel and devise personalized treatments. “Organoids are essentially patients in a dish,” Plenker says. Only unlike real patients, the organoids can be subjected to all sorts of harsh experiments to zero in on the precise chemo cocktails that destroy them in the best possible way.

And they will likely provide a more realistic scenario than drug tests in mice or rats, as animal models aren’t perfect proxies for humans.

These notorious killers don’t kill anyone. Instead, scientists devise the most potent ways to kill them.

The way that cancer proliferates in the body is hard to reproduce in the lab. Stem-cell research made it possible. After scientists spent a decade understanding how various cells multiply and differentiate into other cell types based on molecular cues and nourishment, they were able to make cells grow and fuse into tissues.

To stick together like bricks in a nicely laid wall, cells need a biological scaffold that scientists call an extracellular matrix or ECM, which in the body is made from collagen and other materials. Today, the same collagen scaffolds can be mimicked with a gooey substance called Matrigel—and then seeded with specific cells, which take root and begin to multiply.

Some tissue types were easy to grow—Columbia University scientists grew viable bones as early as 2010.1 Others, like kidney cells, were trickier. They would grow into immature tissues incapable of performing their job of cleaning and filtering blood. It took scientists time to realize that these cells wanted more than scaffolding and food—they needed to “feel at home,” or be in their natural habitat. Kidney cells needed the feeling of liquid being washed over them, the Harvard University group found, when they first managed to grow functioning kidney tissue in 2018.2

Cancers have their own growth requirements. In the body, they manage to co-opt the organism’s resources, but keeping them happy in a dish means catering to their dietary preferences. Different cancers need different types of molecular chow—growth factors, hormones, oxygen and pH levels, and other nutrients. Pancreatic adenocarcinoma thrives in low-oxygen conditions with poor nutrients.3 Glioblastomas feed on fatty acids.4 These nutrients are delivered to organoids via a specific solution called growth medium, which the lab personnel regularly doles out into the dishes.

Plenker is charged with keeping this murderous menagerie alive and well. He is the one who designs the cancers’ dietary menu, a specific protocol for each type. And while his official title is facility manager and research investigator who works closely with David Tuveson, director of the CSHL’s Cancer Center, he is essentially a cancer custodian, a curator of a unique collection that aims to change the paradigm of cancer treatment.

Plenker’s research area is pancreatic cancer—one of the most notorious killers known. Often diagnosed late and resistant to treatment, it is essentially a death sentence—only 8 to 10 percent of patients remain alive five years after diagnosis. The chemo drugs used to treat it haven’t changed in 40 years, Plenker says. In the past decade, physicians tried combining multiple drugs together with relative success. Identifying winning combos can save lives, or at least prolong them—and that’s what the organoids will help clinicians do better.

In a groundbreaking clinical trial called PASS-01 (for Pancreatic Adenocarcinoma Signature Stratification for Treatment), Plenker’s team collaborates with other American and Canadian colleagues to identify the most effective chemo cocktails and to understand the individual patients’ tumor behaviors, which would lead to more personalized treatments.5

Scientists know the same cancer types behave differently in different patients. Typically, all malignancies have the so-called “driver mutation”— the cancer’s main trigger caused by a mutated gene. But tumors also often have “passenger mutations” that happen in nearby genes. These additional mutated genes can generate various proteins, which may interfere with treatment.

Or not. Scientists call these mutated gene combinations tumor mutational signatures, which can vary from one patient to the next. With some cancers, doctors already know what mutations signatures they may have, but with pancreatic cancer they don’t have good tale-telling signs, or biomarkers. “There aren’t many biomarkers to help clinicians decide which chemo may be better for which patient,” explains oncologist Grainne O’Kane, who treats pancreatic cancer patients at the Princess Margaret Hospital in Toronto, Canada.

That’s the reason O’Kane participates in the PASS-01 trial—it will give doctors a better view into the exact specifics of their patients’ malignancies. As they take their patients’ biopsies, they are sending little cancer snippets to the CSHL to be grown into organoids, which will be subjected to chemo cocktails of various combinations to design more personalized regiments for them.

The hospital treats all patients with the so-called standard of care chemotherapy, which is more of a one-size-fits-all approach. Some patients will respond to it but others won’t, so the goal is to define the second line of chemo defense in a more personalized fashion. “That’s where the biopsies we send to Tuveson’s lab might be useful,” O’Kane says. “They can help us find something to benefit patients after the first line of chemo stopped working.”

Organoids are patients in a dish. Unlike real patients, organoids can be subjected to experiments.

Scientists can try all kinds of combos on the tumorous organoids, which they can’t do in living people. “You can treat 100 organoids with 100 different compounds and see which one works, or which compound does a good job and which ones don’t work at all,” Plenker says. That would also allow scientists to define the precise amount of chemo, so doctors wouldn’t have to over-treat patients with harsh drugs that create sickening side effects. Ultimately, organoids should take a lot of guesswork out of the process.

With about 150 patients’ adenocarcinomas already collected, the team hopes to come up with some answers. O’Kane says her team already has three patients for which they were able to design the more personalized second line of defense chemo, based on what their organoids revealed. They haven’t yet tried it, because the trial has only started recently, but this would be the next step.

“Being able to piece all this information together in real time as patients are moving through their therapies can really improve the outcomes,” O’Kane says. And while they may not be able to save all of those who graciously donated their biopsy snippets to science, it will help build better treatments in the future. “Even if we won’t be able to help these specific patients we’re hoping to use this info in the future clinical trials,” O’Kane says.

Organoids can also help understand how cancer develops. This is particularly true for breast cancers, says Camilla dos Santos, associate professor and a member of the CSHL Cancer Center. She studies the inner life of human mammary glands, more commonly referred to as breasts, and is also part of the cancer custodian crew. The hormonal changes that women go through during pregnancy subsequently modify breast cancer risk, sometimes lowering it and sometimes increasing—a complex interplay of the body’s chemicals.

“We know that women who get pregnant for the first time before they turn 25 years old, have a 30 percent decrease in breast cancer incidents later in life,” dos Santos says. “When they turn 60 or 70, 30 percent of them will not develop cancer.” On the contrary, those who are pregnant past 38 have a 30 to 50 percent increase in developing aggressive breast cancer types. Clearly, some molecular switches are involved, but they are very hard to study within the body. That’s where organoids can provide a window into the surreptitious process.

Using breast organoids, scientists can model the complex life of mammary glands at various stages of a woman’s life. And while most women wouldn’t want their breasts poked and pierced when they are pregnant or breastfeeding, many donate their tissues after breast reduction surgery or prophylactic mastectomy due to high-risk mutations like the BRCA gene.

That’s where organoids shine because scientists can not only grow them, but also give them the pregnancy hormonal cues, which will make cells generate milk, stop lactating, or do it again—and study the complex cellular interactions that take place in real life.

There’s a lot to study. At birth, mammary glands are similar in both genders—just little patches of the mammary epithelium tissue. But when puberty hits, the female glands fill up with the so-called mammary tree—a system of ducts for future milk production, which fully “blooms” in pregnancy.

“When a woman becomes pregnant, the duct tree expands, growing two types of cells—luminal and myoepithelial ones,” explains Zuzana Koledova, assistant professor of Masaryk University in Czech Republic who also uses organoids in her work. When the baby is born, the luminal cells, which line the inside of the ducts, produce the proteins that comprise milk.

The myoepithelial cells reside outside the ducts and work as muscles that squeeze the ducts to push milk out. Dos Santos likens this pregnancy mammary gland growth to the changes of the seasons. The images of sprouting ducts look like blossoming trees in the spring while later they shrivel like plants do in the fall.

The body governs these processes via the molecular machinery of hormones, which stimulate breast cells growth during pregnancy, and later cause them to die out. The two pregnancy-related hormones, prolactin and oxytocin, are responsible for milk production. Prolactin induces the luminal cells to make milk while oxytocin makes the myoepithelial cells contract. Once the baby is weaned, the levels of these hormones drop, causing cells to shrink back to their non-pregnant state.

With organoids scientists can observe these cellular dynamics at work. Koledova’s team had watched breast organoids secrete milk based on biological cues. They even recorded movies of cells pumping tiny milk droplets in the dish they were growing in. Using tiny snippets of donated breast tissue, the team grew the organoids inside the Matrigel matrix in the growth media and then added the two pregnancy hormones into the mix, explains Jakub Sumbal, a mammary gland researcher in Koledova’s group.

As they began to secret proteins that compose milk, the organoids, which looked like little domes inside the dish, changed from translucent to opaque. “At first, you can see through them, but then as they produce these proteins, they kind of darken,” Sumbal says. “And you can see them pushing out these little droplets.”

Cancer patients would no longer have to undergo chemotherapy by trial and error.

Dos Santos’s team, who also did similar work, outlined molecular changes that follow such dish-based hormonal cues in their recent study.6 In response to hormonal messages, cells produce proteins, which they display on their surfaces, like status symbols. During pregnancy the burgeoning cells prepping for milk production display the “proteins flags” that make them look important, attracting nourishment. When it’s time to die, they commit a cellular suicide.

They signal to the bypassing macrophages—immune system cleanup crew—to devour them. “They essentially say ‘come eat me!’ to the macrophages,” dos Santos says. “Because I’m no longer needed.”

The ability to mimic these processes in a dish, allows scientists to study the molecular switches that trigger breast cancer development—or minimize it. Scientists know that cancerous cells can hide from the immune system and even co-opt it into protecting themselves. They do it by displaying their own “do not eat me” protein flags on the surface and avoid destruction.

“Sometimes cancer cells can recruit specific types of immune cells to protect them,” dos Santos says. “They can not only say ‘do not eat me,’ but say ‘come hang out with me’ to the macrophages, and the macrophages will send suppressive signals to the B-cells or T-cells, the body defenders.” It is as if the cancer requests protection—a crew of guardians around it to defend against other cells that would otherwise wipe it out.

Scientists can’t telescope into the body to peek at these interactions, but they now can watch these stealth battles unfolding in a dish. “Right now we are looking at the proteins that are secreted by the organoids—the proteins that go on the surface of the organoids’ cells and what they would communicate to the immune system,” dos Santos says.

“Even when there’s no immune system surrounding them, they would still be doing that.” There’s a way to mimic the immune system, too. Scientists can add B-cells, T-cells, macrophages, and other players into the growth medium and watch the full-blown cellular warfare in action. “That’s the next step in our research,” dos Santos says.

Understanding what hormonal fluxes trigger breast cancer, and how it recruits other cells for safekeeping, can give scientists ideas for pharmaceutical intervention. “We can find drugs that pharmacologically turn off the switches that trigger cancer or interrupt its signaling for protection,” dos Santos says. “That opens novel ways to treat people.”

Can organoid research lead to a new standard of care for cancer patients? That’s the ultimate goal, researchers say. That’s why Plenker works at keeping his collection of cancer glops alive and well and thriving—he calls it a living biobank. And he keeps a stash in the cryogenic freezer, too.

He is also developing protocols that would allow commercial companies to grow organoids the same way chemical industries make reagents or mice suppliers grow rodents for research. A benefit of organoid experiments is they don’t involve animals at all.

Hospitals may one day start growing organoids from their patients’ biopsies to design and test personalized chemo cocktails for them. Once science crosses over to that reality, the entire treatment paradigm will change. Cancer patients won’t have to undergo chemotherapy by trial and error.

Instead their cancer organoids will be subjected to this process—knocked out by a gamut of drug combinations to find the winning one to use in the actual treatment. Plenker notes that once enough data is gathered about the tumors’ mutational signatures, scientists may create a database of tumor “mugshots” matching them to the chemo cocktails that beat them best.

And then just sequencing a biopsy sample would immediately inform oncologists what drug combo the patient needs. “We may be about 10 years away from that,” Plenker says, but for now there’s a lot more research to do. And a lot more cancers to grow.

By: Lina Zeldovich

Lina Zeldovich grew up in a family of Russian scientists, listening to bedtime stories about volcanoes, black holes, and intrepid explorers. She has written for The New York Times, Scientific American, Reader’s Digest, and Audubon Magazine, among other publications, and won four awards for covering the science of poop. Her book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, will be released in October 2021 by Chicago University Press. You can find her at LinaZeldovich.com and @LinaZeldovich.

Source: The Cancer Custodians – Issue 102: Hidden Truths – Nautilus

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Critics:

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.

Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV).

These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.

Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy.

The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.

Further reading

Mammograms Pick Up Swelling Related To The Covid-19 Vaccine Study Says

When she found a lump in her left breast during a routine self-check, Boston primary care physician Dr. Devon Quasha knew exactly what to do. She immediately scheduled a diagnostic mammogram and ultrasound at Massachusetts General Hospital for early January.

Quasha didn’t notice much of a reaction to the vaccine at first, but a couple of days before her appointment her left arm began to hurt.
Tender, swollen lumps developed under her left armpit, along with a large swelling above her collarbone — all areas where there are lymph nodes, the body’s filters for germs.
“You have lymph nodes above and below your collarbone,” Quasha said. “You don’t want to feel those. It was scary when I felt it.”
Lymph nodes contain immune cells that help fight invaders. That’s why it made sense to Quasha that the nodes were reacting to the vaccine, building antibodies as they were designed to do. But she couldn’t be sure.
The swelling was only on the left side where she had gotten the shot — the same side as the worrisome lump. Was it a reaction to the vaccine or another sign of breast cancer?

‘It was like a wildfire’

After the ultrasound, Quasha’s radiologist was concerned. She told Quasha she considered the lump she had felt in her breast to be of little significance, but the lymph nodes that showed up as white blobs on her mammogram were another matter. In non-pandemic times, that finding would set off alarm bells, requiring the need for further investigation, even an immediate biopsy.
Yet Quasha had just had the vaccine. After talking it over with her, Quasha said her doctor decided not to do a biopsy at that time. Instead she told Quasha to come back for a follow-up ultrasound in six weeks.

“I cannot tell you how many women are showing nodes on mammograms and people thought it was going to be not that common,” said Lehman, who is also a professor of radiology at Harvard Medical School.
Tales of unnecessary biopsies spurred the patient care committee of the Society of Breast Imaging (SBI) to put out an advisory in January: Ask your patients about their Covid-19 status, and record the date and which arm received the vaccine. Consider that before automatically scheduling a biopsy.
“We wanted to advocate that women don’t always need to have a biopsy,” said Dr. Lars Grimm, associate professor of radiology at Duke University School of Medicine and one of the authors of the SBI advisory. “Because oftentimes the default if you see swollen lymph nodes in a patient would actually be to recommend doing a biopsy.”
Mass General’s Lehman agreed. “When you hear hoofbeats, don’t think zebra,” she said. “If a woman had a vaccine in the arm on the same side, and the lymph nodes are swollen, this is a normal biological response. It’s totally expected. It just doesn’t make sense to start imaging.”
That does not mean that women who wish to be sure about their cancer status cannot have a biopsy, Grimm stressed. “You actually have some women who want to biopsy,” he said. “You might tell them, ‘Hey, I think this is due to your Covid vaccine, and I’m sure that it’s going to resolve in a few weeks on its own and you’re going to be fine.’ But that patient tells you, ‘I’m not going to be comfortable waiting, I want to know now.’ “

Focus on screening to save lives

For Quasha, the knowledge that many women were experiencing the same type of reaction to the vaccine was a welcome relief from worry. After a discussion with her doctor, she said she no longer needs the follow-up screening. “I was very reassured,” Quasha said. “The point here is that there are a number of side effects from the vaccine which are not dangerous but can sometimes increase patient anxiety.”
Instead of bringing women back in for an unnecessary ultrasound, radiology centers should be focused on scheduling women who have missed or are overdue on their mammogram, Lehman said.
“We need to take care of the large percentage of women who didn’t get screened because of the shutdowns during Covid,” she said. “At Mass General alone, we failed to screen 15,000 women because of Covid, and we’re still trying to get them back in.
“This isn’t where I need to start doing axillary ultrasounds, because someone had a vaccine and the node swelled. It’s just not being practical or pragmatic or putting our patient’s needs first,” she said. It’s not just breast cancer, Lehman stressed. Lymph nodes in other parts of the body are also reacting to the Covid-19 vaccines, causing people with other forms of cancer to undergo unnecessary procedures.
“There have been some false scares and some unnecessary biopsies because people didn’t think to ask, and they assume that the node was the cancer coming back,” she said.

What to do?

To avoid unnecessary worry, SBI recommends women schedule any routine, annual breast screening before getting the Covid-19 vaccine. If a woman has already had the vaccine, or is soon scheduled to do so, the society suggests waiting at least four to six weeks after the second dose before scheduling your appointment.
At Mass General, Lehman and her team have gone a step further. They are screening all women regardless of vaccine status, but telling those with no history of cancer that any swelling in the lymph nodes that might be connected to a Covid-19 vaccine is benign — meaning not cancerous.
“This follows the American College of Radiology recommendations that if you have a known inflammatory cause you can say it’s benign,” said Lehman, who recently published a paper on the hospital’s procedures.
“If their concern is a swelling or tenderness after the vaccine in their armpit, we suggest that they wait four to six weeks, talk to their doctor, and if it persists, then we have them come in to do an evaluation of it,” she said.
Whatever you do, experts stress, don’t skip getting your breast cancer screening when it is recommended. A study published Tuesday in the journal Radiology that followed over half a million women made the point clearly: Women who skip even one scheduled mammography screening before they are diagnosed with breast cancer have a significantly higher risk of dying. In fact, the risk of having a fatal breast cancer within 10 years of diagnosis was 50% lower for women who had regular breast screenings, the study said.

By: 

Source: Mammograms pick up swelling related to the Covid-19 vaccine, study says – CNN

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New Technique From Cambridge Cancer Researchers Will Enable More Targeted Tumour Biopsies

Cancer researchers in Cambridge have developed an advanced computing technique using routine medical scans that could enable doctors to take fewer, but more accurate, tumour biopsies.

They have combined CT (computed tomography) scans with ultrasound images to create a visual guide for medics that enables them to use more targeted biopsies to sample the full complexity of a tumour.

One day the technique could even allow clinical biopsies to be replaced with virtual biopsies, to spare patients invasive procedures.

The research was led by Professor Evis Sala, from the Department of Radiology, co-lead of the Cancer Research UK Cambridge Centre’s advanced cancer imaging programme, who said: “This study provides an important milestone towards precision tissue sampling. We are truly pushing the boundaries in translating cutting-edge research to routine clinical care.”

Most cancer patients undergo one or several biopsies in order to capture their tumour’s heterogeneity – that is the full genetic variety of cells within it.

Understanding this is key for selecting the best treatment, as genetically different cells may respond differently to therapies.

Reducing the number of these biopsies, and ensuring they accurately sample the different cells is therefore crucial, particularly for ovarian cancer patients.

High grade serous ovarian (HGSO) cancer is the most common type of ovarian cancer and referred to as a ‘silent killer’ because its early symptoms can be hard to pick up. Survival rates have not improved much in 20 years.

HGSO tumours also have a high level of heterogeneity – and we know that patients with more genetically-different patches cancer cells tend to have poorer responses to treatment.

Top Stories on Cambridge Independent

Prof Sala leads a multi-disciplinary team of radiologists, physicists, oncologists and computational scientists using innovative computing techniques to reveal tumour heterogeneity from standard medical images.

The new study involved a small group of patients with advanced ovarian cancer, who were due to have ultrasound-guided biopsies prior to starting a course of chemotherapy.

Patients in the study first had a standard CT scan, which uses X-rays and computing to create a 3D image of the tumour, by taking multiple image ‘slices’ through the body.

The process of radiomics, which uses high-powered computing to analyse and extract additional information from the data-rich CT scan images, was then used to identify and map distinct areas and features of the tumour.

The researchers then superimposed the ultrasound image of the tumour and the combined image – which successfully captured the diversity of cancer cells – was used to guide the biopsy procedure.

Co-first author Dr Lucian Beer, from the Department of Radiology and CRUK Cambridge Centre ovarian cancer programme, said: “Our study is a step forward to non-invasively unravel tumour heterogeneity by using standard-of-care CT-based radiomic tumour habitats for ultrasound-guided targeted biopsies.”

Co-first author Paula Martin-Gonzalez, also from the programme, added: “We will now be applying this method in a larger clinical study.”

The study was welcomed by Fiona Barve, 56, a science teacher living near Cambridge, who was diagnosed with stage 4 ovarian cancer in 2017 after visiting her doctor with abdominal pain. She immediately underwent surgery and chemotherapy and has been cancer-free since March 2019.

Fiona, who is now back to teaching three days a week, said: “I was diagnosed at a late stage and I was fortunate my surgery, which I received within four weeks of being diagnosed, and chemotherapy worked for me. I feel lucky to be around.

“When you are first undergoing the diagnosis of cancer, you feel as if you are on a conveyor belt, every part of the journey being extremely stressful. This new enhanced technique will reduce the need for several procedures and allow patients more time to adjust to their circumstances. It will enable more accurate diagnosis with less invasion of the body and mind. This can only be seen as positive progress.”

The feasibility study involved researchers from the Department of Radiology, CRUK Cambridge Institute, Addenbrooke’sl, Cambridge University Hospitals NHS Foundation Trust and collaborators at Cannon, and was facilitated through the CRUK Cambridge Centre Integrated Cancer Medicine programme.

The progamme’s aim is to revolutionise cancer treatment using the integration of complex patient data from multiple sources – blood tests, biopsies, medical imaging, and genetic tests – to inform and predict the best treatment decisions for each individual.

The study was funded by Cancer Research UK and The Mark Foundation for Cancer Research.

Read more

The breast cancer scan developed by CRUK Cambridge Institute that could replace invasive tissue biopsies

Babraham Institute study of Oxford University’s Covid-19 vaccine underscores importance of second dose

By Paul Brackley

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Phospho Biomedical Animation

Being able to easily track cancer is vital in all stages of the disease. Doctors have long been able to monitor the disease with scans and by taking small tissue samples (biopsies), but now a new technique is becoming available to them: the liquid biopsy, which can deliver a lot of detailed information about a patient’s tumour from a simple blood sample. So how does it work? Inside a tumour, cells are growing at a high rate, but while many cancer cells are growing, some are also dying in a process called apoptosis. As dying cancer cells break up, they release fragments of their DNA. Some of that DNA can get into the blood stream, after which it’s called circulating tumour DNA (or ctDNA). This circulating tumour DNA is ready for scientists to fish out with a simple blood sample. Because of advances in DNA sequencing technology, doctors can pick up on these traces of DNA, and use them to track the mutations present in a cancer. Finding out this information helps doctors keep track of a patient’s tumour and whether treatment is working, or find out early if a new scan or different treatment is needed. For more information, see http://scienceblog.cancerresearchuk.o…http://scienceblog.cancerresearchuk.o..

Collateral Damage Of Covid-19: More Than 200 International Cancer Trials Suspended

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As we continue to treat and discharge patients with Covid-19 from hospitals throughout the US, we are acutely aware of patients avoiding the ER for fear of contracting Covid-19.Messaging that reflects not only the safety but necessity of seeking care in the setting of life threatening conditions is vitally important to assure the health of the American people.

Deaths from heart attacks, strokes and sepsis, reflected in data measuring excess mortality—deaths beyond what we would have solely expected from Covid-19—remind us of the “other” casualties of the pandemic.But other types of casualties from the pandemic include cancer patients, many of whom have not been able to receive necessary surgeries or treatment during the height of the lockdown, along with those who may have not been able to be enrolled in trials using investigational approaches and novel therapies.

“The battle against cancer is formidable even in normal circumstances; Covid-19 adds to this battle by not only predisposing this population to higher morbidity and mortality but has also forced the majority of the cancer institutions in the U.S. to shut down the clinical trials in cancer patients to deal with the present crisis”, said Wasif M. Saif, M.D., Deputy Physician-in-Chief and Medical Director, Northwell Health Cancer Institute, Lake Success, New York,

“I call the Covid-19 pandemic and cancer situation a “two-front war“. The first fight is with cancer — a disease that claims 600,000 lives each year in the U.S. Data from published studies during this pandemic clearly suggests cancer was associated with an increased risk of death of patients three times higher than those without cancer, and also increased intensive care unit admission and ventilation support,” added Saif.

With these issues in mind, there is no doubt that efforts to conduct medical research in just about every discipline has been significantly affected by the pandemic. Certainly, oncology is one area where ongoing research is vital to impacting patient mortality and decisions regarding cutting edge treatments.

In fact, based on findings of a recent study, more than 200 international cancer trials have been suspended as a result of disruption of normal clinical operations globally from Covid-19. The effects were most apparent in the US and in Europe, but also in Asia to some degree, based on the results of the study. The effects of this disruption will likely be incalculable in terms of progress and mortality data that we may see both in the near and long term.

Researchers analyzed data from ClinicalTrials.gov looking specifically at patient enrollment during the critical early months of the pandemic. They used a survey to understand the effects on 36 investigators (between March 23 to April 3) conducting cancer- related clinical trials at various institutions across multiple countries. A separate analysis by a health care data analytics firm, IQVIA, also looked at the factors affecting more than 200 ongoing clinical trials.

Results of the survey demonstrated that 60% of institutions in the US and 86% in Europe are enrolling now enrolling patients at a reduced rate compared to prior to the pandemic. The main factors affecting enrollment, based on survey data, included lack of access to patients themselves during the lockdown, investigator concern related to patient safety, lack of research staff, along with mode of cancer treatment and type of cancer.

At the time of the survey in March to early April of 2020, it was noted that patient enrollment in clinical trials had precipitously declined, particularly in the US and in Europe. In fact, only 20% of institutions in the US and 14 % in Europe resumed enrollment at their pre-pandemic rate. Meanwhile, about 60% of the enrollments in Asia had not changed.

If you look at institutions that continued to conduct trials with reduced enrollment rates, 23% cited patient care and type of cancer therapy encompassing the route of administration, as two of the main considerations adversely affecting patient enrollment. Additional concerns included lack of research or support staff, resources, and well as patient safety. Aside from this, risk vs. benefit was the primary consideration for patients being enrolled in ongoing trials.

Similar trends were also observed in the case of initiating new trials with patient care, type of cancer therapy, and route of administration being the main considerations. Researchers also expressed concern about therapy that required IV administration compared with oral approaches, since oral medications could be taken in the home setting.

In evaluating regulatory and operational challenges related to Covid-19 patients overwhelming healthcare systems, nearly 60% of researchers said that Covid-19 had moderate or high impact leading to delayed or cancelled patient visits, and close to 80% of researchers believed that such protocol irregularities would lead to incomplete records and research.

“The biggest delayed consequence of the COVID-19 pandemic would probably be in delaying cancer drug development, with its own consequences both for the cancer patients as well as for the pharmaceutical industry,” said Saif. Beyond this, financial considerations also come into play in any calculation regarding the toll of the pandemic on cancer clinical trials.

“Sites have to bear the brunt of an ever-changing clinical landscape while tackling potential loss of revenue,” explained Saif. “In clinical research, a major portion of site revenue comes from industry sponsored trials. Payments to sites are based on enrollment, patient visits completed and timely data entry. In many sites, enrollment to studies had to be limited to ensure patient and staff safety.  Concern for safety has also led to the cancellation of many non-essential study procedures. Less recruitment and more cancellations mean less revenue sites will receive.”

The use of alternative technologies to reduce the need for in-person visits for research and evaluation was crucial during the pandemic. Such approaches included telemedicine, but also virtual monitoring of data and study documentation, as well as remote electronic health record access for those conducting patient evaluation and follow-up. Directly shipping drugs to patients as well as avoidance of specific immunosuppressive regimens also constituted ways that researchers altered their approaches to conducting research.

“The Covid-19 pandemic gave all of us a crash course of telehealth and provided a new tool to interact and manage cancer patients,” offered Saif. “But it is important to remember that this is a population who was previously reluctant to digital communication—even in a blizzard, I remember having 80% patients showing up.”

Saif further said that “Telehealth can help us to interview but misses the human touch, and most importantly physical examination which in some cases is crucial including measurement of a tumor mass or others.”On the upside, Saif stressed that” it [telehealth] can offer a platform to manage immunocompromised patients and carries the potential to see second-opinions in a quick manner allowing us to save resources at the same time.”

Data from ClinicalTrials.gov noted that more than 200 interventional oncology trials were suspended during the months of March and April—62 suspended during March and 139 suspended during April. Looking at the breakdown of suspended trials, 29 were phase 1, 72 phase II, 11 phase III, with the remainder classified as “other”.

Saif sums it up simply: “ The Covid-19 pandemic has changed the way we treat cancer and perform cancer trials; first and foremost, we need to carve out a long-term plan to care for our patients in anticipation of another wave of COVID-19 now or in Fall.”

“We not only need to resume the clinical research but gain acceleration urgently to move on with development of cancer drugs simultaneously with treatments for Covid-19,” he offered. “But don’t forget the human factor, “the fear” by the patients and their families to return to cancer centers – we need to reassure that we are a safe facility. This pandemic has forced us to culminate a rationalization basis for cancer services, both diagnostic and therapeutic. Not only institutions were required to develop guidelines under multidisciplinary teams, but many national and governmental organizations also laid out guidelines about who and how to treat.”

“This pandemic not only stretched health systems in terms of constraints related to workforce of health care providers due to their own illness or family members but also threatened to exhaust the assets, including capacity of hospital beds, ventilators, PPE introduced by the financial impact of COVID-19. It is hoped that the effect of this rationalization in cancer care will last long and allow us to analyze and fix the issues of health disparity, such as access to cancer services, socioeconomic and ethnic differences,” concluded Saif.

Going forward, it will be vital to mitigate the impact of future shutdowns on ongoing cancer trials, not to mention basic cancer care and surgeries. This will help to guide us in the future with a clear plan when the next pandemic strikes.

“The current paradigm for clinical trials in the U.S. requires both patient and researcher to be in direct contact with one another—a patient enrolled in a clinical trial receives the cancer care prescribed by the trial at the hospital the researcher is at,” said Miriam A. Knoll, M.D., DABR, a radiation oncologist, and a Forbes healthcare contributor, “With the advent of expanded telehealth coverage across the U.S. due to COVID-19, researchers have an unprecedented opportunity to expand access to clinical trials.”

“The next major hurdle will be how quick the regulatory oversight of trials can be adapted to these new researcher-volunteer relationships, to ensure optimal care, safety, and research integrity,” Knoll added.

Follow me on Twitter. Check out my website.

I am an emergency physician on staff at Lenox Hill Hospital in New York City, where I have practiced for the past 15 years. I also serve as an adviser and editor to Medscape Emergency Medicine, an educational portal for physicians, and an affiliate of WebMD. My other time is spent with my private house call practice, DR 911, providing medical care to both travelers and residents in Manhattan. I have a keen interest in medical technology and public health education.

Source: https://forbes.com

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Dr. Cardinale B. Smith, Chief Quality Officer for Cancer, shares information cancer patients need to know regarding COVID-19.
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