Information

Regarding cancer cells and radio-frequency ablation


Are cancer cells destabilized if near a strong electromagnetic field over a long period of time? I read this technique of using radio-frequency ablation and heat shock to kill cancer cells. I don't know if this is viable but maybe a person could wear a device like a pacemaker right over the area of a tumor that emits strong E.M. pulses over say a month or a year. Could this destabilize the tumor ?


I think you're referring to radio frequency or microwave ablation. It works by heating the tissues up with electromagnetic radiation, just like you'd use to microwave food, but it's heating you instead. Healthy cells have better repair mechanisms and survive these treatments better. Cancer cells tend to have poor repair ability and can be killed more easily. I've heard of injecting metal nanoparticles which collect in the tumor due to the enhanced permeability and retention (EPR) effect. The nanoparticles respond to the microwaves much more powerfully than cells do and get hotter, burning the tumor from the inside out.


Ablation and Other Local Therapy for Kidney Cancer

Whenever possible, surgery is the main treatment for kidney cancer that can be removed. But for people who are too sick to have surgery or don't want to have surgery, other treatments can sometimes be used to destroy the kidney tumor. These approaches are usually considered for small (no larger than 4 cm or1½ inches) kidney cancers. There is much less data on how well these treatments work over time than there is for surgery, but they might be helpful for some people.


How ablation destroys cancer to prolong lives

Ablation, a minimally invasive tumour-destroying technique using focused radiation, is proving effective. So why is it not more widely known?

Illustration: Thomas Paterson

Illustration: Thomas Paterson

Last modified on Tue 7 Aug 2018 17.17 BST

S even years ago, when Heather Hall was informed by her oncologist that her kidney cancer had spread to the liver, she initially assumed she had just months to live. “I’d been on chemotherapy for a while, but they’d done a CT scan and found three new tumours,” she says. “But they then said that, because the tumours were relatively small, they could try to lengthen my prognosis by removing them with ablation.”

Hall underwent a course of microwave ablation, a minimally invasive treatment where specialists known as interventional radiologists use hollow needles to deliver intense, focused doses of radiation to heat each tumour until it is destroyed. While ablation technologies – they also commonly include radiofrequency ablation and cryoablation, which destroys tumours using intense cold – are not tackling the underlying cause of the disease, their impact can be enormous as they relieve pain and often prolong survival for many years, all at a low cost.

Studies based on data gathered over the past 10 years show an increasing number of cases of terminally ill patients who have lived for well over a decade after being treated with repeated ablations. Hall’s treatment was successful, but two years later, another two tumours had appeared in her liver, in different locations. Once again they were removed with microwave ablation. Over the past seven years, she has had four separate treatments. “There’s some pain in the immediate aftermath and I’ve felt quite ill for a week afterwards,” she says. “But it seems to have slowed down the progression of the disease, and I still have full function of my liver. With surgery, they would have had to cut a section of it away.”

While there have been many breakthroughs in cancer treatment heralded by the media in recent years – most notably the advances in immunotherapy and combination therapies – the considerable advances in ablation technology and resulting impact on patient survival, have consistently slipped beneath the radar. Not so long ago, the only option for patients such as Hall would have been full or partial removal of an organ, greatly reducing quality of life. But now, with increasingly powerful and efficient devices, interventional radiologists are able to destroy drug-resistant tumours in a growing number of diseases ranging from sarcomas to prostate cancer.

A US interventional radiologist using a radiofrequency ablation probe. Photograph: Robert J Polett/Design Pics/Getty Images/Perspectives

“When we were first using ablation we could only treat the simplest tumours – for example, the ones in the middle of the liver, away from the blood vessels, because the devices were less powerful and predictable,” says Matthew Callstrom, a professor of radiology at the Mayo Clinic, Minnesota. “But now, for example, with microwave ablation – which works by radiating an energy field out of the tip of the needle into the tumour, heating the water within the cancer cells until they are destroyed – you can tune the shape and diameter of that field to prescribe exactly how deep it goes into the tissue. This means we can safely go after more and more complex tumours.”

Major studies published in the past couple of years have confirmed the survival benefits. Last year, the results of the Clocc trial – a five-year study of 119 patients across 22 centres in Europe – showed that patients with colorectal cancer that had metastasised to the liver and who received ablation in addition to drug treatment lived significantly longer on average than those who received drugs alone.

“We work closely with oncologists to determine who is most likely to benefit from this and who isn’t,” says Andreas Adam, professor of interventional radiology at King’s College London. “But it can have huge benefits. For example, I had a patient with breast cancer that had spread to the liver. I ablated the tumours, destroyed them completely and every few months or years, another tumour would develop and I’d ablate again. She went on to live for almost 10 years.”

With ablation treatment allowing many patients to live for far longer, it has the potential to change the perspective on some diagnoses. Patients with metastatic disease who go on to live for another decade or more in relatively little discomfort, often come to view their condition as more like a chronic illness. “It’s a strange feeling because you are still living with an illness which is likely to be terminal sooner rather than later,” Hall says. “But it’s no longer in the forefront of your mind. I’ve even been able to return to work part-time.”

However, not every patient with metastatic disease is a suitable candidate for ablation. Interventional radiologists typically only use the technique on patients with 10 tumours or fewer. Any more, and the only viable options are treatments such as chemotherapy or immunotherapy. “You wouldn’t dream of ablating 50 tumours, because if someone has 50 visible tumours, it’s likely that they have another 100 developing that are not yet visible, and so they need drug treatment to treat the disseminated disease,” Adam says.

But in the coming years, ablation is likely to become available to more and more patients, allowing interventional radiologists to tackle cancers in ever more complex locations.

Among the most promising methods is a technology called irreversible electroporation, which involves electrodes being inserted through the skin into a tumour, allowing a high voltage to be generated across the cancer cell membranes, causing them to self-destruct. This is only offered by a small handful of specialised centres in the world, but is expected to become more widespread over the next decade. “It’s a non-thermal approach, so you can go into more sensitive areas such as the pancreas, or ablate tumours which are in the centre of the liver,” Callstrom says.

One day, interventional radiologists may even be able to ablate the most difficult cancers of all – deep brain tumours. The Israeli company Insightec is developing a device that can use focused ultrasound to destroy brain lesions. Because these tiny pulses of energy can be detected on MRI scanners, surgeons can calibrate them to the exact millimetre. “Each pulse generates a single ablation the size of a grain of rice,” Callstrom says. “Because it’s so tiny this allows you to basically tattoo the tumour and so avoid the boundary to any blood vessels or neurons.”

So for the many patients who have cancer that doesn’t respond to any form of drug treatment, there is now often a way of managing and prolonging their lives, which wasn’t possible before.

“The results of these studies have completely changed the thinking regarding some cancers,” Callstrom says. “With patients with metastatic sarcomas, for instance, people used to think that if the drugs failed, that was that. But now we can monitor them. And every time new tumours pop up, we ablate them.”

This article was amended on 7 August 2018 to make clear that microwave ablation treatment is conducted by interventional radiologists, rather than surgeons.


Radioiodine Ablation and Treatment for Papillary and Follicular Thyroid Cancer

Frequently Asked Questions

What is radioiodine ablation?
Radioiodine ablation is radiation therapy in which radioactive iodine is administered to destroy or ablate residual healthy thyroid tissue remaining after thyroidectomy.

What is radioiodine treatment?
Radioiodine treatment is radiation therapy in which radioactive iodine is administered to destroy suspected or known thyroid cancer by irradiating that tissue.

What is the difference between ablation and treatment?
Many physicians use &ldquoablation&rdquo and &ldquotreatment&rdquo interchangeably. However, other physicians use &ldquoablation&rdquo to mean the administration of radioiodine to eliminate any normal thyroid tissue remaining in the neck after initial surgery and &ldquotreatment&rdquo to mean the administration of radioiodine for the elimination of known or suspected metastatic disease in the neck or elsewhere.

Why do I have any thyroid tissue left after my surgery? I thought my surgeon took it all out.
Although your surgeon removed your thyroid gland, most surgeons leave behind small amounts of thyroid tissue to minimize any damage to the nerve that controls your voice box. This nerve is called the recurrent laryngeal nerve and runs behind your thyroid tissue. Your surgeon may also leave some thyroid tissue behind to make sure some of your parathyroid glands remain intact. These glands control your body&rsquos calcium levels and are usually located within or behind your thyroid tissue.

Why do I need an initial radioiodine ablation when my physician believes he has removed all of my thyroid carcinoma?
Most physicians will recommend that patients with thyroid carcinoma undergo at least one ablation radiation therapy with radioiodine. Research and fifty years of experience suggest that the combination of surgery, radioiodine ablation, and thyroid hormone replacement can reduce the chances of your thyroid carcinoma recurring. However, there are some situations in which your physicians may not recommend an initial ablation with radioiodine.

What are the criteria for not receiving an ablation with radioiodine?
Radioiodine ablation may not be recommended depending on several factors. These include the size of the original thyroid cancer, the number of sites involved, the lack of any involvement of the borders of the thyroid or adjacent tissues, and a lack of evidence that the cancer has spread&hellip

If radioiodine ablation is recommended, what are its goals?
Radioiodine ablation has four goals.


A Closer Look at Killing Cancer Cells with Heat

In a study conducted on mice engineered to contain human breast cancer cells examined the use of nanoprobes targeted to tumor cells as a method to direct heat to a tumor. Anti-tumor antibodies were linked to very small spheres containing iron oxide pellets. Injection of these 'bioprobes' led to binding of the particles on the surface of the tumor cells.

The chemical nature of the iron in the complexes causes them to rotate rapidly when an alternating magnetic frequency (AMF) is applied in the vicinity of the tumor. The spinning motion generates heat that quickly raises the temperature of tumor cells above 46°C/115°F, causing death of the tumor cells. For this technique to be useful, it is critical that the applied frequency is not harmful to surrounding tissues.

In the mouse experiments the applied treatment significantly decreased tumor growth. Importantly, the affect was proportional to the amount of heat delivered via AMF. The most effective, non-toxic treatment corresponded to low amplitude AMF with a prolonged delivery time. Since this study was performed, new nanoparticles have been developed that respond better to AMF potentially reducing the amount of AMF necessary to treat tumors. 12


Radiofrequency Ablation Recovery

More Injection information:

Immediately after the RFA, the patient is shifted to a recovery room for 15 minutes to an hour (if sedation was used) where his/her vital signs are continuously monitored. Depending on the area treated, a superficial burning pain with hypersensitivity, similar to a sunburn feeling may be experienced. Sometimes a slight numbness of the skin over the same area may also be experienced.

A few precautions and tips for the first day or two after RFA are:

    An ice pack may be used intermittently to numb the pain and reduce swelling on the injection site. Ice packs must be used for 15 to 20 minutes at a time with a break of at least two hours in between to avoid skin injury. Heat packs are usually not advised on the injection site after RFA.

Pain relief after RFA is typically experienced 1 to 3 weeks after the injection. 1 It is advised to rest for several days before returning to normal activities. Patients may engage in regular activities but should let pain levels be their guide for the first few days. Since many patients have been de-conditioned over many months or years as a result of their pain, physicians might prescribe a guided physical therapy regimen to allow them to increase their strength and activity tolerance in a safe manner.

The radiofrequency ablation treatment is a relatively safe and low-risk procedure. However, some people may experience certain side effects and/or complications from this treatment. It is advised to discuss the potential risk of developing any adverse reactions or side effects of RFA with a doctor prior to this treatment.


Risks of Radiofrequency Ablation in the Facet and Sacroiliac Joints

Although rare, serious risks may occur during or after the radiofrequency ablation procedure. These risks may be associated with the RFA procedure or the sedation provided prior to the treatment.

  • Radiofrequency ablation procedure-related risks. A few examples of risks associated with the RFA procedure are:
    • Hyperesthesia—an excessive, abnormal sensitivity over the skin of the injection site
    • Superficial skin infections over the injection site
    • Damage to surrounding blood vessels and nerves during needle insertion resulting in excessive bleeding and/or irreversible neurologic damage causing long-term numbness and tingling
    • Heat damage to structures adjacent to the target nerve
    • Allergic reaction to the anesthetic used to numb the skin

    As with any injection procedure, treating a facet or sacroiliac joint with radiofrequency ablation must involve careful consideration of benefits versus risks. It is advisable to discuss and understand the potential risks of radiofrequency ablation with a doctor before opting for this treatment method.


    Ultrasound can selectively kill cancer cells

    A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.

    Ultrasound waves—sound waves with frequencies higher than humans can hear—have been used as a cancer treatment before, albeit in a broad-brush approach: high-intensity bursts of ultrasound can heat up tissue, killing cancer and normal cells in a target area. Now, scientists and engineers are exploring the use of low-intensity pulsed ultrasound (LIPUS) in an effort to create a more selective treatment.

    A study describing the effectiveness of the new approach in cell models was published in Applied Physics Letters on January 7. The researchers behind the work caution that it is still preliminary—it still has not been tested in a live animal let alone in a human, and there remain several key challenges to address—but the results so far are promising.

    The research began five years ago when Caltech's Michael Ortiz, Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering, found himself pondering whether the physical differences between cancer cells and healthy cells—things like size, cell-wall thickness, and size of the organelles within them—might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death. "I have my moments of inspiration," Ortiz says wryly.

    And so Ortiz built a mathematical model to see how cells would react to different frequencies and pulses of sound waves. Together with then-graduate student Stefanie Heyden (Ph.D. '14), who is now at ETH Zurich, Ortiz published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the so-called resonant growth rates of cancerous and healthy cells. That gap meant that a carefully tuned sound wave could, in theory, cause the cell membranes of cancerous cells to vibrate to the point that they ruptured while leaving healthy cells unharmed. Ortiz dubbed the process "oncotripsy" from the Greek oncos (for tumor) and tripsy (for breaking).

    Excited by the results, Ortiz applied for and received funding to continue the research through Caltech's Rothenberg Innovation Initiative (RI2), an endowed program launched with funding from the late Caltech trustee Jim Rothenberg and his wife, Anne Rothenberg, to support research projects with high commercial potential. Ortiz also recruited doctoral student Erika F. Schibber (MS '16, Ph.D. '19), whose research involved the study of vibrations on satellites, to work on the project.

    (L to R) Jian Ye and Peter P. Lee of City of Hope. Credit: Eliza Barragan, Ph.D/City of Hope

    Ortiz then invited Mory Gharib (Ph.D. '83), Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering, to attend a meeting of his research group. Gharib, a prolific inventor, has shepherded numerous research developments from the lab to the market. For example, a prosthetic polymer heart valve he designed was implanted in a human for the first time in July, and he also created a smartphone app for monitoring heart health an eye implant he designed to prevent glaucoma-related blindness has been implanted in more than 500,000 patients since 2012.

    Intrigued by the project, Gharib pitched the idea to one of his advisees, David Mittelstein. As a graduate student in the MD-Ph.D. Program that is run by Caltech and the Keck School of Medicine of USC, Mittelstein was already working on the aforementioned prosthetic polymer valve with Gharib. But, in the oncotripsy project, he saw the opportunity to participate in research from its theoretical conception to its proof of concept.

    "Mory and Michael really empowered me to take the lead on this project, designing and building ways to test Michael's theory in the real world," says Mittelstein, who will defend his dissertation at Caltech in mid-February before heading back to USC to complete his medical degree.

    Mittelstein assembled a team to tackle the project, recruiting ultrasound expert Mikhail Shapiro, a professor of chemical engineering at Caltech. Shapiro recently devised a system that allows ultrasound to reveal gene expression in the body and has designed bacteria that reflect sound waves so that they can be tracked through the body via ultrasound.

    In the Shapiro Lab, Mittelstein began subjecting hepatocellular carcinoma, a common liver cancer, to various frequencies and pulses of ultrasound, and measuring the results.

    Meanwhile, Caltech trustee Eduardo A. Repetto (Ph.D. '98) introduced Ortiz to Peter P. Lee, chair of the Department of Immuno-Oncology at City of Hope, a cancer and research center in Duarte. As a physician-scientist, Lee is passionate about getting new treatments to patients. "When I heard about it, I thought it was intriguing and that, if it worked, could be a revolutionary way of treating cancer," Lee says. Other City of Hope researchers, including postdoc Jian Ye and oncologist M. Houman Fekrazad, also joined the project.

    Erika F. Schibber. Credit: California Institute of Technology

    With additional funding from Amgen and the Caltech–City of Hope Biomedical Research Initiative, Mittelstein built a pilot instrument at City of Hope to mirror the one at Caltech, enabling his colleagues there to test samples without having to transport them back and forth between Duarte and Pasadena. Over time, Lee and his team at City of Hope expanded the repertoire of cancer cell lines being tested, drawing samples from humans and mice to include colon and breast cancer. They also tested a variety of healthy human cells, including immune cells, to check how the treatment affects these cells.

    The hope, Lee says, is that ultrasound will kill cancer cells in a specific way that will also engage the immune system and arouse it to attack any cancer cells remaining after the treatment.

    "Cancer cells are quite heterogeneous, even within a single tumor," Lee explains, "so it would be almost impossible to find a range of settings for the ultrasound that could kill every single cancer cell. This would leave surviving cells that could cause a tumor to regrow."

    More than 50 million cells die in your body every day. Most of those deaths occur when cells simply grow old and die naturally through a process called apoptosis. Sometimes, however, cells die as the result of infection or injury. A healthy immune system can tell the difference between apoptosis and injury, ignoring the former while rushing to the site of the latter to attack any invading pathogens.

    If ultrasound can be used to cause cell death in a way that the body's immune system recognizes as injury, instead of as apoptosis, this could lead to the site of the tumor being flooded with white blood cells that could attack remaining cancer cells.

    So far, all of the testing has been done in cell cultures in petri dishes, but the Caltech–City of Hope team plans to expand the testing to solid tumors and, eventually, living animals. Back in the Ortiz lab, Schibber used the results of the lab tests to refine the mathematical models, digging deeper to make sure that the researchers understand exactly how the sound waves are killing the cancer cells.

    Credit: David Mittlestein

    "We're learning more about how different cancer cells vibrate and sustain damage over many cycles of insonation, a process that we term 'cell fatigue,'" says Schibber, who defended her thesis on the topic in 2019 and is now a postdoctoral researcher in aerospace at Caltech. In Shapiro's lab, Mittelstein found that the formation of tiny bubbles (a process called cavitation) that could also cause some of the damage. Together, these developments are providing a conceptual basis for understanding the trends observed in the experiments.

    Mittelstein hopes to stay involved in the project after his dissertation defense but, above all else, is eager to see the research continue and to one day lead to an effective cancer treatment.

    "This is an exciting proof-of-concept for a new kind of cancer therapy that doesn't require the cancer to have unique molecular markers or to be located separately from healthy cells to be targeted. Instead we may be able to target cancer cells based on their unique physical properties," he says.

    The Applied Physics Letters paper is titled "Selective ablation of cancer cells with low intensity pulsed ultrasound." Co-authors include Caltech undergraduate student Ankita Roychoudhury and Leyre Troyas Martinez, an undergraduate student working on a Caltech Summer Undergraduate Research Fellowship (SURF).


    TUMOR FACTORS

    Tumor size and location are the two most important factors that govern whether RCCs can be treated successfully. Because heat decreases exponentially from the RF source, large tumors (>5 cm) pose a significant challenge for RF ablation, especially because a 0.5- to 1.0-cm “ablation margin” surrounding the tumor is also preferred (6) . In general, RCC tumors that are ≤3 cm in diameter are ideal for ablation, with near-perfect success rates on postprocedural imaging (7, 8, 9, 10, 11, 12, 13) . Most tumors smaller than 3 cm can also be treated successfully in a single session (7, 8, 9, 10, 11, 12, 13) . Tumors between 3.0 and 3.5 cm in diameter can also be treated successfully with confidence, but multiple ablations and sessions may be required (7, 8, 9, 10, 11, 12, 13) .

    The location of the tumor (exophytic, parenchyma, or central) also influences ablation results. Even larger exophytic tumors are almost always treated successfully, with ≥70% requiring only a single RF session (7, 8, 9, 10, 11, 12, 13) . Parenchymal tumors may be more difficult to treat, but centrally located tumors represent the largest obstacle for successful ablation. The presence of a central component in a tumor larger than 3 cm is reported to be a significant predictor of failure (7) .


    Radio frequency ablation

    Hi, I have adrenal cancer with mets to the liver. I am stage 4 and not actively undergoing treatment - however for the last 12 months everything has remained stable, with even small reductions. I have asked to be referred to liver specialist to see if rfa is possible. My oncologist has done this, but seemed quite reluctant, I think a case of why upset the apple cart if things are running smoothly at the moment? I have heard back that rfa is technically possible with what I have but awaiting final decision from radiologist.

    Just wondered if anyone has any stories to share regarding this treatment. I guess I am worried about stirring things up - but also feel don't want to leave things and then find tumours too big to treat.

    Re: radio frequency ablation

    I am not familiar with adrenal cancer so am not able to comment on your oncologists thoughts but would like to say something regarding liver mets. I have stage 4 BC with mets to the liver and was given a prognosis of 6-9months in April. My oncologist insisted that because BC is not a localised disease there was no point in considering surgery, even though the disease was not active anywhere else in my body. I sought a second opinion from The Christie Hospital in Manchester because I had read that the oncologist there was referring BC patients to a liver specialist. To cut a very long story short - I met their criteria - and had a liver resection at the end of June. My liver function is now normal again and as far as I am aware at this present time I have lengthened my prognosis from months to maybe a few years. My local oncologist still remains negative but has a completely different attitude to the oncologist/surgeon I met in Manchester. What I am trying to say is stick with your gut feeling and follow-up on your thoughts regarding surgery/ablation whilst you are well and the tumours have shrunk and are stable. I was told that if I had thought about it all for much longer, I would have been inoperable. Sometimes you have to fight a little for what you feel is right for you - it shouldnt be that way - but sadly it is and I am just grateful that I had the courage to act on my intuition. I hope you see the liver specialist and he is able to help you - wishing you the best of luck and well done for 'rocking the boat' and asking for another opinion. Let me know how it goes. Max x