Friday, November 26, 2021

Proton therapy: a success story that started 25 years ago

At the Swiss Paul Scherrer Institute's Center for Proton Therapy, they treat cancer patients and do research for optimized radiotherapy.

Text: Paul Scherrer Institute/Brigitte Osterath

On 25 November 1996, the Center for Proton Therapy at the Paul Scherrer Institute treated a cancer patient using the spot-scanning technique for the very first time – a world premiere. This technique developed at PSI scans and irradiates deep-seated tumors with a pencil-thin beam of charged particles, killing cancer cells with extreme precision while preserving the surrounding healthy tissue. Meanwhile, this technique has become a standard procedure worldwide and since 1996 has been used to treat around 2000 cancer patients at PSI alone – over a third of them children and young people. The fact that the success story started at PSI was more than just a coincidence.

It was Monday, and the team was gathered in the control room at the Center for Proton Therapy. "We were huddled together, peering anxiously at the monitor relaying images from the treatment room," recalls Martin Grossmann, a physicist with the Center for Proton Therapy (CPT) at PSI. Back in the 1990s he was part of a team of 15 researchers led by Hans Blattmann, Eros Pedroni and Gudrun Goitein developing a new technology for treating cancer patients: spot scanning, also known as pencil beam scanning.

The moment of truth came on 25 November 1996: a human patient lay waiting in the treatment room. The 62-year old man from the Canton of Lucerne had malignant skin cancer that had already formed metastases in his brain. The purpose of the intervention was to irradiate these rogue metastases using the new technique.

Despite meticulous preparations, the team was nervous. "You can treat as many plastic dolls or models as much as you want, but when you have a live patient lying there, it’s a totally different experience," says the medical physicist Tony Lomax, one of the development team. That Monday he helped to place the patient in the exact position for the proton beams to precisely target the area of the body to be irradiated. The tolerance was a question of millimeters: "A proton beam is like an extremely sharp tool," Martin Grossmann stresses. "There is no room for error."

A huge success
The team of specialists ensured that the technology functioned smoothly and eventually everyone was able to breathe a sigh of relief: the treatment had gone exactly as planned – just as Martin Grossmann and Tony Lomax had expected. "We were all firmly convinced we had mastered the technology. We made a huge effort to ensure that everything was absolutely safe for the patient," Grossmann notes.

In the following year, CPT moved on to successfully treat several other cancer patients. The medical world was initially skeptical – the technology seemed too unmanageable at the time. During the ten years up to 2008, the Paul Scherrer Institute was the only facility in the world to use this technique. Since then, spot scanning has become established worldwide and now ranks as standard procedure for proton therapy.

Eradicating the tumor
"Proton therapy has completely revolutionized the battle against cancer," says Damien Weber, senior clinician and head of CPT. In proton therapy, a proton beam – a concentrated beam of rapidly moving, charged particles – kills cancer cells by destroying their DNA. Conventional radiation therapy works on the same principle, but uses X-rays rather than protons to destroy the malignant cells.

Protons have a big advantage over more energy-intense radiation, however, Weber goes on to explain. They can be precisely targeted to the specific area of the body, where they unleash their destructive effect. "Undesirable side-effects caused by radiation are therefore much less common, which makes the method especially suitable for children, but also for tumors in particularly sensitive or inaccessible areas of the body." Tumors in the region of the head, neck or spine are typical candidates for treatment.

For a long time the medical profession favored the scattering technique for proton therapy. With this method, the proton beam is spread out and, using an individually tailored metal aperture plate, filtered to match its shape to the size and contour of the tumor. Today this is still the preferred method for treating eye tumors. Not so for deeper-seated tumors.

"We already knew the spot scanning technique would offer a lot of advantages here," says Tony Lomax. The malignant tissue is scanned with the proton beam – "a bit like sketching its outline with a pencil," Lomax explains. Or rather rubbing it out with an eraser. The exact position of the tumor is determined beforehand with the help of imaging techniques such a CT or MRI scan, and the proton beam programmed so that precisely the right amount of charged particles is targeted at the areas to be treated.

PSI’s location advantage
Looking behind the scenes at the Center for Proton Therapy, it soon becomes clear why this technology could only have been developed at PSI rather than in a hospital, for example. The radiation unit (called a gantry) itself is the size of a large truck, and even bigger and more complex equipment is needed to generate the proton beams and deliver them to the gantry.

"Here we are actually working with applied accelerator physics," says Martin Grossmann. “We need measurement devices that control the path of the beam. We need ultrafast electronics to control the magnets used. And above all we need highly qualified people with the skills to build such a machine. These can’t be found in a hospital.”

The concept of spot scanning first arose in Japan. "But our team at CPT was brave enough to say at the time: let’s actually try using that technique," Grossmann. The resulting success story has been a blessing for cancer patients over the past 25 years – and beyond.

Click images to expand!
Gantry 1 at PSI 
World’s first proton therapy facility to employ the spot scanning method
(Photo: Paul Scherrer Institute)

Gantry 3, the newest treatment station at PSI
(Photo: Paul Scherrer Institute)

Gantry 3 (close-up of  the treatment station)
(Photo: Scanderbeg Sauer Photography)

How pencil beam scanning conquered the world
(Graphic: Paul Scherrer Institute/Mahir Dzambegovic)

About PSI
The Paul Scherrer Institute PSI develops, builds and operates large, complex research facilities and makes them available to the national and international research community. The institute's own key research priorities are in the fields of matter and materials, energy and environment and human health. PSI is committed to the training of future generations. Therefore about one quarter of our staff are post-docs, post-graduates or apprentices. Altogether PSI employs 2100 people, thus being the largest research institute in Switzerland. The annual budget amounts to approximately CHF 400 million. PSI is part of the ETH Domain, with the other members being the two Swiss Federal Institutes of Technology, ETH Zurich and EPFL Lausanne, as well as Eawag (Swiss Federal Institute of Aquatic Science and Technology), Empa (Swiss Federal Laboratories for Materials Science and Technology) and WSL (Swiss Federal Institute for Forest, Snow and Landscape Research). 

Wednesday, April 14, 2021

New hydrogel can repair tears in human tissue

EPFL scientists have developed an injectable gel that can attach to various kinds of soft internal tissues and repair tears resulting from an accident or trauma.

Our soft tissues can be torn during a ski accident, a car accident or an accident in the home, for example. And surgeons can have a hard time binding the tissue back together, as stitches often do more harm than good. According to Dominique Pioletti, the head of the Laboratory of Biomechanical Orthopedics at EPFL’s School of Engineering, such surgeries don’t always produce optimal outcomes because the repaired tissue usually doesn’t heal properly. This tends to be the case for tears in cartilage and the cornea, for instance. 

Researchers around the world have been trying for years to develop an adhesive for soft tissue that can withstand the natural stresses and strains within the human body. Pioletti’s group has now come up with a novel family of injectable biomaterials that can bind to various forms of soft tissue. Their bioadhesives, in the form of a gel, can be used in a variety of injury-treatment applications. Their research has just been published in Macromolecular Rapid Communications.

Monday, January 18, 2021

Snap-freezing reveals a truer structure of brain connections

Scientists at EPFL (near Lausanne, Switzerland) have used a snap-freezing method to reveal the true structure of the connections that join neurons together in the adult brain.

Most synaptic connections in the adult brain are situated on dendritic spines; small, micrometer-long, protrusions extending from the neurons’ surface. The spines’ exact size and shape determine how well signals are passed from one neuron to another.

These details become very important when neuroscientists want to model brain circuits or understand how information is transmitted between neurons across the brain’s neuronal circuits. However, their small size and the difficulties in preserving brain tissue in its natural state have always left the question open as to what the true structure of the dendritic spine is.

Scientists from EPFL’s School of Life Sciences have now used a snap-freezing method of liquid nitrogen jets, combined with very high pressures, to instantaneously preserve small pieces of brain tissue. The researchers, from the labs of Graham Knott and Carl Petersen, then used high-resolution, 3D imaging with electron microscopes to reveal how the true dendritic spine structure was similar to that shown in previous studies, except for one important aspect: The instant freezing method showed dendritic spines with significantly thinner necks.

This finding validates a considerable body of theoretical and functional data going back many years, which shows that dendritic spines are chemical, as well as electrical, compartments isolated from the rest of the neuron by a thin and high-resistance neck. Variations in the neck diameter have an important impact on how a synapse influences the rest of the neuron.

“As well as revealing the true shape of these important brain structures, this work highlights the usefulness of rapid freezing methods and electron microscopy for obtaining a more detailed view of the architecture of cells and tissues,” says Graham Knott.

Friday, May 22, 2020

The coronavirus’ rampage through the body

SARS-CoV-2, the virus that causes COVID-19, can severely damage lungs, but in serious cases it doesn’t stop there—clinicians have observed body-wide damage due to the coronavirus. As researchers begin to better understand the pathology of the disease, new treatments can be deployed to help save lives.

Tuesday, August 27, 2019

Revolutionising the CRISPR method

14.08.2019 | News

Researchers at ETH Zurich have refined the famous CRISPR-Cas method. Now, for the very first time, it is possible to modify dozens, if not hundreds, of genes in a cell simultaneously.
Genes and proteins in cells interact in many different ways. Each dot represents a gene; the lines are their interactions. For the first time, the new method uses biotechnology to influence entire gene networks in one single step. (Visualizations: ETH Zurich / Carlo Cosimo Campa)

Everyone’s talking about CRISPR-Cas. This biotechnological method offers a relatively quick and easy way to manipulate single genes in cells, meaning they can be precisely deleted, replaced or modified. Furthermore, in recent years, researchers have also been using technologies based on CRISPR-Cas to systematically increase or decrease the activity of individual genes. The corresponding methods have become the worldwide standard within a very short time, both in basic biological research and in applied fields such as plant breeding.

Smart interaction between proteins

19.08.2019 | News

Very little was known till now about DNA repair by homologous recombination, which is fundamental for human health. Now an ETH research group has for the first time isolated and studied all the key proteins involved in this process, laying the foundation for investigating many diseases.

Which proteins are essential for cell division? The biochemist Philipp Wild (left) and his colleagues Ilaria Piazza and Christian Dörig examine the results from the mass spectrometer. (Photograph: ETH Zurich / Adrian Henggeler)

Within our body, the process of cell division is constantly creating new cells to replace old or damaged ones. The genetic information is also duplicated and passed on to the new cells. Complex interaction of many different proteins ensures a smooth process. This is because these proteins immediately repair any errors that creep in during DNA duplication. However, the same protein machinery also performs another function: in germ cells that divide to from gametes – egg cells and sperm – it is responsible for mixing the genetic information of the original maternal and paternal side during cell division. The same mechanism therefore has to resolve two conflicting problems: in normal cell division, called mitosis, it ensures genetic preservation, while in the cell division to produce gametes, or meiosis, it ensures genetic diversity. 

Sunday, July 21, 2019

Chinese Scientists Say They’ve Found a Safer Alternative to CRISPR

Researchers from China’s Peking University have developed a new gene-editing technology —  and they think it shows promise as a CRISPR alternative for fighting human diseases.

According to a paper published on Monday in the journal Nature Biotechnology, this new technology, LEAPER, which stands for “leveraging endogenous ADAR for programmable editing of RNA,” works similarly to CRISPR-Cas13, targeting RNA molecules as opposed to DNA like the well-known CRISPR-Cas9.

But while CRISPR-Cas13 relies on both a guide RNA and the Cas13 enzyme to make its edits to RNA, the LEAPER system needs just one component known as an arRNA.

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