radiotherapy centre - Gamma Knife

Why Does Stereotactic Radiosurgery Primarily Treat The Brain?

If someone is prescribed a treatment plan that consists of stereotactic radiosurgery, they can enter the radiotherapy centre confident that they are being treated by one of the most effective, accurate and oldest radiosurgical treatments available.

The principle of stereotactic radiosurgery, as pioneered by Lars Leksell’s Gamma Knife in the late 1940s, is that multiple small beams of radiation that converge on a particular point can have a much greater effect without damaging the surrounding tissue and minimising overall exposure.

This treatment, whilst adjusted and refined over the past half-century, has been consistently used and effective even before there were effective ways to map treatments using MRI and CT scans. 

This naturally leads to a big question; if the Gamma Knife is so effective, why has the stereotactic principle not been widely applied to other forms of radiotherapy treatment outside of the brain and spine?

The answer is complex and one that medical researchers are doing their utmost to try and change.

The Sea Of Life

The almost tautological answer for why the Gamma Knife specifically is not used to treat other parts of the body is that it was only designed for the brain and relies on a very specific set of medical apparatus that has only been used in the head and cannot be used anywhere else.

Part of this is that the frame system that keeps the head in place for a Gamma Knife treatment is based on the Horsley-Clarke frame initially used to create an atlas of various animal brains before being applied to the human head over the course of four decades.

This tool, albeit heavily modified by Mr Leksell and others, is as fundamental and vital to the success of Gamma Knife as the source of radiation itself. This is why the treatment was tested and used before the widespread availability of three-dimensional medical imaging.

It meant that thanks to some rather complex mapping, a series of skull X-rays could be triangulated to position the stereotactic beams in order to treat patients effectively. Once CT scans and MRIs came in, this only made the process even more accurate.

A lot of this can be credited to Mr Leksell’s work himself, who famously said there was no tool too accurate for use on the brain, but whilst an accurate approach is mandatory for obvious reasons, it is also, relatively speaking, easier to achieve.

The skull helps keep everything in place and there is less variation, relatively speaking, with tumour and lesion positions, allowing for consistency and greater accuracy. 

Pair this with the stereotactic frame keeping the head from moving during treatments and it is perhaps understandable how the Gamma Knife started as a highly effective targeted treatment and has only gotten more accurate with time.

By contrast, the rest of the body is far less consistent and mobile. Organs are constantly moving in the body, not just in terms of pulsing, contracting and relaxing, but also shifting positions based on the position of the body.

Organs change shape depending on their use, muscles such as the diaphragm affect their shape, and even posture and the way people lie down can alter the shape, size and position of organs, particularly those in the abdomen.

This is a major problem when planning radiotherapy because the act of breathing creates a moving target that affects treatments, often requiring wider beams and more collateral damage to healthy tissue to ensure that all cancerous cells are destroyed.

There are ways to mitigate some of these issues, such as through the use of frames and casts to at least keep a body part securely in place during treatment, but there are a lot more variations than there are for the brain, requiring not only different treatments but a different treatment philosophy.

There have been attempts to change this over the years, primarily through increasing the speed at which medical images are produced and interpreted, and this could lead to Gamma Knife-like treatments becoming possible with that level of accuracy in the future.

In order for this to be accomplished, however, there needs to be a close to real-time form of three-dimensional imaging of body parts that can be used to plan treatments the same day they are executed, as unlike the brain there is the potential for much greater organ movement.

This concept, known broadly as real-time adaptive radiotherapy, is one that is at least conceptually possible, but it requires a widely-used real-time imaging system that, as of 2024 at least, has not been widely used.

doctors prepares the patient for the procedure on the Gamma Knife

Who Was The First Person To Be Treated With The Gamma Knife?

Precision is key when it comes to any treatment related to the brain, and part of the reason why people are often prescribed a trip to a radiotherapy centre for stereotactic radiosurgery is precisely because of this precision.

Lars Leksell once noted that no tool can be too refined for the human brain, and this became the motivation for him, alongside a desire for bloodless neurosurgery, to develop what became the Gamma Knife, the first-ever stereotactic radiosurgery technique and still one of the most widely used in the world.

It is a critical piece of equipment that has helped to ease the suffering of countless people and help treat many different types of brain cancer. However, who was the first to receive treatment using this pioneering technique? 

It depends somewhat on the definition of stereotactic radiosurgery.

Stereotactic Surgery With Radiation

In 1947, Mr Leksell started to develop the stereotactic frame, the critical part of the Gamma Knife technique.

However, the infamous perfectionist was initially wary about exactly what type of surgical system he would use. Radiotherapy was widely used by the end of the Second World War to treat other forms of cancer, but in the absence of MRI or CT scanners, the techniques involved were far less precise.

Mr Leksell would never have allowed that regardless, but he also was acutely aware that the distribution technologies for radiation therapy that existed at the time were perhaps not precise enough for the systems he had devised, meaning that the first radiation surgery using the stereotactic technique was not technically radiosurgery.

In 1948, a patient came to see him with a craniopharyngioma, a pea-sized benign tumour that does not spread and grows incredibly slowly. Because it does not move, it was the perfect test for the polar stereotactic method Mr Leksell used.

However, instead of using narrow beams of radiation, as would be standard with the Gamma Knife, the treatment instead consisted of phosphorus, which punctured the cyst and destroyed it from the inside.

His solution was a diagrammatic coordinate system that consisted of a complex series of concentric circles that compensated for X-ray divergence by calculating the difference between the tube and the developing material.

In a career filled with remarkable innovation and success, this system was one of Lars Leksell’s few failures. First of all, it relied on pneumoencephalography, itself a somewhat archaic imaging method that was not universally used, and the unintuitive coordinates system confused a lot of surgeons, making it difficult to actually apply to neurosurgery.

Regardless, the success of this procedure inspired him to look for an accurate alternative in the field of radiotherapy. It would not take him long to find success.

X-Ray Stereotactic Radiosurgery

With the frame system already a proven success, the next step was to find an alternative treatment system to probes and radioactive injections, both of which required invasive surgery to achieve.

In 1951, Mr Leksell figured out the centre-of-arc radiation principle that proved that multiple small doses of radiation could be focused onto a central point and be highly accurate without damaging healthy tissue surrounding it.

Whilst the principle was effective, exactly which form of radiation could be used at the time was still a point of contention. Gamma rays and ultrasound were considered, but ultimately X-rays were the first radiation outlet to be used.

After some initial experimentation, the first two cases that were successfully treated were both for trigeminal neuralgia, an extremely painful nerve disorder known as the “suicide disease” due to its reputation as being one of the most painful conditions in medicine.

A common treatment for the condition is to intentionally damage the trigeminal nerve that causes the pain, usually undertaken by using a probe or needle to damage the point where the nerve splits into three.

Using the stereotactic frame with a 280-kilovolt X-ray tube, the two people he treated were free of pain for at least two decades, highlighting the potential for the technique, even if an alternative source of radiation was required.

Initially, he tried to use a synchrocyclotron to use proton beams to destroy lesions in the brain, but the system proved to be too complicated and soon abandoned the idea after its introduction in 1958.

By 1960, however, Mr Leksell had found out about cobalt-60, a form of gamma radiation that was more accessible for clinical use and could be integrated into the stereotactic system he already had in place.

This ultimately enabled him to realise his dream of creating a bloodless neurosurgery that could be used as an alternative to conventional neurosurgery in a wide variety of cases in spite of initial scepticism.

Radiotherapy Centre - doctor touches virtual kidneys

Can Personalised Radiotherapy Defeat Bladder Cancer?

Radiotherapy has been in use since around the turn of the 20th century, making it a very well-established area of medicine. Nevertheless, like any other form of medicine, nothing has stood still; as well as establishing more kinds of cancer (and other ailments) that radiotherapy can treat, its use has been refined and new technology developed.

Alongside that has emerged a wealth of research that goes on to this day, highlighting where and when the treatment is most effective, as well as highlighting problems such as temporary and lasting side effects.

What all this has achieved is to enable every radiotherapy centre that exists today to offer better treatment and a wider range of options to patients than was ever the case in the past.

Personalisation Research Shows Promise

Among the areas of research in recent years is the use of more personalised medicine. This approach rejects the assumption that there is a standard one-size-fits-all approach to treatment and operates on the theory that each patient has requirements that are best met by tweaking the treatment according to a specific combination of characteristics.

New research on personalised care has produced some interesting conclusions in the area of muscle-invasive bladder cancer, suggesting this may be a more effective approach to delivering radiotherapy to sufferers.

A study by the Institute of Cancer Research in London, co-funded by bodies in Australia and New Zealand and published in the journal European Urology, has indicated that the use of personalised radiotherapy can be particularly effective for patients with this form of cancer.

A particular difference about this approach is that the amount of radiation delivered to any given part of the body will vary in each session, reducing side effects while in no way diminishing the impact the radiation has on the cancer.

Explaining the significance of this approach, Professor Robert Huddart, one of the leaders of the research, said it “has allowed us to deliver effective treatment safely and allowed us to use a high dose which promises to cure more patients, with relatively few long-term side effects”.

He added that further research would find out more about the effectiveness of this approach in treating cancer in comparison with other methods.

How The Research Was Carried Out

The research split 345 bladder cancer patients into three groups, one of which was treated in a standard way, while the other two received adapted treatment plans, with each patient getting a different treatment each time. One of the latter two groups saw patients receiving higher radiation doses in each session.

Group Leader at the Institute for Cancer Research, London Professor Emma Hall, said: “As medical technologies continue to improve, it means that we can investigate delivering more complicated and personalised forms of radiotherapy to treat certain cancers.”

Such treatments may be of benefit to more than just bladder cancer patients, but help sufferers from many other forms of cancer that are treated with radiotherapy, using modified approaches to suit the circumstances of each patient.

Other Personalisation Research

Indeed, investigating ways to develop the use of personalisation across a range of cancer treatments (not just radiotherapy) using the power of new technologies like artificial intelligence (AI) is central to a new project headed up by the Universita Cattolica in Rome.

Known as the Horizon IHI product, the stated aim is that of developing “Thera4Care – Theranostics Ecosystem for Personalised Care,” (theranostics being the name given to the deployment of next-generation personalised therapies).

With funding of €28 million and 29 partners in industry and academia, this may go a long way towards further advancing the personalisation of radiotherapy for cancer treatments.

This does not necessarily mean that if you come to our radiotherapy centre you will be receiving a personalised treatment. Part of the reason for that is that you may have a cancer where there is already a clear treatment path to take that would not be enhanced by attempting to personalise it.

Alternatively, it may be your condition is in an area where there is insufficient research to date to indicate clearly what benefits (if any) would be gained by taking a novel, non-standard approach to treatment. It is by no means certain at this time that all cancer treatment will be personalised in the future, even after much research has been done.

What you can be assured of is that the radiotherapy treatment you will receive will be the best available, based on the latest research and knowledge, in order to obtain the most optimal outcome for somebody in your condition, whether that includes an element of personalisation or not.

Radiotherapy, like other cancer treatments, will continue to change and advance, but we can provide you with the best treatment there is today.

modern radiotherapy techniques - first linear accelerator technology IMRT

Exploring the Delayed Use of Radiotherapy in Treating Cancer

One of the most comforting aspects of entering a radiotherapy centre is that whilst many of the therapies and technologies being used are new, the underlying concept behind the treatment has been established for over a century.

This means that the properties of radiation as a therapeutic treatment are very well-established, anyone who is recommended a course of radiotherapy will be made completely aware of what to expect and treatments are designed to maximise the benefits whilst minimising harm.

The Gamma Knife is one of the greatest examples of this, as its use of stereotactic beams precisely located at specific points means that it can destroy harmful lesions, tumours and growths on the brain without incision and with as little harm to healthy tissue as possible.

Radiotherapy has technically existed since 1896, but the Gamma Knife and the modern era of radiotherapy took over half a century to emerge, and even half a century after that there are still constant evolutions and developments in modern radiotherapy techniques to make it more effective and able to treat even more patients.

Part of the reason it took so long was due to technological evolution; modern radiotherapy is very dependent on computers, which only existed theoretically in the 19th century through concepts such as the Analytical Engine.

By the 1940s and 1950s, when radiotherapy emerged in a more modern, recognisable form, computers existed and were developing at such an exponential rate that they could be used to safely control radiation dosages in a way that was at the time unprecedented.

However, there was not only a technological shift but also a cultural one, one that required people to look at radiation for what it could do for us and not be swayed by overly optimistic views of a radioactive utopia.

The Fall Of Radiomania

The discovery of X-rays by Wilhelm Rontgen, and later the radium experiments by Marie and Pierre Curie meant that the early 20th century was dominated by a belief that radioactivity would be a major positive part of everyone’s lives.

Water dispensers were “infused” with radioactivity based on somewhat dubious claims about the connection between the benefits of health springs and the presence of radioactivity in said wells.

This spread to intentionally radioactive cosmetics, toothpastes, cigarette packaging and revitalising tonics were all advertised using extremely twisted and manipulated evidence.

Radiation was an effective therapy not because it encouraged healing but because it destroyed particularly dangerous cells, masses and growths and ensured that no trace of them was left, which allowed healthy tissue to recover over time.

In the 1910s, there were a lot of products that proudly marketed themselves as containing some form of radioactive substance, although due to the expense of using actual radium at the time, most of these products thankfully contained none.

The Radium Brand Creamery Butter had no radium in it, and whilst the cosmetic brand Tho-Radia did, it would get rid of any radioactive materials by 1937. Other existing products such as spring water or hot spring spas would capitalise by advertising the trace amounts of radium.

However, whilst some products of the radiomania era accidentally made themselves safer by lying about the amount of radium in them, others, unfortunately, highlighted why radiation needs to be used responsibly.

The deaths of Marie Curie and the Radium Girls highlighted that irresponsible use of radiation in research and industrial manufacturing respectively could cause significant harm. The latter, in particular, led to changes in occupational health and safety laws to hold companies responsible.

The final shift and the catalyst that ended the unintentional restrictions of radiomania for good was the case of Eben Byers.

An industrialist and amateur golfer, Mr Byers would suffer a significant injury to his arm in 1927 after falling from his bunk bed on a sleeper train. Whilst his arm recovered, he would have persistent pain for the rest of his life.

A doctor recommended that he try a radium salt solution known as Radithor, and within three years he had taken 1400 doses, giving him a radium intake of around 1000 microcuries (when the base tolerance level is estimated to be 0.1 microcuries).

This caused a lot of major health complications, and he died on 31st March 1932, leading to a fundamental change in medical safety legislation and the perception of radioactivity in the wider world.

When radiation therapy emerged as a treatment for cancer, it was grounded in the practical goal of precisely targeting and eliminating harmful parts of the body. Over time, advancements have refined its precision and effectiveness, offering hope and healing to countless patients.

cancer radiotherapy - Cancer woman lying in bed

Understanding How Radiotherapy After Surgery Helps Prevent Cancer Recurrence

There are so many different forms of cancer, each of which relies on a treatment plan that can vary significantly from one diagnosis to another.

In some cases, a visit to a radiotherapy centre will be enough to destroy certain types of early-stage cancer early and help prevent it from intensifying or metastasising.

However, in other cases, radiotherapy will be used as an adjuvant treatment to remove not only the main cancerous mass but also as many cancer cells as it is safe to remove at one point.

In many cases, radiotherapy, chemotherapy and surgery, the three frontline treatments for battling most types of cancer, will be used in some combination, with the former two either being used to shrink the tumour to make it safe to surgically remove, destroy the remaining cancer cells not directly excised through surgery, or some combination of both.

They can also be used with targeted cancer drugs or immunotherapy treatments to help make them more effective. They can also be used in lower doses over a longer period to stop cancer from coming back.

What Is Recurrence?

After a diagnosis and a course of treatment, during which all of the cancer cells that can feasibly be removed have been, the cancer that a person was diagnosed with is no longer considered a threat to their health.

This is typically described as a cancer being in remission, as oncologists are hesitant to say someone is cured of cancer or is cancer-free without being able to prove that this is the case.

Complete remission, in many cases, is a declaration that tests show that there is no detectable evidence of cancer, which can sometimes mean someone is cancer-free but does not always.

Recurrence is when a cancer returns at least a year after treatment, either in the same place it was initially found or the same cancer might have moved to another point in the body.

If the cancer stops appearing on tests but then starts to again before then, it is not typically considered a recurrence but more that the cancer was damaged but did not truly go away instead.

How Often Does Cancer Recurrence Take Place?

Because there are a lot of different cancer types that behave in different ways, the likelihood of recurrence will differ tremendously depending on the type of cancer, where it is in the body, what has caused it, the types of treatment used and when it was diagnosed.

In general, early-stage cancers that are treated immediately are less likely to come back, which is one of many reasons why it is important to get tested as soon as possible to at least rule out the possibility of certain types of cancer.

Cancers that have not spread are also less likely to return, so cancer types that seldom spread such as basal cell carcinoma also rarely come back.

As well as this, recurrence is most common in the first two years after treatment, so every day that the cancer stays in remission means that it is decreasingly likely that it will come back

It is not always easy to predict, although with certain more common cancer types where the behaviour of the malignancy is better known, there is more understanding of the types of maintenance treatments that can be done to manage symptoms without harming the quality of life.

How Does Radiotherapy Help?

Radiotherapy can help in a wide range of ways to reduce recurrence or stop it entirely, depending on the treatment pathway, the nature of the cancer itself and how often it is used.

With early-stage cancer treatments, cancer radiotherapy may be the only course of treatment used and destroys all detectable cancer cells in a single course. This is often true with early-stage brain cancers, as the highly accurate stereotactic radiosurgical treatments used help to destroy cancer cells without destroying the brain.

Outside of radiotherapy being a primary treatment path, there are other ways in which radiotherapy can help with the avoidance of recurrence.

It can be used to shrink tumours, making them easier to remove and reducing the chance of micrometastases following surgery. It can also be used after surgery to destroy cancer cells in the local area.

Beyond this, it can also be used as a recurring treatment, either following remission to destroy any remaining cancerous cells that are possible to remove from the body or as a long-term maintenance treatment to keep someone in complete remission.

Each treatment will be chosen carefully to ensure it is the right option for an individual person and their circumstances, so not every person will have the same course of radiotherapy treatment at the same time.

radiotherapy centre - first linear accelerator technology IMRT

What Conditions Were First Treated with Radiotherapy? A Historical Look

A referral to a radiotherapy centre for treatment means that a person is going to receive non-intrusive, effective and versatile treatment for a wide variety of conditions.

Brain tumours, as well as certain types of lesions and growths in the brain, are more safely managed using stereotactic radiosurgery than through other treatments, and this being the case highlights the progression in technology and medical understanding when it comes to radiation therapy.

However, radiotherapy was first discovered in the late 19th century, and within a year of this was already being used experimentally to treat various types of conditions.

Once the efficacy of radiotherapy was established, what were the conditions it was first used to treat?

The First Four Treatments

Given the scale and scope of the evolution of radiotherapy over nearly 130 years, it is quite astonishing just how quickly it was being used to treat various medical conditions, and even was used in attempts to treat certain forms of cancer.

A lot of this can be credited to the work of Léopold Freund, a Nobel Prize runner-up, the first person to suggest that X-rays can be used to treat disease, and the first person to successfully treat a patient using radiotherapy, although not the first to actually attempt it.

By the dawn of the 20th century, he was already seen as an expert in the field and had established four classes of medical conditions that even at this early stage could be treated by radiotherapy, as well as a group of conditions where radiation was used more experimentally.

Here are the four conditions, as well as the first-line treatment used today to showcase just how much radiotherapy has evolved over the years

Hypertrichosis

Often confused with hirsutism, hypertrichosis is a rare set of conditions that cause excessive hair growth on a person’s body, typically in places where they would not ordinarily have hair.

Sometimes known as werewolf syndrome, hypertrichosis is typically treated with hormone treatments, avoiding certain hair growth medications such as minoxidil or removing the hair that is already there.

Typically, this takes the form of either laser surgery or electrolysis, but in 1900 Mr Freund suggested that radiation could also remove unwanted body hair.

As people who have undergone long-term radiation therapy or chemotherapy can attest, there is a connection between radiation and a loss of hair, but within 15 years the effects of unnecessary radiation would be a cause of concern in the medical world and other treatments would take its place.

The Necessary Removal Of Hair

Mr Freund separated hypertrichosis from other situations where it could be necessary to remove hair in order to treat the disease.

This could include preparing an area for surgery or removing hairs to avoid infection or irritation, such as ingrown hairs.

These would typically not be managed through radiation but instead some kind of short-term hair removal treatment such as shaving, waxing, removal creams or plucking unwanted hairs out.

Inflammatory Skin Affections

Because the earliest form of radiation therapy involved the use of X-rays, they were most effective at treating conditions close to the skin. As a result of this, skin inflammations were a common way early radiotherapists would determine how effective radiation was as a treatment.

This included conditions such as eczema and acne, both of which are skin conditions that cause what Mr Freund described as “inflammatory affections”, which manifests as redness and irritation in the former, and spots in the latter.

Using radiation therapy is not undertaken for skin inflammations that do not have their origins in skin cancer, with a wide range of alternative options for treatment used in its place, from simple emollients to topical steroids depending on the intensity of the conditions.

Interestingly, phototherapy, a form of radiotherapy where the affected area is put under a lamp that emits ultraviolet radiation, is still an option from specialist dermatologists for some forms of eczema.

Malignant Skin Conditions

One of the first successful uses of radiotherapy was in the treatment of lupus by both Mr Freund and his research partner Eduard Schiff, primarily because it would be easy to determine the difference between the treated and untreated area of a butterfly patch flare-up on the face.

As lupus is a multifaceted condition that has a wide range of symptoms, it is typically treated by either managing the symptoms, such as using hydroxychloroquine, steroid creams or anti-inflammatory medication or through using immunosuppressant medication.

Part of the reason why radiotherapy worked is because of this, but given the nature of lupus as a condition that affects people in waves, radiotherapy was not seen as a front-line solution.

However, epithelioma, or abnormal growths on the skin, are often treated with radiation therapy as a routine procedure.

Better known as basal cell carcinoma, epithelioma is a form of skin cancer that rather unusually does not spread to other areas, meaning that it is seldom a threat to life. 

However, it can also be easily treated with cancer radiotherapy in what is commonly a routine procedure.

radiotherapy centre - radiotherapy

The Fall Of Radioactive Therapy And Rise Of Radiotherapy

Radiotherapy is one of three front-line treatments used in the treatment of lesions, tumours and malignant cancers, and the earlier a cancer diagnosis is acquired, the more likely it is that visiting a radiotherapy centre is the primary, if not only, treatment pathway for patients.

This has been the case for nearly a century since Henri Coutard’s method of protracted-fractional radiation doses allowed for the aggressive benefits of radiation to be maximised whilst limiting exposure to radioactivity.

It took a fundamental shift in the scientific community’s relationship with radioactivity and a greater focus on safety and care when it came to exposure to radiation in order for this to occur.

The Importance Of Why

After William Roentgen discovered X-rays, it created a wave of interest in the new field of radioactivity and specifically radiotherapy, at the time known as Roentgentherapy after him.

Within a year of the first X-ray, people with cancer had been treated with radioactive materials with varying degrees of success and control in the tests.

The problem was that researchers knew that it worked, but were far less sure about why it worked, due to a lack of understanding about radiation and a misunderstanding about the causes of cancer.

Radiotherapy for cancer was discovered largely by accident, therefore; cancer was believed at the time to be a parasite that could be disinfected using radiation and it was only the result of chance that Victor Despeignes, Emil Grubbe, Eduard Schiff and Léopold Freund figured out its potential for fighting cancer.

This potential became the dominant driving force both in medicine and wider culture, despite a lack of an answer to the question of why it seemed to work. This is vital because this lack of understanding within the medical community at the time and lack of communication outside of it led to a lot of people getting the wrong idea as to why it worked.

This led to a phase known as radium mania or radiomania, where radioactivity was used as an inappropriate ingredient for a wide variety of products that had no clue how radiation helped to treat cancer but associated it with vigour and vitality.

This included a line of makeup products containing radium known as Tho-Radia, famous for both trying to falsely claim a connection to Marie and Pierre Curie via a similarly named but irrelevant doctor, and a highly successful marketing campaign featuring a blond woman lit from underneath as if she had a radioactive glow.

The most infamous of these, however, was Radithor, a radium salt solution sold as a generic restorative, which in the most unusual way possible led to the rise of radiotherapy as a serious medical practice by making people take radiation seriously.

Power And Responsibility

Radiation therapy is exceptionally powerful, but that power in modern radiosurgery and radiotherapy is used carefully, sparingly and proportionally to the condition being treated.

Part of that came from the Coutard method of fractionalised doses, but another part of that came through a stark reminder of the care that needs to be taken with the power of radiation.

This started in the 1920s with the Radium Girls, a group of watch-dial painters who had become deeply ill with radiation poisoning as the result of a callous disregard for their safety by management.

By 1925, Harrison Martland had proved decisively that their deaths were caused by radium ingestion, which led to a decade-long legal battle and one of the first successful cases brought against a company for their dereliction in the duty of care to their employees.

Around the same time, a young industrialist and aspiring golfer by the name of Eben Byers had hurt his arm after falling from his bed whilst riding in the sleeper carriage of a train. 

He was suggested Radithor by his doctor and would proceed to take 1400 doses of the radioactive solution between 1927 and 1930, only stopping when the effects of cancer started to take serious effect. He died on 31st March 1932.

This led to the end of a period of rank irresponsibility when it came to radiation and a rather universal understanding that its powerful effects on treating tumours and lesions needed to be harnessed carefully and used sparingly.

It led to the end of radioactive therapies and the rise of more advanced radiation therapy, which after increasingly sophisticated treatment systems became a primary front-line treatment alongside chemotherapy and surgery, with a combination of all three used as appropriate to help treat a devastating disease.

,

SBRT bei NSCLC (Dr Kuczer – 2024)

Radiation Oncology specialist, Dr. Kuczer

 

3D-CRT vs. SBRT

 

Respiratory Motion Management

Conventional (ITV-based)
– Contour and treat full tumor ROM

Accelerator beam gating
– Patient breathes normally; beam only on while patient is in a certain phase of the respiratory cycle

Active breathing control
– Patient holds breath in a certain position; beam only on in that phase of the respiratory cycle

Dynamic tumor tracking
– Patient breathes normally; tumor is tracked; beam always on and moves with tumor

Regardless of the motion management used, an additional “CTV/PTV” margin around our target is needed to ensure that we hit it.

 

 

Curative Indication - NCCN Guidelines – NSCLC

 

Curative Indication - NCCN Guidelines – NSCLC

  • Surgical resection is the preferred local treatment
    – An anatomical resection with lobectomy or segmentectomy is preferred to wedge resection
    – Includes sampling of at-risk ipsilateral hilar and mediastinal LN
  • SBRT for patients who are medically inoperable or refuse surgery
    –Limitations: High volume (DM > 5cm) and  “ultra-central” tumors should be treated more cautiously (e.g. 10 instead of 3 fractions)
    –Limited data yet supporting the addition of systemic therapy to SBRT

Potential SBRT Toxicity Depends on Tumor Site

Risk of toxicity can be reduced through risk-adapted dose-fractionation

 

Outcomes of SBRT for Early Stage NSCLC

 

Take Home Pearl and Further Indications of SBRT for NSCLC

 

Reirradiation of Recurrent disease

 

  • Feasibility of treating with curative intent depends on site of primary (P) and recurrent (R) tumors
  • Advanced treatment techniques are particularly useful for sparing normal tissue (e.g., IMRT, SBRT, protons)
    – Reirradiating central structures (e.g., esophagus, airway) most challenging
    – Long-term toxicity is the major concern – impacted by dose/fraction

SBRT in the Management of Stage IV NSCLC

Palliative Radiation For Symptom Relief

  • Pain
    –Bone metastases
  • Neurologic symptoms
    –Spinal cord compression
    –Brain metastases
  • Bleeding
    –Endobronchial tumor
  • Dyspnea/Dysphagia
    –Tumor obstruction causing SVC, respiratory distress or esophageal narrowing

Is all metastatic disease the same?

  • No! Lung cancer has M1a, M1b and M1c designations because the metastatic state at diagnosis impacts prognosis; a small subset of patients may be cured
  • “Oligometastatic” refers to a situation where distant metastases may be limited in number (typically defined as < 5 mets in < 3 organs), and potentially curative treatment can be delivered prior to the development of widespread disease

 

UT Southwestern Randomized Phase II Trial

  • Iyengar et al, JAMA Oncol, 2018
  • 29 patients, oligometastatic NSCLC with < 5 sites of disease (EGFR/ALK negative), PR or SD after induction chemo, randomized to +/- SAbR
  • SAbR à ↑ M-PFS (3.5à9.7mo)

 

SABR-COMET Randomized Phase II Trial

  • Palma et al, Lancet, 2019
  • 99 patients, variety of oligometastatic cancers with < 5 sites of disease, PR/SD on systemic therapy, randomized 1:2 to +/- SAbR (at ablative doses)
    – Most common histologies: breast, lung, colorectal, prostate
  • SAbR à ↑ M-PFS (6à12mo, p<0.001) & M-OS (28à41mo, p=0.09)
    – Also ↑ G2 or higher toxicity, but no difference in QOL

 

Multi-Institutional Randomized Phase II Trial

  • Gomez et al, J Clin Oncol, 2019
  • 49 patients with oligometastatic NSCLC with < 3 sites of disease, SD/PR after Pt-based doublet or EGFR/ALK inhibitor, randomized to maintenance systemic therapy +/- local consolidative surgery/RT
  • RT à ↑ M-PFS (4.4à14.2mo) and M-OS (17à41mo, p=0.02)

 

The Future…

Immunotherapy May Change Our Approach to Locoregional Management Too

A stronger immune response may be elicited by leaving a tumor in and irradiating it, rather than removing the largest source of antigenic stimulation.

 

 

 

The Future……Aktive Protokolle

PACIFIC-4 / RTOG 3515

Inclusion Criteria

  • Clinical Stage I/II node negative (T1 – T3 N0)
  • Medically inoperable or refuse surgery
  • ECOG PS 0-2
  • All comers for histology and PDL-1 status
  • Sync/Metach allowed

The Future…A Few Examples of Active Clinical Trials in Lung Cancer

CAVE: Not all new substances proofed to be safe with SBRT. Additional surveys needed!

  • NRG LU002: Adds RT (to all sites of disease) to systemic therapy for oligometastatic NSCLC
  • NRG LU004: Adds immunotherapy to IMRT or 3-D CRT for stage II-III NSCLC with high PD-L1 expression (instead of chemotherapy)
  • PACIFIC 4 and NRG/S1914: Adds consolidative immunotherapy to SBRT for stage I NSCLC
  • AEGEAN: Adds neoadjuvant immunotherapy to surgery for resectable stage II-III NSCLC
  • ALCHEMIST: Evaluating adjuvant use of targeted agents for resected NSCLC
  • RTOG 1308: Compares proton therapy to photon therapy for LA-NSCLC
  • NRG LU005: Adds immunotherapy to chemoradiation for limited-stage SCLC
  • NRG CC003: Hippocampal avoidance PCI for SCLC

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SBRT bei NSCLC

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Radiotherapy Centre - doctors looking at the image

How Radiotherapy Can Be Used In Combination With Drugs

Our radiotherapy centre can now treat a very wide array of conditions. The technology of radiotherapy has been developed over the last 120 years to offer hope and extend life to sufferers of various forms of cancer.

This has become more adroit over time, with particular tools like the gamma knife being able to direct the beams more precisely than ever in sensitive areas like the brain.

Whether it is brain, prostate, head, neck, cervix, or eye, radiotherapy has been fine-tuned to deliver better results in each case. However, oncologists will often use radiotherapy in conjunction with other treatments, such as chemotherapy or surgery, to deliver the best possible results.

A New Breakthrough?

This is especially so with chemotherapy. New combinations are being trialled all the time and some provide impressive results that lead to them becoming established practices. The next to do so might be a combination of radiotherapy and a drug called AZT1390, which has been shown in new research to be safe as well as effective.

In results presented to the annual meeting of the American Association for Cancer Research earlier this month, it was revealed that the use of the drug prevents the cancer cells from repairing their DNA in the wake of radiotherapy as effectively as they normally would.

Explaining how the drug supports radiotherapy and the importance of its development, Dr. Jonathan T. Yang of the Memorial Sloan Kettering Cancer Center, who presented the findings, noted that most glioblastoma patients do not live for more than two years beyond diagnosis and progress to date on treatments has been slow.

“Despite efforts to improve survival, the current standard of care continues to be a backbone of radiotherapy with or without temozolomide without much innovation in the past two decades,” he remarked.

Dr Yang added: “This context highlights both the urgent need to develop new medicines and the historical challenges of developing novel therapeutics for this devastating disease.”

How Inhibiting Cancer Cell DNA Recovery Helps Radiotherapy

A key feature of how radiotherapy works is that it kills cancer cells by damaging their DNA, preventing them from reproducing. However, a problem that can occur, including in glioblastomas, is that cancer cells can then activate what is known as the ATM cell signalling pathway, which can repair much of the disrupted strands of DNA.

This mechanism limits the effectiveness of radiotherapy, but AZT1390 acts as an inhibitor, stopping this response and therefore slowing or even halting the pathway, meaning the cells do not repair the DNA and will therefore not be able to reproduce.

A key problem with many drugs is they have not been able to penetrate the blood-brain barrier, preventing them from supporting radiotherapy aimed at shrinking brain tumours. However, AZT1390 has been designed to do this and the latest trials have now provided firm indications that it is a safe drug as well as an effective one.

Studies showed that patients given the drug only had fairly mild, manageable and usually reversible side effects from the treatment, which indicates that using them will not have a major negative impact.

Dr Yang noted that if the early data indicating the significant effectiveness of the drug is backed up by further studies, it could provide a major new weapon in the fight against glioblastomas.

Since around half of all cancer patients receive radiotherapy, any additional or complementary treatments that increase its effectiveness will clearly have a large impact, helping increase survival rates and potentially providing useful data for future research to make further advances.

Other Ways Drugs Can Support Radiotherapy

The use of inhibitors to stop cells from repairing their DNA is just one of the ways drugs can help radiotherapy be more effective. For example, anti-angiogenic drugs can halt the growth of blood vessels in tumours, depriving them of the blood and oxygen they need to grow and thrive. While metabolic inhibitors prevent enzymes from binding, curbing cell growth.

If you have been diagnosed with cancer and need radiotherapy, there are very good reasons that you may not have that treatment alone, but the use of drugs of the kinds mentioned above to help make the treatment more effective.

That means when you come to speak to our oncologists and other experts, the plan for your treatment may have more elements to it than you might have previously imagined. But that is also a reflection of the fact that there are now more weapons in the fight against cancer.

It may be that AZT1390 is soon added to this arsenal after further research. But many drugs already have a role to play and more are sure to come in the years ahead.

Radiotherapy Centre - vegetable cutting

How Eating The Right Sort Of Foods Aids Radiotherapy

Facing a battle against cancer can be one of the most daunting prospects anyone can be confronted with. It is not just the reality of our mortality – since we will all die eventually – but the uncertainty of outcome, both for you and your loved ones.

At the same time, a cancer diagnosis can bring out the fighter in many people. The best attitude anyone can have is not a fatalistic one, but a determination to do what not takes to beat the disease, or at least to extend life as long as possible. This is often the attitude of those who are always determined to make the most out of every single day life brings.

However, there will be inevitable compromises. Radiotherapy centre visits will be regular events and therefore will mean there are many days when you don’t have the freedom to go about your normal business or pursue your preferred activities.

Also, the treatment is likely to bring a range of side effects, which can include symptoms like fatigue, hair loss, nausea, skin changes and – for those whose treatment focuses on the abdomen – stomach trouble, and urinary problems like incontinence. For those with cancers in the pelvic areas, the consequences can include sexual dysfunction and infertility.

This will inevitably mean that while you want to continue life as normally as possible, it will never be exactly normal. Some things will change.

Why Your Diet Must Change

While these are the consequences of treatment, there are also some aspects of your lifestyle you need to alter yourself, including your diet.

This is because the effects of radiotherapy on your body can make you vulnerable to certain problems that can arise when you consume food, either making bad things worse or simply making normal things into a problem. At the same time, however, there are foods that can help you cope better with the treatment and are therefore an ally in your cancer battle.

Firstly, there are the foods you should cut out of your diet. For example, if you like fish you can still enjoy this when it is cooked well, but you must avoid raw fish and shellfish, such as sushi, clams or oysters. Smoked salmon, soft-boiled eggs, soft cheese and cheese made with unpasteurised milk should also be avoided.

The reason is that all these can contain a lot of bacteria. That might normally just mean a small bout of tummy trouble, although you can get worse food poisoning. But when you undergo radiotherapy, your immune system will be weakened and that means any bacteria you ingest could be much more harmful to you.

In the same way, you should avoid other risky food choices such as unpeeled fruit and vegetables, while any impact of radiotherapy on your gut, causing stomach upsets and diarrhoea, will be made worse by spicy food such as curries.

If you have treatment around the chest, throat or mouth, avoid sharp-edged or crunchy food, while acidic fruits like citrus or tomatoes can actually cause burns or cuts. Alcohol does this too, so sadly you should avoid that as well. Avoid Saturated fats too. These are bad for you anyway but are hard to digest, which will make any gastric symptoms worse.

What You Should Eat

However, there are also foods you can and should eat that will do you a lot of good, as these can help you suffer fewer and less unpleasant side effects and recover from the therapy faster and more easily. This means you should be eating lots of nutrient-rich products.

While highly acidic fruits may bring problems, others are very good for you, offering lots of fibre and vitamins. Grains, vegetables and lean meats are also very good in providing healthy proteins.  

Carefully choosing the ingredients in your meals is an important step, but it is not the only issue. It is likely your appetite will be affected by your treatment and this effect may vary, so you should monitor this. But in most cases, your appetite will be reduced, so the wisest approach is to make your meals smaller but more frequent.

By doing this, you generally will not eat less, while avoiding getting bloated by consuming a big meal. At the same time, if your appetite is greatly reduced, the quality of the proteins and nutrition you get will help to compensate for a smaller intake.

Planning For Healthy Eating

To ensure you eat well, you need to plan ahead. That means discussing these matters with your doctor to ensure you are eating all the right things and eliminating others, but it also means making sure you are correctly stocked up with the right kinds of food at home.

Because radiotherapy will compromise your immune system, especially if used alongside chemotherapy, you may find you go out less and therefore eating out is something you may not do. This may not be a bad thing, for if you do eat out you will have to be very careful about what you choose.

What To Drink

Alcohol has already been mentioned here as something to avoid. Among its harmful effects is that it is a diuretic, reducing your water when you need to stay hydrated. It is very important to make sure you drink a lot, not least as this will help flush any toxins out of your body sooner, limiting their effect at a time when your immune system is weaker.

Water is the obvious thing to consume, but there are also lots of other healthy alternatives. Because you need to avoid acidic and sugary foods, you should not consume soft drinks, or cordials with high sugar content.

Taking these steps may mean you forego some of your favourite foods and drinks, but it will be worth it because it will make it easier to cope with radiotherapy, reduce additional problems, lower health risks at a time when you are vulnerable and may also establish some good habits.

The last of these factors may be worth thinking about after successful treatment. It might be tempting to celebrate the ‘all clear’ with a hearty meal and a few glasses of wine, but in the longer run, eating and drinking healthily will help you achieve the long, healthy life your radiotherapy treatment may have done so much to increase your chances of enjoying.