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Cells in your body have work to do, and they wear out. This means that they have to be replaced, and most cells in your body participate in the replacement cycle by replicating themselves from time to time. Very few of the normal cells in your hand or foot are replicating at any given time; most are in the resting or quiescent phase of the cell cycle of division. That doesn’t mean that they’re resting in terms of their normal function, but they’re resting from the cell cycle of reproduction.
The fibroblasts in Dupuytren's and Ledderhose disease have got muddled, and they have begun to participate more actively than they should in the cell cycle. This means that not only are they eagerly doing their job of making collagen, but they are also replicating themselves more than they should.
This over-enthusiastic replication is what makes them vulnerable to radiation therapy.
Much of what the cell does is governed by instructions carried in DNA in its nucleus. DNA sometimes gets damaged – particularly by high-energy radiation – and since repairing DNA incorrectly often leads to the death of the cell, evolution has favoured highly conservative, elaborate and effective methods to get it right. Mistakes will happen, however, and cells that repair damaged DNA incorrectly will normally die.
For a cell to duplicate itself, it has the tricky job of replicating its own DNA. This is a complicated and delicate process involving unzipping the DNA molecule down the middle, copying the two unzipped strands, and zipping them (and copies) up again. DNA carries a lot of information (about 3 billion base pairs, or 3Gb) and this process takes roughly a day, at a rate of about 40 000 base pairs each second.
While this molecular magic is happening, the cell is in a sense on autopilot, unable to follow instructions from the temporarily disabled DNA. Damage to the DNA at this moment is much more difficult to repair accurately than if it happens when the cell is resting. Evolution has developed ways to deal with damage caused during the replication of DNA, but it is inevitably not as reliable as repair work done in other phases of the cell cycle.
We are constantly bathed in radiation – including radio waves, microwaves, thermal infrared, and visible light. These kinds of radiation contain too little energy to ionise tissue that they pass through.
Some radiation, however, carries so much energy that when it passes through tissue it may tear electrons away from any atoms that it collides with. Energetic radiation of this kind can be carried by the high-energy photons that we call x-rays or gamma rays, and by high-energy sub-atomic particles such as electrons, protons, neutrons and carbon ions.
Life has evolved to deal with ionising radiation of this kind – we are bathed in small quantities of this radiation from the sun and from various exotic sources in space – but not too much of it. Cells damaged by ionising radiation can repair themselves, even when the damage happens to the DNA, but are at their most vulnerable when replicating themselves.
Radiotherapy works by creating high-energy, ionising radiation, and pointing it at the problematic tissue, usually a neoplasm or tumour. This ionising radiation damages many of the cells in the tissue, but while quiescent cells can usually repair damage to their DNA, replicating or proliferating cells find it much more difficult, and are the damage often proves lethal.
Radiation therapy is gauged to kill replicating cells while doing as little damage as possible to the quiescent cells. Since Dupuytren's and Ledderhose disease are characterised by proliferating fibroblasts, the therapy is designed to single out these replicating cells and kill them, while damaging the normal cells as little as possible.
The most common protocol for Dupuytren's and Ledderhose disease divides the total dose of radiation into two series of 5 days each.
Why?
Radiation may take time to kill cells, and sometimes it takes days of treatment for cells to start dying. Furthermore, since the phase of replicating the DNA takes about a day, by fractionating the dose over several days, fibroblasts that were quiescent but then begin to replicate may be caught on the hop.
This explains why each series is divided into 5 days – maximising the chance of catching the fibroblasts at their most vulnerable.
But some fibroblasts may remain quiescent throughout the 5 days, and, like other quiescent cells, quietly repair any damage they suffer to their DNA. The second series of 5 days, two, three or four months later, is intended to catch any surviving fibroblasts when they, too, begin to replicate.
The damaged cells may keep dying for months after the treatment. This is why the full effect of the treatment may take months to make themselves felt, and also why side effects (including sore skin and tiredness) sometimes appear long after the end of the treatment.
Some clinics offering radiation treatment for Dupuytren's and Ledderhose disease use x-rays generated by a relatively low energy (250 kV) radiation source called orthovoltage units. This kind of radiation delivers most of its energy at the surface of the target and successively less as it penetrates the tissue. To prevent damage to the skin, a bolus is laid on top of the area to be irradiated so that the dose at the skin is not much higher than the dose delivered to the nodules beneath its surface. The x-ray photons ionise tissue all the way through the hand or foot, but the beams are designed to deliver the highest intensity in the nodules.
Higher energy x-rays (1-20 MV) from megavoltage linear accelerators deliver most of their energy beneath the surface of the target. For this reason, a bolus is not normally used by the clinics that offer megavoltage treatment for Dupuytren's and Ledderhose disease.
Linear accelerators with higher energies (>6 MV) can also produce beams of electrons or heavier particles.
Electrons don’t penetrate far, depositing most of their energy in the first centimeter or two below the skin, making them ideal for treating Dupuytren's and Ledderhose disease. Because electrons scatter in air, the machine that delivers them is fitted with a cone that guides (or collimates) the beam. The cone, which almost touches the skin surface, is a give-away that electrons are being used.
Protons cause little ionisation as they pass through tissue, until they reach the end of their path where they release all their energy. This allows the practitioner to deliver almost all the dose to the target tumour. Very few clinics own the highly specialized linear accelerators that generate proton beams.
Some clinics use an IMRT (Intensity-modulated radiation therapy) machine to irradiate the nodules. This is currently the most technologically advanced machine for providing radiotherapy. It uses a computer-controlled linear accelerator to move around the target in such a way as to deliver radiation directly to the nodule, with minimal radiation passing through any given area outside the target.
To achieve this result, the nodule must not move relative to the head of the machine during the process and must be in exactly the same place from one day's treatment to the next.
This means that you will start your therapy with a simulation during which your radiation oncologist will position your hand or foot and scan it with computed tomography (CT), magnetic resonance image (MRI), or an x-ray. This will allow them to locate the nodules and cords and direct the radiation beam appropriately.
The radiation oncologist may tattoo your hand or foot with a small dot to ensure that the hand or foot is always precisely in the same place relative to the radiation beam.
They will then create a mould or foam sponge to hold your hand and fingers in exactly the same position each time.
With other kinds of machines that do not have the same precision, the team will either use a standard shield or design a personalised shield to ensure that the radiation is confined to the nodules and cords in your hand.
Clinics that do not use computer-controlled machines want to provide a radiation field that includes all of the nodules and cords and extends beyond them for 1 or 2 cm to try to ensure that diseased tissue that has not yet formed nodules is included. Under these circumstances, a personalised shield is unnecessary and a generic one will do.
Since the exact position of the target is not crucial, the oncologist will position the hand or foot during the first session, photograph it in place, and use that photograph to position the hand or foot in subsequent sessions.
In these clinics, the first session is not a simulation.
Radiation therapy is completely painless.
“Radiation” is associated with frightening things like nuclear bombs and accidents at nuclear power stations.
We can’t perceive it.
We can’t see it or smell it or taste it or feel it.
It penetrates our body and causes unfelt damage, leading to terrible burns, cancer, mutations, radiation sickness, and death.
Even when it’s used therapeutically, it works by damaging and killing cells.
Technicians stand behind thick lead shields.
So yeah, it’s scary.
So why do we use it?
Because it can stop the progress of cancer by killing the cancer cells and can stop or slow the progress of Dupuytren's and Ledderhose disease.
And because it can do those things without causing burns, cancer, mutation, sickness or death.
A little vocabulary: Grays measure absorbed radiation; 1Gy is one joule of energy absorbed per kilogram of matter. 1 mGy is one milliGrey, or one thousandth of a Gray.
Medical X-rays and scans use very low doses of radiation - around 1-10 mGy.
Therapeutic radiation is delivered at thousands of times higher doses - preventive doses may be around 50Gy, while curative doses are often around 70Gy. Lymphomas, Dupuytren’s and Ledderhose disease are typically treated with 20 to 30 Gy.
You may read statements or see charts showing that if a human is exposed to 5Gy or more they will usually die in less than a month.
So how can Dupuytren's and Ledderhose disease be treated with 30Gy? It’s because the lethal 5Gy is absorbed in a single dose by the whole body. If the person concerned weighs 75kg, then they absorb 5x75=375 joules of radiation.
The weight of tissue irradiated in Dupuytren's or Ledderhose disease is perhaps 100g, or 0.1kg, so the total energy absorbed amounts to 30x0.1=3 joules of radiation. This is normally fractionated into 2 series of 5 sessions, giving 0.3 joules at each session.
Thus, the damage provoked by the lethal 5Gy (corresponding to 375 joules) is 1250 times greater than that of one of the therapeutic sessions (consequent on 0.3 joules).
Dangerous? Perhaps, but we live in a world of dangerous things like cars and banks and avian flu. You deal with dangerous things all the time. They haven't killed you yet.
Scary?
Not so much.
I should add that the cells that are irradiated do not become radioactive. This means that blood cells that happen to be irradiated do not carry any trace of radiation away from the irradiated area.
The radiation targets neither the nodules nor the cords, but the active fibroblasts.
Perhaps this analogy will help.
On an ancient building site, workers are making bricks. At first, they just pile them up in heaps. Later, once the heaps get pretty big, they also start laying them down as paths, then as roads. Workers are scurrying around all over the place, but if you watched using a timelapse camera, you'd never see them, only the heaps getting bigger and then the roads forming.
Now aliens arrive.
They have instructions to stop the piles and the roads. But the workers are invisible to their slowed-down senses.
They know there's no way they can dismantle the piles and roads from orbit.
So they target the area with their anti-worker ray gun.
They don't focus only on the heaps, or on the roads. They target the entire area where they think the workers might be active.
Of course, that's mainly the heaps and the roads, but they don't expect the workers to only be in those very obvious areas. So they start from the piles and roads, but they broaden the aim of their raygun, hoping to zap all those scurrying workers.
So with this kind of vision of how fibroblasts are building nodules and cords, Prof Seegenschmiedt and many other oncologists believe that the area irradiated should not be limited to nodules or cords, but extend a couple of centimetres around, as well.
In that way we hope to zap all those busy little fibroblasts.
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Contact information provided below for radiation oncologists who have treated for Dupuytren's Contracture or Ledderhose . Comments or opinions expressed here or on DART are not intended to diagnose or prevent disease. Advice or comments should not be relied upon unless confirmed by your treating physician. No doctor-patient relationship is intended and members are advised to consult their doctors for medical advice. No representation is made about the quality or professional competency of the listed doctors. This listing provided as a place for you to begin your own research. If you find the contact info outdated or in error, please comment on DART where it can be corrected. You might also google the doctor or clinic to find updated contact information. Many of these doctors also practice at secondary locations that may be closer to you. Check their website. In addition to their clinical practice, many of these radoncs are also on the faculty of local medical schools where they teach radiation oncology. If you have doctor or clinic information not listed below, please share with DART so it can be made available to others looking for treatment in that location. some photos from dupuytrens.org Thank you.
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