Low Energy Photon Therapy (LLLT) for Vascular Disease and Venous Leg Ulcers
LLLT uses wavelengths in the red and near-infrared (NIR) spectrum. Several studies in cell culture and animal models show that these wavelengths stimulate cellular reactions, including synthesis of ATP, vasodilation and inhibition of inflammatory processes.
In addition, LLLT produces less complex DNA damage that is more readily repaired than proton therapy. Nevertheless, both treatment modalities cause dose-streaking effects in normal tissue.
Targeted Cancer Therapy
Unlike conventional radiation therapy, which can damage healthy tissue and cause side effects, proton therapy delivers high levels of targeted radiation directly to the tumor. Because of this, patients are at a lower risk for developing cancer-related side effects.
Using a combination of active and passive targeting strategies, drug delivery can be optimized to enhance cancer cell selectivity and lethality. Passive targeting involves the use of a drug’s shape, size and surface chemistry to increase particle circulation and tumor accumulation; while active targeting focuses on the incorporation of chemical moieties (e.g. peptides, sugars, aptamers, antibodies) that bind to receptors on the surface of cells or inside the cell, and promote selective drug uptake and distribution within a tumor lesion.
In a type of targeted chemotherapy known as molecularly targeted therapy, your doctor will use drugs that target specific alterations in the genes or proteins found on cancer cells. This form of treatment can be used alone or in combination with other cancer therapies.
Your doctor can identify these abnormal molecular changes through a biopsy, where they remove a small sample of the tumour and test it for certain genetic alterations. Alternatively, cancer cells may shed DNA fragments into the bloodstream and these can be detected with newer, more precise genetic tests that measure the activity of specific molecules.
A type of radiation therapy in which a radioactive compound is linked to a cell-targeting molecule, such as a monoclonal antibody and then injected into the body. The targeted radionuclide binds to the protein found on the surface of some cancer cells and can help kill the cancer cells while sparing healthy cells.
During treatment, you will be positioned in the immobilization device and then moved into the gantry, which is a large donut-shaped device. The radiation therapist will then deliver the prescribed dose to the tumour. To minimize the amount of radiation that is delivered to non-tumor tissues, your doctor will carefully align the beam with the shape and depth of the tumour. In order to ensure that the particles are positioned exactly where they need to be, the radiation oncologist will take a series of low-energy X-ray images called simulation scans.
Vascular Disease Treatment
Vascular disease is a common condition that causes blockages, narrowing or weakening of blood vessels. This can reduce oxygen and nutrient delivery to the body’s tissues, which can cause pain and damage tissues. This condition can also lead to nonhealing wounds (venous ulcers) that are hard to treat with traditional therapies.
Photon therapy uses high-energy radiation to target cancer cells and destroy them. The radiation comes from positively charged particles called protons. Protons, unlike rays of light, have physical mass and stop at the tumor site, eliminating the exit dose that can harm surrounding healthy tissues. This makes proton therapy less likely to harm critical organs and tissues near the tumor, which can reduce the risk of treatment-related side effects.
Radiation oncology specialists plan the path of the protons using imaging tests, such as MRI or CT scans, to find the area that needs to be treated. Then you lie on a table as the machine aims energy beams at your body. The radiation oncology team adjusts the machine as needed to reach the exact location of the tumor.
Modern linear accelerators (Linacs) are often equipped with multiple photon energies to allow physicians to choose the right energy for each patient’s case. The different photon energies have different penetrating capabilities and other dosimetric properties. Low energy photons are better able to penetrate and spare the skin, while higher energy photons are more effective in targeting deep-seated tumors.
The photon energy synthesis method allows the creation of a new photon energy by linear combination of a lower and a higher photon energy. The generality of the method was tested by using standard photon reference beam data from a wide range of energies published in the British Journal of Radiology supplement 25 (13) to create IMRT plans with varying intermediate photon energy. The 3D dose distributions were verified by Gamma analysis on water phantoms. The results indicate that the synthesis of photon energies achieves good dosimetric accuracy with all the criteria.
Venous Ulcer Treatment
Venous leg ulcers are a common problem for people with diabetes, because the disease can damage blood vessels, tissues and nerves in the feet and legs. When the blood flow is disrupted, it can cause a skin wound that does not heal well and can lead to infection or gangrene. Treatment of venous ulcers focuses on cleansing the skin, administering antibiotics and managing blood circulation with compression.
A placebo-controlled study found that LEPT increased the percentage of ulcers healed compared to standard care. In the study nine patients with venous ulcers were randomized to receive either LEPT or conventional treatment, and the researchers measured the percentage of ulcer area reduction at six weeks. The study found that the average reduction in ulcer size for LEPT was 54%, while the conventional treatment saw only a 27% reduction in ulcer size.
The researchers used a standardized clinical plan for each patient case. Three 3DCRT, IMRT and VMAT plans were generated, using the actual TrueBeam 10MV photon. Then they duplicated each plan with the same dose, but with varying intermediate photon energies. The plans were analyzed using 3D Gamma analysis to compare the results. The dose matrix showed that the plan with TB-10MV photons had the best quality, followed by Esyn-10MV and then a mix of TB-10MV and Esyn-10MV photons.
Two RCTs and one follow-up study identified. Two of the RCTs (40 and 60 people) compared subfascial endoscopic perforator surgery plus compression with compression alone. Both of the studies showed that venous surgery was equally effective at increasing healing rates compared with compression alone (ulcers healed in 65% with surgery and 89% with compression; low-quality evidence).
The third RCT (34 people) compared the effectiveness of a laser versus a sham laser to reduce ulcer size, but did not show any significant differences between treatments. The fourth RCT (69 people) compared the effect of multilayer high-compression bandages versus a single layer of a non-elastic compression bandage, but did not show a difference in the number of ulcers that healed (no statistically significant difference; low-quality evidence).
Pain Management
For years, researchers have used light therapy to treat a number of medical conditions, most notably venous ulcers. This treatment involves exposing the skin to specific wavelengths of light, essentially acting like a flashlight to emit a single, narrow beam of monochromatic light, which is then applied to the surface of the skin. The benefits of this approach have been confirmed in several randomized clinical trials, with patients showing improved wound healing and reduced pain after just a few treatments.
More recently, scientists have begun using a different approach to photon energy synthesis. The principle behind this method is to essentially “mix” any two photon energies into one that is dosimetrically equivalent to the original plan using existing linear accelerator technology and published reference beam data (2). This suggests that there may be no need to equip a Linac with more than two photon energies, which could significantly reduce the cost of radiation therapy equipment.
In terms of cancer treatments, there is also a growing use for this type of therapy in radiation oncology. This is particularly true in the area of proton beam therapy (PBT), where mixed energy photons can improve the quality of radiation treatment plans (3).
The new term for these noninvasive therapies is photobiomodulation therapy, or PBM. This is a more accurate term that highlights the fact that these technologies are not just focused on the blue-to-near-infrared spectrum that was originally the focus of research, but now spans the entire range of wavelengths. It also better reflects the fact that most research is focused on the CCO activation pathway that Tiina Karu has identified as the primary mechanism of action of these therapeutics (4).
As the field has grown, a formal case for the terminology shift was made in the flagship journal of radiomedicine and laser surgery, with Juanita Anders, Raymond Lanzafame, and Praveen Arany writing a 2015 editorial that argued that this change was both necessary and expeditious (5). The editorial was formally adopted by the International Society for Photobiomodulation (ISPB) in 2016. This nomenclature shift has since become a standard in clinical practice.