Questions and Answers / NEXT GENERATION PDT

  • What are the features of the Next Generation of Photosensitizers and (PDT) Photodynamic Therapy?
    A. NGPDT is an advanced form of photodynamic therapy (PDT); a treatment which uses light to destroy cancer tissue. In both Next Generation PDT and PDT patients are given a photosensitizing agent. Traditionally, PDT has been confined to treatment of superficial lesions or localized problems that can be either directly visualized or reached with devices called endoscopes that are inserted into body openings. This Next Generation PDT on the other hand is aimed at treating whole regions and tumors deep in the body.
  • How does it work?
    A. Next Generation Photodynamic therapy is a minimally invasive treatment method developed for use in a wide range of diseases characterized by hyper proliferating (actively and rapidly dividing cells. Using a photosensitizing drug and laser or LED light, PDT can selectively destroy targeted tissues.

    The Three essential components of PDT are:

    • A photosensitizing agent
    • A non-thermal light source
    • Oxygen

    Treatment of disease with Photodynamic Therapy is a two-stage process. The first stage is the intravenous or oral injection of the photosensitizer and after a number of days, or hours, the tumor to be treated is exposed to non-thermal light of the specific wavelength needed to activate the drug. The delay between injection of the sensitizer and its activation is designed to allow the drug to accumulate selectively in the tumor tissue.

    The second stage is the delivery of light to the tumor by a light source or fiberoptic bundle. A fiberoptic cable carries light from the light source device to the point where the light is to be applied. The photosensitizing drug retained in the tumor cells is activated by the light and the energy absorbed by the drug is then transferred by a natural conversion to oxygen within the tissues. This produces a highly reactive form of the oxygen, termed singlet oxygen, which causes lethal destruction within the cancer cell.

    This type of treatment offers some significant advantages, including:

    • Minimal side effects relative to conventional treatment
    • Minimally invasive therapy
    • An increased potential for disease site access, due to the use of lasers/LED’s, and the flexibility and small size of fiber optics
    • Treatment on an outpatient basis

    Compared with surgery or radiotherapy, PDT is a relatively benign procedure, which produces good results from a functional standpoint. It is generally well tolerated and can be repeated, so does it not limit future treatment options.
  • What types of cancer be treated with NGPDT?
    A. Due to the nature of NGPDT Treatment, most types of cancer are treatable including deep seated, metastatic, and late stage cancers. Nearly 85% of applicants to our clinics are deemed suitable. In general as long as the patient is mobile and able, they can be considered for treatment. There are however some cases that cannot be treated with NGPDT due to the complications that can arise from rapid necrosis of tissue around major arteries and some other areas of the body. Late stage palliative patients will sometimes require special assessment in order to determine the likely benefits they can receive from treatment. Our Patient Application process seeks to identify these possible complications before any treatment commences and advise the patient accordingly.
  • How much does NGPDT Treatment cost?
    A. The cost of NGPDT Treatment can vary depending on the number of treatment courses a patient requires. Early stage cancers can often be successfully treated with one or two(2) treatment courses at most, while late stage or metastatic cancers can often require three(3) treatment courses. A 8 Day NGPDT treatment course costs 110,000 RMB (Approx. 17,500.00 USD dependent on exchange rate) and includes a personal driver for the length of your stay if needed, and a translator if required. Treatment costs do not include accommodation, food, or flights, however we can assist with organization of these facets if needed. During the Patient Application process our doctors will let a patient know how many NGPDT treatment courses will likely be required.
  • What types of diseases and cancers can benefit from the therapy?
    A. There is a long list of medical conditions that respond favorably to this therapy and many more possible uses that are suggested by laboratory studies. These are: Cancer, Eye disease, vascular disease, rheumatoid arthritis, psoriasis and many skin diseases, acne, bacterial, viral and fungal diseases and many others.
  • What is the mechanism that "kills" the cancer?
    A. The damage to cancer cells results from a multi-step process. First the photosensitizer is administered which leads to the selective accumulation on the target cancer cells. Following a period of time specific for each agent to allow the photosensitizer to clear from normal tissue, light is applied. Because the agent molecules are light sensitive, they are energized and become unstable and electrons are donated to oxygen in the immediate vicinity creating a special type of reactive oxygen species called ‘singlet’ oxygen. These molecules too are unstable and also off-load energy to the adjacent cellular structures of the cancer cells which damages and in many cases ‘kills’ the cancer.
  • How quickly does it work?
    A. This process of damage to cancer cell begins immediately and in many cases the effects of the therapy are apparent at the end of the therapy session.. Some of the cells may be killed and fragmented immediately. Likewise, other cancer cells can be injured but not sufficiently to cause immediate death. They may be affected enough to simply not be able to reproduce. The body can recognize this damage and ‘program’ the cell to be progressively eliminated and removed; a process known as apoptosis. In many cases this is a milder and gentler method of elimination of the cancer cells since this process results in less inflammation and reaction. Another rather prompt result of the treatment is coagulation and stasis of blood flow in the vessels that supply the tumor.
  • What is a "typical" course of therapy?
    A. Because advanced forms of PDT are relatively new treatments and the side-effects and after-effects are still not completely understood, certain individuals should definitely NOT attempt to receive it.These include people:

    • who are bed-ridden, non-ambulatory (cannot walk independently), or confined to wheelchairs.
    • who are on supplemental oxygen most or all of the time and are too sick to travel.
    • who are suffering from severe cachexia, i.e., the wasting syndrome.
    • whose tumors compromise a major blood vessel. (Breaking down the tumor could lead to hemorrhaging.)
    • whose tumors involve the spinal column (where removal of the tumor could lead to collapse of the vertebrae).
    • with severe jaundice with a history of vascular or clotting problems.
    • with the disease known as porphyria (a light-sensitizing condition).
    • who are clinically depressed (and are unlikely to follow through with treatment).

  • What happens after the therapy?
    A. There are four principle effects of the therapy that begin shortly following the administration of the agent and the application of the appropriate light.

    • If enough light energy has reached the agent on the tumor there can be outright death of cancer cells. The body attempts to remove these dead cells through the process of inflammation.
    • Sometimes the cells are damaged and they are rendered incapable of functioning properly and multiplying; they eventually die in a process named apoptosis.
    • Because the agent also accumulates on the blood vessels, following the application of light the blood can coagulate and the flow diminish or cease.
    • Additionally, with fragmentation of the cells the body can react by forming antibodies to the tumor.

    What each patient experiences during this process depends on many variables. If the size of the tumor is small and is not in a critical area there can often be few if any symptoms. Other factors such as; 1. large tumors that have spread to lungs, 2. liver and/or brain tumours, or a compromised immune defence from previous chemotherapy creating a challenging environment for the body to breakdown and flush cancerous/dead cells. Symptoms of pain or discomfort in the area of tumor necrosis, weakness, tiredness etc. can also be present.
  • Does it need to be repeated?
    A. For solitary superficial tumors such as skin cancer the complete response rate can approach 98%. Since the area can be observed easily, if there is no sign of recurrence, no further treatment would be necessary. However with increasingly serious cancers, especially those which have spread to lymph nodes and/or metastasized (spread to distant areas of the body) the usual diagnostic tests (MRI's, Cat scans, ultrasound, PET scans, tumor markers, biopsy etc.) are usually used to monitor progress and the therapy repeated as necessary. Benefits are generally realized from the initial therapy forwards.
  • How long do the benefits from therapy last?
    A. While the benefits of cancer destruction or damage (apoptosis), stasis, coagulation of vessels feeding the tumor and the potential production of tumor specific antibodies (auto vaccination) begin soon or immediately after the initiation of the photodynamic therapy, the benefits can extend far out into the future. Every case is different, but if in fact the latter process of tumor specific antibody formation takes place this is a lifelong recognition of the tumor cells. If the patient is fortunate enough to have the complete elimination of the tumor the benefit is obvious. Where there is significant reduction of tumor and the remaining problem has been dealt a significant blow from death of tumor cells, apoptosis and reduction in blood flow to the tumor there can be a favourable prolongation of quality life as well as increased longevity. Too, if the patient and physician feel, as a result of the treatment significant benefits were realized, the therapy can be repeated without the risk of 'resistance build up' to the treatment
  • How will my blood tests change following NGPDT?
    A. The following levels may drop within a few days of light therapy and may take from 3 to 6 weeks to recover.

    HB (Haemoglobin)
    RBC (Red Blood Cell Count)
    HC (Hematocrit)

    The reason for this possible decrease is red blood cell disruption (of cell membrane) caused by light irradiation during NGPDT.

    The following values may rise within days of NGPDT and may take many months to recover.

    WBC = Specifically Neutrophils may increase in the absence of infection following NGPDT therapy.

    ALP (Alkaline Phosphatase )
    ALB (Albumin)
    AST (Aspartate Transaminase)
    ALT (Alanine Transaminase)
    GGT (Gamma Glutamyl Transpeptidase)
    These values may rise because of inflammation, necrosis, apoptosis and the livers inability to digest proteins and fats. For this reason a diet with more carbohydrates and vegetables is recommended.

    After NGPDT the body produces more antibodies due to the immune response and thus may cause CA markers to rise. Before treatment rises in CA levels would be correlated tumour progression, however in the NGPDT paradigm a rise in CA markers after treatment does not indicate tumour progression but is more indicative of tumor breakdown.

    TBIL (Total Bilirubin)

    If total bilirubin rises this is not usually associated with NGPDT and may be an indicator of other problems:

    • 1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.
    • 2. Hepatic: Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.
    • 3. Post hepatic: Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or in the bile duct)

  • Does insurance cover the cost of NGPDT?
    A. If the therapy is provided in a jurisdiction where the medical authorities have approved the agent for the specific medical indication, insurance or government payment is usually covered. However, because this is a recently introduced therapy in many areas the costs of the treatment are not covered. In the UK, PDT using Visudyne®, a potentially sight saving procedure in cases of the leaky type of age related macular degeneration, is restricted to patients only if they have already lost the sight in the 'other' eye. Hopefully, as clinical studies increasingly substantiate the benefits of this therapy, insurance coverage will be universally applied, since in many cases the therapy may represent a significant cost savings over conventional surgery, chemotherapy and radiation.
  • Why isn't this therapy more available?
    A. Medicine is by its very nature a conservative enterprise. The motto: 'above all else do not harm' is ever present in the consciousness of most physicians. Any new therapy or medication must for ethical, moral and legal grounds be proven to be the least toxic and most effective possible option for a particular treatment. As this principle applies to the traditional therapies for cancer it is difficult for advanced forms of Photodynamic Therapy not to compare favourably, in the light of the severity of the side effects of the present therapies being widely used.

    One of the problems with the adoption of this new therapy is that it may to a great extent replace the current therapies. The highly trained and skilled cancer surgeons, oncologists and radiation therapists could potentially be made redundant or even obsolete with the significant technical medical advances presently under investigation. This group represents a powerful and influential group who control entry into the medical system, sit on the consultant committees of the FDA, insurance companies and advise them on the payment (or non payment) of 'new' therapies. They have a possible conflict of interest if they are asked to give advice or decide on approvals for technologies which might put themselves out of business, or at the very least allow a powerfully competitive technology to enter the medical environment. These factors and others may play a part in the ongoing availability to patients likely to benefit from these treatments.
  • Why have I not heard about this before?
    A. The use of PDT has been limited in the past to the treatment of localized areas due to the limited availability of advanced photosensitizers and light treatment devices. Although some Physicians may have heard of the therapy many doctors not associated with treating cancer and even oncologists have little in-depth knowledge of, or understanding of the fundamentals and principles involved in this therapy. Also until recently there have been few articles in the general press dealing with the therapy so it is understandable that the general public has heard little to nothing about Next Generation PDT. Fortunately, news travels fast in the age of the internet and with an increase in the availability of the therapy, aswell as the advances in photosensitizers and light delivery systems, we feel many people investigating advantageous cancer therapies will include PDT as a preferred treatment option. We hope this comprehensive source of information will further the general knowledge of the technology and increase the consciousness of the benefits and advances being made in Photodynamic Therapies today.
  • My Doctor is skeptical about the therapy. How do I get him to examine the facts and evidence?
    A. The internet has made information of a highly technical or medical nature accessible to all people, not just professionals. It is possible for a concerned individual to research a topic such as PDT and become more informed on the fundamentals than the vast majority of physicians. It is not uncommon for a physician to have several patients arrive each day for consultation armed with a thick stack of downloaded pages from the internet and a vast and detailed knowledge of their specific diagnosis. The days of Doctor as 'God' and all knowing with a foreign sounding technical vocabulary know only to an elite few is past. Many Doctors lead busy professional lives with work schedules that leave little time for 'keeping up' with the latest developments and the many advances in Medicine. As more information and corroboration of the favorable benefits of light therapy appear in the professional literature as well as the lay press there will naturally follow an increasing knowledge and acceptance of the therapy.
  • How is it possible that light can penetrate deeply into the body?
    A. It is sometimes asserted that light cannot penetrate the human body more than a few millimeters or at most a few centimeters. Therefore, skeptics say, it is impossible to perform photodynamic therapy (PDT) for deep-seated tumors. Yet this statement contradicts common-sense and experience. If you put an ordinary light, such as a laser pointer, up to your fingers, you can see the red light penetrate right through the bone and out the other side. Even with a light source as weak as a flashlight, if you shine it on your palm in a darkened room, some red light will emerge through the other side. The ability of light to penetrate tissues to depths much greater than a few millimeters has been confirmed scientifically, Dr. Harry T. Whelan of the Medical College of Wisconsin and NASA's Marshall Space Flight Center in Huntsville, Alabama, is an expert on the use of light-emitting diodes in medicine. He writes "Spectra taken from the wrist flexor muscles in the human forearm and muscles in the calf of the leg demonstrate that most of the light photons at wavelengths between 630 and 800 nanometers (nm) travel 23 centimeters (cm) through the surface tissue and muscle between input and exit at the photon detector." Twenty-three centimeters is 9+ inches. Logically, therefore, if you illuminate the whole body, front and back, with light in the range of 700nm to 1300nm almost any part of the human body can be treated. This is roughly the range of wavelengths the most advanced agent are being developed for optimum treatment.

    Because light in the near-infrared (NIR) region (700-1300 nm) has decreased absorption by either blood or water compared with visible light (400–650 nm) tissue penetration of NIR photons may be up to 10–15 cm and still maintain half its initial energy level. Importantly, with NG PDT laser technology utilizing a pulsed mode function tissue penetration of Near Infra Red photons (wave length 1200+nm) up to 10 to 20cm so deep tumor may be treated successfully.

    Light is visible to the human eye as the colors of the rainbow, which have wavelengths ranging from 400 to 700 nm. Red light has the longest wavelength, ranging from 622 to 700 nm. Light at wavelengths greater than 700 nm is characterized as infrared and is invisible to the human eye. Most experimental and commercial photosensitizers absorb light in the range of 630 to 820 nm.

    For instance, Photofrin (which is approved by the Food and Drug Administration (FDA) to treat several forms of cancer) has a ‘small peak of absorption at 630 nm. ALA (Levulan) also absorbs at 630 nm. The experimental chlorin derivative Foscan absorbs at 652 nm. Visudyne, which is FDA approved for the treatment of macular degeneration, absorbs at 690 nm. Another chlorin derivative, SQN-400, absorbs in the infrared range at 740 nm. And certain bacteriopurpurins absorb light as high as 800 to 820 nm.
  • What is singlet oxygen?
    A. When photosensitizers (light sensitize molecules which selectively accumulate on cancer cells) are illuminated with certain colors of light they absorb the energy and become 'excited'. With this extra energy, they become unstable and 'off-load' or donate energy as electrons to oxygen in the immediate vicinity and create a special form of oxygen named 'singlet' oxygen. These singlet oxygen molecules also are highly unstable and 'off-load' energy by donating electrons, oxidizing (damaging) the nearby structures in the cancer cells.
  • How does it lead to tumor death or destruction?
    A. When the structures in the cancer cell are oxidized, the resulting damage to the internal microstructures (mitochondria, lyposomes, nucleus or cell membrane etc.) leads to death or damage of the abnormal cells. Because advanced photosensitizers are highly selective the damage to the cancer cells is highly specific.
  • How long does it last/how much of an area does it affect?
    A. Photosensitizers selectively accumulate on diseases cells and following the application of light, singlet oxygen is generated. Singlet oxygen has a short life-span (milliseconds) and a very small area of effect (microns) so the damage from the oxidation of microstructures is confined very selectively to the cancer cell. The greater the selectivity of the photosensitizer, the better the localization of the damage from singlet oxygen formation to the cancer.
  • How does the next generation of PDT differs from "traditional" PDT?
    A. Although the next generation of PDT and PDT are both based on the principle of using light to kill pre-sensitized cancer cells, the next generation of PDT differs from PDT in several important ways.

    First, the sensitizing agent used in the next generation of PDT is in many cases more cancer-selective than the first Generation agents typically used in PDT. The agents licensed by the FDA for use in PDT are for the most part hematoporphyrins, derived from pig and ox blood. These blood-derived photosensitizers accumulate in all the tissues of the body, not just in the cancer tissue and are very slow to be metabolized and excreted.

    Patients who are given these agents must therefore be careful to avoid light for periods of weeks at a time or risk serious burns to the skin.

    By contrast, some advanced agents such as Photosoft are 95% metabolized and cleared from the body within 24 hours, freeing patients from the need to hide from the sun for weeks after treatment.

    Second, because the blood-derived photosensitizers are less powerful (they have a much lower yield of singlet oxygen, the molecules that help to damage or destroy tumor cells) they are not useful for the treatment of deeper seated problems. Instead, fiber-optic catheters or endoscopes must be inserted into the body to bring the light directly to the seat of the tumor, and this limits the scope of the technique considerably. If a tumor cannot be physically reached either by endoscopy or with interstitial insertion of needles and fiberoptic bundles into the tumor it essentially cannot be treated. Also widespread metastatic cancer cannot be treated with these less than optimal photosensitizers developed many decades ago. By contrast, because advanced agents are much more sensitive to longer wavelength light and more powerful than existing ‘approved’ photosensitizers they can be activated at higher wavelengths, which allows a greater depth of penetration and a higher yield of singlet oxygen. In the next generation of Photosensitizers activation takes place from outside the body, minimizing the need for intrusive procedures such as endoscopy or laparoscopy. Next Generation PDT is a much less intrusive technique than PDT and there are fewer side effects because of the lack of specificity of Photofrin (it accumulates in all tissues, not just in cancer tissues) and its relative lack of sensitivity (it has to be activated by direct application of light, necessitating the use of endoscopes or fiber-optic catheters), the number and type of cancers that are suitable candidates for treatment with classical PDT are relatively few.

    Metastatic, deep-seated and larger tumors are not treatable with PDT agents that are not rapidly cleared from the body and do not have higher wave length activations. In addition, Photofrin one of the first generation agents with FDA approval has other drawbacks such as protracted and generalized light sensitivity: it takes several weeks to clear from the human body and during this time patients remain exquisitely light-sensitive, risking serious burns if their skin is exposed to sunlight to even artificial light.

    Next Generation PDT represents a major advance over classical PDT. The photosensitizers used are clearly superior to Photofrin and the other first Generation sensitizers that have so far been developed. New photosensitizers are much more cancer-specific, accumulating preferentially in cancer tissue, and are quickly cleared from the body. Using advanced protocols with oral administration of the agent, patients can typically go about their business and need not remain captive in their homes or a hospital environment, fearing serious skin reactions. Many PDT patients benefitting form the next generation of PS also do not need invasive endoscopic treatment procedures. Because these photosensitizers are so much more light-reactive and efficient they can be activated from outside the body, reducing or eliminating the need for direct illumination via fiber-optic catheters and endoscopes.

    A decade ago, Dr Jacob Lieberman wrote: "I can foresee that, in the near future, photodynamic therapy, alone or in combination with other conventional techniques, will be able to successfully treat most, if not all, cancers and other life-threatening diseases.

    Many authors have written enthusiastically about the potential of PDT and maintained the hope that some day there would be a form of light therapy that would fulfill the enormous promise of the early work in this field. The scientific community now seems to have achieved that breakthrough in the form of Next Generation PDT.
  • How effective is it?
    A. The effectiveness of Next Generation PDT, as with any therapy, depends on many factors. Considerations are:

    • Tumor load (amount of tumor) and location in body
    • Tumor being adjacent to important and critical structures
    • Tumor spread (metastases) to critical structures such as the lungs, brain or liver
    • Previous chemotherapy resulting in a compromised immune system
    • Overall health of patient

    With improving protocols and effectiveness of photosensitizer agents we feel patients even with advances stages of cancer may in many cases, benefit from this form of therapy. A number of clinical studies are collected from well recognized Universities which document the degree of effectiveness of PDT for many types of cancers. These clinical studies are found on the pubmed area of the New England Journal of Medicine website
  • Can Next Generation PDT help metastatic disease?
    A. Next Generation PDT is effective in treating metastatic cancer because even metastatic microscopic cancer cells that are too small to be seen with traditional diagnostic imaging techniques (PET, CT scan, X-ray) are killed with the whole body treatment of NGPDT. Killing these cancer cells with PDT has been proven in numerous scientific studies.
  • Can it treat deep tumours?
    A. Because light in the near-infrared (NIR) region (700-1300 nm) has decreased absorption by either blood or water compared with visible light (400–650 nm) tissue penetration of NIR photons may be up to 10–15 cm and still maintain half its initial energy level. NG PDT uses a combination of highly light sensitive molecules which attach to tumor throughout the body with deeply penetrating laser and LED light to effectively treat deep tumors.
  • What evidence is there that it works?
    A. The observation that certain light sensitive molecules 'cling' to abnormal cell and with light lead to selective death of tumor cells has been proven beyond any doubt. This was observed nearly one hundred years ago and culminated with the approval by the FDA of Photofrin for use in various types of lung and esophageal cancer in the mid 1990's. Since that time photosensitizing agents have been approved by various Medicines Authorities around the world for use in skin cancers (Metvix), head and neck cancer (Foscan), eye conditions (Visudyne), multiple cancer indications (Alasens, Photogen, Photosens) and others. Over 35,000 scientific journal articles appear in search of Medline on the internet and the New England Journal of Medicine, one of the US's most prestigious and respected medical journals has a vetted list of over 7500 articles on 'PDT and Cancer'. At this time dozens of clinical studies are appearing every month in professions publications around the world. Nearly a thousand clinical studies on PDT are found on the pubmed area of the New England Journal of Medicine website "
  • How long does the benefit last from the therapy?
    A. While the benefits of cancer destruction or damage (apoptosis), stasis, coagulation of vessels feeding the tumor and the potential production of tumor specific antibodies (auto vaccination) begin soon or immediately after the initiation of the photodynamic therapy, the benefits can extend far out into the future. Every case is different, but if in fact the latter process of tumor specific antibody formation takes place this is a lifelong recognition of the tumor cells. If the patient is fortunate enough to have the complete elimination of the tumor the benefit is obvious. Where there is significant reduction of tumor and the remaining problem has been dealt a significant blow from death of tumor cells, apoptosis and reduction in blood flow to the tumor there can be a favourable prolongation of quality life as well as increased longevity. Too, if the patient and physician feel, as a result of the treatment significant benefits were realized, the therapy can be repeated since no 'resistance builds up' to the treatment.
  • How does this therapy compare with traditional therapies IE: surgery / chemotherapy / radiation therapy?
    A. An article a study from the Maxiill facial Unit, University College London Hospitals NHS Trust, Eastman Dental Institute, UK. Published in the Lancet Once, December 1, 2000; 1: 212-9 Dr. Colin Hopper states:

    "Photodynamic therapy (PDT) is a minimally invasive treatment with great promise in malignant disease. It can be applied before, or after, chemotherapy, ionizing radiation, or surgery, without compromising these treatments or being compromised itself*. Unlike radiotherapy and surgery, it can be repeated many times at the same site. Response rates and the durability of response with PDT are as good as, or better than, those with standard locoregional treatments. Furthermore, there is less morbidity and better functional and cosmetic outcome. This comment is based on a study of PDT for head and neck cancer using the photosensitizer Foscan®. A number of studies applying this technology to many types of cancer document the efficacy and in some case the superiority over traditional methods of cancer therapy i.e. surgery, chemotherapy and radiation therapy. It is our feeling that further developments and improvements in light delivery systems and photosensitizers will improve the result for many cancer indications and could result in patients opting for PDT rather than conventional therapies considering the significant side effects and potential complications inherent in surgery, chemo and radiation therapy."

    NOTE: Chemotherapy does in many cases have a drastic negative effect on the immune system. Chemotherapy prior to PDT will greatly diminish the possibility of an immune reaction 'vaccine' to the tumor.
  • Can Next Generation PDT be combined with surgery, chemotherapy, and/or radiation?
    A. The traditional therapies for cancer treatment usually begin with a diagnostic work up often leading to a confirmation by biopsy (obtaining a surgical specimen and subjecting it to microscopic pathological examination for the presence of cancer cells). If the tumor is solitary and in a non-critical area, the option of surgical removal (excision) is usually offered to the patient. In many instances, because it is sometimes difficult if not impossible to know fully whether the primary tumor has spread to regional lymph nodes and/or distant parts of the body, if the biopsy shows malignant cells the surgeon may also take samples of nodes and see if they show evidence of malignant cell spread. If this is the case, and in some cases even if this test is negative chemo and/or radiation therapy is recommended as 'insurance' against growth of these malignant growths that might or have spread. Some studies have shown the benefits of Chemo in general to be only about 2.5% in spite harsh side effects and the mutagenic nature of the chemotherapy agents (this is often not explained sufficiently in many authorities opinions.) A number of clinical studies have already shown light therapy to be as good as or better than the historical approaches (i.e. for head and neck cancer) and studies in recurrent breast cancer of the chest wall, where surgery, chemo and radiation have failed to keep the cancer from returning, light therapy has proven to be overwhelmingly effective in completely eliminating the cancer.

    Also, one of the great advantages with PDT is there is nothing that keeps light therapy from being used even after surgery, chemo and radiation. Substantial cost reductions are inherent in the PDT technology. However, the therapy may not be as effective if the previous therapy has significantly weakened the immune system.

    Consider the cost differences (financial, emotional, physical pain, personal loss) between a seven hour surgery for types of esophageal malignancies versus a 30 minute out patient PDT therapy.
  • Does it matter if a patient has had prior chemotherapy?
    A. One experienced clinician in PDT states: 'It can be applied before, or after, chemotherapy, ionizing radiation, or surgery, without compromising these treatments or being compromised itself.' Many studies, however, have shown the presence of a strong and uncompromised immune system is a critical element for the full benefit of the PDT therapy and chemo therapy causes significant damage and lessening of the immune response. It follows that chemotherapy given before PDT will diminish the beneficial response from the agent and light. Also many studies had shown that a competent immune system in combination with PDT leads to the production of an 'auto vaccination' and tumor specific antibodies. If chemotherapy is given soon after the therapy this process would also reduce the effectiveness of the overall favorable response. Fortunately however, many patients have received significant favorable responses with PDT, in spite of having prior heavy chemotherapy etc.
  • What are the side effects?
    A. The usual side effect associated with 'first Generation' agents such as Photofrin, the one approved for use by the FDA in the US and the EMEA in the EU, has been prolonged photosensitivity or 'sun-burn'. This is caused by residual agent remaining in skin and tissue for up to 90 days following intra-venous (by vein) administration. Foscan, the agent approved in the EU for treatment of head and neck cancer, likewise can lead to burning of the skin with sun exposure for up to a month or more.

    Fortunately, the agents used in the next generation of PDT clear quickly from the body's skin and normal tissue and there is essentially no light sensitivity.

    Another symptom noted frequently is discomfort in the area of the tumor. This is not so much a 'side' effect as a 'direct' effect of the therapy resulting in tumor damage and/or death. The body attempts to eliminate the unwanted dead cells in the inflammatory process which is associated with discomfort, swelling, heat and redness.
  • Can the treatment be repeated and does cancer grow a tolerance to it?
    A. Because most photosensitizers are non toxic in therapeutic amounts, they are not recognized by the cells as a foreign material. In fact, they can almost be compared to 'trojan horses' since they enter the cell attached to a 'carrier' molecule called a lipo-protein in the same manner that sugars are transported into the cell also attached to lipo-proteins. To the cell they seem the same as sugar 'candy' entering for their enjoyment and nourishment. The cells 'see' no need to build a defense against this process so no 'resistance' develops in the cancer cells. The therapy (and agent) can therefore be repeated many times and no resistance 'builds up' to the process.
  • What is a Photosensitizer Agent?
    A. Most photosensitizers are from a class of naturally occurring compounds named porphyrins or Tetrapyrroles which are among the most commonly occurring natural compounds in the world. For example, the chlorophylls are the primary photosynthetic pigments in higher plants, algae and bacteria. Other tetrapyrroles (porphyrins, chlorins and corrins) include cobalamin (vitamin B12) and heme/hemoglobin . Many natural porphyrins in the body are breakdown products from recycled hemoglobin and are intrinsically 'light sensitive'. These accumulate in tumor naturally and cause cancer cells to 'auto-fluorescence'. The first Generation photosensitizer approved for use in cancer treatment, Photofrin, is derived from pig or cow hemoglobin while some of the more advanced agents are either chlorophyll derivatives or chemically compounded. What is common to all these agents is the propensity to selectively accumulate on tumor cells and be energized by light. These are the vital elements that make the therapy so effective in the treatment of cancer and other diseases.
  • Why do photosensitizers also selectively accumulate on cholesterol plaques, new vessels, viruses, bacteria and fungus?
    A. Otto Warburg won the Noble Prize in 1931 for documenting the basic metabolism of cancer cells differs from normal cells. Cancer cells have a 'Lactic Acid', anaerobic (no oxygen) metabolism with highly negatively charged micro structures (mitochondria) while normal cells are characterized by Aerobic (oxygen) metabolism. Because photosensitizers tend to precipitate in an acid environment (such a cancer cells) and have elements on the molecule that are positively charged they adhere to the negative charges on the structures in the cancer cells. Likewise, because viruses are made of RNA (ribonucleic acid) and gram positive bacteria have a cell wall with a large proportion of an ester of lactic acit, the same accumulation of agent on viruses and gram positive bacteria takes place.

    The aspect of photodynamic therapy which affects vasculature and blood stasis is exploited in the use of the therapy for improvement of AMD. Due to a selective uptake in areas of choroidal neovasculature of certain photosensitizers, (Visudyne™ is the approved FDA agent of choice at the present time) light can be applied which leads to the selective thrombosis (closure) of the leaking vessels and the interruption of progressive damage to the maculae and consequent decrease in vision.

    PDT is now an established therapy for the treatment of 'wet' neo vascular Age Related Macular Degeneration (AMD) and some other retinal diseases associated with leaky new vessels.
  • How are photosensitizers given?
    A. Typically, earlier photosensitizers have been given in an intravenous form but the Next Generation of PDT has pioneered the use of PS in an oral and inhalation form. This is possible since the agent is amphiphilic; (dissolves easily into the bloodstream while entering easily through the lipid cell membrane). The oral administration has obvious advantages in ease of administration, cost reductions from avoiding the need for IV set up and greater patient acceptance.
  • What type of light is used?
    A. Each photosensitizer (light sensitive) agent has a certain color in the visible spectrum (or specific wave-length in the NIR) of light at which they are massively energized. The technical term for this is 'peaks of absorption'. The agents can be most powerfully activated (and therefore generate the greatest yields of 'cancer killing' singlet oxygen) by illuminating the treatment area with colors and wave lengths of light which match these peaks.

    The light source used in PDT has historically been LASER light delivered through fiberoptic bundles via an endoscope (tubes inserted into the lungs or esophagus to visualize areas suspected of harbouring cancer). The laser light could then be used to activate the agent collected on the tumor, leading to reduction or elimination of the tumor. This treats the localized area of cancer but does not address the possible small bits of tumor (metastases) that often spread from the primary into regional lymph nodes or distant sites. Additionally, laser light could be used with direct illumination of the tumor in the case of skin cancer or visible external tumors.

    To treat larger areas or the whole body the Next Generation PDT technology utilizes a device (Whole Body Light Delivery System) with tens of thousands of Light Emitting Diodes (LEDs) . These hi-tech light sources can be selected for the particular wave-length that specifically activates the photosensitizer. One additional advantage of using this light form is the possibility of using a mixture of LEDs (red and infra-red) to simultaneously activate multiple peaks of activation of the photosensitizer.
  • How are blue, red and infra-red wave lengths use to treat different types of problems?
    A. Light is a form of energy that is familiar to us. However, the part of light that is visible to us is only about 10% of this spectrum of energy. The full range extends from ultra-violet (invisible), through all the colors of visible light into infra-red (invisible). Ultra-violet light has a very short wave length (370-390nanometers), is highly energetic yet only penetrated a small distance into the skin (because this wave length is greatly absorbed by hemoglobin). This is why UV light causes ‘sun burns’ on the skin but does not result in damage to deeper tissues or organs. In contrast, infra-red light (700-1300 nanometers) penetrates deeply into tissue, up to 25 cm. (12 inches) but does not possess very significant energy compared to uv light. Beyond this range water absorbs significant energy and limits the penetration of energy at the middle and far IR wavelengths. The band between 650-1300nm is called the optical or therapeutic window and the next generation of photosensitizer which have been specifically developed to optimize effective treatment of tumor and medical condition promises to revolutionize the safe and effective treatment of deep, advanced and metastatic cancer and other medical problems.

    These factors determine what colors (wave lengths) are utilized to treat the various areas of the body.

    • Blue light, only penetrates a short distance into the skin and photosensitizers with peaks of absorption in the blue range are used for the treatment of skin lesions (skin cancer, warts, psoriasis etc.) because a powerful yet superficial therapy can be delivered.
    • Red light, which penetrates much deeper into the tissue, and photosensitizers with peaks of absorption in the 630-690nm range (red) are used to treat intermediate to deep tumors.
    • Infra-red light, which has deep penetration into the tissue, and agents with peaks of absorption in the infra-red range (700-1300) are appropriate for the therapy of deep tumors.

    Photosoft has peaks of absorption in the blue, red and infra-red so LED arrays are chose to contain both red and infra-red light sources. Consequently, agent that has accumulated on tumor even in the deepest part of the body is activated by the deeply penetrating near infra-red light sources.
  • Can Photodynamic Therapy be used to treat liver metastases?
    A. A study from Germany and a FDA clinical trial undertaken by Life Science Oncology in the US suggests the potential efficacy of photodynamic therapy (PDT) in the treatment of liver metastases. Results of the German study were presented at the annual meeting of the Radiological Society of North America in December 2002. A research team led by Kerstin Engelmann, MD, of Johann Wolfgang Goethe University in Frankfurt-am-Main, treated five patients using a photosensitizing drug called SQN 400. This agent, manufactured by Scotia QuantaNova (SQN), is activated by infrared light at a wavelength of 740 nanometers. SQN 400 is the trade name of a chemical called meta-tetra (hydroxyphenyl) bacteriochlorin (mTHPBC), which is a chemically modified form of chlorophyll, or chlorin.

    All patients in the study had colorectal cancers that had spread to the liver, and all had been treated previously with chemotherapy. One had also received radiation therapy, and another had undergone the surgical removal of half his liver.

    Laser light was delivered through a catheter five days after the injection of the photosensitizer. Dr. Engelmann reported complete destruction of the cancer in three of five patients at follow-up examinations done three months after treatment. There were some serious side effects with SQN 400. Patients had to avoid bright electrical light for several days and direct sunlight for four weeks following treatment, due to the drug's photosensitizing effect and its slow elimination from the body. Three of the five patients reported local pain during injection. One reported that pain then spread to the shoulder. Several patients experienced minor burns. There are some significant differences between PDT using SQN 400 and some of the other advanced photosensitizers. These are absorbed and eliminated more quickly, and therefore have fewer side effects and less discomfort. Also, the source of lighting in Next Generation PDT is whole-body red and infrared light that is administered externally, not through fiber optic catheters, making for a noninvasive procedure.

    Despite the differences, this study does show that the combination of light at high wavelengths and green chlorin-based photosensitizers is a promising cancer treatment. In the authors' words, "This pilot study establishes that the procedure can eliminate metastatic liver tumors in some patients." But as they properly point out, more study is needed to see how useful the treatment is when compared with other ways of eliminating liver tumors.
  • Will my physician or oncologist know about older forms of PDT and the huge advances made in recent years?
    A. Many physicians are already aware of PDT as it has become an established cancer treatment over the past ten years. However, they may be unaware of rapid advances in PDT technology, as recent technology has enabled us to accelerate the progression of PDT in our research and development labs. It is in the patient's best interest that everyone concerned is thoroughly informed. Physicians may find out about older forms of PDT as well as the many significant developments in PDT via the internet, medical journals, scientific studies/medical trials and through accessing published articles in the professional journals under the topic of PDT.