Cellular Aspects of PDT of Cancer
Photodynamic therapy initiates a set of complex reactions in cells. These photochemical reactions are targeted at many structures, such as cell membranes, mitochondria, DNA, and microtubules. Exposure to optical radiation is likely to be followed by generation of free radicals and calcium production. As the membrane damage progresses, other electrolytic changes can be observable. The involvement of many systems produces a sub-lethal cellular damage, which may cause apoptosis. Indirect effects, such as ischemic necrosis caused by vascular damages, can be important in vivo. Photodynamic effects can be modulated by changing the dose and injection rate. Furthermore, photosensitizers can be conjugated with lipoproteins, liposomes, and some other chemical substances. There is much to be studied. In the future, more systemic studies will be carried out to refine the dependence of PDT results on cell types, photosensitizers, and therapeutic conditions. However, there is good reason for optimism because the gained knowledge underlies a firm basis for clinical trials under way.
Economic Aspects of PDT of Cancer
In conclusion, let us dwell on the prospects for PDT application in the treatment of cancer. To begin with, we shall estimate the prevalence of this pathology and the economic damage caused by malignant tumors.
Everybody on Earth feels the negative psychogenic effect of cancer. In 2001, according to the World Health Organization, cancer was first diagnosed in 10 million people and more than 6 million people died of cancer. Most often, cancer strikes the lung (lung cancer) and gastro-intestinal tract (stomach cancer, esophagus cancer, large-intestine cancer, and rectum cancer). Lung and gastro-intestinal cancer constitutes 47 percent of ten most frequent cancer locations. They also account for 42 % of cancer-provoked deaths around the world.
Cancer causes a substantial damage to economy. According to the National Institutes of Health, the economic damage due to cancer in 2001 reached $ 180.2 billion in the U.S. alone.
By way of example, consider the economic efficiency of PDT in the treatment of the most frequent forms of cancer. Let us consider accessible tumors. As is known, PDT is most efficient at early stages. Lung and gastrointestinal cancer can rarely be diagnosed at early stages. As a result, despite all of its merits, PDT contributes little to the economy in these cases. The situation changes drastically in the case of skin cancer.
Photodynamic therapy, both in Russia and abroad, is applied in 65 to 70 percent of patients with skin cancer. In this case, PDT yields a 100% therapeutic efficiency.
Photodynamic therapy of skin cancer normally requires a single session under outpatient conditions, whereas a routine brachytherapy (near-focus X-ray therapy) lasts for 2 to 3 weeks. In this sense, PDT provides a much better economic efficiency. Photodynamic therapy has a similar effect in the case of other superficial malignant tumors. For example, it goes for mammary-gland cancer, tongue cancer, mucous cancer, lower-lip cancer, melanoma metastases, and other tumors.
Endoscopy-based PDT yields good clinical and economic results. In this case, PDT makes it possible to recover the functioning of a tumor-obturated esophagus, trachea, and large bronchi. Fiber-optics PDT can treat other tumor-stricken internal organs. For example, it can be used in the treatment of hard-to-reach tumors located in the pancreatoduodenal region and common hepatic duct.
Hence, the PDT advantages are as follows:
Photodynamic therapy is applied when surgery is contraindicated because of the tumor spread and serious associated diseases. Photodynamic therapy is targeted at tumor cells, and it causes no damage to healthy tissues. Due to this, when PDT has destroyed a tumor, normal cells begin to propagate and fill the organ's frame. This is of special importance for PDT of thin-walled and tubular organs (such as the stomach, large intestine, esophagus, trachea, bronchi, and urinary bladder). Photodynamic therapy avoids perforation of the organ's wall.
Photodynamic therapy produces a targeted effect. A photosensitizer is selectively accumulated in a tumor, and it is rapidly eliminated from healthy cells that surround the tumor. Due to this, red light causes a selective damage to the tumor, not surrounding tissues.
Photodynamic therapy avoids the systemic effect on the human being (in the case of chemotherapy of tumors, this effect does take place). Photodynamic therapy treats a region exposed to light. As a result, the patient is not subjected to an unwanted systemic effect. This makes it possible to prevent the patient from all side effects, typical of chemotherapy (such as nausea, vomiting, stomatitis, loss of hair, and inhibition of hematopoiesis).
Photodynamic therapy is cost-effective. For a majority of patients, PDT is a noninvasive or minimally invasive method. It is also a tolerant, local, and inexpensive technique, which can treat a variety of malignant tumors (primary, relapsing, and metastatic).
The Ministry of Health of Russia analyzed the results of PDT application in Moscow Medical Centers. Photodynamic therapy was employed to treat malignant tumors of the skin, mammary gland, mucous membrane of the oral cavity, tongue, lower lip, larynx, lung, esophagus, stomach, urinary bladder, and rectum.
From 1992 to 2001, PDT was used to treat more than 1,600 tumors in 408 patients. Most of the patients had been treated earlier with routine methods, such as surgery, X-ray therapy, and combined treatment. Some of the patients had not been treated earlier owing to serious age-related and associated diseases. The rest of the patients received palliative PDT. They had extended obturating tumors of the esophagus, trachea, large intestine, large bronchi and the cardiac portion of the stomach. Photodynamic therapy was performed to recanalize stenosed organs and to improve the quality of life. Follow-up studies had been made for 2 months to 9 years. Photodynamic therapy produced a beneficial effect in 94.4 percent of the patients. Of these, 56.2 percent showed a total tumor resolution and 38.2 percent showed a partial tumor resolution.
Photodynamic therapy is an advanced therapeutic technique, which is successfully employed in Russia, USA and Europe. At present, new photosensitizers and optical sources are being developed for PDT and fluorescent diagnosis.
Photodynamic therapy is a promising, cutting-edge, and cost-effective method for treatment of malignant and non-malignant diseases. To disseminate information about this technique, PDT-oriented workshops and schools should be arranged for physicians.