Despite the latest advances in oncology, the problem of treating malignant diseases has not been resolved yet. In most cases, the treatment is beneficial at early stages of cancer. However, two thirds of patients reveal advanced cancer. Only a half of them undergo special treatment. However, surgery, radiotherapy, and combined treatment have limited capabilities for advanced cancer. The rates of recovery and five-year survival are below 10 percent after such treatments. Most of the patients die of relapses and metastases, which appear after radical treatment during the next two years. Until recently, there was no adequate technique for the treatment of such patients.

Besides that, many patients (up to 25 percent) have operable cancer, but cannot undergo surgical treatment. This is because of serious associated diseases and age-related disorders. These patients often undergo organ-saving surgical treatment. However, such treatment also has a high rate of local relapses. Until the last decade, there was no adequate treatment for these patients either.

The advent of photodynamic therapy (PDT) has considerably extended oncologic capabilities. Photodynamic therapy is a therapeutic technique for malignant diseases, and it is new in principle. This technique uses the photodynamic damaging of tumor cells by means of photochemical reactions.
     Photodynamic therapy is a two-component therapeutic technique. The first component is a photosensitizer, which is accumulated in tumors. It remains in tumor cells longer than in healthy cells. The second component is optical radiation whose wavelength corresponds to the photosensitizer’s absorption maximum. The local irradiation of a tumor containing the photosensitizer brings about photochemical reactions in it. These reactions generate singlet oxygen and free radicals that produce a toxic effect on tumor cells. As a result, the tumor resolves, and tumor cells are substituted by connective tissue.

Photodynamic therapy causes a local damage. On the one hand, this is due to the selective photosensitizer accumulation in tumor cells. On the other hand, the treatment is performed using a narrow and targeted laser beam.
     Photodynamic therapy offers a number of advantages over traditional techniques for malignant tumors (such as surgical operation, radiotherapy, and chemotherapy). First, PDT is highly selective and targeted in action. Second, it is free of surgical risks, serious damages, and systemic complications. Third, PDT sessions can be repeated as many times as needed. Fourth, a single PDT procedure enables both the treatment and fluorescent diagnosis. Finally, most patients exhibit tumor resolution after a single PDT cure, which can be performed under outpatient conditions.

Over the last several years, PDT was successfully applied with different photosensitizers. This technique was employed in the treatment of a variety of malignant tumors. Most of these tumors were cancers of the skin, lower lip, tongue, mouth, larynx, lung, urinary bladder, gastrointestinal organs, and genitals (T. J. Dougherty, 1988; S. Marcus, 1992; H. I. Pass, 1993; O. K. Skobelkin with co-workers, 1992; and E. F. Stranadko with co-workers, 1992 to 1997).

Photodynamic Therapy Trends

1. The first trend deals with early-stage cancer. The treatment is based on a radical program, aimed at the patient’s complete recovery. The program is used to treat skin cancer (such as multiple cancer, extended superficial cancer, as well as cancer with inconvenient locations on the face and concha of auricle). It is also employed to treat cancer of the lung, esophagus, genitals, and urinary bladder (such as superficial and multiple nodular cancer).
2. The second trend is concerned with advanced cancer of the trachea, large bronchi, esophagus, and cardiac portion of the stomach. In this case, PDT is employed to recanalize tubular organs. As compared to laser photodestruction, PDT has fewer complications and longer remission periods.
3. The third trend is based on the combined application of PDT and other techniques (such as polychemotherapy). This approach is employed to treat relapsing cancer of the skin, lower lip, and tongue. It is also used to treat intracutaneous metastases of melanoma and intracutaneous metastases and relapses of mammary gland cancer.

Currently, PDT is being tested for other applications. For example, PDT is applied in the surgical pretreatment for minimizing the volume of resection. It is also used in some nonradical treatments performed on tumors of cerebral and biliary-digestive regions. In these cases, PDT improves surgical and therapeutic efficiencies. Photodynamic therapy can also produce considerable palliative and hemostatic effects. This is of special importance for treating extended decaying tumors.
     Photodynamic therapy is a harmless technique, and patients show good tolerance to it. As a result, PDT can be effectively combined with surgery, radiotherapy, and chemotherapy. Furthermore, short-term PDT treatment under outpatient conditions offers a great economic benefit.

The disadvantage of PDT is that the patient should remain heliophobic for a long time after photosensitizer introduction. This requirement is associated with to the photosensitivity of the patient’s skin. In order to avoid possible complications, the patient should exercise great caution. This is particularly important at the stage of acquiring clinical experience.
     The aim of the current manual is to outline PDT capabilities to the clinical practitioners of different branches (such as therapists, surgeons, and gynecologists). This manual will also be of interest to oncologists and dermatologists in terms of PDT application. This manual was written by an expert group of the State Research Center for Laser Medicine, affiliated with the Ministry of Public Health of the Russian Federation. The authors of this manual have a many-year clinical experience in PDT application.

Photodynamic Therapy Equipment
     As a source of optical radiation, PDT widely employs argon pumped dye lasers and copper vapor lasers (emitting at the wavelength of 630 nm). The last decade has seen an increasing number of PDT procedures performed with Photofrin photosensitizers and their analogs. These photosensitizers can work with gold vapor lasers (emitting at the wavelength of 627.8 nm). Gold vapor lasers are cheaper and smaller because they do not need water cooling.
     As an example of an argon pumped dye laser, consider the Innova-200 laser therapy system (manufactured by American Company “Coherent”).

1. Performance specification of an American argon pumped dye laser
   (Innova 200 laser therapy system):
   
   Radiation mode:       continuous wave
   Output power:       up to 5 W
   Radiation wavelength:      630 nm
   Readiness time:      5 min
   Power meter:      Available
   Automatic exposure timer:    1 to 9,999 sec
   Guaranteed operation life:   1,000 h (the dye needs replacing every 1,000 hours of work)
   Power supply:      30 kW, three-phase current
   Cooling agent:       Water
   Cooling agent flow:      9.5 liter/min
   Weight:         250 kg
2. Performance specification of a Russian tunable dye laser pumped by a copper vapor laser
   (Yakhroma 2 laser therapy system):
   
   Radiation mode:       pulsed (pulse repetition rate: 10,000 pulses/sec)
   Output power:       up to 3 W
   Radiation wavelength:      600 to 660 nm (depending on the dye)
   Readiness time:      not less than 60 min
   Power meter:        Available
   Automatic exposure timer:    50 to 750 sec
   Guaranteed operation life:   500 h (the dye needs replacing every 2 to 4 hours of work)
   Power supply:        5 kW, three-phase current
   Cooling agent:      Water
   Cooling agent flow:      2 to 4 liters/min
   Weight:         400 kg
   

Parameters that are of special importance for physicians operating laser systems are as follows: the output power, readiness time (the shorter, the better), and guaranteed operation life. The last parameter shows the time during which the laser will produce laser pulses of a specified power. When this time expires, the output power of laser pulses gradually decreases. This arises from the fading of the dye, which needs replacing. Hence, an essential disadvantage of lasers of this type is the need for replacing dyes or gas cylinders.

Diode lasers have a number of advantages over the above-described lasers. First, they are small and cost-effective. Second, diode lasers do not require water cooling. Third, they can operate off the 220 V supply line. Fourth, diode lasers have a longer operation life (without any replacement). However, diode lasers cannot produce a required power at the wavelength of 630 nm.
     Laser radiation is delivered to a tumor through single quartz fibers. Such fibers are 1.5 to 3 meters in length and 400 to 600 micrometers in diameter.
     In Russia, quartz fibers are manufactured by the Moscow Institute of Applied Problems of Fiber Optics. They come in a wide range of modifications:

• with a microlens (KM-3),
• with a cylinder-shaped diffuser (KTs-3) (which can be 0.5, 1.0, 2.0, 3.0, and 4.0 cm long),
• with a sphere-shaped diffuser (KS-3), and
• with different side reflectors  (KTsB-3) (which can be 0.5, 1.0, 2.0, and 4.0 cm long).

In the United States, quartz fibers are manufactured, for example, by PhotoTherapeutics, Inc. These fibers come:

• with a sphere-type diffuser (model 4402), and
• with cylinder-shaped diffusers (models 4405, 4410, and 4430 of lengths 0.5, 1.0, and 3.0 cm, respectively).

Photodynamic therapy of internal organs is performed using commercially available endoscopes:

• laryngoscopes and bronchoscopes are employed to treat cancer of the larynx,
• bronchoscopes (such as the Friedel rigid bronchoscope and the Schtortz flexible bronchoscope) are used to treat cancer of the trachea,
• fibrogastroscopes (such as the Olympus fibrogastroscope) are employed to treat cancer of the esophagus and stomach,
• rectoscopes find use in the treatment of cancer of the rectum,
• fibrocolonoscopes are used to treat cancer of the colon, and
• Schtortz cystoscopes are employed to treat cancer of the urinary bladder.

When cancer affects internal organs, PDT should be performed using an endoscopic video system.
     To deliver optical radiation to superficial tumors, one should use light-guiding fibers with a microlens at the end. Such light-guiding fibers produce a round patterna clear spot. The fiber is located at some distance from a tumor. It should be positioned such that the light spot would cover the tumor and part of surrounding tissue. The light spot should lap 2 to 3 cm over the tumor. Large tumors and tumors of irregular shapes should be irradiated using several light-guiding fibers.
     Photodynamic therapy can also be performed using nonlaser radiation sources, such as light-emitting diodes (LEDs) and gas-discharge lamps with light-filters.

Photosensitizers
     As photosensitizers, present-day medicine employs a number of dyes. They are as follows: Photofrin (USA and Canada), Photosan (Germany), HpD (China), Photohem (Russia), Benzoporphyrin derivative (Canada), 5- aminolevulenic acid (Europe and USA), Aspartate chlorin e6 (Japan), and some others. Much more photosensitizers are being tested on laboratory animals. In Russia, PDT of malignant tumors is performed using the Photohem photosensitizer.

Photohem is a photosensitizer of the first generation. It is attributed to the group of hematoporphyrin derivatives. This compound is made of defibrinated blood of animals according to a special technique. This photosensitizer was developed at the M. V. Lomonosov Moscow Institute of Fine Chemical Technology. Photohem development was headed by Professor A. F. Mironov. The Pharmacological State Committee authorized this photosensitizer for industrial production and medical application in adult people (Extract from Protocol No. 4 of the Pharmacological State Committee Session, March 14, 1996).

Photohem is a mixture of monomeric and oligomeric hematoporphyrin derivatives. Its maximum absorption falls at the wavelength of 630 nm. This photosensitizer comes in sterile 50-ml vials. It represents a dark violet powder. The Photohem sample weighs 260 mg, whereas the active medium weighs 200 mg. It should be kept in dark storage at a temperature of not more than -5°C. Although this compound can be stored for 2 years, it perishes in frequent unfreezing.

Photodynamic Therapy Procedure
     Photosensitizer Introduction
     Photohem should be dissolved shortly before its intravenous injection. When a working solution is made, the vial is wrapped in light-tight paper. After that, 40 ml of a physiological solution are added under sterile conditions. The vial is shaken and held for 3 to 5 min to let the foam settle down. A requisite Photohem dose is calculated from the patient’s weight and an 0.5 percent concentration of the active medium (i. e., 1 ml of the prepared solution contains 5 mg of the compound). The Photohem injection is calculated on the basis of 1 to 2 mg per 1 kg of the patient’s weight. The solution is injected intravenously as an idle jet.

Photohem can also be applied interstitially or topically. In the case of interstitial introduction, an 0.5 percent Photohem solution is used. The solution amount depends on the tumor size. It usually ranges between 0.2 to 1.0 ml. In the case of topical application, a Photohem solution should be combined with dimethylsulfoxide in a 10:1 proportion. The use of dimethylsulfoxide enhances Photohem penetration into tumor tissues.

Energy Density, Power Density, and Exposure Time
     The PDT exposure time depends on the effective energy density of optical radiation (E).
     Energy density is measured in Joules per square centimeter (J/cm²). It is determined empirically and depends on the tumor’s type, histology, and location. Usually, the radiation energy density (E) is ranges between 50 and 600 J/cm². In the case of superficial tumors of the skin and mucous membrane, the radiation energy density (E) is in a range of 50 to 150 J/cm². In the case of advanced basal cell carcinoma, exophytic squamous cell carcinoma, metatypical cancer, and adenocarcinoma of internal organs with infiltration, the radiation energy density (E) ranges between 200 and 300 J/cm².

Another important PDT parameter is the radiation power density (P_s). It is measured in Watts per square centimeter (W/cm²). The radiation power density (P_s) is determined by dividing the output power at the fiber’s end into the exposed area (the light spot area):

  Pв
P_s=----
        S

Here, P_s is the radiation power density (W/cm²), P_B is the output power at the fiber’s end (W), and S is the exposed area (the light spot area) (cm²). The output power at the light-guiding fiber’s end can be measured using a power meter.
     The exposure time (T) is measured in seconds (s). It is determined by dividing the given energy density (E), which should be administered to a tumor, into the radiation power density (P_s):

T = E / P_s.

In order to simplify calculations, we shall give a table of radiation power density (P_s) as a function of both the output power at the light-guiding fiber’s end (P_B) and the light spot area (S).

Example 1. Let us calculate the exposure time of squamous cell carcinoma. Let the light spot diameter (D) be equal to 2 cm, the given energy density (E) be equal to 300 J/cm², and the output power at the light-guiding fiber’s end (it is measured by the power meter) (P_B) be equal to 0.5 W.
      In this case, we can look up the necessary value in the table. When P_B = 0.5 W and S = 3.14 cm², we obtain

P_s = 0.16 W/cm².

The exposure time can be calculated as follows:

T = E/P_s = 300 (J/cm²) / 0.16 (W/cm²) = 1875 sec = 31 min.

Example 2. Let us calculate the exposure time (T) when P_B = 1.5 W. From the table, we find that P_s = 0.48 W/cm². Hence, the exposure time is as follows:

T = 300 (J/cm²) / 0.48 (W/cm²) = 625 sec = 10.5 min.

When a light-guiding fiber with a cylindrical diffuser is used, the radiation power is calculated for 1 cm of the diffuser’s length:

P_d = P_vi/d.

     Here, P_d is the optical radiation power per 1 cm of the diffuser’s length (W/cm of length), d is the diffuser’s length (cm), and P_vi is the integral power at the fiber’s end (W). If there is no power meter at hand, the integral power P_vi can be approximately set equal to the output power of the radiation source decreased by 10 to 15 percent.
     The exposure time (in seconds) for a cylinder-shaped diffuser is given by

T_d = E/P_d,

     where Е is the given power density (W/cm²) and P_d is the optical radiation power for 1 cm of the diffuser’s length (W/cm of length).

Example 3. Let us calculate the exposure time for a tumor of a tubular organ of a diameter of 1 cm. Suppose that the irradiation is performed using a light-guiding fiber with a cylinder-shaped diffuser of a length of 2 cm. The size of the circular tumor is 1.5 cm. The given radiation energy density is 300 J/cm². The integral output power at the end of a fiber with a cylinder-shaped diffuser (P_vi) is 0.8 W. In this case, one obtains:

P_d = 0.8W / 2 cm = 0.4 W/cm of length,
T = 300 / 0.4 = 750 sec = 12.5 min.

Example 4. Let us calculate the exposure time (T) when P_vi = 0.8 W and when the tumor size is 0.5 cm. The given energy density of optical radiation is 300 J/cm².

P_d = 0.8 W / 0.5 cm = 1.6 W/cm of length,
T = 300 / 1.6 = 187 sec = 3 min.

Indications to PDT of Malignant Tumors
     General Indications to PDT

1. In the case of early primary cancer and early relapses, PDT is indicated to patients with serious associated diseases and age-related disorders. It is performed according to a radical program when traditional therapeutic techniques (such as surgery and radiotherapy) are contraindicated.
2. In the case of advanced tumors of tubular organs (such as the esophagus, cardiac portion of the stomach, trachea, rectum, as well as the main, intermediate, and lobe bronchi), PDT is performed to recanalize these organs. It is employed as a palliative therapeutic technique.
3. In the case of advanced decaying tumors complicated by intracutaneous metastases, PDT is combined with radiotherapy and chemotherapy. In this case, PDT is employed to stop bleeding and decrease the tumor volume.

Indications to PDT of Skin Cancer:

1. Basal cell carcinoma, squamous cell carcinoma, and metatypical carcinoma T_1-3N₀M₀;
2. Relapsing and residual tumors that are resistant to traditional therapeutic techniques;
3. Multiple tumors;
4. Extended tumors;
5. Tumors with inconvenient locations on the periorbital region, nasolabial fold, nose wings, concha of auricle, and external acoustic duct); and
6. Patients’ refusal to the treatment with routine techniques.

Indications to PDT of the Oropharyngeal Region:

1. Squamous cell carcinoma T_1-3N₀M₀ characterized by the high risk of developing complications in elderly patients and patients with associated diseases after radiotherapy and surgery;
2. Tumors that are resistant to routine treatments,
3. Relapsing and residual tumors,
4. Patients’ refusal to the treatment with routine techniques.

Contraindications to Photodynamic Therapy
     Absolute Contraindications:
     Cardiovascular deficiency, respiratory insufficiency, hepatic diseases, renal diseases at the decompensation stage, systemic red lupus, and cachexy.

Relative Contraindications:
     Allergic diseases as well as regional and distant metastases.
     While considering the patient’s indications and contraindications to PDT, the physician has to employ the individual-base approach. The physician should also estimate the tumor process, risk of traditional treatment, and severity of associated diseases and possible complications.

Estimation of PDT Results
     The tumor resolution period after PDT depends on a number of factors. The most important of them are as follows: the tumor size, infiltration depth, tumor location, and radiation energy density. Normally, the tumor resolution period ranges from 2 days to 3 weeks.
     When PDT is used to treat ulcerated and infiltrating tumors, it produces a pronounced damaging effect. It is characterized by extensive and deep hemorrhagic necrosis. In this case, the debridement of necrotic tissues and epithelization of the treated site may take from 2 to 10 weeks. The exact time of resolution period depends on the tumor size, necrotic depth, and PDT parameters. After the treatment, most patients exhibit good esthetic and functional results.

Criteria for Estimation of PDT Results

1. A complete tumor resolution is verified by the absence of observable and palpatable defects. This should also be confirmed by negative results of cytological and histological examinations.
2. Partial regression is verified when the maximum tumor size decreased not less than by 50 percent, the tumor became invisible, but cytological and histological examinations show tumor cells. A tumor relapse after PDT is verified in the same manner.
3. The absence of the therapeutic effect is verified when the tumor size decreased less than by 50 percent and when the patient revealed no changes.

In the case of skin cancer, PDT demonstrated a 100-percent clinical effect. A complete tumor resolution was observed in 90 percent of cases. The rest of the patients, who usually had extended skin tumors, showed a partial tumor resolution.
     In the case of other tumor locations, PDT efficiency was somewhat lower: between 70 and 90 percent. A decrease in the PDT efficiency was associated with changes in the blood supply (for example, owing to tumor relapses after radiotherapy). It was also related to engineering difficulties in the administration of an adequate optical radiation dose to the entire tumor.
     In the case of early malignant tumors, PDT efficiency ranged between 90 and 100 percent. A complete tumor resolution was observed in 55 to 70 percent of the patients.

Complications of Photodynamic Therapy
     An essential disadvantage of Photohem and other photosensitizers is that they remain in the skin for a long time. However, when photosensitizers are retained in the skin even at small concentrations, they make the skin highly photosensitive and phototoxic. As a result, when patients violates heliophobic conditions, they receive a first-degree burn. It usually affects the patients’ face and open parts of the body. The burning is normally followed by skin pigmentation. When patients are often exposed to bright light for short periods of time, they may reveal pigmentation without burning.

Photodynamic therapy may bring about violent photochemical reactions and significant necrobiotic changes. The decay products of these reactions can cause intoxication and hyperthermal reactions. These phenomena often take place in the case of multiple and extended tumors. In particular, this goes for ulcerated extended tumors.
     Within the next few days after a PTD session, almost all of the patients develop an edema. It arises from photochemical reactions in biological tissues owing to interstitial light scattering. The most pronounced edema develops after PDT of the skin of the face. This edema does not require special treatment and disappears within 3 to 4 days after the PDT session.

In rare cases, PDT with Photohem may cause herpes, which often affects the patient’s lips. Herpetic lesions may develop within 3 days to 2 weeks.
     Photodynamic therapy of the esophagus may cause esophagitis. When optical radiation is overdosed, PDT may cause remote development of circular scars.
     The PDT of bronchogenic or lung cancer may cause suppurative endobronchitis, which needs antiphlogistic treatment. The PDT of exophytic obturating cancer of the major bronchus is followed by bronchial tree sanitation performed 2 to 3 days later. The bronchial tree sanitation is needed to remove the detritus.

When PDT is used to treat superficial cancer of the urinary bladder, it may cause fibrosis of the urinary bladder wall, followed by a decrease in the urinary bladder volume. This effect takes place when the entire surface of the urinary bladder is subjected to irradiation.
     Some patients may develop remote parestesia and induration of subcutaneous cellular tissues in the exposed site.
     In general, the rate of complications associated with PDT does not exceed 5 percent.

Prevention of Complications
     As was mentioned, Photohem penetrates the skin and remains in it for a long time. After the intravenous photosensitizer injection, the patient should observe heliophobic conditions for 3 to 4 weeks. This means that he or she has to avoid bright sunlight, both direct and scattered. Under indoor conditions, the patient can be illuminated by light of not more than 50 lux.

To prevent complications associated with the enhanced photosensitivity, the patient should employ sunscreen agents and compounds. These agents should be applied soon after the Photohem introduction. Sunscreen agents should contain compounds that filter out the wavelength of the Photohem maximum absorption. In particular, these agents should readily absorb radiation at the Soret band (400 nm). Such sunscreen ointments are produced by many cosmetic companies (for example, by L’Oleral).

Basic photodynamic mechanisms took effect 5 to 7 days after a PDT session. In this case, it is recommended that the patient should take antioxidant compounds (such as beta-carotene, vitamins C and E).

The proper selection of optical radiation doses makes it possible to avoid complications associated with the photodynamic destruction of tumor and healthy cells. The maximum radiation power density is often limited by laser capabilities, whereas the radiation energy density depends on the physician’s experience, tumor features, and tumor location.  The radiation energy density determines the rate of photodynamic destruction, the depth of necrotic lesions, and the injury of surrounding and underlying tissues.

In order to decrease the rate and severity of complications, one needs to employ special methods for separation of the total dose of photosensitizer and optical energy. The application of these methods makes it possible to improve the PDT efficiency.

Directive Instructions for Photodynamic Therapy
     Application in Oncology
     Photodynamic therapy is a new promising technique for the treatment of cancer without operation. This technique is applied when traditional methods are contraindicated or ineffective. Photodynamic therapy has treated tens of thousands of patients. It was found to be effective in the treatment of both early and advanced cancers. For example, PDT was employed to treat relapses and intracutaneous metastases of mammary gland cancer. It was also used to treat gynecological cancer, urinary bladder cancer, as well as obturating cancer of the esophagus, trachea, and large bronchi (when it was necessary to recover the orifice of tubular organs).

Mechanism of action. After an intravenous photosensitizer introduction, a tumor accumulates it. Low-energy laser radiation excites the photosensitizer. Photochemical reactions generate singlet oxygen and other highly active free radicals. These substances produce a toxic effect on tumor cells. When the tumor resolves, it is replaced by normal connective tissue. As a result, the patient recovers.
     In 1992, the State Research Center for Laser Medicine, affiliated with the Ministry of Public Health of the Russian Federation was the first across the CIS to apply PDT in the treatment of cancer of various locations.

By now, we have accumulated data on the follow-up study of 350 patients (approximately 1,500 tumors). The study was performed in the course of 6 months to 6 years. The general PDT efficiency ranged between 90 and 95 percent. Of these, 55 to 60 percent accounted for a complete tumor resolution.
     Currently, PDT is a cutting-edge technique for the treatment of malignant tumors. It is successfully applied in many regions across Russia. At present, new photosensitizers and optical sources are being created and tested. They will be employed both in the PDT and fluorescent diagnosis of tumors.

Indications to PDT of Skin Cancer:

1. Relapsing and residual tumors that are resistant to traditional therapeutic techniques;
2. Multiple tumors;
3. Locally extensive tumors (the tumor node can be 10 cm in diameter [or more], whereas its infiltration can be up to 1 cm in depth);
4. Inconvenient location of tumors (such as the periorbital region, concha of auricle, nose wing, and nasolabial fold); as well as
5. Patients’ refusal to surgery and radiotherapy.
   
   Clinical entities: basal cell carcinoma, squamous cell carcinoma, and metatypical carcinoma.

Indications to PDT of Cancer of the Mucous Membrane of the Mouth, Tongue, and Lower Lip:

1. Squamous cell cancer T_1-2N₀M₀. The tumor node can be up to 3 cm in diameter, whereas its infiltration should be less than 1.0 cm in depth;
2. High risk of complications after radiotherapy and surgical treatment in elderly patients and patients with associated diseases;
3. Tumors resistant to routine therapeutic techniques; and
4. Patients’ refusal to the treatment with traditional methods.

Indications to PDT of Lung Cancer:

1. Central cancer T_1-2N₀M₀ affecting the trachea, major, intermediate, and lobe bronchi (PDT is not contraindicated even in the case of atelectasis, exophytic cancer, and endophytic cancer [even with circular lesions]);
2. High risk of complications after surgery and radiotherapy in elderly patients and patients with associated diseases; as well as
3. Patients’ refusal to the treatment with traditional methods.

Indications to PDT of Esophagus Cancer:

1. Primary cancer T₁N₀M₀, when surgical and/or combined treatments are contraindicated;
2. Early cancer relapses after radiotherapy;
3. Patients’ refusal to the treatment with routine therapeutic techniques; and
4. Palliative PDT performed to recanalize obturating tumors.

Indications to PDT of Stomach Cancer:

1. Primary cancer T₁N₀M₀ of any histological structure, which exhibits mucous and submucous membrane growth;
2. Early relapses in anastomosis;
3. Palliative PDT of stenosing cancer of the cardiac portion of the stomach (with admissible transfer to the esophagus), which is performed to recanalize the organ; and
4. Patients’ refusal to the treatment with traditional techniques.

Indications to PDT of Urinary Bladder Cancer:

1. Superficial cancer of the urinary bladder (primary or relapsing cancer);
2. Exophytic cancer T₁N₀M₀ of the urinary bladder, affecting its bottom and sidewalls (PDT can be applied to multiple lesions, irrespective of the previous treatment); as well as
3. Relapsing tumors, inefficiency of traditional treatment, and indications to cystectomy.

Indications to PDT of Mammary Gland Cancer:

1. Padget cancer Т_1-2N₀M₀;
2. Relapsing cancer of the mammary gland after surgical treatment;
3. Intracutaneous metastases after surgical and combined treatments (PDT is not contraindicated in the case of the simultaneous administration of radiotherapy and chemotherapy); as well as
4. Primary mammary gland cancer T_1-2N₀M₀ (the nodular form) when the patients refuse completely to the surgical treatment and/or when they have serious associated diseases.

Indications to PDT of Rectum Cancer:

1. Rectum cancer T₁N₀M₀ when surgical treatment is contraindicated; and
2. Palliative PDT, which is performed to recanalize organs obturated by tumors.

References

1. Dougherty, T. J., Kaufman, J. E., Goldfarb, A., et al., “Photoradiation therapy for the treatment of malignant tumors,” Cancer Res., Vol. 33.33, pp. 2628-2635, 1978.
2. Dougherty, T. J., “Photodynamic therapy,” In: Medical Radiology Innovations in Radiation Oncology, H. R. Winters and L. J. Peters, Editors, pp. 175-188, 1988.<
3. Marcus, S. L., “Clinical photodynamic therapy: the continuing evolution,” In: Photodynamic Therapy: Principles and Chemical Applica­tions, Marcel Dekker, Inc., New York, pp. 1-58, 1992.
4. Pass, H. I., “Photodynamic therapy in oncology: mechanisms and clinical use,” J. Natl. Cancer Inst., Vol. 85, 6 443-56, 1993.
5. Stranadko, E. F., “Experimental and clinical development of the laser photodynamic therapy method for malignant tumors using Russian photosensitizers of the first and second generations, Laser Market, No. 11-12, pp. 20-26, 1994.
6. Stranadko, E. F., Skobelkin, O. K., Litvin, G. T., et al., “Clinical photodynamic therapy of malignant neoplasms,” In: Photodynamic Therapy of Cancer II, Proc. SPIE, Vol. 2325, pp. 240-246, 1995.
7. Stranadko, E. F., Skobelkin, O. K., Litvin, G. T., et al., “Photodynamic therapy of human malignant tumors: a comparative study between Photogem and tetrasulfonated aluminium phthalocyanine,” Proc. SPIE, Vol. 2625, pp. 440-448, 1996.