1. Experience of Using Photodynamic Therapy for Cancer with Chlorin-Series Photosensitizers

A.A.Radaev, E.Ph.Stranadko

Table 1. Nature of pathology, number of pathologic seats, and number of patients treated with PDT technique in 1998 – 2001

Photodynamic therapy (PDT) method was applied for early stages of cancer with the purpose of complete recovery of patients with neoplasms of skin, breast, oral mucosa, Vater papilla, vulva, and PDT was applied as well for inoperable patients with palliative purpose – for recanalization of caval organs with stenosis caused by tumor, reduction of the tumor mass volume, improvement of patients life quality. Patients with multiple intracutaneous metastases of breast cancer and melanoma were observed separately, and in the latter case PDT was applied with the purpose to keep back metastases growth and prevent from further metastases-formation.

PDT method was applied to the patients aged from 35 to 92 years old. Many elderly patients had contra-indications to traditional methods of treatment, such as surgery and radiotherapy. Nevertheless after application of radical treatment with PDT method no grave systematic complications were detected.

Majority of treated patients had disease of recurrent character after application of traditional methods of treatment. Only 27 % of patients treated with PDT had primary malignant neoplasms, and in 4 cases PDT was applied to treat residual tumors after non-efficient treatment with radiotherapy and laser vaporization.

Patients with malignant neoplasms of skin (skin cancer, intracutaneous metastases) had prevailing multiple lesions, the number of tumor seats of some patients reached 40 and more. Many patients with skin cancer had the seats of disease located in the face area, what resulted in high risk of undesirable cosmetic consequences in case of radical surgery, and PDT in such cases was the method of choice.

As the result, therapeutic effect of PDT was recognized in 100 % of cases, with complete tumor resorption for 61 patients (63 %), and partial tumor resorption – for 36 patients (37 %) (Table 2).

Table 2. Results of PDT application in 1998 – 2001

CR – complete tumor resorption; PR – partial tumor resorption;

* – palliative PDT with the purpose of recanalization.

Radical programme of PDT was applied to 64 patients. As result of the treatment, complete tumor resorption was achieved for 52 patients (81 % of cases), partial resorption – for 12 patients. PDT method was well accepted even by the patients with serious attendant diseases, and in many cases PDT proved to be the only possible method of treatment. Thus, PDT was applied for treatment of patient I. with Vater papilla cancer (68 years old, case № 3105), not liable for surgery because of pronounced attendant all-somatic pathology. Applied PDT allowed to achieve full recovery with tumor-free period of 33 months. It is necessary to point out that it was the first time in Russian medical practice that PDT was applied in the case with such pathology.

In treatment of skin cancer, even in cases with extensive and multiple lesions PDT served as a good alternative to surgery, providing good and excellent cosmetic results and high efficiency. Also, the terms of hospitalization were shortened. Thus, patient A. (case № 6192) came in for treatment in the Head & Neck Department with extensive infiltrating tumor of skin in the right cheek (size of neoplasm: 3.0 x 3.5 x 0.7 cm). After diagnostics the patient was treated with single PDT, that led to complete tumor resorption with good cosmetic effect, and, considering the fact that total period of hospitalization was 18 days, the period starting from beginning of treatment until discharge was minimal – 3 days.

Organ-preserving nature of PDT allowed to apply this method for treatment of residual tumors and postradial recurrences for cancer of oral mucosa. Thus, patient I. with cancer of oral mucosa (case № 2528) got radical remote gammatherapy of 75 Gray that did not result in complete recovery – there was a residual tumor. Further follow-up with gammatherapy was impossible, and postradial transformations of tissues created unfavourable conditions for surgery. Application of PDT led to complete recovery of the patient, and to the present the tumor-free period is more than 2 years.

Palliative PDT with the purpose of recanalization of caval organs obturated by tumor was applied to treat 13 inoperable patients.

10 patients had esophagus cancer and stomach cancer with extension to esophagus. 7 patients had squamous-cell cancer, 3 patients had adeno-carcinoma. 4 patients had  extent of section with esophagus stenosis  from 2 to 6 cm, 6 patients had the extent from 7 to 12 cm. 4 patients had been submitted to recanalization with YAG-Nd laser, 2 patients had 10 and 12 sessions with short-term effect. At the moment of the therapy application start the condition of all patients was aggravated with disphagia, cakhexia, and systematic disorders.

3 patients had cancer of trachea and big bronchial tubes of IV stage: the1st patient had squamous-cell cancer with athelectasis of upper lobe of the right lung; the 2nd patient had squamous-cell cancer with athelectasis of lower lobe of the right lung; the 3rd patient had squamous-cell cancer with trachea stenosis and two main bronchial tubes, hypoventilation of both lungs and difficult breath.

The results of application of palliative PDT, aimed at recanalization of caval organs, obturated by tumor, are presented in Table 3.

Out of 10 patients with cancer of esophagus and cardial section of stomach 4 patients got one PDT course, 4 patients got two PDT courses, and 1 patient with esophagus cancer and extent of lesion of middle- and lower-pectoral part of esophagus of 12 cm got five PDT courses. As result of PDT application, 9 patients showed pronounced effect of recanalization with restored nutrition through mouth. 3 patients out of the group gained 15 – 20 % of body weight during the first month after PDT. Effect of recanalization lasted for 3 – 7 months, after that with aggravation of symptoms of disphagia and detection of tumor stenosis come-back PDT was repeated.

Patient K. with recurrent cancer of lower one-third part of esophagus after surgery had extent of tumor stenosis of lower one-third esophagus part of 12 cm. He had pronounced disphagia, difficulty with passing even liquid nutrition, the patient was emaciated and was liable only to symptomatic therapy. Application of PDT endoscopic course has led to considerable extension of esophagus opening, in 2 days after the procedure passing of nutrition was restored. The patient was discharged with considerable improvement and was under observation in satisfactory condition for 7 months. Considerable improvement of patient’s condition after PDT and absence of distant metastases-formation allowed him to undergo radical surgery, the patient died 1 day after surgery because of thromboembolia of lung artery.

Only one patient with extent of esophagus lesion of 12 cm after PDT courses for 5 times had short-term improvement of nutrition passing (and contrast mass passing during X-ray researches), that was why the patient was put gastrostoma.

Pronounced effect of recanalization was detected for all 3 patients with lung cancer, with elimination of short breath and difficult breath after 3 – 4 days of PDT application. During bronchoscopy researches after the first PDT course the partial (50 %) restoration of bronchi opening was detected, after 2 – 3 PDT courses – complete recovery of the opening with X-ray detection of hypoventilation and athelectasis elimination and restoration of transparency (aireness) of lungs’ tissue.

Table 3. Application of PDT for recanalization of caval organs, obturated by tumor, for inoperable patients

One patient from that group (patient L., case № 8240), had central cancer of the right lung with tumor obturation of lobe bronchi and athelectasis of lobe. The patient was in a grave state, there were metastases in lymphatic nodes of mediastinum, and the case was defined as not liable to surgery. The patient was treated with PDT method. Due to PDT application complete recanalization of bronchi was achieved as well as straightening of athelectasis, improvement of lungs’ ventilation ability. General state of the patient considerably improved, and surgery-anesthetic risk was reduced. It allowed him to carry out radical surgery, the observation period from beginning of the treatment was 17 months. Thus, in this case PDT application allowed to transfer the patient from not-liable to surgery state to liable to surgery state.

Among 4 patients who underwent palliative PDT in connection with multiple intracutaneous metastases of melanoma and breast cancer, pronounced therapeutic effect was detected in all cases. One patient (patient C., case № 3705) with multiple intracutaneous metastases of breast cancer had 25 metastases on the front pectoral side 2 years later after radical mastectomy. After PDT treatment course, the growth of intracutaneous metastases of breast cancer was completely suppressed, and duration of remission was 21 months.