**5. Discussion**

As previously reported, we were able to find only a few studies on the use of PDT in children in dental, dermatological, and ophthalmological practice in literature [19–22]. Reports on the use of PDT in the treatment of retroperitoneal tumors in children could not be found. In our study, we relied on the results of a preliminary trial, during which the scheme and mode of PDT were developed [23]. Radachlorine (FS of the second generation) was used as FS, which has a greater selectivity of accumulation (in comparison with FS of the first generation), which provides a greater depth of damage to tumor tissue due to shifts of absorption maxima to a longer wavelength spectrum (650–670 nm), intact surrounding tissues during illumination and low skin phototoxicity. A good clinical efficacy of PDT with Radachlorine as FS in the treatment of tumors of different localization has been demonstrated in the publications of a number of authors. Moreover, different forms of drug formulation make it possible for both local, including intra-focal, and systemic administration of Radachlorine.

In the work of Sukhova T.E. [27], the response of basal cell skin cancer in its various clinical forms, stages, histological types, course of the disease, and tumor localization to PDT with intra-focal administration of Radachlorine and Photoditazine was studied. The study included 74 patients with primary and recurrent basal cell carcinoma of the skin of stage I–II. The patients of group I (n = 45) were injected with Radachlorine (0.5–1 ml / 1 cm2 of the tumor surface), patients in group II (n = 34) had Photoditazine (0.3–0.5 ml/1 cm2 of the tumor surface). The light dose was 300 J/cm2 , the illumination wavelength was 662 ± 3 nm for all patients. As a result of the therapy, a complete regression of basal cell skin cancer was established in 43 patients from group I (95.5%) and in 31 from group II (91.2%). At the same time, PDT with Radachlorine FS significantly improved the results of treatment of the ulcerative form of tumor compared with PDT using Photoditazine FS (92.8% vs. 77.8%, respectively, p < 0.05).

Filonenko E.V. et al. [28] used Radachlorine in the treatment of precancerous and tumor diseases of the cervix in 30 patients. Radachlorine was administered once by a 30-minute intravenous infusion at a dose of 1.0 mg/kg body weight 3 hours before illumination (wavelength 662 nm, energy density 300–350 J/cm<sup>2</sup> ). A good clinical result was achieved in 26 patients (86.7%), it was assessed as complete regression of the tumor, in 4 (13.3%)—as partial regression. It is important that during and after the treatment, there were no adverse reactions to the administration of Radachlorine and PDT.

Vashakmadze L.A. et al. [29] reported on the intraoperative use of Radachlorine in patients with a high risk of local tumor recurrence after surgical treatment. The study included 17 patients with morphologically confirmed operable primary or recurrent retroperitoneal tumor. Intraoperative photodynamic therapy was performed with Photogem (five patients), Radachlorine (seven patients), and Photoditazine (five patients). In nine cases, the tumors had the structure of liposarcoma, in 4—leiomyosarcoma, in 2—gastrointestinal stromal tumor, in 1—neurogenic tumor, in 1—hemangiopericytoma. Photosensitizers were administered intravenously: Photohem 48 hours before surgery at a dose of 2.5–3.0 mg/kg, Radachlorine and Photoditazine—at doses of 0.7 and 0.7–1.0 mg/kg, respectively 2–3 hours before the resection stage of the operation. The tumor bed was illuminated after a complete tumor removal within intact tissues from one or more positions, depending on the location of tumor foci. The illumination energy density was 30 J/cm2 , the duration of the exposure session depended on the illumination area. The accumulation of photosensitizer in the tumor tissue was assessed after removal of the neoplasm using local fluorescence spectroscopy by means of the diagnostic

unit "Spectrum." The researchers observed a relapse of the disease after surgical treatment with intraoperative PDT sessions in six (out of 17) patients within a period of 2–6 months. Three patients (out of six) developed local relapses of the disease 2, 4, and 6 months after the treatment (surgery accompanied by intraoperative PDT). The authors remarked that PDT was performed in patients who developed local relapses of the disease at the stage of testing the technique, choosing the modes and radiation dose. The researchers made conclusions about the safety of photodynamic therapy and the precision of the photosensitizer accumulation used to retroperitoneal sarcoma tissue, which was confirmed by local fluorescence spectroscopy data.

The work of this research group was the most interesting and similar in structure to our study. Like other research groups, we expected a good clinical response associated with the high selectivity of Radachlorine and, consequently, with the high photodynamic activity of the drug. Modern fiber-optic technology facilitates the delivery of light of the desired wavelength and energy flux density to tumors located almost anywhere in the body. Local illumination, together with the protection of sensitive tissues at the edge of the area, allows for specific treatment of the tumor without destroying normal tissues outside the treated area. The combination of surgical treatment with intraoperative PDT was used to increase the efficacy of surgical interventions and reduce the number of local relapses.

Analysis of the data of our study showed that in the group of patients receiving therapy according to the protocol, without the additional use of photodynamic therapy, the number of deaths was 12, therefore the survival rate was 74.5%. In patients of the study group who received photodynamic therapy in addition to the standard therapy, the number of fatal outcomes during the 5-year follow-up period was less and amounted to four cases. The survival rate, respectively, was higher—91.3%. Comparison of 5-year survival curves in the control and study groups according to the nonparametric log-rank criterion showed a significant difference in the groups (p = 0.030). At the same time, the average survival time before the onset of death in patients who received photodynamic therapy significantly exceeded the mean survival time in patients who received therapy according to the protocol, without additional use of PDT, i.e., 56 months vs. 47 months, respectively (p < 0.050).

There was no statistically significant difference in the analysis of relapse-free survival in patients of clinical groups: in the study group, relapse occurred in 8.7% of patients, in the comparison group—in 14.9% of patients (p = 0.357). The mean survival time to relapse in both groups had no significant difference and made up 55 months in patients receiving photodynamic therapy versus 52 months in patients not receiving photodynamic therapy (p = 0.357).

Nevertheless, the obtained data regarding relapse-free survival are optimistic. Firstly, preclinical studies have shown the possibility of combining PDT regimens that inhibit primary tumor growth and stimulate antitumor immunity [30–32]. In this case, PDT is a potential method that is due to its immunological mechanisms, can strengthen the control of primary and metastatic tumors, and consequently, facilitate recovery and improve the quality of life in cancer patients. Secondly, the selectivity of photosensitizer accumulation in the tumor can be artificially increased by targeted delivery of the drug to tumor cells. Currently, several techniques to selectively target photosensitizer to the tumor are being developed. Search for transport systems that provide even higher selectivity and precision is described in the world literature [33]. We believe that the method is promising in terms of further research and the accumulation of clinical experience, and the development of exposure modes will allow assessing its effectiveness and impact on the recurrence rate in extra-organ retroperitoneal tumors.

*Photodynamic Therapy in Complex Therapy of Retroperitoneal Tumors in Children DOI: http://dx.doi.org/10.5772/intechopen.101884*
