Intraoperative fluorescent spectroscopy and photodynamic therapy of recurrent pelvis minor tumors with local radiation damage

This work presents the results of performing intraoperative photodynamic therapy (IOPDT) on 22 patients with recurrent pelvic tumors

(cervical cancer – in 18 patients, cancer of the corpus uteri – in 3 patients, cancer of the anal canal – in 1 patient). Prior to the PDT procedure, the patients were injected with photolon photosensitizer (PS) at a dose of 1.0–1.1 mg/kg. After the injection of PS, local fluorescence spectroscopy of tumor lesions was performed to determine the accumulation of drug in various areas of tumors and healthy tissue. Intraoperative laser irradiation was carried out 3–5 hours after the photolon injection with light at 662 nm wavelength using "Latus-2" laser device with a power density of 140 mW/cm² and the density of light energy of 40–60 J/cm², the number of irradiation fields was 3–5 depending on the anatomical features.

The follow-up period after surgical treatment combined with PDT was from 6 to 24 months. Analyzing the immediate results of the treatment, there were no undesirable events or increase in the number of postoperative complications compared to patients treated without IOPDT. Were registered: transient increase in ALT and AST levels – in 5 patients (13.6%), reduction of oxygenation during anesthesia – in 20 (90.9%), transient fevers in the postoperative period – in 7 (31.8%).

It was noted that IOPDT with photolon drug, while slightly extending the time of the operation, is well tolerated by patients and does not lead to an increase in the number of early postoperative complications or the length of hospitalization.

1. Zlokachestvennye novoobrazovaniya v Rossii v 2015 godu [Malignant neoplasms in Russia in 2015], by eds Kaprin A.D., Starinskii V.V., Petrova G.V. Мoscow, MNIOI im. P.A. Gertsena – filial FGBU NMITS radiologii Minzdrava Rossii Publ., 2017. pp. 18–19.

2. Datta N.R., Stutz E., Liu M., Rogers S., Klingbiel D., Siebenhüner A., Singh S., Bodis S. Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: A systematic review and meta-analysis, Gyn. Oncology, 2017, Vol. 145(2), pp. 374–385.

3. Monk B.J., Tewari K.S., Koh W.-J. Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions, J. Clin. Oncol., 2007, Vol. 25, pp. 2952–2965.

4. Kostyuk I.P., Vasil'ev L.A., Krest'yaninov S.S. Classification of locally spread neoplasms of pelvis minor and secondary tumor lesions of the bladder, Onkourologiya, 2014, No. 1, pp. 39–43. (in Russian)

5. Buytaert E., Dewaele M., Agostinis P. Molecular effectors of multiple cell death pathways initiated by photodynamic therapy, Biochim. Biophys. Acta., 2007, Vol. 1776(1), pp. 86–107.

6. Mroz P., Yaroslavsky A., Kharkwal G.B., Michael R. Cell Death Pathways in Photodynamic Therapy of Cancer, Hamblin Cancers, 2011, Vol. 3, pp. 2516–2539.

7. Ahmad N., Feyes D.K., Agarwal R., Mukhtar H. Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle arrest and apoptosis, Proc. Natl. Acad. Sci. USA, 1998, Vol. 95, No. 12, pp. 6977–6982.

8. Rogatkin D., Shumskiy V., Tereshenko S., Polyakov P. Laser-based non-invasive spectrophotometry – an overview of possible medical application, Photonics & Laser in Medicine, 2013, Vol. 2, No. 3, pp. 225–240.

9. Mycek M.-A., Pogue B.W. Handbook of biomedical fluorescence. New-York, Marcel Dekker Inc., 2003. 665 p.

10. Douglass H.O. Jr., Nava H.R., Weishaupt K.R., Boyle D., Sugerman M.G., Halpern E., Dougherty T.J. Intra-abdominal applications of hematoporphyrin photoradiation therapy, Exp. Med. Biol., 1983, Vol. 160, pp. 15–21.

11. Tochner Z., Mitchell J.B., Harrington F.S., Smith P., Russo D.T., Russo A. Treatment of murine intraperitoneal ovarian ascitic tumor with hematoporphyrin derivative and laser light, Cancer Res., 1985, Vol. 45(7), pp. 2983–2987.

12. Veenhuizen R.В., Marijnissen J.P., Kenemans P., Ruevekamp-Helmers M.C., 't Mannetje L.W., Helmerhorst T.J., Stewart F.A. Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma, Br. J. Cancer, 1996, Vol. 73(11), pp. 1387–1392.

13. Suzuki S.S., Nakamura S., Sakaguchi S. Experimental study of intra-abdominal photodynamic therapy, Lasers Med. Sci., 1987, Vol. 2, pp. 195–203.

14. DeLaney T.F., Sindelar W.F., Tomas G.F., DeLuca A.M., Taubenberger J.K. Tolerance of small bowel anastomoses in rabbits to photodynamic therapy with dihematoporphyrin ethers and 630 nm red light, Lasers Surg. Med., 1993, Vol. 13(6), pp. 664–671.

15. Major A.L., Rose G.S., Svaasand L.O., Lüdicke F., Campana A., van Gemert M.J. Intraperitoneal photodynamic therapy in the fischer 344 rat using 5-aminolevulinic acid and violet laser light: a toxicity study, J. Photochem. Photobiol., 2002, Vol. 66, pp. 107–114.

16. Griffin G.M., Zhu T., Solonenko M., Del Piero F., Kapakin A., Busch T.M., Yodh A., Polin G., Bauer T., Fraker D., Hahn S.M. Preclinical evaluation of motexafin lutetium-mediated intraperitoneal photodynamic therapy in a canine model, Clin. Cancer Res., 2001, Vol. 7(2), pp. 374–381.

17. Ross H.M., Smelstoys J.A., Davis G.J., Kapatkin A.S., Del Piero F., Reineke E., Wang H., Zhu T.C., Busch T.M., Yodh A.G., Hahn S.M. Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog, Surg. Res., 2006, Vol. 135(2), pp. 323–330.

18. DeLaney T.F., Sindelar W.F., Tochner Z., Smith P.D., Friauf W.S., Thomas G., Dachowski L., Cole J.W., Steinberg S.M., Glatstein E. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors, Int. J. Radiat. Oncol. Biol. Phys., 1993, Vol. 25(3), pp. 445–457.

19. Hahn S.M., Fraker D.L., Mick R., Metz J., Busch T.M., Smith D., Zhu T., Rodriguez C., Dimofte A., Spitz F., Putt M., Rubin S.C., Menon C., Wang H.W., Shin D., Yodh A., Glatstein E. A Phase II trial of intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis and sarcomatosis, Clin. Cancer Res., 2006, Vol. 12(8), pp. 2517–2525.

20. Rigual N.R., Shafirstein G., Frustino J., Seshadri M., Cooper M., Wilding R.N.G., Sullivan M.A., Henderson B. Adjuvant intraoperative photodynamic therapy in head and neck cancer, JAMA Otolaryngol Head Neck Surg, 2013, Vol. 139(7), pp. 706–711.

21. Filonenko E.V., Saribekyan E.K., Ivanova-Radkevich V.I. Capabilities of intraoperative photodynamic therapy for treatment of locally advanced breast cancer, Biomedical Photonics, 2016, Vol. 5, No. 1, pp. 9–14. (in Russian)

22. Pankratov A.A., Suleymanov E.A., Lukyanets E.A., Venediktova Y.B., Plyutinskaya A.D. Experimental confirmation for selection of irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers, Biomedical Photonics, 2017, Vol. 6, No. 2, pp. 12–20. (in Russian)

23. Suleymanov E.A., Kaprin A.D., Filonenko E.V., Homyakov V.M., Grishin N.A., Moskvicheva L.I., Urlova A.N. Intraoperative fluorescence diagnosis of peritoneal dissemination in patients with gastric cancer, Biomedical Photonics, 2016, Vol. 5, No. 3, pp. 9–18. (in Russian)

24. Vashakmadze L.A., Filonenko Е.V., Butenko А.V., Kirillov N.V., Khomyakov V.M. Long-term outcomes for surgical treatment in patients with locally advanced and disseminated gastric cancer combined with intraoperative photodynamic therapy, Biomedical Photonics, 2013, Vol. 2, No. 1, pp. 3–10. (in Russian).