ORIGINAL ARTICLES
This article represents the study of safety and efficiency of intraoperative photodynamic peritoneal therapy (IOPDT) developed in P.A. Herzen Moscow Cancer Research Institute. IPPDT was performed in 84 patients with locally advanced and disseminated gastric cancer. The control group included 100 patients with surgical treatment only. All patients underwent subradical or palliative subtotal distal gastroectomy or total gastrectomy with D2, D3 lymph node dissection. For IOPDT group Photohem was administrated intravenously in dose 2,5 mg/kg 48 h prior to operation, the session of peritoneal irradiation was performed after completion of the surgery (with laser device LFT-630-01 «Biospec», wavelength 630nm, light dose 6 J/cm2). IOPDT of peritoneum was associated with good tolerance, did not increase the rate and severity of post-operative complications. The efficiency of IOPDT was assessed with adjusted survival rates in study and control groups by Kaplan-Meier analysis. IOPDT significantly improved the prognosis in patients with subradical treatment, with metastasis in less then 15 lymph nodes. The use of IOPDT after surgery in this group of patients contributed to increase of median survival rate from 29.3 up to 43.6 months, annual survival rates from 80.0±5.7% to 93.7±4.2%, 3-year survival rates from 45.5±7.6% to 82.1±7.1%. Accordingly, IOPDT did not improved outcomes for palliative surgery R1–R2 and in patients with more than 15 involved lymph nodes.
Treatment outcomes in 82 patients with primary and recurrent oral and lower lip cancer after photodynamic therapy with photosensitizer Photolon alone or combined with other methods of cancer treatment are represented. According to type and extent of the tumor the single dose of Photolon for intravenous administration accounted for 0.8–2.5 mg/kg, light dose – 100–400 J/cm2 (with wave length of 661 nm). 57 patients had PDT alone; 5 patients – in combination with distant radotherapy; 11 – with distant radiotherapy and polychemotherapy; 9 – with 252Cf interstitial therapy and polychemotherapy. For these patients 3-year overall survival rates were 85.1±4.8%, 3-year reccurence-free survival – 72.2±4.7%. The PDT for recurrent tumors, in cases when other methods were exhausted or impossible, allowed complete tumor response in 82.9% of patients, in 72.9% of them – 3-year disease free survivance. For PDT combined with distant radiotherapy (including concurrent polychemotherapy) the complete response was observed in 100% of patients with primary tumor and in 66.7% of patients with recurrent tumor. For PDT combined with interstitial neutron therapy all patients had complete tumor response. The study showed that this combination allowed decreasing the total radiation dose and radiation dose on adjacent normal tissue, thus, decreasing radiation injury.
Treatment outcomes in patients with age-related vascular degeneration due to formation of subretinal neovascular membrane (SNM) of two groups: photodynamic therapy (PDT) with Photosens alone (18 patients) and in combination with anti-VEGF therapy with Lucentis (20 patients). For both groups Photosens was administrated i.v. in single dose of 0.05 mg/kg. The irradiation was performed on the 3rd day (the wave length 675 nm, light dose 120 J/cm2, total light dose did not exceed 500 J/cm2). The number of sessions accounted for 3 to 5 per week according to clinical manifestation of SNM. Patients with multimodality treatment had intravitreal administration of Lucensis in dose 0.05 ml (0.5 mg). The study showed that combination of PDT and anti-VEGF therapy improved vision better and with more stable effect then PDT alone. Thus vision improvement and decrease of SNM activity occurred in 50% of patients with PDT alone and in 60% of patients with multimodality treatment. For 2-year follow-up in the group of PDT alone the vision gradient gradually decreased compared with baseline vision (from 0.11 to 0.06), in the group of multimodality treatment gradual increase of vision gradient was noticed (from 0.03 to 0.155). The superior efficiency of PDT combined with anti-VEGF therapy compared with PDT alone in patients with age-related vascular degeneration was confirmed by study of vision, fundus angiography and average thickness of retina in foveola in both groups.
The study of efficiency of intraoperative photodynamic therapy (PDT) with Photosens as the step of combined modality treatment in patients with IIIВ and IIIС stages of breast cancer was performed. The long-term outcomes were evaluated in two groups of patients: group 1 – after radical extended mastectomy combined with chemotherapy, radiotherapy and chemo- and hormonal therapy (138 patients), group 2 – the same treatment combined with intraoperative PDT (36 patients). For the patients with PDT photosens was administered i.v. in single dose 0.3 mg/kg for 2 h before surgery. The irradiation of operative field was performed single time (the light dose 30 J/cm2), with separate irradiation of subclavian, axillar and adjacent regions (the light dose 50 J/cm2). The results showed that intraoperative PDT was associated with better recurrence-free survival rates in patients with breast cancer: in the PDT group the average recurrence free survival was 44.9±3.4 months, in the group without PDT — 35.3±2.1 months. The obtained results confirm that intraoperative PDT for locally advanced breast cancer can be used successfully for devitalization of cancer cells on the wound superface and for prevention of intraoperative tumor dissemination and post-operative recurrence.
LITERATURE REVIEWS
The review of recent development in diagnosis of premalignancy and early cancer in colon is represented. The results of several diagnostic methods which are supplemental for convenient colonoscopy, are described. Thus, NBI system (narrow spectrum endoscopy) and FICE combined with system for magnifying endoscopy significantly improve sensitivity and specifity of diagnostic method. However, the serious disadvantage is coloration of intestinal contents into different shades of red, impeding visualization of small structures and lesions. For detection of dysplasia of different degree in patients with colon polyps high levels of sensitivity and specifity were shown in the methods of magnifying and zoom-endoscopy (93.8% and 64.6%, respectively), confocal laser endomicroscopy (81% and 82%, perspectively), and optic coherent tomography (92% and 84%, respectively). The one of the most recent method – immunophotodiagnosis, showed high efficiency for detection of dysplasia and early cancer in patients with colon polyps: the sensitivity was 78.6%, specifity – 100%. Autofluorescence and fluorescence diagnostics with exogenous photosensitizers. The studies showed that autofluorescence diagnosis was valuable method for differential diagnosis of colon tumors (sensitivity was 85%, specifity – 81%).
CASE-REPORTS
The case of unusual course of brain tumor process – metachronous development of breast cancer brain metastasis and then development of malignant glioma is reported. The surgical treatment for both tumors were performed with intraoperative fluorescence diagnosis and photodynamic therapy. Due to multimodality treatment the patient was alive for 15 months from diagnosis of IV stage breast cancer (brain metastasis).
The case of successful use of photodynamic therapy (PDT) combined with electrocautery for treatment of patients with cancer or lower third esophagous is reported. The patient had well-differentiated adenocarcinoma with underlying intestinal metaplasia and I– III displasya. The organ-preserving endoscopic treatment was performed: PDT with phogem (2 courses) combined with electrocautery of tumor (3 sessions). Photogem was administered i.v. in dose 3.0 mg/kg 48 h prior to each session of irradiation (635 nm, light dose 150 J/cm2). Three months after treatment additional PDT in described regimen was performed for residual tumor. The followup accounted for 14 years, the complete regression of esophageal tumor with good functional result without scar deformation and stenosis was observed.
The results of fluorescence diagnosis with alasens in patient with sigmoid polyps are represented in the article. Fluorescence study gave a suspicion of malignant transformation in one of polyps. According to morphological data there was a well-differentiated colon adenocarcinoma with underlying tubular adenoma in suspicious region. Thus, fluorescence data showed malignant tumor prior to routine histological study, which was misdiagnosed for routine colonoscopy and biopsy without fluorescence diagnosis.