Intraductal photodynamic therapy and its combination with intra-arterial chemoinfusion in the treatment of inoperable patients with Klatskin tumor

Background: A palliative or symptomatic treatment is indicated for 70-80% of patients with Klatskin’s tumor because of the advanced lesion volume and the patient’s grave condition. Hepatic arterial infusion chemotherapy, chemoembolization, radioembolization are successfully used in the treatment of hepatocellular carcinoma and liver metastases. Aim: to estimate the immediate and long-term results of photodynamic therapy (PDT) and its combination with hepatic arterial infusion in inoperable patients with Klatskin tumors. Methods: Between 2010 and 2021, 83 palliative PDT sessions (from 1 to 8, average 2.4) were performed in 82 patients as a single treatment or in combination with hepatic arterial infusion. In all cases, percutaneous transhepatic biliary drainage was previously performed; no chemotherapy was applied. Two groups of 48 patients were stratified according to the ECOG status (2-3) and the numbers of PDT sessions (no more than two). The treatment group of the combination therapy consisted of 24 patients (13 male, 11 female) aged 38 to 85 (mean 63) years with the ECOG status of 2-4 (mean 2.4). This group received PDT with hepatic arterial infusion using a GemCis regimen. On average, 1.4 PDT sessions were performed, the treatment started on the 89th (27-225) day after the biliary drainage. The hepatic arterial infusion was performed on the 2d-3th day after the PDT. The control group received only PDT and consisted of 24 patients (13 male, 11 female) aged 51 to 83 (66 on average) years, with the ECOG status of 2-3 (mean 2.6). On average, 1.4 PDT sessions were performed, starting on the 106th (32-405) day after the biliary drainage. Results: There were no serious adverse events associated with PDT in both groups. Toxic complications of hepatic arterial infusion were observed in 13 of 24 patients (54%): I-II grade hematological (54%) and gastrointestinal (69%); all were eliminated with medical therapy. Complications of the percutaneous transhepatic biliary drainage in three patients (hemobilia, n=2, and sepsis, n=1) were estimated as grade III by the CIRSE classification (2017) and successfully treated without surgery. In the combination treatment group, the overall mean survival and median survival were higher than those in the control group: 327.9±39.8 days (10.9 mo) versus 246.9±31.2 days (8.2 mo) and 275 days versus 244 days. However, these differences did not reach the statistical significance (p=0.12). Conclusions: PDT is a safe method of a palliative treatment of critically ill patients with Klatskin tumor (ECOG 2-3). PDT alone has limited clinical efficacy. A combination of PDT and hepatic arterial infusion does not cause serious complications and may increase the survival rates.