Percutaneous Hepatic Perfusion Procedure May Extend Life for Patients With Inoperable Cholangiocarinomas

The use of a percutaneous hepatic perfusion procedure (PHP) with CHEMOSAT for inoperable intrahepatic cholangiocarinomas (iCCA) or extrahepatic cholangiocarinoma (eCCA) with liver metastases may help to extend the lives of patients with these conditions, according to a study published in Clinical & Experimental Metastasis. PHP is a locoregional treatment for inoperable primary and secondary liver malignancies.

“PHP enables high-dose chemotherapy of the liver with reduced systemic exposure and thus fewer systemic side effects,” the study authors wrote. “While there is [sic] reliable data on PHP in metastatic uveal melanoma, studies on the effectiveness of PHP in other solid tumors such as CCA are very limited. Since there are currently no results from prospective studies on PHP in CCA, there is an urgent need for data from real-world studies to better classify the effectiveness and safety of PHP in this rare tumor entity.”

The study involved a retrospective analysis of 17 patients who received a total of 42 PHP procedures between October 2014 and September 2020 at the Hannover Medical School in Germany. The authors of the retrospective, monocentric study sought to evaluate PHP as a palliative treatment for unresectable liver dominant CCA. Among the 17 patients, 16 were evaluable for response after 1 patient died without follow-up imaging 13 weeks following the first PHP with no identifiable relationship to the treatment, according to the study authors.

Following the first PHP, 1 patient (6%) had a complete response (CR), 3 patients (18%) had a partial response (PR) in the first follow-up exam, and 7 patients (44%) had stable disease (SD). Further, 5 patients (31%) had progressive disease (PD), 1 of which was limited to extrahepatic progression only. Of the 17 treated patients, there was an overall response rate (ORR) of 25% and a disease control rate (DCR) of 75%.

Among these patients, additional PHP treatments were administered to 2 patients with PR, 6 patients with SD, and 1 patient with PD limited to extrahepatic progression. Subsequent follow-up exams found that the overall best therapy response was PR in 78% of patients and SD in 22%. There was 1 patient administered a total of 8 PHP treatments within 30 months.

Median progression-free survival (PFS) was 3.5 (95% CI:2.2–7.4) months with a similar median hepatic PFS of 3.6 [95% CI: 2.6–9.5] months. Median survival calculated from the initial diagnosis of iCCA or CCA liver metastases was 27.6 [95% CI: 16.5–37] months. From initiation of the first PHP, median survival was 9.9 months [95% CI: 3.8–21], with a 1-year survival rate of 41%, according to the study.

The investigators noted that treatment options for inoperable CCA are limited, and a median survival of 2.5 month to 6 months is expected; however, survival can be extended to approximately 12 months with first-line chemotherapy with gemcitabine and cisplatin. All patients in the study population were previously administered systemic therapy. The investigators said that the study findings highlight the potential for longer survival with PHP treatment even after exhausting systemic therapy options.

There were no significant complications reported during the PHP treatments. There was significant hemotoxicity reported with grade 3/4 thrombocytopenia after 50% of PHP treatments, anemia after 26% of PHP treatments, and leukopenia after 21% of PHP treatments; however, these were deemed transient and clinically manageable. There were no PHP-related deaths reported.

The investigators said that the toxicity rates were consistent with previously published PHP values and with first-line systemic therapy with gemcitabine/cisplatin in CCA.

In terms of limitations, the authors said that the retrospective study design may have caused adverse events to be underestimated, especially because some patients were partially assigned from a distance and monitored close to home. As such, follow-up laboratory values were not available for all patients at the specified times.

The authors noted that the new edition of the German S3 cancer guideline "Diagnostics and Therapy of Hepatocellular Carcinoma and Biliary Carcinomas" now includes PHP with melphalan for inoperable iCCA or eCCA liver metastases. They noted that the results of this study indicate that for patients with inoperable, treatment-refractory iCCA and CCA liver metastases, PHP may be an effective and safe treatment option that could extend life in a palliative setting.

“Overall, this study shows that the palliative concept of PHP has the potential to prolong life in patients with inoperable, treatment-refractory iCCA and CCA liver metastases,” the authors wrote. “In order to assess which intra-arterial therapy or combination therapy is advantageous for which patient group, further, preferably prospectively randomized studies with larger numbers of patients, are necessary.”

Reference

Dewald, C.L.A., Becker, L.S., Meine, T.C. et al. New perspectives in unresectable cholangiocarcinoma? Evaluation of chemosaturation with percutaneous hepatic perfusion as a palliative treatment option. Clin Exp Metastasis (2022). https://doi.org/10.1007/s10585-022-10193-4. Accessed December 6, 2022.