Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma

Background: Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort. Methods: Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Results: In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001). Discussion: Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers

Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma

Background: A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA. Methods: We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center. Results: In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p &lt; 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39). Conclusions: This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.</p

Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Background: Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. Patients and Methods: A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle–Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. Results: After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0–39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. Conclusion: HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials

ASO Visual Abstract: Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma - A Systematic Review and Meta-analysis

Hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine has been explored as a means to control cancer in the liver. In this systematic review (https://doi.org/10.1245/ s10434-022-11439-x), 478 patients with unresectable intrahepatic cholangiocarcinoma (iCCA) were identified from nine studies; survival outcomes of 154 patients were used in the meta-analysis. HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a pooled 3-year overall survival (OS) of 39.5% (95% confidence interval (CI) 31.5–47.4%) and a weighted median OS of 29.0 months (range 25.0–39 months)

Nationwide treatment and outcomes of perihilar cholangiocarcinoma

Background Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed to analyse the outcomes of patients with pCCA in a nationwide cohort. Methods Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival. Results A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7-5.7) months. Three-hundred-ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti-cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2-34.0), 12.2 (95% CI 11.0-13.3), 14.5 (95%CI 8.2-20.8) and 2.9 (95% CI 2.6-3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non-academic and 32% in academic centres (P ), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7-11.7) months in academic centres compared to 4.9 (95% CI 4.3-5.4) months in non-academic centres (P ). Conclusions In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population-based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients

Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma

Background and aims: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes. Methods: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions. Results: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54–70). The median OS was 13 months (95% CI 7.9–18.1) in the EBD and 7 months (95% CI 0.0–17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2–4) for the EBD group and 2 (1–3) for the PTBD group (P = 0.77). Discussion: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers

Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. Design, Setting, and Participants: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. Main Outcomes and Measures: Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. Results: A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P =.01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P =.32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P =.07). Conclusions and Relevance: This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option