Treatment Of Unresectable Intrahepatic Cholangiocarcinoma Research Articles

Trans-arterial chemoembolization and radioembolization for treatment of intrahepatic cholangiocarcinoma

Trans-arterial therapies performed by interventional radiology, including chemoembolization and radioembolization, have been increasingly utilized for the treatment of unresectable intrahepatic cholangiocarcinoma. There is increasing evidence demonstrating the safety and efficacy of these interventions in patients with advanced disease. This review provides an overview of trans-arterial chemoembolization and radioembolization for unresectable intrahepatic cholangiocarcinoma, summarizes current evidence, and explores future directions for locoregional therapies.

Comparison of hepatic arterial infusion chemotherapy with mFOLFOX vs. first-line systemic chemotherapy in patients with unresectable intrahepatic cholangiocarcinoma.

Background: Systemic chemotherapy (SC) remains the only first-line treatment for unresectable intrahepatic cholangiocarcinoma (iCCA). Hepatic arterial infusion chemotherapy (HAIC) has been recently proven to be effective in managing hepatocellular carcinoma (HCC). Hence, our study aims to investigate the safety and efficacy of HAIC in treating unresectable iCCA patients. Methods: We reviewed 146 patients with unresectable iCCA who had received HAIC or SC between March 2016 and March 2022 in a retrospective manner. Outcomes of patients and safety were compared between the HAIC and SC groups. Results: There were 75 and 71 patients in the HAIC and SC groups, respectively. The median OS in the HAIC and SC groups was 18.0 and 17.8 months (p = 0.84), respectively. The median PFS in the HAIC and SC groups was 10.8 and 11.4months (p = 0.59), respectively. However, the HAIC group had significantly longer intrahepatic progression-free survival (IPFS) than the SC group (p = 0.035). The median IPFS in the HAIC and SC groups was 13.7 and 11.4months, respectively. According to the OS (p = 0.047) and PFS (p = 0.009), single-tumor patients in the HAIC group appeared to benefit more. In addition, the overall incidence of adverse events (AEs) was lower in the HAIC group than that in the SC group. Conclusion: Our study revealed that HAIC was a safe and effective therapeutic regimen for unresectable iCCA with better intrahepatic tumor control when compared to SC. Meanwhile, patients with single tumor were more likely to benefit from HAIC than SC.

Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma.

Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC). To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC. This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings. Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma—A Prospective Feasibility Study

PurposeTo evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsThis prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. ResultsTwenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9–7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0–33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8–31.0 months) versus 10.7 months (95% CI, 8.0–13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7–20.7 months) versus 37.3 months (95% CI, 16.5–58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. ConclusionsFirst-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma.

Transarterial radioembolization (TARE) is a liver-directed treatment for unresectable intrahepatic cholangiocarcinoma (ICC). The aim of this study is to evaluate factors affecting outcomes of TARE in heavily pretreated ICC patients. We evaluated pretreated ICC patients who received TARE from January 2013 to December 2021. Prior treatments included systemic therapy, hepatic resection, and liver-directed therapies, including hepatic arterial infusion chemotherapy, external beam radiation, transarterial embolization, and thermal ablation. Patients were classified based on history of hepatic resection and genomic status based on next-generation sequencing (NGS). The primary endpoint was overall survival (OS) after TARE. Fourteen patients with median age 66.1 years (range, 52.4-87.5), 11 females and 3 males, were included. Prior therapies included systemic in 13/14 patients (93%), liver resection in 6/14 (43%), and liver-directed therapy in 6/14 (43%). Median OS was 11.9 months (range, 2.8-81.0). Resected patients had significantly longer median OS compared to unresected patients (16.6 versus 7.9 months; p=0.038). Prior liver-directed therapy (p=0.043), largest tumor diameter >4 cm (p=0.014), and >2 hepatic segments involvement (p=0.001) were associated with worse OS. Nine patients underwent NGS; 3/9 (33.3%) and had a high-risk gene signature (HRGS), defined as alterations in TP53, KRAS, or CDKN2A. Patients with a HRGS had worse median OS (10.0 versus 17.8 months; p=0.024). TARE may be used as salvage therapy in heavily treated ICC patients. Presence of a HRGS may predict worse OS after TARE. Further investigation with more patients is recommended to validate these results.

DEB-TACE with irinotecan versus C-TACE for unresectable intrahepatic cholangiocarcinoma: a prospective clinical study.

Objectives: DEB-TACE with irinotecan and C-TACE were compared with regards to safety and efficacy for the therapy of intrahepatic cholangiocarcinoma (ICC). Methods: Institutional Review Board approved our trial and we registered it in the Chinese Clinical Trial Registry (ChiCTR1900022856). Forty patients with biopsy-confirmed ICC were randomised to either receive DEB-TACE or C-TACE treatment with 20 patients in each treatment arm. The primary endpoints objective response rate (ORR) and progression free survival (PFS) using the mRECIST to evaluate the tumours. The secondary endpoints were overall survival (OS) and safety. The chi-square was used to analyse the data. The Kaplan-Meier method and Cox analysis were used to evaluate the survival data. Results: ORR (70% in DEB-TACE group vs. 20% in C-TACE, p = .001) at 1month after therapy, ORR (50% vs. 15%, p = .018) at 3months and DCR (70% vs. 30%, p = .011) at 6months, while no difference was found in other groups. (all p > .05) The median PFS with DEB-TACE was longer than that with C-TACE (8.0months vs. 3.0months) (p = .042). Although the median OS was longer with DEB-TACE than with C-TACE (11.5months vs. 9.0months), the difference was not statistically significant (p = .280). The Cox regression analysis demonstrated that TACE sessions (p = .017) and low CA125 levels (p = .001) were independent favourable prognostic factors. The most frequent adverse event was elevated transaminase levels (20/20 in DEB-TACE group vs. 15/20 in C-TACE group) (p = .047). Conclusion: Our prospective study suggested better ORR and PFS with DEB-TACE with irinotecan as compared to C-TACE with irinotecan in the treatment of unresectable ICC.

Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma.

To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group)were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P=0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P=0.004) and disease control rate (DCR; 82.1% vs 36.8%, P=0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.

Abstract No. 4 ▪ ABSTRACT OF THE YEAR Radioembolization with yttrium-90 glass microspheres as first-line treatment for unresectable intrahepatic cholangiocarcinoma: a prospective phase 2 clinical trial

For patients with unresectable intrahepatic cholangiocarcinoma (IHC), the current standard of care first-line treatment is gemcitabine with cisplatin, based on the ABC-02 trial which demonstrated a median OS of 11.7 months. This therapy is complicated by severe (grade 3-4) adverse events in 70% of patients. A recent phase 2 trial demonstrated 22 months median OS when cisplatin-gemcitabine chemotherapy was used with concomitant radioembolization as first line treatment, but 71% of patients had grades 3-4 toxicities, which were mostly related to the chemotherapy. The purpose of our trial was to evaluate the safety and efficacy of yttrium-90 (Y-90) glass microsphere radioembolization as first-line treatment without chemotherapy for unresectable IHC.

Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety.

This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC). We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan-Meier curves, while Cox analysis was used to identify factors affecting the prognosis. The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0months and 8.0months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient. DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival.

Transarterial Infusion Chemotherapy with FOLFOX Could be an Effective and Safe Treatment for Unresectable Intrahepatic Cholangiocarcinoma.

Background Transarterial infusion (TAI) chemotherapy with the FOLFOX regimen has shown good efficacy and safety in the treatment of hepatocellular carcinoma (HCC). However, it has not been reported in intrahepatic cholangiocarcinoma (ICC). Methods The data of consecutive patients with unresectable ICC who underwent TAI with the FOLFOX regimen from November 2016 to September 2019 were retrospectively analyzed. Treatment effectiveness and safety were evaluated and compared using the Kaplan–Meier method, log-rank test, Cox regression models, and χ2 test. Results Twenty-nine patients were included in the study. The median overall survival (OS) was 16.2 months (95% CI, 13.0–19.4). The median progression-free survival (PFS) was 8.7 months (95% CI, 6.2–11.1). Twenty-seven patients were included in the efficacy analysis. There were 0, 10, 13, and 4 patients with CR, PR, SD, and PD, respectively, based on mRECIST criteria. The ORR was 37.0%, and the DCR was 85.2%. There were 27 patients (93.1%) who experienced grade 1-2 AEs, while only 1 patient experienced grade 3 AEs. Conclusion TAI with the FOLFOX regimen could be an effective and safe treatment for unresectable ICC.

HELIX-ICC: An-open label phase II trial of induction systemic mFOLFIRINOX followed by concurrent hepatic arterial infusion of floxuridine and systemic mFOLFIRI for unresectable intrahepatic cholangiocarcinoma.

TPS500 Background: The majority of patients with intrahepatic cholangiocarcinoma (ICC) present with advanced liver dominant disease rendering them unresectable. The current standard of care supports palliative treatment of unresectable ICC with gemcitabine plus cisplatin. Alternatively, continuous liver-directed therapy using a surgically implanted hepatic arterial infusion (HAI) pump allows for maximal treatment of liver tumors with limited systemic side-effects and can facilitate conversion to a resectable status. No prospective clinical trial has utilized FOLFIRINOX in combination with HAI floxuridine-dexamethasone for ICC. Methods: HELIX-ICC is a first-line, single-center, single-arm, phase II clinical trial enrolling patients with liver-dominant unresectable or multifocal ICC. Only patients with microsatellite stable cancer and no prior liver radiotherapy will be included. Patients are administered dose-modified FOLFIRINOX systemically for 4 cycles over 8 weeks. Those with evidence of disease control on restaging imaging and laparoscopy will proceed to HAI pump placement. Treatment continues with two 28-day cycles of combined HAI floxuridine (1.08 mg/kg) with dexamethasone for 14 days and systemic dose-modified FOLFIRI starting on day 15. The primary objectives are to evaluate the safety and efficacy (disease control rate [DCR] at 6 months) of this novel treatment approach that utilizes our institutional dose-reduced HAI floxuridine protocol in combination with modified systemic regimens to facilitate control of liver disease and maximize patient quality of life (QoL). HELIX-ICC includes many exploratory analyses through longitudinal collection of blood samples, liver biopsies (including an end of trial research biopsy), and QoL metrics (Table). The study is open to n = 30 with an initial safety run-in of 6 patients, of which 4 have enrolled at the time of submission. This study is designed to allow for drop out of 9 patients, with total accrual of 21 patients to protocol completion achieving 80.2% power at 0.05 significance to detect a 25% increase in DCR at 6 months. Clinical trial information: NCT04251715. [Table: see text]

Addition of thermal ablation to systemic chemotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma: a propensity score matching analysis

ABSTRACT Objectives To retrospectively compare the survival outcomes of thermal ablation plus chemotherapy to those of chemotherapy alone in patients with unresectable intrahepatic cholangiocarcinoma (ICC). Methods 189 patients with unresectable ICC who received thermal ablation plus chemotherapy or chemotherapy alone as the initial treatment were identified . To avoid potential bias, 1:1 matching between groups was performed through propensity score matching. Overall survival (OS) was the primary endpoint. Clinical and tumor factors related to OS were analyzed through univariate and multivariate analyses. Results Of the enrolled patients, 55 received ablation plus chemotherapy, and 134 received chemotherapy alone. The median OS was 16.267 months for patients treated with combined therapy and 6.067 months for patients treated with chemotherapy alone (p = 0.000). The benefit of ablation plus chemotherapy was also preserved in the matched cohort, with a median OS of 15.233 months in the combined treatment group and 7.967 months in the chemotherapy group (p = 0.009). Univariate and multivariate analyses indicated that the type of treatment was an independent factor of OS (p < 0.05). Conclusions The combination of thermal ablation and systemic chemotherapy provides an opportunity to improve the prognosis of patients with unresectable ICC.

Safety and initial efficacy of ablative radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma.

Purpose: To investigate safety, response, and survival after ablative glass microsphere 90Y radioembolization for unresectable intrahepatic cholangiocarcinoma.Materials and Methods: A retrospective review of 37 radioembolizations in 28 patients treated with single compartment dose of ≥190 Gy encompassing >75% of the largest tumor was performed. Tumors were assessed for stage, morphology, and arterial supply. Response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), freedom from progression (FFP), progression-free survival (PFS), overall survival (OS), biochemical hepatic function, performance status, and adverse events were investigated.Results: The median highest dose per patient was 256.8 Gy (195.7–807.8). Objective response at 3 months was 94.1% (complete 44.1% and partial 50%). Median OS was not reached and the 30-month OS rate was 59%, with a median follow-up of 13.4 months (5.4–39.4). FFP in the radiated field and overall FFP at 30 months were 67% and 40%, respectively. Favorable arterial supply was associated with improved OS (p = 0.018). Unfavorable arterial supply was associated with worse OS [HR 5.7 (95% CI 1.1–28.9, p = 0.034)], and PFS [HR 5.9 (95% CI 1.9–18.4, p = 0.002)]. Patients with mass-forming tumors had a survival benefit (p = 0.002). Laboratory values and performance status did not significantly change 3 months after radioembolization. Grade 3 and 4 adverse events occurred in 2 (7.1%) patients.Conclusions: Radioembolization of unresectable intrahepatic cholangiocarcinoma with ablative intent has a high response rate, promising survival, and is well tolerated.

Efficacy and Safety of Apatinib in Treatment of Unresectable Intrahepatic Cholangiocarcinoma: An Observational Study.

PurposeUnresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC.Patients and MethodsA total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. The drug-related adverse effects were also monitored.ResultsBased on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded.ConclusionApatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

Hepatic artery infusion pumps

The preferential blood supply from the hepatic artery to liver tumors allows for the regional delivery of chemotherapy, commonly referred to as hepatic artery infusion chemotherapy via a subcutaneous pump. Hepatic artery infusion chemotherapy has been demonstrated to improve overall survival in select patients with colorectal liver metastasis and is a promising treatment for unresectable intrahepatic cholangiocarcinoma. This review focuses on the technical aspects of hepatic artery infusion pump placement.

Drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres for treatment of unresectable intrahepatic cholangiocarcinoma.

Objective: This study aimed to evaluate the efficacy and safety of doxorubicin-loaded drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres (CSM) in treating unresectable intrahepatic cholangiocarcinoma (ICC).Methods: 88 unresectable ICC patients who received DEB-TACE treatment with CSM were retrospectively enrolled in this study. Information about treatment response, survival and adverse events were collected. The Kaplan-Meier curve was used to evaluate progression-free survival (PFS) and overall survival (OS), and factors affecting OS were determined by Cox's proportional hazards regression model.Results: Tumor response of the whole sample of 88 patients was partial response (PR) in 58 (65.9%) patients, stable disease (SD) in 19 (21.6%) and progressive disease (PD) in 11 (12.5%) at one month after therapy, with no complete responses (CR). The median PFS and OS were 3.0 months and 9.0 months respectively. Cox's proportional hazards regression analysis disclosed that subsequent treatment was an independent favorable prognostic factor, while cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastasis were the three prognostic factors associated with poor survival in ICC patients. Besides, common adverse events included nausea/vomiting, abdominal pain and transient elevation of liver transaminase in patients treated by DEB-TACE with CSM.Conclusion: DEB-TACE with CSM is safe and well-tolerated for unresectable ICC patients, with a low complication rate and a relative benefit in terms of survival. Subsequent treatments including systemic/loco-regional treatments is an independent favorable prognostic factor, but cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastases are the three prognostic factors associated with poor survival.

Stereotactic body radiation therapy is associated with improved overall survival compared to chemoradiation or radioembolization in the treatment of unresectable intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy. For patients with locally advanced, unresectable disease, numerous liver-directed therapy options exist, including chemoradiation (CRT), stereotactic body radiation therapy (SBRT), and transarterial radioembolization (TARE). There is no randomized data to inform clinicians regarding the optimal treatment modality. MethodWe used the National Cancer Database (NCDB) to study the overall survival (OS) of patients with ICC treated with CRT, SBRT, and TARE. We used Cox proportional hazards modeling and inverse probability of treatment weighting (IPTW) to account for confounding variables. ResultsWe identified 170 patients with unresected ICC treated with SBRT (n = 37), CRT (n = 61), or TARE (n = 72). SBRT was associated with higher OS compared to CRT (hazard ratio [HR] = 0.37; 95% confidence interval [CI] 0.20–0.68; p = 0.001) and TARE (HR = 0.40; 95% CI 0.22–0.74; p = 0.003). On multivariable analysis, SBRT remained associated with higher OS compared to CRT (HR = 0.44; 95% CI 0.21–0.91; p = 0.028) and TARE (HR = 0.42; 95% CI 0.21–0.84; p = 0.014). After IPTW (Bonferroni-adjusted significance threshold, α = 0.017), SBRT again had a statistically significant association with higher OS compared to CRT (HR = 0.22; 95% CI 0.11–0.44; p < 0.0001) and was nominally associated TARE (HR = 0.58; 95% CI 0.37–0.91; p = 0.019). ConclusionsWe found SBRT is associated with higher OS when compared to CRT or TARE for the treatment of unresectable ICC. Due to the retrospective nature of the study and potential selection bias, these findings should be evaluated prospectively.

A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma.

Purpose: The aim of this pooled analysis was to evaluate the clinical efficacy and safety of transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).Methods: We searched the Cochrane Library, Embase, PubMed, SCI with the English language from inception to October 2018. A pooled analysis was conducted using Stata software.Results: There were 16 eligible studies included in this pooled analysis. The pooled median overall survival (OS) from 12 studies was 14.3 (95% CI: 11.9–17.1) months. Based on Response Evaluation Criteria in Solid Tumors (RECIST), no complete response was reported, and the median of partial response, stable disease and progressive disease were 11.5% (range: 4.8–35.3%), 61.5% (range: 42.9–81.3%) and 22.7% (range: 12.5–52.4%) respectively. The pooled disease control rate (DCR) from nine studies was 77.2% (95% CI: 70.2–84.2%). According to the type of microspheres, subgroup analysis was performed, the median OS in the glass microspheres group was 14.0 (95% CI: 9.1–21.4) months, and 14.3 (95% CI: 11.5–17.8) months in the resin microspheres group. The DCR was 77.3% (95% CI: 63.5–91.1%) and 77.4% (95% CI: 66.8–87.9%) in the glass and resin microspheres groups respectively. Most of the side effects reported in the included studies were mild and did not require intervention.Conclusion: TARE with 90Y microspheres is safe and effective for patients with unresectable ICC with acceptable side effects. And it seems that the type of microsphere has no influence on therapeutic efficacy.

Transarterial Radioembolization (TARE) vs Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a disease of high mortality characterized by aggressive, local infiltration. Surgery is the only curative treatment, but is only an option for a small proportion of patients. For patients unable to receive surgery, there is no established standard treatment, although several options exist, including chemotherapy, conventional external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT), chemoradiation, ablation, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE), namely in the form of yttrium-90 (Y-90) microspheres. We studied the overall survival (OS) of patients with ICC treated with primary SBRT vs TARE. We identified 18,344 patients diagnosed between 2005 and 2015 with histologically confirmed ICC using the National Cancer Database (NCDB). We included only patients age ≤85 with a Charlson-Deyo comorbidity score (CDCS) ≤2 (n=14,212). We limited our analysis to patients without nodal or distant metastasis (n=5,006). After excluding patients who received other locoregional treatment modalities or systemic monotherapy, we identified 129 patients who received either primary TARE or SBRT, defined as EBRT to a dose of ≥30 Gy in ≤5 fractions. Chi square test and t-test were used to compare clinical characteristics between treatment cohorts. Univariate log-rank test and cox multiple regression were used for statistical analysis to test the association of covariates with survival. The SBRT cohort was characterized by older age (mean 71 vs 65, p=.007) and more recent diagnosis (p=.005). There was no difference between the treatment cohorts with regard to T-stage (p=.21), CDCS (p=.58), or use of chemotherapy (p=.20). When only patients with available tumor size were analyzed (n=109), the TARE cohort was characterized by larger tumors (mean 74 vs 47 mm, p<.001). Univariate log-rank testing showed improved OS with SBRT over Y-90, with a median OS of 24.2 months vs 19.8 months (p=0.016). On multivariate analysis, treatment with SBRT was associated with improved OS (HR=0.40, 95% CI .21-.77, p=.006). In contrast, age (p=.11), year of diagnosis (p=.87), tumor size (p=.61), T-stage (p=.11), CDCS (p=.50), or chemotherapy (p=.39) were not significantly associated with OS. When the analysis was limited to patients with known tumor size, treatment modality remained the only statistically significant variable associated with OS. SBRT is associated with higher OS when compared to TARE in the treatment of unresectable ICC, independent of other variables including tumor size and stage. However, these results should be interpreted cautiously given the retrospective nature of the data and the inherent limitations of the NCDB. Further validation of these findings using other datasets or, potentially, a prospective study is required.

Chemoembolization versus radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma in a single institution image-based efficacy and comparative toxicity.

Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC). Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n=25, 39 treatments) or CE (n=15, 35 treatments). Comparative analysis was performed using Student's t and fisher-exact tests. Multivariable-logistic regression was also performed. Median ages were 60 and 64years for CE and Y90 groups, respectively (p=0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p>0.9). Overall response rate (CE 6%, Y90 4%; p>0.9) and disease control rate (CE 46%, Y90 48%; p>0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden. Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.