Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Analysis of hospital incidence and direct medical costs of intrahepatic cholangiocarcinoma in Spain (2000-2018).

INTRODUCTION: Intrahepatic cholangiocarcinomas (iCCA) are aggressive tumors, often diagnosed in advanced stages and with limited curative treatment options. Their incidence has raised in the past years, increasing their associated economic burden. This study aimed to measure hospital incidence and mortality of iCCA and to evaluate direct medical costs. METHODS: Records of admissions due to iCCA between 1 January 2000 and 31 December 2018 were obtained from a Spanish National discharge database. Hospital incidence and mortality were measured within the hospitalized population and medical costs were assessed for specialized healthcare. RESULTS: Admission files corresponded to 23,315 patients, with a median age of 73 years (IQR = 17) and 55.9% of males. Cholangiocarcinoma presented a hospital incidence of 6.9 per 10,000 persons in 2018, increasing significantly over the study period. In-hospital mortality was 31.5% in the year 2018 and remained stable over the study period. The mean annual direct medical cost of secondary care was €9417 per patient in the year 2017, and increased significantly between 2000 and 2008, stabilizing after 2009. CONCLUSION: The incidence of iCCA in Spain increased over the past years. The medical costs of iCCA per patient stabilized after 2008 but total costs are expected to increase if incidence continues to raise.

Race, ethnicity, and socioeconomic factors in cholangiocarcinoma: What is driving disparities in receipt of treatment?

BACKGROUND AND OBJECTIVES: Race/ethnicity and socioeconomic factors are associated with worse cancer outcomes. Our aim was to determine the association of these factors with receipt of surgery and multimodality therapy for cholangiocarcinoma. METHODS: Patients with cholangiocarcincoma in the National Cancer Database were identified. Racial/ethnic groups were defined as non-Hispanic White, non-Hispanic Black, Asian, and Hispanic. Socioeconomic factors were insurance status, income, and education. RESULTS: Of 12 095 patients with non-metastatic cholangiocarcinoma, 42% received surgery. Black race was associated with decreased odds of receiving surgery (odds ratio [OR]: 0.66l; P < .001) compared to White patients. Socioeconomic factors accounted for 21% of this disparity. Accounting for socioeconomic and clinicopathologic variables, Black race (OR: 0.73; P < .001), uninsured status (OR: 0.43; P < .001), and Medicaid insurance (OR: 0.63; P < .001) were all associated with decreased receipt of surgery. Of 4808 patients who received surgery, 47% received multimodality therapy. There were no racial/ethnic or socioeconomic differences in receipt of multimodality therapy once patients accessed surgical care. Similar results were seen in patients with advanced disease who received chemotherapy as primary treatment. CONCLUSION: Racial/ethnic and socioeconomic disparities exist in treatment for cholangiocarcinoma, however only for primary treatment. In patients who received surgery or chemotherapy, there were no disparities in receipt of multimodality therapy. This emphasizes the need to improve initial access to health care for minority and socioeconomical disadvantaged patients.

Yttrium-90 Radioembolization Is Cost Effective in Intrahepatic Cholangiocarcinoma: A SEER Medicare Population Study.

PURPOSE: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. MATERIALS AND METHODS: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. RESULTS: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). CONCLUSIONS: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.

Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database.

OBJECTIVE: The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC). METHODS: The 2004-2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models. RESULTS: Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16-1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01-1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04-1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65-0.82, p < 0.001). CONCLUSIONS: ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.

The Socioeconomic Burden of Cholangiocarcinoma Associated With Opisthorchis viverrini Sensu Lato Infection in Northeast Thailand: A Preliminary Analysis.

The northeast of Thailand, which is the poorest region of the country, has the highest incidence of cholangiocarcinoma (CCA) worldwide. This is associated with infection with the liver fluke Opisthorchis viverrini. Although an estimated 20,000 people die every year of this disease, the socioeconomic impact of this mortality on the victims' family and the community in which he or she lived remains unknown. Here, we provide background information on the socioeconomic groups most effected by CCA and provide a qualitative estimate of the likely financial burden on the family and community. Most victims of CCA are small-scale farmers. Mortality occurs most commonly in males between the ages of 40 and 65, having either children or grandchildren to support. Costs can be divided between premortality with the family paying for transport and accommodation to the hospital, as well as costs not covered by the Thai Universal Health Coverage scheme. The main costs, however, are likely to be postmortem with loss of income and potentially the loss of a major contributor to farm work. What is urgently required is a quantitative estimate of the costs of CCA and long-term studies of the families and communities affected to determine where and how the burden of CCA falls.

Preoperative biliary drainage versus direct surgery for perihilar cholangiocarcinoma: A retrospective study at a single center.

Perihilar cholangiocarcinoma (pCC, also known as a Klatskin tumor) is the most common type of cholangiocarcinoma (CC). Preoperative biliary drainage (PBD) is indicated for pCC patients with acute cholangitis or patients who need portal vein embolization (PVE). However, the routine performance of PBD in other patients with pCC is still controversial. The current study retrospectively examined patients with pCC who did not undergo PVE and who did not have cholangitis who were seen at this Hospital to assess the advantages and disadvantages of PBD. This study also sought to find an optimal value of total bilirubin (TB) to indicate performing PBD. Between 2009 and 2014, after excluding patients with acute cholangitis and PVE, patients who had undergone hepatectomy for pCC were enrolled in this study. First, the surgical outcomes and postoperative outcomes were compared between PBD group and direct surgery group. Second, ROC curve analysis of a subgroup of patients was performed to find the best cut off value of TB for indicating the PBD. Third, the costs for patients, including the total charges and the charges per day were compared between the two groups. Subjects were 218 patients in total. Fifty-five patients underwent PBD. This group had a longer operative time [390 (210-700) vs. 360 (105-730) min, p = 0.013], and a longer hospital stay [20 (9-48) vs. 17 (6-93) days, p = 0.007], but underwent vascular resection and reconstruction less often [8 (14.5%) vs. 50 (30.7%), p = 0.019]. Mortality and morbidity were comparable between the two groups. ROC curve analysis of a subgroup of patients indicated that the cut-off value for total bilirubin was 218.75 µmol/L (12.4 mg/dL). The total hospital charges and the charges per day did not differ significantly for the two groups. Disadvantages of PBD were a longer operating time and a longer duration of hospitalization, but the short-term surgical outcomes and hospital charges of PBD group were comparable to the direct surgery group. PBD should be considered for patients when the diagnosis is still suspicious of pCC. Based on the current data, the optimal cut-off value for preoperative TB was 218.75 µmol/L (12.4 mg/dL) to indicate PBD for patients with pCC.

[Robot-assisted liver resection]. / Roboterassistierte Leberresektion.

Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

Secure, low-cost technique for laparoscopic hepatic resection using the crush-clamp method with a bipolar sealer.

INTRODUCTION: Laparoscopic hepatectomy is difficult because surgeons must perform the transection using many (four and more) energy devices and without direct manual maneuvers. Here we introduce hepatic transection by the classical method with a few (two or three) energy devices. MATERIALS AND SURGICAL TECHNIQUE: We performed laparoscopic hepatectomy for 40 patients with hepatic tumor and liver dysfunction. For parenchymal transection, we used bipolar radiofrequency coagulation forceps connected to a voltage-controlled electrosurgical generator and ultrasonic dissector. The demarcation of the liver surface was made by an ultrasonic dissector. Along the demarcation line, the blades of a BiClamp were opened slightly and inserted into the hepatic parenchyma. We clamped slowly, softly, and gradually, and a small amount of hepatic parenchyma was consequently coagulated and fractured. After the crush, the small vessels and intrahepatic bile duct that were sealed were left as atrophic strings, and the strings were divided by an ultrasonic dissector. Large vessels and Glisson's sheaths were left because of the small clamp. Large Glisson's sheaths and hepatic veins were ligated with a titanium clip or autosutures, and cut without bile leakage or bleeding. The mean operation time of the procedure was 196.9 min, mean blood loss was 69.9 mL, and mean postoperative hospitalization was 9.5 days. No blood transfusions were needed. Two cases had perioperative complications-one involving right shoulder pain and the other involving ascites due to liver dysfunction-but there were no serious postoperative complications. DISCUSSION: The present results appear to demonstrate that this simple and safe method helps decrease intraoperative bleeding and shorten hospital stay.

Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

BACKGROUND/AIMS: Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. METHODOLOGY: Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. RESULTS: Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. CONCLUSIONS: Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

Tannenbaum and metal stents in the palliative treatment of malignant distal bile duct obstruction: a comparative study of patency and cost effectiveness.

BACKGROUND: Stent clogging is the major limitation of palliative treatment for malignant biliary obstruction. Metal stents have much better patency than plastic stents, but are more expensive. Preliminary data suggest that the recently designed plastic (Tannenbaum) stent has better duration of patency than the polyethylene stent. This study aimed to compare the efficacy and cost effectiveness between the Tannenbaum stent without side holes and the uncovered metal stent for patients with malignant distal common bile duct obstruction. METHODS: In this study, 47 patients (median age, 73 years, range, 56-86 years) with inoperable malignant distal common bile duct strictures were prospectively randomized to receive either a Tannenbaum stent (n = 24) or an uncovered self-expandable metal stent (n = 23). The patients were clinically evaluated, and biochemical tests were analyzed if necessary until their death or surgery for gastric outlet obstruction. Cumulative first stent patency and patient survival were compared between the two groups. Cost-effectiveness analysis also was performed for the two study groups. RESULTS: The two groups were comparable in terms of age, gender, and diagnosis. The median first stent patency was longer in the metal group than in the Tannenbaum stent group (255 vs 123.5 days; p = 0.002). There was no significant difference in survival between the two groups. The total cost associated with the Tannenbaum stents was lower than for the metal stents (17,700 vs 30,100 euros; p = 0.001), especially for patients with liver metastases (3,000 vs 6,900 euros; p < 0.001). CONCLUSIONS: Metal stent placement is an effective treatment for inoperable malignant distal common bile duct obstruction, but Tannenbaum stent placement is a cost-saving strategy, as compared with metal stent placement, especially for patients with liver metastases and expected short survival time.