e24165 Background: Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared to other classes of chemotherapeutic agents, even with adequate premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. Methods: This was a retrospective cohort study conducted at a single site hematology/oncology infusion center. The fixed-rate arm consisted of patients from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary endpoint was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary endpoints included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation due to HSRs. Results: Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (OR 1.67, 95% CI 0.89-3.15; p= 0.1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. Conclusions: The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting. Primary and secondary endpoints. Fixed (N=240) Titration (N=239) OR 95% CI p-value Primary Endpoint Rates of immediate HSR 17 (7.1%) 27 (11.3%) 1.67 0.89- 3.15 0.110 Secondary Endpoints Severity of immediate HSR N=17 N=27 Grade 1 10 (58.8%) 8 (30.8%) 0.637 Grade 2 6 (35.3%) 12 (46.2%) 0.157 Grade 3 1 (5.9%) 6 (23.1%) 0.059 Rates of immediate HSR with first or second dose combined N=471 infusions N=453 infusions 26 (5.5%) 37 (8.2%) 1.52 0.91-2.56 0.111 Taxane administration time (min) N=239 N=232 1-hour infusion 71.8 92.8 3-hour infusion 187.6 201.6 Rates of medication discontinuation due to immediate HSR N=26 N=37 1 (3.8%) 8 (21.6%) 6.90 0.81-59.17 0.069
Comparing the Rates of Hypersensitivity Reactions During First-Dose Taxane Infusions: Fixed-Rate Versus Stepwise Titration
PURPOSE Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared with other classes of chemotherapeutic agents, even with premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. METHODOLOGY This was a retrospective cohort study conducted at a single-site hematology/oncology infusion center. The fixed-rate arm consisted of patients treated from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients treated from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary end point was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary end points included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation because of HSRs. RESULTS Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (odds ratio, 1.67 [95% CI, 0.89 to 3.15]; P = .1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. CONCLUSION The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting.
Liver Transplantation for Non-HCC Malignancies: Cholangiocarcinoma, Neuroendocrine Tumors, HEHE, and Colorectal Metastases
Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. The aim of this study was to analyze the long‐term outcomes for obese patients undergoing LT, including a noninvasive weight loss program and combined LT and sleeve gastrectomy (SG). Since 2006, all patients referred for LT with a body mass index (BMI) ≥35 kg/m2 were enrolled. Patients who achieved weight loss (BMI <35) underwent LT alone, and those who did not underwent simultaneous LT + SG. Analysis of long‐term outcomes for patients ≥3 years posttransplant was performed. Since 2006, there were 36 in the weight loss intervention (LT cohort) and 13 in the LT + SG cohort with >3 years of follow‐up, whereas overall, a total of 29 patients underwent LT + SG. Patients in the LT cohort had less severe obesity at enrollment (40.0 ± 2.7 vs. LT + SG cohort 46.0 ± 4.5; P < 0.001). In the LT cohort, 83.3% (30 of 36) achieved >10% loss in total body weight (TBW) pre‐LT. Three years posttransplant, 29.4% of patients in the LT cohort maintained >10% loss in TBW, whereas 100% of the LT + SG patients did (P < 0.001). Patients who underwent LT + SG maintained a significantly higher percentage of total body weight loss after 3 years of follow‐up (LT cohort 3.9 ± 13.3% vs. LT + S G cohort 34.8 ± 17.3%; P < 0.001). Patients in the LT + SG also had a lower prevalence of hypertension, insulin resistance, and hepatic steatosis and required fewer antihypertensive medications and lipid agents at last follow‐up. Conclusion: Whereas weight loss before transplantation was achieved by obese patients, weight regain was common in the LT cohort. Combined LT + SG resulted in more effective and more durable weight loss, as well as fewer metabolic complications at last follow‐up. (Hepatology 2018).
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.