RESUMEN
BACKGROUND: Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available. AIM: To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time. METHODS: A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups. RESULTS: Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) vs 4 (2.9-11.8) mo (REG), P = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) vs 5.2 (4-7.2) mo (CBZ), P = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) vs 4.9 (1.6-11.7) mo (CP-B), P = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors. CONCLUSION: This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.
RESUMEN
PURPOSE: Evaluate the impact of fecal incontinence (FI) and chronic constipation (CC) on the quality of life (QoL) in a large population and determine if a threshold of symptom scores was associated with alterations to QoL. METHODS: A total of 422 outpatients with FI (n = 186), CC (n = 186), and mixed FI-CC (n = 50) referred for anorectal manometry were included prospectively. All patients completed a set of questionnaires to evaluate the severity of FI and CC (respectively Jorge and Wexner and KESS scores) and their impact on QoL (Gastrointestinal Quality of Life Index (GIQLI)). RESULTS: The study population included 81.8% women. The QoL was altered to the same degree for both FI and CC, with significant more marked impairments in patients with mixed FI-CC (median GIQLI: 91 (71-108) vs. 91 (73-108) vs. 81 (57-97) respectively, p = 0.05). The symptom severity significantly but weekly correlated with the GIQLI score (r2 = - 0.454 for FI and r2 = - 0.483 for CC, p < 0.001). Thus, the large dispersion of the data flawed the identification of a threshold for symptom severity that could predict major impairment to QoL. CONCLUSION: The QoL was equally altered for FI and CC. Although the symptom score severity was slightly but significantly associated with alterations to QoL, it was not possible to determine a threshold for symptom scores that predict an alteration to QoL. Therefore, the evaluation of QoL in parallel to the assessment of the symptom score is required to endorse the entire spectrum of the severity of CC or FI.