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Background: The efficacy and safety of enfortumab vedotin combined with pembrolizumab (EV-PEMB) was investigated as a first-line treatment for advanced urothelial carcinoma (UC) in a phase III clinical trial (EV-302). The trial findings indicated significant prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy with a favorable safety profile. However, EV-PEMB is costly and it is unknown whether it is cost-effective compared to chemotherapy. This study aimed to conduct a cost-effectiveness analysis of EV-PEMB versus chemotherapy as a first-line treatment for advanced UC from the perspective of the Chinese healthcare system. Methods: A Markov model with three distinct health states was developed to assess the cost-effectiveness of EV-PEMB as a first-line treatment for advanced UC versus chemotherapy based on the EV-302 trial. Drug costs were obtained from national tender prices. Other expenses and utility values were sourced from the literature or expert advice. The findings of the study included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We conducted a one-way sensitivity analysis and probabilistic sensitivity analysis to ensure the model's robustness. Results: The EV-PEMB regimen demonstrated a gain of 3.22 QALYs at $375,420.24, compared to the chemotherapy regimen with 1.70 QALYs at $23,369.67. ICER for EV-PEMB compared to chemotherapy was at $232,256.16 per QALY gained. In China, at a willingness-to-pay threshold of $38,133 per QALY, EV-PEMB has a 0% probability of being cost-effective as a first-line treatment for advanced UC compared to chemotherapy. Conclusion: From the perspective of the Chinese healthcare system, EV-PEMB is unlikely to be a cost-effective first-line treatment option for advanced UC compared to chemotherapy.
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Objective: To investigate the clinicopathologic features of pituitary adenoma with neuronal differentiation. Methods: Four patients with mixed gangliocytoma-pituitary adenomas between January 2011 and January 2021 and 111 new-onset patients with adenomas between January 2019 and June 2021 who attended the First Affiliated Hospital of Fujian Medical University were included in the study. The histological and immunohistochemical findings were analyzed. Neuronal differentiation marker staining was performed on new-onset adenomas, and the related literature was reviewed. Results: Altogether, more than 100 mixed gangliocytoma-pituitary adenoma cases have been reported in the literature until now, of which pituitary-specific POU-class homeodomain transcription 1 (PIT1) positive adenomas are more frequently observed. In the present study, all 4 patients we described were female, aged 29 to 53 years (mean 39 years). Clinically, 3/4 patients presented with acromegaly, and 1/2 patients presented with headache. Histologically, the tumor was composed of two distinct mixed components. The one was a population of neoplastic ganglionic cells with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm embedded in a fibrillary background. Stains of chromograninA (CgA), synaptophysin (Syn), Calretinin (CR) were positive. Axotomy-like expression was observed in neurofilament (NF) staining. PIT1 was expressed in partial ganglionic cells in all cases. The other component was a population of small uniform cells with round nuclei and acidophilic cytoplasm. Prolactin (PRL) and growth hormone (GH) were positive in all 4 cases. PIT1 was positive in the nuclei of adenomas. Although adenomas and ganglionic regions varied in histology, there was a population of cells with neuronal differentiation expressing PIT1. Additionally, axotomy-like expression of NF staining could be seen in a distant area of adenoma regions. A total of 111 cases of adenomas without ganglionic cells were included in this study, including 7 cases with neuronal differentiation. Among them, 4 cases were prolactinomas, 2 cases were somatotroph adenomas, and 1 case was corticotroph adenoma. 6/7 cases were PIT1-positive adenomas. And the remaining one case is T-PIT-positive adenoma. Conclusions: Mixed gangliocytoma-pituitary adenomas are rare tumors with neuronal differentiation. The majority of MGAs are associated with endocrinopathies, mainly acromegaly. Our results suggest that PIT1-positive pituitary adenomas may have neural differentiation potential, which may not be unusual. This indication supports the possibility that the neuronal transdifferentiation of adenomatous cells is a possible mechanism, and the underlying mechanism requires further elucidation.