Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder, with a 1% yearly risk of progression to multiple myeloma (MM). Evolution of M‐spike and serum free light chain (sFLC) during follow‐up could identify patients at high risk of progression. In this region‐wide study, including 4756 individuals, 987 patients with MGUS were identified, and baseline factors as well as evolving involved FLC (iFLC) were evaluated as potential markers for risk of progression from MGUS to MM. Furthermore, evolving iFLC and M‐spike were assessed quarterly for a median of 5 years. At baseline, patients that progressed had significantly higher iFLC compared to non‐progressors. The risk factors of M‐spike >1.5 g/dL, age >65 years and iFLC >100 mg/L were all independently associated with increased risk of MGUS to MM progression. For patients that had any two or three risk factors, the 5‐year cumulative probability of progression was significantly higher (31%) compared to no risk factors (2%). Evolving iFLC >100 mg/L during follow‐up was consistently associated with increased risk of progression. Based on our observations, we propose to include iFLC as a monitoring tool for all MGUS patients. Furthermore, we recommend a quarterly monitoring in all high‐risk patients. Finally, we suggest that the risk of MGUS progression should be stratified with age, M‐spike, and iFLC at baseline.
Background: Combined large cell neuroendocrine carcinoma (C-LCNEC) is pulmonary large cell neuroendocrine carcinoma (LCNEC) mixed with other components, such as adenocarcinoma (AD), squamous cell carcinoma (SCC), etc. The clinical characteristics and prognostic factors of C-LCNEC remain unclear. This study aimed to describe the distinct features between C-LCNEC with different components and explore the treatment strategy.Methods: We retrospectively collected data of 114 C-LCNEC patients who underwent surgically resection and analyzed their clinical characteristics and prognosis.Results: In our final cohort, 82 (72%) were LCNEC combined with adenocarcinoma (LCNEC/AD), while 32 (28%) were LCNEC combined with squamous cell carcinoma (LCNEC/SCC). LCNEC/AD was more likely to occur in female, younger adults, with visceral pleural invasion and with driver gene expression. However, univariate analysis showed no significant difference in DFS and OS between them (P¼0.837 and P¼0.852), while adjuvant chemotherapy (P¼0.001 and P¼0.003) and preoperative CEA level (P¼0.026 and P¼0.009) were independent predictors. C-LCNEC patients receiving adjuvant chemotherapy had longer DFS and OS, including stage I patients (P ¼ 0.006 and P ¼ 0.031), and the benefit of etoposide-based chemotherapy in stage II or III patients was greater than the other regimens (P ¼ 0.038 and P¼0.020). EGFR and ALK mutations were present in 5.8% (17/66) and 6.1% (4/66) of C-LCNEC patients, respectively, and they responded well to targeted therapy.Conclusions: LCNEC/AD was the most common type of C-LCNEC, and there were many differences between different combined components. Adjuvant chemotherapy, especially etoposide-based chemotherapy, was a beneficial option for resected C-LCNEC.
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