Cutaneous histiocytoses in children

Cutaneous histiocytoses constitute a heterogeneous group of diseases characterised by the cutaneous accumulation of cells with the cytological and phenotypic features of macrophages or dendritic cells. The clinical spectrum ranges from self-resolving, skin-limited conditions to severe, multiorgan disease with a high morbidity rate. Until recently, cutaneous histiocytoses were classified according to the immunophenotype of the pathological cells, with differentiation between Langerhans cell histiocytosis (LCH) [CD1a+, CD207 (langerin)+] and non-Langerhans cell histiocytosis (CD68+, CD163+, CD1a?, CD207?). Over the last 12 years, a number of new pathophysiological findings (in particular, molecular pathology results) regarding histiocytoses have contributed to a new classification based on molecular alterations, as well as on clinical and imaging characteristics and the phenotype. The most frequent entities in children are juvenile xanthogranuloma and LCH.     

Assessment of a Radiomic Signature Developed in a General NSCLC Cohort for Predicting Overall Survival of ALK-Positive Patients With Different Treatment Types

BackgroundThe purpose of the study was to investigate the potential of a radiomic signature developed in a general non–small-cell lung cancer (NSCLC) cohort for predicting the overall survival of anaplastic lymphoma kinase (ALK)-positive (ALK⁺) patients with different treatment types.Materials and MethodsAfter test-retest in the Reference Image Database to Evaluate Therapy Response data set, 132 features (intraclass correlation coefficient > 0.9) were selected in the least absolute shrinkage and selection operator Cox regression model with a leave-one-out cross-validation. The NSCLC radiomics collection from The Cancer Imaging Archive was randomly divided into a training set (n = 254) and a validation set (n = 63) to develop a general radiomic signature for NSCLC. In our ALK⁺ set, 35 patients received targeted therapy and 19 patients received nontargeted therapy. The developed signature was tested later in this ALK⁺ set. Performance of the signature was evaluated with the concordance index (C-index) and stratification analysis.ResultsThe general signature had good performance (C-index > 0.6; log rank P < .05) in the NSCLC radiomics collection. It includes 5 features: Geom_va_ratio, W_GLCM_Std, W_GLCM_DV, W_GLCM_IM2, and W_his_mean. Its accuracy of predicting overall survival in the ALK⁺ set achieved 0.649 (95% confidence interval [CI], 0.640-0.658). Nonetheless, impaired performance was observed in the targeted therapy group (C-index = 0.573; 95% CI, 0.556-0.589) whereas significantly improved performance was observed in the nontargeted therapy group (C-index = 0.832; 95% CI, 0.832-0.852). Stratification analysis also showed that the general signature could only identify high- and low-risk patients in the nontargeted therapy group (log rank P = .00028).ConclusionThis preliminary study suggests that the applicability of a general signature to ALK⁺ patients is limited. The general radiomic signature seems to be only applicable to ALK⁺ patients who had received nontargeted therapy, which indicates that developing special radiomics signatures for patients treated with tyrosine kinase inhibitors might be necessary.     

ALK阳性非小细胞肺癌靶向治疗耐药机制及预后标志物的研究进展

棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase, EML4-ALK)融合占非小细胞肺癌(non-small cell lung cancer, NSCLC)患者的3%-5%。随着对该驱动基因的深入研究，以Crizotinib为代表的ALK抑制剂逐渐被开发并应用于临床。然而，不同患者对ALK靶向治疗的反应存在差异，且多数ALK靶向治疗患者最终会不可避免地出现耐药，导致肿瘤进展。利用预后标志物监测患者疗效及时改变治疗方案，以及根据耐药机制选择个体化的后续治疗，可以有效地改善患者的预后。本文将对ALK抑制剂的耐药机制以及相关的预后标志物展开综述，探讨ALK靶向治疗疗效预测以及耐药患者后续治疗方案的选择。