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Since autophagy and the immune microenvironment are deeply involved in the tumor development and progression of Lower-grade gliomas (LGG), our study aimed to construct an autophagy-related risk model for prognosis prediction and investigate the relationship between the immune microenvironment and risk signature in LGG. Therefore, we identified six autophagy-related genes (BAG1, PTK6, EEF2, PEA15, ITGA6, and MAP1LC3C) to build in the training cohort (n = 305 patients) and verify the prognostic model in the validation cohort (n = 128) and the whole cohort (n = 433), based on the data from The Cancer Genome Atlas (TCGA). The six-gene risk signature could divide LGG patients into high- and low-risk groups with distinct overall survival in multiple cohorts (all p < 0.001). The prognostic effect was assessed by area under the time-dependent ROC (t-ROC) analysis in the training, validation, and whole cohorts, in which the AUC value at the survival time of 5 years was 0.837, 0.755, and 0.803, respectively. Cox regression analysis demonstrated that the risk model was an independent risk predictor of OS (HR > 1, p < 0.05). A nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its robust predictive capacity. KM analysis revealed a significant difference in the subgroup analyses’ survival. Functional enrichment analysis revealed that these autophagy-related signatures were mainly involved in the phagosome and immune-related pathways. Besides, we also found significant differences in immune cell infiltration and immunotherapy targets between risk groups. In conclusion, we built a powerful predictive signature and explored immune components (including immune cells and emerging immunotherapy targets) in LGG.

Background and purpose: Leptomeningeal metastasis (LM) is a rare but detrimental complication in patients with non-small cell lung cancer (NSCLC). Although whole brain radiotherapy (WBRT) is used to eliminating cancer cells or microscopic foci, it is becoming less favorable due to the concerns over neurocognitive toxicity. This study aimed to re-evaluate the role of WBRT in the setting of modern targeted therapy. Materials and methods: From December 2014 to March 2019, 80 NSCLC patients with cytologically and/or radiologically proven LM diagnosis were retrospectively analyzed. Results: The median OS (mOS) after diagnosis of LM was 8.0 (95%CI: 4.4 to 11.6) months, and the one-year OS was 39.4%. The mOS for EGFR-mutated LM patients was 12.6 (3.0 to 22.2) months versus only 4.1 (2.8 to 5.4) for patients with wild-type EGFR (P < 0.001). Younger patients (< 53.5 yrs.) appeared to have a better OS than older patients (≥53.5 yrs.) (12.6 vs. 6.1, P = 0.041). No survival benefits were found in EGFR-mutated patients who received WBRT (P = 0.490). In contrast, mOS was significantly prolonged in wild-type EGFR patients with WBRT versus non-WBRT (mOS: 8.0 vs. 2.1, P = 0.002). Multivariate analysis indicated that WBRT (P = 0.025) and younger age (P = 0.048) were independent prognostic factors that predicted prolonged survival for wild-type EGFR LM patients from NSCLC. Conclusion: Our study demonstrated that WBRT has clear survival advantages for patients with wild-type EGFR, and molecular biological stratification of LM patients for WBRT is highly recommended.

A 36-year-old Chinese woman was diagnosed with diffuse midline glioma and received radiotherapy and chemotherapy. Ten months later, bone metastases were confirmed by pathological biopsy. This case is one of a handful of cases in which an adult patient with diffuse midline glioma had multiple bone metastases. Better diagnostic methods and more appropriate treatment strategies for diffuse midline glioma are urgently needed, requiring further investigations into the mechanisms underlying metastases.

Dear Editor, Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) patients correlates with dismal outcomes, and the detection sensitivity of conventional diagnosis of lymphoma is restricted. 1-4 Circulating tumor DNA from cerebrospinal fluid (CSF-ctDNA) has played an important part in the application of liquid biopsy for patients with CNS cancers. 5 In this study, we provided new insights into feasibility of CSF-derived biomarkers for CNS relapse diagnosis in DLBCL patients. In clinical setting, the diagnosis of CNS involvement is based on several clinical risk factors including individual international prognostic index (IPI), number of extranodal involvement (testicular/adrenal/kidney), and serum lactate dehydrogenase (LDH). 6 CNS-IPI, which is a six-risk-factor model developed by a German group (five IPI factors with kidney/adrenal involvement) for CNS diagnosis, has been validated and proved to be useful in clinical settings. 7 Other reported biological risk factors for CNS involvement included MYC gene rearrangements or MYC (MYC proto-oncogene) and BCL2 (B-cell lymphoma 2) dual translocations. 8,9 To assess the correlation between CSF-ctDNA and CNS involvement in DLBCL, targeted mutational profiling was performed on CSF-and plasma-derived ctDNA together with matched systemic tumor tissues in 67 DLBCL patients clinically diagnosed as high risk for CNS involvement (Figure S1, Table S1). Genomic landscape of this DLBCL cohort in systemic tumor tissue is shown in Figure 1A. Considering both single nucleotide variant (SNV) and copy number variant (CNV), commonly mutated genes cohort included Pim-1 proto-oncogene (PIM1, 37.3%), lysine methyltransferase 2D (KMT2D,33.3%), BCL2 (27.5%), myeloid differentiation primary response 88 (MYD88, 27.5%), B-cell translocation gene 2 (BTG2, 23.5%), and tumor protein p53 (TP53, 23.5%). Majority of altered genes were involved in four important pathways including epigenetic regulation This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.