Association of public health insurance with cancer-specific mortality risk among patients with nasopharyngeal carcinoma: a prospective cohort study in China.

Objective: Health insurance programs are effective in preventing financial hardship in patients with cancer. However, not much is known about how health insurance policies, especially in Southwest China with a high incidence of nasopharyngeal carcinoma (NPC), influence patients' prognosis. Here, we investigated the association of NPC-specific mortality with health insurance types and self-paying rate, and the joint effect of insurance types and self-paying rate. Materials and methods: This prospective cohort study was conducted at a regional medical center for cancer in Southwest China and included 1,635 patients with pathologically confirmed NPC from 2017 to 2019. All patients were followed up until May 31, 2022. We determine the cumulative hazard ratio of all-cause and NPC-specific mortality in the groups of various insurance kinds and the self-paying rate using Cox proportional hazard. Results: During a median follow-up period of 3.7 years, 249 deaths were recorded, of which 195 deaths were due to NPC. Higher self-paying rate were associated with a 46.6% reduced risk of NPC-specific mortality compared to patients with insufficient self-paying rate (HR: 0.534, 95% CI: 0.339-0.839, p = 0.007). For patients covered by Urban and Rural Residents Basic Medical Insurance (URRMBI), and for patients covered by Urban Employee Basic Medical Insurance, each 10% increase in the self-paying rate reduced the probability of NPC-specific death by 28.3 and 25%, respectively (UEBMI). Conclusion: Results of this study showed that, despite China's medical security administration improved health insurance coverage, NPC patients need to afford the high out-of-pocket medical costs in order to prolong their survival time.

Leptomeningeal metastasis from de novo metastatic nasopharyngeal carcinoma: a case report.

Background: Leptomeningeal metastasis (LM) have a poor prognosis and rare studies have reported LM from nasopharyngeal carcinoma (NPC). Immune checkpoint inhibitor (ICI) was the standard first line treatment for metastatic NPC and was reported to improve intracranial response and survival in several types of cancer. Case Description: In this case presentation, we present a case of a 26-year-old man with de novo metastatic NPC who initially complained of left cervical masses. A PET/CT and MRI scan revealed multiple liver, bone and brain metastasis. The patient received initial anti PD-1 antibody camrelizumab combined with chemotherapy, followed by radiotherapy to local and regional lesions. Two weeks after that, the patient experienced transient unconsciousness, persistent fatigue and pain in both lower limbs. Then MRI revealed leptomeningeal linear enhancement, hydrocephalus and increased multiple intracranial metastatic lesions. So the patient was diagnosed of LM. The therapeutic regimen then consisted of whole brain radiotherapy combined with oral capecitabine. A partial response was demonstrated and the progression-free survival (PFS) was 5 months since the diagnosis of LM. To our knowledge, this is the first case of LM from NPC treatment with ICI. Conclusions: This case highlights the diagnosis and treatment of LM from NPC, and provides an optional regimen after ICI failure.

A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for low grade glioma.

Background: As a common primary intracranial tumor, the diagnosis and therapy of low-grade glioma (LGG) remains a pivotal barrier. Cuproptosis, a new way induces cell death, has attracted worldwide attention. However, the relationship between cuproptosis and LGG remains unknown. Our study is all about finding out if there are any genes related to coproptosis that can be used to predict the outcome of LGG. Methods: RNA data and clinical information were selected from Cancer Genome Atlas (TCGA) datasets and the Genotype-Tissue Expression (GTEx), 5 lncRNAs (GAS5.AS1, MYLK.AS1, AC142472.1, AC011346.1, AL359643.3) were identified by Cox univariate and multivariate regression, as well as LASSO Cox regression. In the training and test sets, a dual validation of the predictive signature comprised of these 5 lncRNAs was undertaken. The findings demonstrate that the risk model is able to predict the survival regression of LGG patients and has a good performance in either the KM curve approach or the ROC curve. GO, GSEA and KEGG were carried out to explore the possible molecular processes that affecting the prognosis of LGG. The characteristics of immune microenvironment were investigated by using CIBERSORT, ESTIMATE and ssGSEA. Results: We identified five lncRNAs related with cuproptosis that were closely associated with the prognosis of LGG and used these five lncRNAs to develop a risk model. Using this risk model, LGG patients were then divided into high-risk and low-risk groups. The two patient groups had significantly distinct survival characteristics. Analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differential genes of the two patient groups were primarily concentrated in neural active ligand-receptor interaction and cytokine-cytokine receptor interaction. The ssGSEA score determined the information related to immune infiltration, and the two groups were differentially expressed in immune subpopulations such as T cells and B cells as well. Conclusion: Our study discovered 5 cuproptosis-related lncRNAs which contribute to predicting patients' survival of LGG and provide ideas for the exploration of new targets for LGG in the future.

Suppression of circ_0008932 inhibits tumor growth and metastasis in osteosarcoma by targeting miR-145-5p.

Osteosarcoma (OS) is a common type of primary malignant tumor. Although the pathogenesis of OS has been extensively studied, the underlying molecular mechanisms have remained to be fully elucidated. Accumulating evidence has revealed that dysregulation of various circular RNAs (circRNAs) is associated with tumorigenesis and recent studies have indicated that circRNA circ_0008932 is aberrantly expressed in tumors. In the present study, the expression and detailed function of circ_0008932 in OS were elucidated. The levels of circ_0008932 in OS samples and cell lines were examined using reverse transcription-quantitative PCR. A cell model with circ_0008932 knockdown was generated using specific small interfering RNA (si-circ_0008932). Cell viability was determined by a Cell Counting Kit-8 assay, the cell migratory/invasive capacity was evaluated using Transwell assays and cell apoptosis was assessed by flow cytometry. The results suggested that circ_0008932 was upregulated in most primary OS tumors, suggesting that circ_0008932 is associated with the development of OS. In the in vitro assays, si-circ_0008932 inhibited the proliferation, migration and invasion of OS cells, while apoptosis was promoted. A luciferase reporter assay revealed that circ_0008932 may downregulate microRNA (miR)-145-5p through direct binding. Furthermore, the expression of miR-145-5p was negatively correlated with circ_0008932 levels in OS specimens. In addition, further functional studies indicated that miR-145-5p inhibitors eliminated the effects caused by si-circ_0008932 in OS cells. In comparison, the changes in the biological behavior of OS cells transfected with si-circ_0008932 were enhanced by miR-145-5p. In summary, circ_0008932 may be a novel oncogenic factor during the progression and development of OS by targeting miR-145-5p; more importantly, circ_0008932 may be a potential therapeutic target for OS.

Transcriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma.

Although the abnormal expression of members of the E2F family has been reported to participate in carcinogenesis in many human types of cancer, the bioinformatics role of the E2F family in melanoma is unknown. This research was designed to detect the expression, methylation, prognostic value and potential effects of the E2F family in melanoma. We investigated E2F family mRNA expression from the Oncomine and GEPIA databases and their methylation status in the MethHC database. Meanwhile, we detected the relative E2F family expression levels by qPCR and immunohistochemistry. Kaplan-Meier Plotter was used to draw survival analysis charts, and gene functional enrichment analyses were applied through cBioPortal database analysis. E2F1/2/3/4/5/6 mRNA and proteins were clearly upregulated in cutaneous melanoma patients, and high expression levels of E2F1/2/3/6 were statistically related to high methylation levels. Increased mRNA expression of E2F1/2/3/6 was related to lower overall survival rates (OS) and disease-free survival (DFS) in cutaneous melanoma cases. Meanwhile, E2F1/2/3/6 carried out these effects through regulating multiple signaling pathways, including the MAPK, PI3K-Akt and p53 signaling pathways. Taking together, our findings suggest that E2F1/2/3/6 could act as potential targets for precision therapy in cutaneous melanoma patients.

Efficacy and safety of apatinib in recurrent/metastatic nasopharyngeal carcinoma: A pilot study.

BACKGROUND: There is no standard-of-care for recurrent, metastatic nasopharyngeal carcinoma (rmNPC) after first-line chemotherapy. Here, we report the efficacy and safety data of apatinib in rmNPC patients. METHODS: Thirty-five biopsy-proven rmNPC patients received apatinib at 500 mg/day under a compassionate access programme. Primary end-point was objective response rate (ORR; RECIST v1.1). Kaplan-meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Toxicity was assessed by CTCAE v4.0. RESULTS: 82.9% (29 of 35) of patients had poly-metastatic rmNPC. All patients, except five, were platinum-refractory; 37.1% (13 of 35) received ≥ 2 lines. Median number of apatinib cycles was 4.0 (IQR: 2.0-8.0). ORR was 31.4% (11 of 35 [95% CI: 16.9-49.3]) and disease control rate was 74.3% (26 of 35 [95% CI: 56.7-87.5]); 11 (31.4%) and 4 (11.4%) patients demonstrated response for ≥ 6 and ≥ 12 months, respectively. Median PFS and OS was 3.9 (95% CI: 3.1-5.5) months and 5.8 (95% CI: 4.5-8.0) months, respectively. Among the ≥ 12-month responders, all patients had pre-apatinib EBV DNA titer of <700 (range: 353-622) copies/ml; this was consistent with the association of PFS with pre-apatinib EBV DNA titer (adjusted HR 3.364 [95% CI: 1.428-7.923] for ≥ 4000 copies/ml, P = 0.006). 42.9% (15 of 35) of patients required dose reduction. Nonetheless, only five (14.3%) patients suffered from G3 toxicities (two haematological, one hypertension, one hand-foot syndrome and one elevated aminotransferases). CONCLUSION: Our data suggests potential efficacy of apatinib in rmNPC patients. Although incidence of severe toxicities was low, dose modification was required in 42.9% of patients.

Lactate dehydrogenase kinetics predict chemotherapy response in recurrent metastatic nasopharyngeal carcinoma.

BACKGROUND: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. METHODS: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1-6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. RESULTS: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus <240 (1.34-2.77), p < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDHCTn: LDHCTn-1) were associated with tumour response [partial response versus progressive disease: median value across CT1-6 = 168-190 versus 222-398 (absolute); 0.738-0.988 versus 1.039-1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65-0.80)]. CONCLUSION: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.

[Preliminary study of intensity-modulated radiation therapy for recurrent cervical cancer].

OBJECTIVE: To assess feasibility of intensity-modulated radiation therapy for recurrent cervical cancer. METHODS: Totally 21 patients with recurrent cervical cancer between April 2004 and January 2007 treated with intensity-modulated radiation therapy (IMRT) and conventional external radiation therapy were evaluated. Twenty-one patients treated with IMRT was group A, and the other 18 patients with anterior posterior field radiotherapy was group B. Preliminary outcome and toxicity were evaluated between two groups. RESULTS: All patients completed the prescribed dose. Group A was (50 +/- 11) Gy and group B was (39 +/- 5) Gy. There were no significant differences in the two groups (P > 0.05). The effective rate of group A was 71% (15/21) and of group B 39% (7/18), with a significant difference in the two groups (P < 0.05). The average survival time of group A was (25 +/- 6) months, and of group B (12 +/- 5) months, with a significant difference in the two groups (P < 0.05). In group A, acute grade > or = 3 gastrointestinal, genitourinary, and myelotoxicity were seen in 0, 0, and 2 patients, respectively. While in group B, these were seen in none. CONCLUSIONS: The curative effect of IMRT is better than anterior posterior field radiotherapy. The acute toxicity of IMRT is acceptable.