Identification of clinical prognosis features and significant DNA methylation regulation in pineoblastoma.

BACKGROUND: Pineoblastoma (PB) represents a great challenge for clinical management due to lack of a specific therapeutic regimen. This study aims to identify relevant prognostic factors and potential treatment targets by mining public databases. METHODS: The clinical characteristics and survival data of PB patients were obtained from the SEER database between 2000 and 2019 for Cox regression analysis and nomogram construction. The PB's DNA methylation data was acquired from two GEO datasets, GSE133801 and GSE215240, for bioinformatics analysis. RESULTS: Of 383 PB patients, Cox univariate analysis unveiled that male gender (p = 0.017), age younger than 3 years at diagnosis (p < 0.001) and absence of radiotherapy (p < 0.001) correlated with poorer overall survival (OS), the subsequent multivariate analysis confirmed sex (p = 0.036), age (p < 0.001) and radiotherapy (p = 0.005) as independent prognostic factors for OS. A nomogram showed robust predictive accuracy as evidenced by AUC values (1-year OS: 0.774, 3-year OS: 0.692, 5-year OS: 0.643). DNA methylation analysis observed tumor hypomethylation, notably in promoter regions. Later, the GO enrichment analysis of aberrantly methylated genes indicated associations with embryonic organ development, cellular membrane composition and DNA-binding transcription, while KEGG analysis revealed enrichment in tumor-associated MAPK, calcium and RAS signaling pathways. CONCLUSIONS: The prognosis of PB is closely associated with sex, age and receipt of radiotherapy, potentially linked to aberrations in the RAS and MAPK signaling pathways. The individual case suggests that dasatinib and trametinib are potential targeted therapies for improving PB prognosis.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Identification of a ferroptosis-related gene signature for the prognosis of pediatric neuroblastoma.

Background: Ferroptosis-related genes are correlated with the prognosis of patients with neuroblastoma (NB) remains unknown. This study aims to establish a prognostic ferroptosis-related gene model for predicting prognostic value in pediatric NB patients. Methods: The gene expression array and clinical characteristics of NB were downloaded from a public database. Correlations between ferroptosis-related genes and drug responses were analyzed by Childhood Cancer Therapeutics. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in NB patients from the ICGC cohort. The survival analysis was performed by Cox regression analysis. single-sample gene set enrichment analysis (ssGSEA) was used to quantify the immune cell infiltration correlation. Results: Overall, 70 genes were identified as ferroptosis-related differentially expressed genes (DEGs) from 247 samples. Then, 13 ferroptosis-related genes were correlated with OS in the univariate Cox regression analysis. Five prognostic ferroptosis-related DEGs (pFR-DEGs) (STEAP3, MAP1LC3A, ULK2, MTOR and TUBE1), which were defined as the intersection of DEGs and prognostic ferroptosis-related genes, were identified and utilized to construct the prognostic signature. The correlation between five pFR-DEGs and drug responses was analyzed, and the box plots indicated that MTOR gene expression was highest, suggesting that MTOR expression is related to progressive NB disease. The receiver operating characteristic (ROC) curve showed that the model had moderate predictive power. The survival analysis indicated that the high-risk group had poor overall survival (OS) (P=2.087×10-06). Univariate and multivariate analyses identified the risk score as a significant prognostic risk factor [P=0.003, hazard ratio (HR) =1.933]. Immune cell infiltration correlation analysis showed that the high-risk group was related to more immune cells. Conclusions: The present study indicated a difference in ferroptosis-related gene expression between low- and high-risk NB patients. The ferroptosis-related signature could serve as a prognostic prediction tool. Additionally, immune infiltration might play an important role in different risk groups for NB patients.

Administration of oral maintenance chemotherapy for 1 year following definitive chemoradiotherapy may improve the survival of patients with stage N3 nasopharyngeal carcinoma.

OBJECTIVES: This study aims to evaluate the effectiveness and the optimal maintenance period of oral chemotherapy using S1 following definitive chemoradiotherapy in patients with stage N3 nasopharyngeal carcinoma (N3-NPC). MATERIALS AND METHODS: A retrospective review was performed for N3-NPC treatment with maintenance chemotherapy (MC) [chemoradiotherapy (CRT)-MC] or without MC (CRT-non-MC) following definitive CRT between May 2014 and December 2017. Toxicities during MC were recorded. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared between CRT-MC and CRT-non-MC cohorts. The optimal duration of using maintenance S1 (MC-S1) was also analyzed. RESULTS: A total of 304 patients with stage N3-NPC were identified, of whom 56 were treated with CRT-MC and 248 with CRT-non-MC. After a median follow-up of 48 months, significant differences in OS (74.9 vs. 91.7%; P = 0.003), PFS (60.7 vs. 83.7%; P = 0.001) and DMFS (68.8 vs. 85.5%; P = 0.015) were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leukopenia and fatigue were common but not severe (grade 1-2) side effects of MC. The OS, DMFS and PFS were significantly higher for patients who received S1 administration over a period of ≥12 cycles compared with those who received <12 cycles (3-year OS, 100 vs. 87.5%, P = 0.018; 3-year PFS, 93.9 vs. 67.9%, P = 0.006; 3-year DMFS, 97.1 vs. 67.9%, P = 0.002). CONCLUSIONS: Using MC-S1 in patients with N3-NPC following definitive chemoradiotherapy achieved superior survival rate compared with the patients with non-MC. The side effects of MC-S1 were mild and tolerable. S1 should be maintained for ≥12 cycles.

Modified reduced-volume intensity-modulated radiation therapy in non-metastatic nasopharyngeal carcinoma: A prospective observation series.

BACKGROUND AND PURPOSE: Although the efficacy of "reduced-volume intensity-modulated radiation therapy (IMRT)" in nasopharyngeal carcinoma (NPC) has been confirmed, two issues regarding the necessity of clinical target volume 1(CTV1) delineation and the optimal margin of CTV2 remained undetermined. The current series, utilized de-intensification technique that omitted the contouring of CTV1 and narrowed the margin of CTV2 from 10 mm to 8 mm, namely "modified reduced-volume IMRT" was initiated to evaluate the efficacy and feasibility of this renew technique in a prospective series. PATIENTS AND MATERIALS: Dosimetric analysis was performed in 40 non-metastatic NPC cases to evaluate whether our modification is feasible. Then this de-intensification technique was applied in non-metastatic NPC patients treated in our attending group since late 2014. Survival outcomes focused on local recurrence-free survival (LRFS) and local failure pattern were analyzed. RESULTS: Preliminary dosimetric evaluation of "modified reduced-volume IMRT" showed that the 60 Gy isodose curve generated naturally by this technique could well wrap the target area of CTV1. Subsequent observation series, which included a total of 471 patients and had a median follow-up time of 46.2 months(range,3.7-70.8 months), reported that 4-year estimated LRFS, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.6%, 97.7%, 87.7% and 92.4%, respectively. All local recurrence lesions occurred within 95% isodose lines and were considered in-field failures. CONCLUSIONS: Our de-intensification technique "modified reduced-volume IMRT" was feasible and did not compromise therapeutic efficacy, well-designed multicenter prospective trials are needed for further research.