Maintenance therapy in advanced non-small cell lung cancer: A prime-time for change?

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How students cope with part-time study

This study provides a qualitative test and illustration of a model of how students cope with the demands of part-time study. The model shows that students who are successful in finding the time to complete the requirements of part-time courses do so by adopting three mechanisms; sacrifice, support and the negotiation of arrangements. All three mechanisms operate in four domains, namely work, family, social lives and the self. The mechanisms and domains were related together in a three by four matrix. Data to verify and illuminate the model were gathered by the researchers through an on-line forum discussion on the topic of coping with part-time study. The researchers themselves were studying part-time in a course called Adult Education and Professional Development. Analysis of the data showed that the work domain was very important but little adaptation was possible. The family was seen as the most important domain and all three mechanisms were used. Time was commonly found for part-time study by sacrificing social lives. The self-domain was interpreted as important in establishing motivation and self-determination

Milk Consumption Across Life Periods in Relation to Lower Risk of Nasopharyngeal Carcinoma: A Multicentre Case-Control Study

Background: The much higher incidence of nasopharyngeal carcinoma (NPC) in men suggests sex hormones as a risk factor, and dairy products contain measurable amounts of steroid hormones. Milk consumption has greatly increased in endemic regions of NPC. We investigated the association between NPC and milk consumption across life periods in Hong Kong.Methods: A multicentre case-control study included 815 histologically confirmed NPC incident cases and 1,502 controls who were frequency-matched on age and sex at five major hospitals in Hong Kong in 2014–2017. Odds ratios (ORs) of NPC (cases vs. controls) for milk consumption at different life periods were estimated by unconditional logistic regression, adjusting for sex, age, socioeconomic status score, smoking and alcohol drinking status, exposure to occupational hazards, family history of cancer, IgA against Epstein-Barr virus viral capsid antigen, and total energy intake.Results: Compared with abstainers, lower risks of NPC were consistently observed in regular users (consuming ≥5 glasses of milk [fresh and powdered combined] per month) across four life periods of age 6–12 (adjusted OR 0.74, 95% CI 0.54–0.86), 13–18 (0.68, 0.55–0.84), 19–30 (0.68, 0.55–0.84), and 10 years before recruitment (0.72, 0.59–0.87). Long-term average milk consumption of ≤2.5, >2.5, and ≤12.5, >12.5 glasses per month yielded adjusted OR (95% CI) of 1.00 (0.80–1.26), 0.98 (0.81–1.18), 0.95 (0.76–1.18), and 0.55 (0.43–0.70), respectively (all P-values for trend < 0.05).Conclusion: Consumption of milk across life periods was associated with lower risks of NPC. If confirmed to be causal, this has important implications for dairy product consumption and prevention of NPC

MicroRNA profiling study reveals MIR-150 in association with metastasis in nasopharyngeal carcinoma

© 2017 The Author(s). MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.Link_to_subscribed_fulltex

Impact of adjuvant chemoradiation for adenocarcinoma of stomach after curative gastrectomy in Chinese: A 7-year audit

Background and Aim: Adjuvant chemoradiation (CRT) after curative gastrectomy was introduced to our hospital in 1998. The present study aims to examine the impact of CRT on survival among Chinese. Methods: From our gastric cancer registry, patients who received R0 gastrectomy, with UICC stage II or above, M0 disease and ASA grades I and II were analyzed. Adjuvant CRT was offered and given if patients agreed. The regimen consisted of five cycles of 5-fluoruracil (5FU)/leucovorin chemotherapy and 45 Gy/25 fractions concurrent with cycles 2 and 3. Results: From January 1998 to December 2004, 134 patients fulfilled the criteria. Sixty had surgery alone and 74 patients received CRT after gastrectomy. One hundred and two (76%) patients received radical gastrectomy with D2 lymphadenectomy. Toxicity ≥ grade 3 was seen in 65% of patients without mortality. The overall and relapse-free 5-year survival rates were 45.8% and 42.0%, respectively. On univariate analysis, early disease stage and adjuvant CRT were associated with better prognosis. Cox regression analysis showed that adjuvant CRT (P = 0.01, HR 2.31, 95% CI: 1.4-3.9) predict better survival after adjustment with the other factors. Conclusion: In the present study, postoperative adjuvant chemoradiation is associated with better overall survival in patients with adenocarcinoma of the stomach after curative gastrectomy. © 2010 The Authors. Journal compilation © 2010 College of Surgeons of Hong Kong.Link_to_subscribed_fulltex

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma

Background. The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). Methods. Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m 2 on day 1; gemcitabine 1250 mg/m 2 on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m 2 on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. Results. The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving ≥ 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. Conclusions. Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC. © 2006 Wiley Periodicals, Inc.Link_to_subscribed_fulltex

Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 -9 ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR < 10 -3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection.Link_to_subscribed_fulltex

Prognostic Biomarkers for Survival in Nasopharyngeal Carcinoma: A Systematic Review of the Literature

This systematic review aims to identify prognostic molecular biomarkers which demonstrate strong evidence and a low risk of bias in predicting the survival of nasopharyngeal carcinoma (NPC) patients. The literature was searched for on PubMed to identify original clinical studies and meta-analyses which reported associations between molecular biomarkers and survival, including ≥150 patients with a survival analysis, and the results were validated in at least one independent cohort, while meta-analyses must include ≥1000 patients with a survival analysis. Seventeen studies fulfilled these criteria—two studies on single nucleotide polymorphisms (SNPs), three studies on methylation biomarkers, two studies on microRNA biomarkers, one study on mutational signature, six studies on gene expression panels, and three meta-analyses on gene expressions. The comparison between the hazard ratios of high-risk and low-risk patients along with a multivariate analysis are used to indicate that these biomarkers have significant independent prognostic values for survival. The biomarkers also indicate a response to certain treatments and whether they could be used as therapeutic targets. This review highlights that patients’ genetics, epigenetics, and signatures of cancer and immune cells in the tumor microenvironment (TME) play a vital role in determining their survival

An Exploratory Study of Refining TNM-8 M1 Categories and Prognostic Subgroups Using Plasma EBV DNA for Previously Untreated De Novo Metastatic Nasopharyngeal Carcinoma

(1) Background: NPC patients with de novo distant metastasis appears to be a heterogeneous group who demonstrate a wide range of survival, as suggested by growing evidence. Nevertheless, the current 8th edition of TNM staging (TNM-8) grouping all these patients into the M1 category is not able to identify their survival differences. We sought to identify any anatomic and non-anatomic subgroups in this study. (2) Methods: Sixty-nine patients with treatment-naive de novo M1 NPC (training cohort) were prospectively recruited from 2007 to 2018. We performed univariable and multivariable analyses (UVA and MVA) to explore anatomic distant metastasis factors, which were significantly prognostic of overall survival (OS). Recursive partitioning analysis (RPA) with the incorporation of significant factors from MVA was then performed to derive a new set of RPA stage groups with OS segregation (Set 1 Anatomic-RPA stage groups); another run of MVA was performed with the addition of pre-treatment plasma EBV DNA. A second-round RPA with significant prognostic factors of OS identified in this round of MVA was performed again to derive another set of stage groups (Set 2 Prognostic-RPA stage groups). Both sets were then validated externally with an independent validation cohort of 67 patients with distant relapses of their initially non-metastatic NPC (rM1) after radical treatment. The performance of models in survival segregation was evaluated by the Akaike information criterion (AIC) and concordance index (C-index) under 1000 bootstrapping samples for the validation cohort; (3) Results: The 3-year OS and median follow-up in the training cohort were 36.0% and 17.8 months, respectively. Co-existence of liver-bone metastases was the only significant prognostic factor of OS in the first round UVA and MVA. Set 1 RPA based on anatomic factors that subdivide the M1 category into two groups: M1a (absence of co-existing liver-bone metastases; median OS 28.1 months) and M1b (co-existing liver-bone metastases; median OS 19.2 months, p = 0.023). When pre-treatment plasma EBV DNA was also added, it became the only significant prognostic factor in UVA (p = 0.001) and MVA (p = 0.015), while co-existing liver-bone metastases was only significant in UVA. Set 2 RPA with the incorporation of pre-treatment plasma EBV DNA yielded good segregation (M1a: EBV DNA &le; 2500 copies/mL and M1b: EBV DNA &gt; 2500 copies/mL; median OS 44.2 and 19.7 months, respectively, p &lt; 0.001). Set 2 Prognostic-RPA groups (AIC: 228.1 [95% CI: 194.8&ndash;251.8] is superior to Set 1 Anatomic-RPA groups (AIC: 278.5 [254.6&ndash;301.2]) in the OS prediction (p &lt; 0.001). Set 2 RPA groups (C-index 0.59 [95% CI: 0.54&ndash;0.67]) also performed better prediction agreement in the validation cohort (vs. Set 1: C-index 0.47 [95% CI: 0.41&ndash;0.53]) (p &lt; 0.001); (4) Conclusions: Our Anatomic-RPA stage groups yielded good segregation for de novo M1 NPC, and prognostication was further improved by incorporating plasma EBV DNA. These new RPA stage groups for M1 NPC can be applied to countries/regions regardless of whether reliable and sensitive plasma EBV DNA assays are available or not