Onkologie最新文献

Background: MicroRNAs have been reported to play roles as oncogenes or tumor suppressor genes in human cancers. However, the expression levels of miR-145 in oral squamous cell carcinoma (OSCC) are unclear. The purpose of this study was to investigate the status of miR-145 expression in OSCC and determine its clinical significance.

Patients and methods: We examined miR-145 levels in 62 OSCC tissue samples and cell lines by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The relationship between miR-145 expression and clinicopathologic factors of OSCC patients was analyzed.

Results: The proportion of miR-145 low expression was 82.26% (51/62) among the 62 OSCC patients, and expression levels of miR-145 in OSCC tissue samples and cell lines were significantly lower than in non-tumor controls. miR-145 expression levels were not significantly associated with age (p = 0.607), sex (p = 0.213), location (p = 0.952), histology (p = 0.603), pT stage (p = 0.305), pTNM stage (p = 0.471), and lymphatic metastasis (p = 1.000).

Conclusion: miR-145 may be involved in the early tumorigenesis of oral squamous cells, and might be a potential biomarker in the early diagnosis of OSCC.

Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC.

The results of clinical, preferably randomized controlled trials (RCTs) form the backbone of drug approval decisions and benefit assessments of medical interventions. Whereas drug approval studies often answer at least some of the relevant questions posed in a benefit assessment, the situation is totally different for non-drug treatments and diagnostic tests, as the requirements for market entry are not as high in these fields. Overall it must be concluded that in the past and up to the present time there have been insufficient (financial) incentives for manufacturers or providers of medical interventions to conduct clinical trials concerning patient-relevant benefits both in the field of drugs and particularly in non-drug interventions. This has led to a lack of studies that, in an appropriate comparison with sufficient certainty of results, provide data on the patient-relevant benefits or added benefits of a medical intervention. In this context, it is secondary whether these are 'independent' studies, the more so as 'dependencies' can never be excluded and can become especially problematic in cases where they are not easily recognized by declaration of sponsorship. The Institute of Quality and Efficiency in Health Care (IQWiG) is willing to promote the creation of appropriate funding opportunities for important study projects of clinical research groups fulfilling the criteria for a high-quality patient-oriented clinical trial on a relevant research question, and is currently doing so together with interested parties.

Background: The purpose of this study was to evaluate the effect of legal regulations for clinical trials on study centers participating in investigator-initiated trials (IITs) in the field of hematology/oncology.

Method: Questionnaires were sent out to the heads of hematology-oncology study centers.

Results: Medical units participating in IITs have a good infrastructure and extensive experience in clinical trials. Depending on indication, a high proportion of patients have been treated in studies with the purpose to improve outcome. However, 35% of the responders will reduce their participation in IITs in the future due to a lack of financial support for staff involved in the extensive organizational tasks.

Conclusions: The widely recognized research field in therapy optimization trials in hematology and oncology in Germany is at risk. This will have negative effects on the patients as highly sophisticated protocols will no longer be initiated in several study centers, resulting in the loss of valuable data for the improvement of patient therapy and outcome. To stop this development, legislators as well as regulatory authorities and health insurances need to make the necessary changes in the legal framework.

Academic non-commercial trials are of substantial relevance for both patient care and progress in clinical research. Since the 12th amendment of the German drug law, applications for the initiation of clinical trials at the ethical review boards are much more cost- and time-intensive, particularly for multicenter therapy optimization trials (TOS). To activate a trial, for, e.g., 51 ethical review boards, current curricula vitae (CVs) and certificates on good clinical practice (GCP) and regulations have to be provided for all investigators. After the new amendment of the German drug law in 2012, the process remains complex while the responsibility of the team eligibility has now been transferred to the main investigator at the study site. Therefore, the online database 'QualiPRO' was developed, free of charge and widely accessible for the investigators, their clinical trial units and the coordinating centers of the TOS. Its features ease the process to generate and provide data on the clinical trial activities of any investigator and team member. The database content and architecture follows ethical review board recommendations and the Good Clinical Practice (GCP) of the International Conference on Harmonisation (ICH). After registration of the unit and membership of the team, study staff' members are able to enter and edit data and to print a 'trial' CV. CVs, GCP certificates, licences to practice medicine and more can be uploaded, and, after consent of the investigators, are available to the coordinating centers of TOS. In addition, QualiPRO is an instrument for directors of hospital departments or group leaders to efficiently collect and locally display data on their study activities and on the training status of their staff.

Background: Knowing the status of the internal mammary lymph (IML) nodes is important for accurate staging and appropriate selection of subsequent treatment in breast cancer. We conducted a meta-analysis to clarify the rate of IML node metastasis in breast cancer patients and discussed the importance of this finding.

Methods: We retrieved articles from the literature that reported positive rates of IML node metastasis in breast cancer patients. The quality of the selected articles was assessed using the 'Methodological Index for Non-Randomized Studies'. The heterogeneity was tested, and publication bias was assessed using a funnel plot. Finally, the positive rate of IML node metastasis in breast cancer patients was calculated using the random-effects model.

Results: 15 articles met the inclusion criteria and a total of 4,248 patients were included in the analysis. Heterogeneity across the studies was statistically significant (p = 0.014); thus, the random-effects model was used and the calculated positive rate of IML node metastasis was 23% (95% confidence interval (CI), 0.21-0.25).

Conclusions: Approximately 23% of the breast cancer patients had IML node metastases, for which the prognosis is generally poor. Accurate staging and integrated treatment are necessary to improve the survival of these patients.

Background: The ratio of metastatic to dissected lymph nodes (lymph node ratio; LNR) is a sensitive and superior prognostic factor for lymph node evaluation, but its relationship to cancer subtypes is unclear.

Patients and methods: Data from 469 patients with axillary lymph node metastasis out of 640 early breast cancer cases were retrospectively analyzed. They were classified into 4 molecular subtypes; luminal A, luminal B HER2(+), HER2 overexpression, basal-like. LNRs were compared between groups and with other prognostic factors.

Results: The distribution of LNRs was 35.2% in luminal A, 43.2% in luminal B HER2(+), 46.9% in HER2 over-expression, and 39.1% in basal-like. A significant difference was found between luminal A and HER2 over-expression subtypes (p = 0.023). LNR was significantly correlated with tumor size and lymphovascular invasion, but not with other prognostic factors including menopausal status, laterality, grade, and perineural invasion. An LNR of 29.8% was defined as the cut-off value, and significant differences in survival rates were identified accordingly between basal-like and both luminal A (p = 0.003) and luminal B HER2(+) (p = 0.04).

Conclusion: The LNR differs between some molecular subtypes of breast cancer, and it correlates with certain prognostic factors and survival. These data support using the LNR to assess breast cancer patients.

Background: The feasibility of neoadjuvant chemotherapy (NAC) and the outcome in patients with Federation of Gynecology and Obstetrics (FIGO) IIIC and IV ovarian cancer were assessed.

Patients and methods: 67 patients undergoing interval debulking surgery (IDS) and ≥ 4 courses of platinum-based NAC were analyzed for survival, perioperative morbidity and mortality.

Results: The median follow-up was 30 months. The median progression-free survival (PFS) was 17 months, the overall survival (OS) 34 months. The PFS of patients without residual disease (n = 23; 34.3%) was 31 months (p = 0.003), the OS 65 months (p = 0.001). PFS and OS were significantly longer in patients with no residual disease than in patients with 1-10 mm (n = 34; 47.9%) (p = 0.005 and p = 0.0001, respectively) residual disease. No survival benefit was seen for patients with 1-10 mm compared to > 1 cm (n = 12; 16.9%) residual disease (PFS p = 0.518; OS p = 0.077). 1 patient (1.4%) died; 12 patients needed interventional treatment or operation (16.9%) within the first 30 days postoperatively. Out of these, 5 patients (7.0%) had residual or lasting disability.

Conclusions: NAC and IDS are safe and feasible in this series of patients with unfavorable prognosis. IDS does not change the goal of complete cytoreduction and therefore does not compensate for a less radical surgical approach.