1,721,058 research outputs found
The Anticancer Face of Interferon Alpha (IFN-Alpha): From Biology to Clinical Results, with a Focus on Melanoma
No full textAlpha interferons (IFN) are type I IFNs that have pleiotropic effects on cell functions. A wealth of evidence exists that these cytokines exhibit a variety of biological effects different from those on viral replication, including antitumor activity. IFNs-alpha represent the cytokines exhibiting the longest record of use in clinical oncology for the treatment of over a dozen of cancer types, including some hematological malignancies and solid tumors. Although targeted anticancer agents have recently replaced IFN-alpha in the treatment of certain hematological (e.g. chronic myeloid leukemia) and solid (e.g. renal cell carcinoma) malignancies, this cytokine is still used for the treatment of patients with specific tumor types, such as cutaneous melanoma. Despite the intense work in preclinical tumor models and considerable experience in the clinical use of IFN-alpha, the mechanisms of action underlying tumor response is still a matter of open debate. In this review we describe the evidence supporting the main mechanisms underlying IFN-alpha anticancer effects using both preclinical and clinical findings; moreover, we focus on the results of IFN-alpha for the treatment of patients with high-risk cutaneous melanoma, one of the malignancies most resistant to conventional chemotherapy
Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative locoregional staging of primary gastric cancerCochrane Database of Systematic Reviews
Full text linkBACKGROUND: Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic device for the locoregional staging of gastric cancer, which is crucial to developing a correct therapeutic strategy and ultimately to providing patients with the best chance of cure. However, despite a number of studies addressing this issue, there is no consensus on the role of EUS in routine clinical practice.
OBJECTIVES: To provide both a comprehensive overview and a quantitative analysis of the published data regarding the ability of EUS to preoperatively define the locoregional disease spread (i.e., primary tumor depth (T-stage) and regional lymph node status (N-stage)) in people with primary gastric carcinoma.
SEARCH METHODS: We performed a systematic search to identify articles that examined the diagnostic accuracy of EUS (the index test) in the evaluation of primary gastric cancer depth of invasion (T-stage, according to the AJCC/UICC TNM staging system categories T1, T2, T3 and T4) and regional lymph node status (N-stage, disease-free (N0) versus metastatic (N+)) using histopathology as the reference standard. To this end, we searched the following databases: the Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE, EMBASE, NIHR Prospero Register, MEDION, Aggressive Research Intelligence Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), from 1988 to January 2015.
SELECTION CRITERIA: We included studies that met the following main inclusion criteria: 1) a minimum sample size of 10 patients with histologically-proven primary carcinoma of the stomach (target condition); 2) comparison of EUS (index test) with pathology evaluation (reference standard) in terms of primary tumor (T-stage) and regional lymph nodes (N-stage). We excluded reports with possible overlap with the selected studies.
DATA COLLECTION AND ANALYSIS: For each study, two review authors extracted a standard set of data, using a dedicated data extraction form. We assessed data quality using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. We performed diagnostic accuracy meta-analysis using the hierarchical bivariate method.
MAIN RESULTS: We identified 66 articles (published between 1988 and 2012) that were eligible according to the inclusion criteria. We collected the data on 7747 patients with gastric cancer who were staged with EUS. Overall the quality of the included studies was good: in particular, only five studies presented a high risk of index test interpretation bias and two studies presented a high risk of selection bias.For primary tumor (T) stage, results were stratified according to the depth of invasion of the gastric wall. The meta-analysis of 50 studies (n = 4397) showed that the summary sensitivity and specificity of EUS in discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI 0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1 (early gastric cancer, EGC) versus T2 (muscle-infiltrating) tumors, the meta-analysis of 46 studies (n = 2742) showed that the summary sensitivity and specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93) respectively. When we addressed the capacity of EUS to distinguish between T1a (mucosal) versus T1b (submucosal) cancers the meta-analysis of 20 studies (n = 3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81 to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic involvement of lymph nodes (N-stage), the meta-analysis of 44 studies (n = 3573) showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to 0.87) and 0.67 (95% CI 0.61 to 0.72), respectively.Overall, as demonstrated also by the Bayesian nomograms, which enable readers to calculate post-test probabilities for any target condition prevalence, the EUS accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between-study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status.
AUTHORS' CONCLUSIONS: By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings
Contemporary controversies and perspectives in the staging and treatment of patients with lymph node metastasis from melanoma, especially with regards positive sentinel lymph node biopsy
No full textFluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer
No full textBACKGROUND:
Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC).
OBJECTIVES:
The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC.
SEARCH STRATEGY:
A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials.
SELECTION CRITERIA:
Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival.
DATA COLLECTION AND ANALYSIS:
Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases.
MAIN RESULTS:
Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24).
AUTHORS' CONCLUSIONS:
Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases: in fact, the greater tumor response rate obtained with this HAI regimen does not translate into a survival advantage over fluoropyrimidine alone SCT
Video endoscopic inguinal lymphadenectomy for lymph node metastasis from solid tumors
No full textAim: Inguinal lymphadenectomy (IL) is the standard treatment for inguinal lymph node (LN) metastases from genitourinary neoplasm and other cutaneous malignancies. Video endoscopic inguinal lymphadenectomy (VEIL) is emerging as a new modality for treating inguinal LN metastasis, with the aim of reducing post-operative complications. However, the safety and effectiveness of this new approach is still unclear.
Method: A systematic literature review was performed. Patient characteristics, selection criteria, intra-operative data, number of excised LNs and post-operative outcomes were extracted and described for each study.
Results: Ten series that encompassed data of 236 procedures performed in 168 patients were reviewed. The conversion to traditional IL rates ranged between 0 and 7.7%. Median/mean operation time varied between 60 and 245 min. Wound-related complications and lymphatic collection/seroma ranged between 0 and 13.3% and 4 and 38.4%, respectively. The median/mean number of excised inguinal LNs ranged between 7 and 16. Although only four studies reported a follow-up time longer then 2 years, local recurrence rate was up to 6.6%.
Conclusions: VEIL is safe and feasible for experienced surgeons with advanced laparoscopic skills and familiarity with groin anatomy. The post-operative morbidity appears lower compared to the open procedure, mainly for wound/skin related complications. The number of harvested LN and the regional recurrence rate is comparable to that of conventional groin dissection. Before VEIL technique can be considered suitable for routine clinical practice, comparable oncological outcomes and lower post-operative morbidity should be assessed in a randomized controlled trial. (C) 2015 Elsevier Ltd. All rights reserved
Oncomirs: From Tumor Biology to Molecularly Targeted Anticancer Strategies
No full textDeregulation of microRNA (miRNA) promotes carcinogenesis, as these molecules can act as oncogenes or tumor suppressor genes. Here we provide an overview of miRNA biology, discuss the most recent findings on miRNA and cancer development/progression, and report on how tumor-related miRNAs (oncomirs) are being used to develop novel cancer specific therapeutic approache
Actual false-negative rate prompts the routine use of ultrasound scan before and after sentinel node biopsy in melanoma
No full textRisk-reducing medication for primary breast cancer: A network meta-analysis
No full textThis is the protocol for a review and there is no abstract. The objectives are as follows: To assess the efficacy and acceptability of single agent CPAs for the prevention of primary breast cancer, in unaffected women, at an above average risk of developing breast cancer. Using a network meta-analysis, we also intend to rank single CPAs, based on their efficacy and acceptability (an endpoint that is defined as the inverse of CPA-related toxicity). © 2016 The Cochrane Collaboration
Neoadjuvant chemotherapy in soft tissue sarcomas: Latest evidence and clinical implications
No full textSoft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments
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