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The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
European Review For Medical and... Mar 2020We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.
We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 32271409
DOI: 10.26355/eurrev_202003_20655 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2020Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold...
A closed vitrification system enables a murine ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting activity of microcystins.
Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth (eIVFG) is a robust in vitro model for ovotoxicity testing. However, the follicle preparation process is complex and highly dependent on technical skills. Here, we aimed to use vitrification method to cryopreserve murine immature follicles for a high-content eIVFG, chemical exposure, and ovotoxicity screening. Results indicated that a closed vitrification system combined with optimized vitrification protocols preserved mouse follicle viability and functionality and vitrified follicles exhibited comparable follicle and oocyte reproductive outcomes to freshly harvested follicles during eIVFG, including follicle survival and development, ovarian steroidogenesis, and oocyte maturation and ovulation. Moreover, vitrified follicles consistently responded to ovotoxic chemical, doxorubicin (DOX). We further used vitrified follicles to test the response of microcystins (MCs), an emerging category of environmental contaminants produced by cyanobacteria associated with harmful algal blooms (HABs), and found that different congeners of MCs exhibited differential ovotoxicities. In summary, our study demonstrates that vitrification enables a long-term-storage and ready-to-use ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting effects of MCs.
Topics: Animals; Antibiotics, Antineoplastic; Cryopreservation; Doxorubicin; Endocrine Disruptors; Female; High-Throughput Screening Assays; Mice; Microcystins; Ovarian Follicle; Vitrification
PubMed: 32017985
DOI: 10.1016/j.reprotox.2020.01.009 -
Artificial Organs May 2020An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination...
An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination therapy. Some VAD patients require radiotherapy due to concomitant oncologic morbidities, including thoracic malignancies. This raises the potential of VAD malfunction via radiation-induced damage. So far, only case reports and small case series on radiotherapy have been published, most of them on HeartMate II (HMII, Abbott, North Chicago, IL, USA). Significantly, the effects of irradiation on the HeartMate 3 (HM3, Abbott) remain undefined, despite the presence of controller components engineered within the pump itself. We report the first case of a patient with a HM3 who successfully underwent stereotactic hypofractionated radiotherapy due to an early-stage non-small-cell lung cancer. The patient did not suffer from any complications, including toxicity or VAD malfunction. Based on this case report and on published literature, we think that performing radiotherapy after VAD implantation with the aid of a multidisciplinary team could be performed, but more in vitro studies and cases series are needed to reinforce this statement.
Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Cardiomyopathies; Doxorubicin; Female; Heart-Assist Devices; Humans; Lung Neoplasms; Middle Aged; Radiation Dose Hypofractionation; Radiotherapy, Intensity-Modulated
PubMed: 31769042
DOI: 10.1111/aor.13612 -
Pleura and Peritoneum Sep 2019Multicystic peritoneal mesothelioma (MCPM) is a particularly rare and benign neoplasm that arises from the peritoneum in reproductive aged females. Its etiopathogenesis... (Review)
Review
Multicystic peritoneal mesothelioma (MCPM) is a particularly rare and benign neoplasm that arises from the peritoneum in reproductive aged females. Its etiopathogenesis is still unclear. The current prevailing theory supports the idea that the tumor is the result of an excessive inflammatory process. Because of a lack of clinical and imaging presentation, the diagnosis is intricate, and heavily relies on case reports and short studies. A histological analysis with immunohistochemistry is required for a definitive diagnosis. To date, there is no standard treatment recommended for MCPM. However, some studies suggest proceeding with a cytoreductive surgery and a hyperthermic intraperitoneal chemotherapy combining CISPLATIN and DOXORUBICIN, due to a high incidence of recurrence rate after medical treatment or surgery alone and potential malignant transformation.
PubMed: 31667333
DOI: 10.1515/pp-2019-0024 -
Cells Oct 2019Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the... (Meta-Analysis)
Meta-Analysis
Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis.
Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran's Q test, I statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger's bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508-1.100; of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.
Topics: Biomarkers, Pharmacological; Biomarkers, Tumor; Breast Neoplasms; Drug Resistance, Neoplasm; Female; Humans; MicroRNAs; Prognosis; Transcriptome
PubMed: 31615089
DOI: 10.3390/cells8101250 -
Haematologica Jul 2020Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing...
Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review.
Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been performed in the era of anti-CD20 monoclonal antibody therapy. A comprehensive search (01/2002-01/2019) was systematically performed using Ovid MEDLINE, Ovid EMBASE and Cochrane. Studies were selected from a total of 804, screened based on predefined inclusion/exclusion criteria, and were critically appraised. Three post hoc analyses (RICOVER-60, RCHOP-14/21, GOYA), one prospective database and 10 retrospective series were included. 7,357 rituximab/obinutuzumab-exposed patients were analysed. The median percentage receiving intrathecal prophylaxis was 11.9%. Cumulative CNS relapse incidence ranged from 1.9% at 6.5 years to 8.4% at 5 years. Median time (of medians) to CNS relapse was 10 months. 73% developed isolated CNS relapses, 24% concurrent CNS/systemic relapse, and 3% post-systemic relapse. Reported CNS relapse sites were: parenchymal (58%), leptomeningeal (27%), and both (12%). Event rates were low resulting in limited power within each study to provide robust univariable/multivariable analysis. Intrathecal prophylaxis was not a univariable or multivariable factor associated with a reduction in CNS relapse in any study. We found no strong evidence for the benefit, or indeed genuine lack of benefit, of stand-alone intrathecal prophylaxis in preventing CNS relapse in diffuse large B-cell lymphoma-treated patients using anthracycline-based immunochemotherapy. Current published study designs limit the strength of such conclusions.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Retrospective Studies; Rituximab; Vincristine
PubMed: 31488560
DOI: 10.3324/haematol.2019.229948