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Patient Preference and Adherence 2015The aim of this systematic review was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) treatment in patients with steroid-refractory acute...
PURPOSE
The aim of this systematic review was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) treatment in patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD).
METHODS
An electronic search was carried out on the MEDLINE, EMBASE, Science Citation Index (SCI), and Cochrane Library databases. We included prospective clinical trials in SR-aGVHD treated by ECP. The main endpoints consisted of mortality, exacerbation, or response.
RESULTS
Only seven studies involving 121 patients met the inclusion criteria for further review. Our analysis showed positive results of ECP for aGVHD. The overall response rate (ORR) was 0.71 and the complete response rate (CRR) was 0.71. The efficacy of ECP for skin aGVHD, liver aGVHD, and gut aGVHD were 0.86, 0.60, and 0.68, respectively. However, no sufficient evidence verifies the exact benefit in this review, because the number of patients enrolled in trials is limited and publish bias exists.
CONCLUSION
ECP is an effective therapy for skin, liver, and gut aGVHD, and large double-blind clinical trials are required to prove the outcome of this meta-analysis.
PubMed: 25653504
DOI: 10.2147/PPA.S76563 -
Medicine Jan 2023Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic...
RATIONALE
Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and remains the leading cause of late morbidity and mortality. cGVHD involves a heterogeneous group of organic manifestations, many of which mimic autoimmune diseases such as scleroderma, primary biliary cholangitis, Sjögren syndrome and polymyositis.
PATIENT CONCERNS
A 60-years-old female with a history of allo-HCT developed de novo cGVHD 11 months after allo-HCT with isolated liver involvement. The patient presented with jaundice, cytolysis, cholestasis and concomitant acute digital ischemia. Liver biopsy and autoimmunity tests were performed and were found to be compatible with immune-mediated liver damage. Nailfold capillaroscopy revealed microangiopathy, characterized by avascular areas and some enlarged capillaries resembled an early systemic sclerosis pattern.
DIAGNOSIS
Biliary cholangitis-like and digital ischemia related to cGVHD.
INTERVENTIONS
The patient was treated with high-dose prednisone and ursodeoxycholic acid, and extracorporeal photopheresis. The patient required hospital admission for administration of intravenous prostacyclin due to refractory Raynaud syndrome.
OUTCOMES
After 6 to 8 weeks, the patient achieved a good response, with evident clinical improvement and progressive normalization of liver function.
LESSONS
cGVHD is a multiorgan pathological condition, and this case emphasizes that a multidisciplinary team, including rheumatologists, should be involved in the follow-up of allo-transplant patients to ensure that the clinical complications are adequately addressed. Early intervention is critical for improving patient' prognosis.In addition, we performed a systemic literature review based on published case articles on hepatic cGVHD and digital ischemia published up to August 2022. To the best of our knowledge, this is the first reported case of such an association.
Topics: Humans; Female; Middle Aged; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Cholangitis; Bronchiolitis Obliterans Syndrome; Scleroderma, Systemic; Ischemia; Chronic Disease
PubMed: 36637943
DOI: 10.1097/MD.0000000000032495 -
The Cochrane Database of Systematic... Sep 2012Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycosis fungoides 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.
OBJECTIVES
To assess the effects of interventions for mycosis fungoides in all stages of the disease.
SEARCH METHODS
We searched the following databases up to January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also checked reference lists of included studies for further references to relevant RCTs. We searched online trials registries for further references to unpublished trials and undertook a separate search for adverse effects of interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for mycosis fungoides in people with any stage of the disease. At least 90% of participants in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin-type).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed eligibility and methodological quality for each study and carried out data extraction. We resolved any disagreement by discussion. Primary outcomes were the impact on quality of life and the safety of interventions. When available, we reported on our secondary outcomes, which were the improvement or clearance of skin lesions, disease-free intervals, survival rates, relapse rates, and rare adverse effects. When possible, we combined homogeneous studies for meta-analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the internal validity of all included studies in six different domains.
MAIN RESULTS
The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only (please see Table 1 for definitions of these stages).Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis.Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs.Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments.In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival.
AUTHORS' CONCLUSIONS
This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.
Topics: Antineoplastic Agents; Humans; Mycosis Fungoides; Neoplasm Staging; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 22972128
DOI: 10.1002/14651858.CD008946.pub2 -
The Journal of Heart and Lung... Sep 2017Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is... (Comparative Study)
Comparative Study Review
BACKGROUND
Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is the most common form. This systematic review sought to identify the current evidence base for CLAD-BOS therapies after initial immunosuppressive treatment strategies.
METHODS
The MEDLINE, Embase, and Cochrane Library databases from inception to May 3, 2016, were searched using keywords relating to CLAD-BOS, study designs, and treatments of interest, including extracorporeal photopheresis (ECP), aerosolized cyclosporine, total lymphoid irradiation (TLI), alemtuzumab, and montelukast. Titles, abstracts, and full texts were screened by 2 independent reviewers to identify studies of CLAD-BOS second-line therapy in adult lung transplant patients. Quality was assessed according to the Downs and Black checklist.
RESULTS
Of the 936 individual citations identified, 47 reports of 40 studies met inclusion criteria, including 17 full publications, 11 recent (2015-2016), and 12 older (pre-2015) congress proceedings. Most of the full publications and recent abstracts investigated ECP (n = 11), TLI (n = 5), alemtuzumab (n = 4), and montelukast (n = 2). Most studies were uncontrolled and retrospective. Compared with standard therapy alone, improved lung function and survival was reported for ECP in 2 studies without randomization, with lower-quality evidence for improved lung function for TLI, montelukast, and aerosolized cyclosporine.
CONCLUSIONS
Because most identified studies were of retrospective and uncontrolled design, comparison of treatment effects was limited. Available evidence suggests stabilized lung function after ECP in combination with established immunosuppressive regimens in late-line CLAD-BOS treatment, with fewer data for TLI, montelukast, and aerosolized cyclosporine.
Topics: Allografts; Bronchiolitis Obliterans; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Lung Transplantation; Lymphatic Irradiation; Male; Photopheresis; Primary Graft Dysfunction; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Syndrome; Transplantation Immunology; Treatment Outcome
PubMed: 28662986
DOI: 10.1016/j.healun.2017.05.030 -
Clinical Endocrinology Aug 2008Although recent trial results of anti-CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Although recent trial results of anti-CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1 diabetes. We conducted a systematic review and meta-analysis to determine the efficacy of nonantigen-based immunotherapeutic approaches for preservation of beta-cell function in patients with type 1 diabetes.
METHODS
We searched MEDLINE, EMBASE, Cochrane CENTRAL, reference lists, and content expert files up to September 2006. Eligible studies were randomized controlled trials (RCTs) of antiproliferative agents (methotrexate, azathioprine), monoclonal antibodies (CD3, CD4), T-cell inhibitors (cyclosporin) and other immunotherapeutic agents (photopheresis, linomide, fusidin, buffy coat, intravenous immunoglobulin, BCG, nicotinamide) in patients with newly diagnosed type 1 diabetes followed for > or = 6 months. Pairs of reviewers working independently and with adequate reliability assessed the trials' methodological quality, collected data, and conducted random-effects meta-analyses on measures of preservation of beta-cell function (e.g. C-peptide secretion, insulin independence).
RESULTS
Of the 299 potentially relevant articles identified after an initial search, 20 trials met selection criteria. Meta-analysis of 20 trials (n = 1187 patients) found a small to moderate improvement in beta-cell function with immunotherapy [vs. placebo, effect size 0.37, 95% confidence interval (CI) 0.14-0.6] but there was moderate inconsistency in results across trials (I(2) 65%, 95% CI 39-77%). Subgroup analysis suggested a greater effect of cyclosporin and antiproliferative agents on beta-cell function when used for > or = 6 months (pooled effect size 0.77 vs. -0.11, respectively; P(interaction) = 0.002).
CONCLUSIONS
Long-term immunotherapy may preserve beta-cell function in newly diagnosed patients with type 1 diabetes. Patients and clinicians must await the conduct of rigorous trials reporting on diabetes resolution, adverse events, and other patient-important outcomes.
Topics: Algorithms; Diabetes Mellitus, Type 1; Humans; Immunotherapy; Insulin-Secreting Cells; Pancreatic Diseases; Patient Selection; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18194488
DOI: 10.1111/j.1365-2265.2008.03179.x -
The Cochrane Database of Systematic... Dec 2015Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT) occurring in 8% to 59% of the... (Review)
Review
BACKGROUND
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT) occurring in 8% to 59% of the recipients. Currently, the therapeutic mainstay for aGvHD is corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and re-infusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL) (Issue 9, 2015), MEDLINE (PubMed) and EMBASE (Ovid) databases from their inception to 23 September 2015. We searched the reference lists of potentially relevant studies without any language restrictions. We searched eight trial registers and four conference proceedings on 29 September 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in paediatric patients with aGvHD after HSCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
MAIN RESULTS
We identified no additional studies in the 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of aGvHD in paediatric patients after HSCT is unknown and its use should be restricted within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2015 review update brought about no additions to these conclusions.
Topics: Adolescent; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis
PubMed: 26666580
DOI: 10.1002/14651858.CD009759.pub3 -
The Cochrane Database of Systematic... Feb 2014Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the... (Review)
Review
BACKGROUND
Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic GvHD are corticosteroids that are frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory chronic GvHD. The therapeutic options in these people include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of chronic GvHD in children and adolescents after haematopoietic stem cell transplantation.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (Issue 9, 2012), MEDLINE and EMBASE databases from their inception to 12 September 2012. We searched the reference lists of potentially relevant studies without any language restriction. We searched eight trial registers and five conference proceedings. We also contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in paediatric patients with chronic GvHD after haematopoietic stem cell transplantation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author.
MAIN RESULTS
We found no studies meeting the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs can currently not be evaluated since we have found no such studies. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical grounds in favour of ECP are made, people should be carefully monitored for beneficial and harmful effects and efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis
PubMed: 24569961
DOI: 10.1002/14651858.CD009898.pub2 -
The Cochrane Database of Systematic... Dec 2015Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the... (Review)
Review
BACKGROUND
Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic GvHD are corticosteroids that are frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory chronic GvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is an updated version of a Cochrane review first published in 2014.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of chronic GvHD in children and adolescents after haematopoietic stem cell transplantation.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL) (Issue 9, 2015), MEDLINE and EMBASE databases from their inception to 23 September 2015. We searched the reference lists of potentially relevant studies without any language restriction. We searched eight trial registers and five conference proceedings on 29 September 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in paediatric patients with chronic GvHD after haematopoietic stem cell transplantation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author.
MAIN RESULTS
No additional studies were identified in this 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs cannot be evaluated since the original version of this review and the first review update found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, patients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis
PubMed: 26666581
DOI: 10.1002/14651858.CD009898.pub3 -
The Cochrane Database of Systematic... Dec 2018Early, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell...
BACKGROUND
Early, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers with the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique that relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high-frequency ultrasound (HFUS) with transducer frequencies of 20 MHz or more has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical and/or dermoscopic examination of suspected skin cancer, HFUS may offer additional diagnostic information compared to other technologies.
OBJECTIVES
To assess the diagnostic accuracy of HFUS to assist in the diagnosis of a) cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, b) cutaneous squamous cell carcinoma (cSCC), and c) basal cell carcinoma (BCC) in adults.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles.
SELECTION CRITERIA
Studies evaluating HFUS (20 MHz or more) in adults with lesions suspicious for melanoma, cSCC or BCC versus a reference standard of histological confirmation or clinical follow-up.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and the poor quality of studies, we did not undertake a meta-analysis for this review. For illustrative purposes, we plot estimates of sensitivity and specificity on coupled forest plots.
MAIN RESULTS
We included six studies, providing 29 datasets: 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). We did not identify any data relating to the diagnosis of cSCC.Studies were generally poorly reported, limiting judgements of methodological quality. Half the studies did not set out to establish test accuracy, and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data-driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to lack of visualisation in the test.Derived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies (lower limits of the 95% CIs were 94% and 82%), with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%), respectively. Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities.
AUTHORS' CONCLUSIONS
Insufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between-study heterogeneity, unclear to low methodological quality and limited volume of evidence, we cannot draw any implications for practice. The main value of the preliminary studies included may be in providing guidance on the possible components of new diagnostic rules for diagnosis of melanoma or BCC using HFUS that will require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard healthcare setting, with a clearly defined and representative population of participants, would be required for a full and proper evaluation of accuracy.
Topics: Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Melanoma; Sensitivity and Specificity; Skin Neoplasms; Ultrasonography; Melanoma, Cutaneous Malignant
PubMed: 30521683
DOI: 10.1002/14651858.CD013188 -
The Cochrane Database of Systematic... Dec 2018Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers, which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Optical coherence tomography (OCT) is a microscopic imaging technique, which magnifies the surface of a skin lesion using near-infrared light. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, OCT may offer additional diagnostic information compared to other technologies.
OBJECTIVES
To determine the diagnostic accuracy of OCT for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, basal cell carcinoma (BCC), or cutaneous squamous cell carcinoma (cSCC) in adults.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles.
SELECTION CRITERIA
We included studies of any design evaluating OCT in adults with lesions suspicious for invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC, compared with a reference standard of histological confirmation or clinical follow-up.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). Our unit of analysis was lesions. Where possible, we estimated summary sensitivities and specificities using the bivariate hierarchical model.
MAIN RESULTS
We included five studies with 529 cutaneous lesions (282 malignant lesions) providing nine datasets for OCT, two for visual inspection alone, and two for visual inspection plus dermoscopy. Studies were of moderate to unclear quality, using data-driven thresholds for test positivity and giving poor accounts of reference standard interpretation and blinding. Studies may not have been representative of populations eligible for OCT in practice, for example due to high disease prevalence in study populations, and may not have reflected how OCT is used in practice, for example by using previously acquired OCT images.It was not possible to make summary statements regarding accuracy of detection of melanoma or of cSCC because of the paucity of studies, small sample sizes, and for melanoma differences in the OCT technologies used (high-definition versus conventional resolution OCT), and differences in the degree of testing performed prior to OCT (i.e. visual inspection alone or visual inspection plus dermoscopy).Pooled data from two studies using conventional swept-source OCT alongside visual inspection and dermoscopy for the detection of BCC estimated the sensitivity of OCT as 95% (95% confidence interval (CI) 91% to 97%) and specificity of 77% (95% CI 69% to 83%).When applied to a hypothetical population of 1000 lesions at the mean observed BCC prevalence of 60%, OCT would miss 31 BCCs (91 fewer than would be missed by visual inspection alone and 53 fewer than would be missed by visual inspection plus dermoscopy), and OCT would lead to 93 false-positive results for BCC (a reduction in unnecessary excisions of 159 compared to using visual inspection alone and of 87 compared to visual inspection plus dermoscopy).
AUTHORS' CONCLUSIONS
Insufficient data are available on the use of OCT for the detection of melanoma or cSCC. Initial data suggest conventional OCT may have a role for the diagnosis of BCC in clinically challenging lesions, with our meta-analysis showing a higher sensitivity and higher specificity when compared to visual inspection plus dermoscopy. However, the small number of studies and varying methodological quality means implications to guide practice cannot currently be drawn.Appropriately designed prospective comparative studies are required, given the paucity of data comparing OCT with dermoscopy and other similar diagnostic aids such as reflectance confocal microscopy.
Topics: Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Melanoma; Sensitivity and Specificity; Skin Neoplasms; Tomography, Optical Coherence; Melanoma, Cutaneous Malignant
PubMed: 30521690
DOI: 10.1002/14651858.CD013189