The contraceptive implant - Dove Medical Press

Supplementary materialsTable S1. Use of resources associated with topical carmustineConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUsage distribution (%)Carmustine solution 0.2% in ethanol22.50%Panel of clinical expertsCarmustine solution 10 mg/60 cc alcohol16.67%Carmustine ointment 0.01% petroleum jelly22.50%Carmustine ointment 0.02% ethanol/petroleum jelly38.33%Total100.00%Use of human resourcesHospital pharmacy service pharmacist (min)16.4016.4030.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3305/nh.2013.28.6.6862","ISSN":"02121611","abstract":"Background: Parenteral nutrition (PN) is a costly technology used widely to provide nutrition to patients who have an inaccessible or non-functioning intestine. Two all-in-one systems currently being used are customized formulations and three-compartment bags. Objective: To provide a systematic cost comparison of the two all-in-one PN systems: individualized (made from nutrient solutions) versus commercialized (made from three-compartment bag), both prepared in hospital pharmacies. Setting: This study was conducted in three public Spanish hospitals. Method: We conducted a cost-minimization study to analyze prospectively the total cost of PN bags, accounting for all of the processes involved in preparing and delivering PN bags (cost of manpower, nutrition solutions, medical supplies and quality controls) in three different healthcare settings. To compare therapeutic alternatives of equivalent nutritional value, the study was performed for the most frequently employed formulation and similar to commercial preparations. A univariate sensitivity analysis was performed to evaluate the impact of different rates of use of three-compartment PN bag. Results: 157 routine acts of PN bag preparation (65 customized and 92 three-compartment) were observed and timed over 9 days. Total costs of the 157 PN bags were included in the study. Mean costs of customized bags were higher than three-compartment bags, 51.16 ± 5.63 € versus 39.69 ± 3.00 € respectively (p < 0.01). Manpower costs were responsible for the majority of the differences found (70%). The time to complete an adult bag for the hospital compounded system was a mean of 25.9 minutes longer than the three-compartment system. In scenarios using a three-compartment system for 30%, 70% and 90% of PN provision, a cost savings of 4.3%, 10.1% and 12.9% respectively could be achieved. Greatest rates of changing from customized bags (70% and 90%), in a hospital with 1,800 PN bags/year, might reduce the annual budget by 9306 € and 11,964.8 €, respectively. Meanwhile, in a large facility the savings for 8,000 TPN days would be 64,248 € and 82,605 €, respectively. Conclusions: Since seeking cost-reduction of effective treatments is needed, the use of three-compartment bags for standard adult PN could lead to cost savings. Our data should be helpful for health care providers to calculate their own cost of administer.","author":[{"dropping-particle":"","family":"Berlana","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sabin","given":"Pilar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gimeno-Ballester","given":"Vicente","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Romero-Jiménez","given":"Rosa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zapata-Rojas","given":"Amalia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marquez","given":"Esther","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Martínez-Cutillas","given":"Julio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoenenberger-Arnaiz","given":"Joan Anton","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nutricion Hospitalaria","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2013"]]},"page":"2135–2141","title":"Cost analysis of adult parenteral nutrition systems; three-compartment bag versus customized","type":"article-journal","volume":"28"},"uris":[""]}],"mendeley":{"formattedCitation":"44","plainTextFormattedCitation":"44","previouslyFormattedCitation":"45"},"properties":{"noteIndex":0},"schema":""}44Hospital pharmacy service assistant (min)28.3028.3030.00Use of material resources Solution 0.2% in ethanolCarmustine IV (100 mg vial)1.001.001.00ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Dávila","given":"Carmela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clérigues","given":"M Nieves","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Farmacotecnia","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012"]]},"page":"1–13","title":"Farmacotecnia: boletín informativo [Pharmacotechnics: newsletter]","type":"article-journal","volume":"2"},"uris":[""]},{"id":"ITEM-2","itemData":{"author":[{"dropping-particle":"","family":"Grupo de trabajo de Farmacotecnia de la Sociedad Espa?ola de Farmacia Hospitalaria","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["0"]]},"title":"Información Lista Sociedad Espa?ola de Farmacia Hospitalaria. 2018. [Information list of the Spanish Society of Hospital Pharmacy. 2018]","type":"webpage"},"uris":[""]},{"id":"ITEM-3","itemData":{"author":[{"dropping-particle":"","family":"Hospital Universitario 12 de Octubre (Servicio de Farmacia)","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-3","issued":{"date-parts":[["2010"]]},"publisher":"Hospital Universitario 12 de Octubre","publisher-place":"Madrid","title":"Preparación de Medicamentos: formulación magistral. Volumen I [Drug preparation: master formulation. Volume I]","type":"book"},"uris":[""]}],"mendeley":{"formattedCitation":"51–53","plainTextFormattedCitation":"51–53","previouslyFormattedCitation":"52–54"},"properties":{"noteIndex":0},"schema":""}51–53Absolute ethanol (mL)3.003.003.00Vacuflasc? 500 mL sterile flask (unit)1.001.001.00Needles (unit)2.002.002.00Absorbent sterile cotton gauze (unit)5.005.005.00Gloves (unit)2.402.004.00Solution 10 mg/60 cc alcoholCarmustine IV (100 mg vial)1.001.001.00Ointment 0.01% petroleum jellyCarmustine IV (100 mg vial)1.001.001.00Ethanol 96 (mL)10.0010.0010.00Sterilized petroleum jelly (g)50.0050.0050.00Needles (unit)2.002.002.00Absorbent sterile cotton gauze (unit)5.005.005.00Gloves (unit)2.402.004.00Ointment 0.02% ethanol/petroleum jellyCarmustine IV (100 mg vial)1.001.001.00Absolute alcohol (mL)25.0025.0025.00White petroleum jelly (g)500.00500.00500.00Plastic bottles 100 mL (unit)10.0010.0010.00Needles (unit)2.002.002.00Absorbent sterile cotton gauze (unit)5.005.005.00Gloves (unit)2.402.004.00Use of resources associated with treatmentMean daily dose (mg/day)15.0010.0020.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/0190-9622(90)70112-U","ISBN":"0190-9622 (Print)\\r0190-9622 (Linking)","ISSN":"0190-9622","PMID":"2347966","abstract":"One hundred forty-three patients with cutaneous T cell lymphoma were treated with topical carmustine (BCNU). A complete response was obtained in 86% of those with limited extent (≥ 10%) plaques (Tl stage), in 48% of those with extensive (< 10%) plaques (T2 stage), and in 21% of those with erythroderma. The median time to achieve complete response was 11.5 weeks. Favorable results were obtained in patients with less than 5% involvement treated locally. Mild hematopoietic depression occurred in less than 10% of patients. Erythematous reactions were common, but no secondary cutaneous malignancies occurred. Differences in freedom from relapse or in survival between T2-stage patients with and those without clinical adenopathy were not statistically significant. The 5-year overall survival rate was 77%; the median survival time was 9.4 years. ? 1990, American Academy of Dermatology, Inc.. All rights reserved.","author":[{"dropping-particle":"","family":"Zackheim","given":"Herschel S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Epstein","given":"Ervin H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Crain","given":"William R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Academy of Dermatology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["1990","5"]]},"page":"802–810","publisher":"Elsevier","title":"Topical carmustine (BCNU) for cutaneous T cell lymphoma: a 15-year experience in 143 patients","type":"article-journal","volume":"22"},"uris":[""]},{"id":"ITEM-2","itemData":{"URL":"","accessed":{"date-parts":[["2018","11","28"]]},"author":[{"dropping-particle":"","family":"British Columbia Cancer Drug Manual","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Vancouver: Provincial Health Services Authority (PHSA), 2018","id":"ITEM-2","issued":{"date-parts":[["2018"]]},"title":"Carmustine Monograph","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"54,55","plainTextFormattedCitation":"54,55","previouslyFormattedCitation":"55,56"},"properties":{"noteIndex":0},"schema":""}54,55Time (median) until CR (weeks)18.183.0052.14Tests and additional visitsHemogram analysis (monthly frequency)0.550.171.09Panel of clinical expertsRepresentativeness (%)*66.67%Complete biochemistry (monthly frequency)0.620.620.62Representativeness (%)*16.67%Abbreviations: CR, complete response; IV, intravenous. Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit.Table S2. Use of resources associated with phototherapiesConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioPUVA Phototherapy Use of resources associated with treatmentPUVA sessions (weekly frequency)2.502.503.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/ijd.12425","ISSN":"0011-9059","abstract":"Abstract Background Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Psoralen combined with ultraviolet A (PUVA) is a first-line treatment for early-stage disease. Objectives This study was conducted to assess the clinical effectiveness of and tolerance to PUVA monotherapy in MF. Methods We retrospectively reviewed the files of patients who received PUVA for stage I disease. The study included 31 patients, of whom 32% presented with stage Ia and 67% with stage Ib disease, and 68% presented with patch and 32% with plaque disease. All patients received treatment three times per week. Results Complete response (CR) was achieved in 71% of patients. The median cumulative dose of UVA at CR was 211.7 J/cm2. There was a significant difference in median cumulative dose at CR between patients with plaque and patch disease, respectively, but not between patients with stage Ia and Ib disease. Median disease-free survival (DFS) was 230 weeks. Patients with patch disease achieved longer DFS than those with plaque disease (P = 0.004), although DFS was similar in stage Ia and Ib patients. Of the patients who received maintenance therapy, 58% relapsed. Univariate analysis showed patch disease to be a predictive factor for CR, but no predictors of relapse were identified. A total of 71% of patients developed clinical adverse reactions. Conclusions Psoralen with UVA is a safe and effective treatment for early-stage MF. Patch disease responds more favorably than plaque disease and is associated with a longer period of DFS. Maintenance treatment does not appear to reduce recurrence. Current evidence suggests that the proposed revision to the classification of MF, which takes into account the extent and type of disease, more accurately predicts response to PUVA.","author":[{"dropping-particle":"","family":"Hernández","given":"Zaida","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pe?ate","given":"Yeray","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hernández-Machín","given":"Buenaventura","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pérez-Méndez","given":"Lina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suárez-Hernández","given":"Jose","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hernández","given":"Javier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fernández-de-Misa","given":"Ricardo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Dermatology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2014","4"]]},"page":"1417–1422","publisher":"John Wiley & Sons, Ltd","title":"Treatment of stage Ia and Ib mycosis fungoides with psoralen UVA monotherapy: an observational study in tertiary hospitals in the Canary Islands","type":"article-journal","volume":"53"},"uris":[""]},{"id":"ITEM-2","itemData":{"abstract":"La micosis fungoide (MF) es una enfermedad de curso habitualmente lento que se localiza inicialmente en la piel y puede progresar hacia la afectación sistémica. Los efectos beneficios de la PUVAterapia están documentados por múltiples series, pero hay escasos trabajos sobre el uso de la fototerapia con UVB en el tratamiento de esta dermatosis. Treinta y nueve pacientes con MF fueron tratados en nuestro departamento: 24 con UBV, nueve con PUVA y seis con PUVA + UVB. Los pacientes se clasificaron según los estadios de Vonderheid, estando 31 en estadio I A. Aclararon totalmente de sus lesiones 18 (75%) de los tratados con UVB, siete (78%) de los sometidos a PUVA y cinco (83%) de los irradiados con PUVA + UVB. Los resultados muestran que la fototerapia con UVB es tan efectiva como la fotoquimioterapia en los estadios iniciales de la MF.","author":[{"dropping-particle":"","family":"Martín Gutiérrez","given":"FJ","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortega Resinas","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Camacho Martínez","given":"F","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Actas Dermo-Sifiliográficas","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2000","3"]]},"page":"98–100","publisher":"Elsevier Espan?a","title":"Fototerapia UVB en la micosis fungoide [UVB phototherapy in mycosis fungoides]","type":"article-journal","volume":"91"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/0190-9622(95)90241-4","ISSN":"0190-9622","author":[{"dropping-particle":"","family":"Herrmann","given":"James J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roenigk","given":"Henry H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hurria","given":"Arti","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuzel","given":"Timothy M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Samuelson","given":"Ellen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rademaker","given":"Alfred W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosen","given":"Steven T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Academy of Dermatology","id":"ITEM-3","issue":"2","issued":{"date-parts":[["1995","8"]]},"page":"234–242","publisher":"Elsevier","title":"Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up","type":"article-journal","volume":"33"},"uris":[""]}],"mendeley":{"formattedCitation":"56–58","plainTextFormattedCitation":"56–58","previouslyFormattedCitation":"57–59"},"properties":{"noteIndex":0},"schema":""}56–58 Mean time until CR (weeks)13.8912.6418.00PUVA sessions until CR (n)34.7331.6154.00Tests and additional visitsComplete biochemistry (n)1.001.001.00Panel of clinical expertsRepresentativeness (%)*100.00%Liver function test (n)1.171.002.00Representativeness (%)*100.00%Hemogram analysis (n)2.002.002.00Representativeness (%)*16.67%Creatinine level (n)2.002.002.00Representativeness (%)*16.67%ANA level (n)1.001.001.00Representativeness (%)*16.67%Ophthalmology review (n)1.001.001.00Representativeness (%)*16.67%Phototest/photopatch (n)1.001.001.00Representativeness (%)*16.67%NB-UVB PhototherapyUse of resources associated with treatmentNB-UVB sessions (weekly frequency)2.763.312.58Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"La micosis fungoide (MF) es una enfermedad de curso habitualmente lento que se localiza inicialmente en la piel y puede progresar hacia la afectación sistémica. Los efectos beneficios de la PUVAterapia están documentados por múltiples series, pero hay escasos trabajos sobre el uso de la fototerapia con UVB en el tratamiento de esta dermatosis. Treinta y nueve pacientes con MF fueron tratados en nuestro departamento: 24 con UBV, nueve con PUVA y seis con PUVA + UVB. Los pacientes se clasificaron según los estadios de Vonderheid, estando 31 en estadio I A. Aclararon totalmente de sus lesiones 18 (75%) de los tratados con UVB, siete (78%) de los sometidos a PUVA y cinco (83%) de los irradiados con PUVA + UVB. Los resultados muestran que la fototerapia con UVB es tan efectiva como la fotoquimioterapia en los estadios iniciales de la MF.","author":[{"dropping-particle":"","family":"Martín Gutiérrez","given":"FJ","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortega Resinas","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Camacho Martínez","given":"F","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Actas Dermo-Sifiliográficas","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2000","3"]]},"page":"98–100","publisher":"Elsevier Espan?a","title":"Fototerapia UVB en la micosis fungoide [UVB phototherapy in mycosis fungoides]","type":"article-journal","volume":"91"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/j.1468-3083.2009.03500.x","ISSN":"0926-9959","abstract":"Abstract Introduction? Mycosis fungoides (MF) is a non-Hodgkin?s T-cell lymphoma of the skin that often begins as limited patches and plaques with slow progression to systemic involvement. Narrowband ultraviolet (UV) B therapy has been proven to be an effective short-term treatment modality for clearing patch-stage MF. The effect of psoralen plus long-wave ultraviolet A (PUVA) in the treatment of patch- and plaque-type MF has also been thoroughly documented. Objectives? The purpose of this study was to compare the efficacy and safety of narrowband UVB and PUVA in patients with early-stage MF. Methods? We analysed the response to treatment, relapse-free survival and irradiation dose in 114 patients with histologically confirmed early-stage MF (stage IA, IB and IIA). Results? A total of 95 patients were treated with PUVA (83.3%) and 19 with narrowband UVB (16.7%). With PUVA, 59 patients (62.1%) had a complete response (CR), 24 (25.3%) had a partial response (PR) and 12 (12.6%) had a failed response. Narrowband UVB led to CR in 12 (68.4%) patients, PR in 5 (26.3%) patients and a failed response in 1 (5.3%) patient. There were no differences in terms of time to relapse between patients treated with PUVA and those treated with narrowband UVB (11.5 vs. 14.0?months respectively; P?=?0.816). No major adverse reactions were attributed to the treatment. Conclusions? Our results confirm that phototherapy is a safe, effective and well-tolerated, first-line therapy in patients with early-stage cutaneous T-cell lymphoma, with prolonged disease-free remissions being achieved. It suggests that narrowband UVB is at least as effective as PUVA for treatment of early-stage MF.","author":[{"dropping-particle":"","family":"Ponte","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Serr?o","given":"V","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Apetato","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the European Academy of Dermatology and Venereology","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2010","5"]]},"page":"716–721","publisher":"John Wiley & Sons, Ltd (10.1111)","title":"Efficacy of narrowband UVB vs. PUVA in patients with early-stage mycosis fungoides","type":"article-journal","volume":"24"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1468-3083.2006.01557.x","ISSN":"0926-9959","abstract":"Abstract Background? Several options for treatment of early mycosis fungoides (MF) offer similar success rates. Previous small studies have shown UVB to be at least as effective as PUVA. Objective? To summarize our experience with UVB treatment of early MF. Methods? A retrospective analysis of early-stage MF patients treated by narrow band (NB) or broad band (BB) UVB in our institution between 1996 and 2002. Most patients achieving complete response (CR) were put on maintenance until natural sun exposure was possible and followed up every 3?6 months. The results were compared to those previously reported regarding PUVA. Results? Sixty-eight and 43 patients were treated by NB and BB UVB, respectively. Eighty-six per cent (84 and 89% in NB and BB UVB groups, respectively) of IA and 71% (78 and 44% in NB and BB UVB groups, respectively) of IB patients achieved CR within a mean of 12.8 and 10.6 weeks, respectively. When maintenance was stopped, 65 and 30% had not relapsed after an average follow up of 27 and 222 weeks, respectively. Non-relapse rate was 33 and 48% for those having had vs. those not having had maintenance, respectively. Conclusions? Our results are comparable to all previously reported for skin-targeted treatments, including PUVA and, to our belief, reflect the nature of early MF, in which CR can probably be achieved in most of the patients. Among the responding patients there is no relapse during prolonged follow-up in about one third of the cases. Thus, we believe treatment should be stopped completely following first CR induction and maintenance treatment should be considered for relapsing patients only. Both broad and narrow UVB options are good and future choices should be made on the basis of short- and long-term side-effects.","author":[{"dropping-particle":"","family":"Pavlotsky","given":"F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barzilai","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kasem","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpiro","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trau","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the European Academy of Dermatology and Venereology","id":"ITEM-3","issue":"5","issued":{"date-parts":[["2006","4"]]},"page":"565–572","publisher":"John Wiley & Sons, Ltd (10.1111)","title":"UVB in the management of early stage mycosis fungoides","type":"article-journal","volume":"20"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1111/j.1600-0781.2007.00314.x","ISSN":"09054383","abstract":"BACKGROUND: In recent years, narrow-band ultraviolet B (NB-UVB, 311-313 nm) has been found to be beneficial for early-stages mycosis fungoides (MF). The aim of this study is to investigate the effect of NB-UVB in 20 patients with early-stage MF.\\n\\nMETHODS: Twenty patients (10 women and 10 men, mean age 54 +/- 22 years) with clinically and histologically confirmed MF were enrolled in the study. All of the patients had clinical stage I disease (T1 or T2, N0, M0) with cutaneous involvement, consisting of patch-stage disease of limited extent, in 50% of the cases (stage IA), and more widespread in the other 50% (stage IB). All the patients were treated with NB-UVB therapy until more than 95% clearance of the patient's skin lesions had occurred.\\n\\nRESULTS: A complete response was achieved in 90% of the cases after a mean of 29 +/- 14 treatments within a mean period of 4 months (range 1-8 months), with an average cumulative dose of 25 +/- 16.77 J/cm(2). In the follow-up period, relapse occurred after a mean period of 8 months (range 3-17 months), and then therapy was restarted.\\n\\nCONCLUSION: This study provides evidence that NB-UVB might be an efficient option for stage IA and IB MF patients.","author":[{"dropping-particle":"","family":"Brazzelli","given":"Valeria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Antoninetti","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Palazzini","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prestinari","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Borroni","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Photodermatology Photoimmunology and Photomedicine","id":"ITEM-4","issue":"6","issued":{"date-parts":[["2007","12"]]},"page":"229–233","title":"Narrow-band ultraviolet therapy in early-stage mycosis fungoides: study on 20 patients","type":"article-journal","volume":"23"},"uris":[""]}],"mendeley":{"formattedCitation":"57,59–61","plainTextFormattedCitation":"57,59–61","previouslyFormattedCitation":"58,60–62"},"properties":{"noteIndex":0},"schema":""}57,59–61Mean time until CR (weeks)12.818.7717.38NB-UVB sessions until CR (n)35.3829.0044.80Tests and additional visitsANA level (n)1.001.001.00Panel of clinical expertsRepresentativeness (%)*33.33%Phototest/photopatch (n)1.001.001.00Representativeness (%)*16.67%Abbreviations: ANA, antinuclear antibodies; PUVA, psoralens with ultraviolet A light; CR, complete response; NB-UVB, narrowband ultraviolet B light.Notes: *Representativeness: Proportion of clinical experts who indicated the laboratory test and/or follow-up visit.Table S3. Use of resources associated with TSEBTConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUsage distribution (%)Standard or regular regimen42.50%Panel of clinical expertsDivided or low intensity dose57.50%Total100.00%Use of resources associated with TSEBTStandard or regular regimenDuration of treatment until CR (days)42.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"0003-987X","abstract":"Objective To review the Stanford University experience with total skin electron-beam therapy (TSEBT) of 30 Gy or greater as monotherapy in patients with mycosis fungoides (MF) and compare with subgroups receiving adjuvant nitrogen mustard (HN2), and further update our experience with repeated courses of TSEBT.Design Retrospective study.Setting Academic referral center, multidisciplinary clinic.Patients A total of 180 patients with MF treated from 1970 through 2007 with T2 MF (103 with generalized patch or plaque disease) or T3 MF (77 with tumor disease). Patients with extracutaneous disease were excluded.Interventions Total skin electron-beam therapy with or without adjuvant topical HN2.Main Outcome Measure Clinical response rate, freedom from relapse (FFR), overall survival (OS), and progression-free survival (PFS) after TSEBT.Results The overall response rate (ORR) was 100%; 60% of patients achieved a complete clinical response (patients with T2 MF = 75%, those with T3 MF = 47%). The 5- and 10-year OS rates of the entire cohort were 59% and 40%, respectively. There were no significant differences in FFR (P = .30 for T2 disease; P = .50 for T3 disease), PFS (P = .10 for T2 disease; P = .40 for T3 disease), or OS (P = .30 for T2 disease; P = .50 for T3 disease) between adjuvant HN2 and TSEBT monotherapy cohorts. The ORR was 100% in patients receiving a second course of TSEBT with median FFR of 6 months.Conclusions A TSEBT of 30 Gy or greater is highly effective in treating T2-T3 MF, with better outcomes in T2 disease. There was no clinical advantage to adjuvant HN2 as used in our cohort. Second courses of TSEBT are safe and efficacious and provide clinically meaningful palliation for select patients.","author":[{"dropping-particle":"","family":"Navi","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Riaz","given":"N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Levin","given":"Y","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sullivan","given":"N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Y","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hoppe","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Archives of Dermatology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2011","5"]]},"page":"561–567","title":"The stanford university experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (t2) and tumor (t3) mycosis fungoides","type":"article-journal","volume":"147"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/S0360-3016(97)00127-2","ISSN":"0360-3016","author":[{"dropping-particle":"","family":"Quirós","given":"Peter A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jones","given":"Gleen W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kacinski","given":"Barry M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Braverman","given":"Irwin M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Edelson","given":"Richard L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilson","given":"Lynn D","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Radiation Oncology Biology Physics","id":"ITEM-2","issue":"5","issued":{"date-parts":[["1997","7"]]},"page":"1027–1035","publisher":"Elsevier","title":"Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides)","type":"article-journal","volume":"38"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/0360-3016(94)90103-1","ISSN":"0360-3016","author":[{"dropping-particle":"","family":"Jones","given":"Glenn W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tadros","given":"Alfie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hodson","given":"David I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenthal","given":"Donald","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roberts","given":"John","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thorson","given":"Barbara","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Radiation Oncology Biology Physics","id":"ITEM-3","issue":"4","issued":{"date-parts":[["1994","3"]]},"page":"839–845","publisher":"Elsevier","title":"Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY","type":"article-journal","volume":"28"},"uris":[""]}],"mendeley":{"formattedCitation":"62–64","plainTextFormattedCitation":"62–64","previouslyFormattedCitation":"63–65"},"properties":{"noteIndex":0},"schema":""}62–64TSEB sessions until CR (n)30.50 22.50 40.00 Divided or low intensity doseDuration of treatment until CR (days)21.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.ijrobp.2015.08.041","ISSN":"0360-3016","author":[{"dropping-particle":"","family":"Elsayad","given":"Khaled","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kriz","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moustakis","given":"Christos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scobioala","given":"Sergiu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reinartz","given":"Gabriele","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haverkamp","given":"Uwe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willich","given":"Normann","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weishaupt","given":"Carsten","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stadler","given":"Rudolf","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sunderk?tter","given":"Cord","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eich","given":"Hans Theodor","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Int J Radiat Oncol Biol Phys","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2015","12"]]},"page":"1077–1086","publisher":"Elsevier","title":"Total skin electron beam for primary cutaneous T-cell lymphoma","type":"article-journal","volume":"93"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/0360-3016(94)90103-1","ISSN":"0360-3016","author":[{"dropping-particle":"","family":"Jones","given":"Glenn W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tadros","given":"Alfie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hodson","given":"David 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R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gniadecki","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iversen","given":"Lars","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Skov","given":"Lone","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Petersen","given":"Peter Meidahl","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Loft","given":"Annika","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Specht","given":"Lena","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Radiation Oncology Biology Physics","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2015","5"]]},"page":"138–143","publisher":"Elsevier","title":"Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis","type":"article-journal","volume":"92"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1016/j.jaad.2014.10.014","ISSN":"0190-9622","author":[{"dropping-particle":"","family":"Hoppe","given":"Richard T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harrison","given":"Cameron","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavallaee","given":"Mahkam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bashey","given":"Sameer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sundram","given":"Uma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Shufeng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Million","given":"Lynn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dabaja","given":"Bouthaina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gangar","given":"Pamela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Academy of Dermatology","id":"ITEM-4","issue":"2","issued":{"date-parts":[["2015","2"]]},"page":"286–292","publisher":"Elsevier","title":"Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials","type":"article-journal","volume":"72"},"uris":[""]}],"mendeley":{"formattedCitation":"64–67","plainTextFormattedCitation":"64–67","previouslyFormattedCitation":"65–68"},"properties":{"noteIndex":0},"schema":""}64–67TSEB sessions until CR (n)18.67 12.00 24.00 Tests and additional visitsHemogram analysis (n)1.001.001.00Panel of clinical expertsRepresentativeness (%)*83.33%Complete biochemistry (n)1.001.001.00Representativeness (%)*83.33%Chest x-ray (n)1.001.001.00Representativeness (%)*66.67%CT scan of abdomen and pelvis (n)1.001.001.00Representativeness (%)*83.33%Consultation with radiology specialist, initial (n)1.801.003.00Representativeness (%)*83.33%Consultation with dermatology specialist, initial (n)1.001.001.00Representativeness (%)*16.67%Consultations with specialist, successive (every month)0.500.500.50Representativeness (%)*16.67%Abbreviations: CR, complete response; TSEB, total skin electron beam; TSEBT, total skin electron beam therapy; CT, computerized axial tomography scan.Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit.Table S4. Use of resources associated with topical corticosteroidsConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUsage distribution (%)Beclomethasone TP3.33%Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1001/archderm.134.8.949","ISSN":"0003-987X","abstract":"Objective To determine the effectiveness of topical corticosteroids in the management of mycosis fungoides.Design Prospective study.Setting Academic referral center, Veterans Affairs Medical Center, and private practice.Patients Seventy-nine patients with patch or plaque stage of mycosis fungoides. Fifty-one were stage T1 (less than 10% of skin involved) and 28 were stage T2 (10% or more of skin involved). Seventy-five had patch-stage and 4 had plaque-stage disease as determined by histological examination.Intervention Patients were treated with topical class I to III corticosteroids. Of the stage T1 patients, all used class I corticosteroids, and 4 (8%) also used class II or III corticosteroids. Of the stage T2 patients, 19 (68%) used class I and 12 (43%) used class II or III compounds. Some patients used more than 1 class of corticosteroid. Applications were almost always twice daily. Three stage T1 and 2 stage T2 patients used plastic film occlusion. Baseline and monthly morning serum cortisol levels were obtained during treatment.Main Outcome Measures Response to treatment and side effects.Results The median follow-up period was 9 months. Thirty-two (63%) of stage T1 patients achieved complete remission and 16 (31%) achieved partial remission, for a total response rate of 48 (94%). The comparable figures for stage T2 patients were 7 (25%), 16 (57%), and 23 (82%), respectively. Responses were determined by clinical examination. Thirty-nine patients achieved clinical clearing. In 7 of these, posttreatment biopsy speciments were obtained, and all showed histological clearing. Reversible depression of serum cortisol levels occurred in 10 (13%). Minor skin irritation occurred in 2 patients and localized, reversible skin atrophy in 1.Conclusion Topical corticosteroids, especially class I compounds, are an effective treatment for patch-stage mycosis fungoides.","author":[{"dropping-particle":"","family":"Zackheim","given":"HS","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kashani-Sabet","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amin","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Archives of Dermatology","id":"ITEM-1","issue":"8","issued":{"date-parts":[["1998","8"]]},"page":"949–954","title":"Topical corticosteroids for mycosis fungoides: experience in 79 patients","type":"article-journal","volume":"134"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/j.1396-0296.2003.01639.x","ISSN":"1396-0296","PMID":"24134821","abstract":"ABSTRACT:? Experience at the University of California, San Francisco (UCSF), in the management of patch-stage mycosis fungoides (MF) with topical, predominantly high-potency, corticosteroids is reviewed. The technique of applications is discussed in detail. Approximately 200 patients have been treated. The results are very favorable. The response rate is over 90%. Side-effects are minor. Topical clobetasol is the first-line treatment for early stage MF at UCSF.","author":[{"dropping-particle":"","family":"Zackheim","given":"Herschel S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Dermatologic Therapy","id":"ITEM-2","issue":"4","issued":{"date-parts":[["2003","12"]]},"page":"283–287","publisher":"John Wiley & Sons, Ltd","title":"Treatment of patch-stage mycosis fungoides with topical corticosteroids","type":"article-journal","volume":"16"},"uris":[""]}],"mendeley":{"formattedCitation":"68,69","plainTextFormattedCitation":"68,69","previouslyFormattedCitation":"69,70"},"properties":{"noteIndex":0},"schema":""}68,69Betamethasone TP8.20%Clobetasol TP72.80%Diflorasone TP3.00%Fluocinolone TP3.17%Fluticasone TP0.83%Methylprednisolone TP2.50%Mometasone TP0.50%Triamcinolone TP5.67%Total100.00%Dose (daily applications)Beclomethasone TP2.002.002.00ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"URL":"","accessed":{"date-parts":[["2018","11","19"]]},"id":"ITEM-1","issued":{"date-parts":[["2018"]]},"publisher":"Consejo General de Colegios Oficiales de Farmacéuticos","publisher-place":"Madrid","title":"Bot PLUS: Base de Datos de Información Sanitaria [Bot PLUS: health information database]","type":"webpage"},"uris":[""]},{"id":"ITEM-2","itemData":{"URL":"","accessed":{"date-parts":[["2018","11","22"]]},"container-title":"Ministerio de Sanidad Consumo y Bienestar Social","id":"ITEM-2","issued":{"date-parts":[["2018"]]},"title":"Centro de información online de medicamentos (Aemps - CIMA) [Medicine online information center of AEMPS - CIMA]","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"40,70","plainTextFormattedCitation":"40,70","previouslyFormattedCitation":"41,71"},"properties":{"noteIndex":0},"schema":""}40,70Betamethasone TP1.901.003.00Clobetasol TP 2.001.004.00Diflorasone TP 2.001.004.00Fluocinolone TP 1.831.003.00Fluticasone TP 1.001.002.00Methylprednisolone TP 1.001.002.00Mometasone TP2.002.002.00Triamcinolone TP 1.831.003.00Use of resources associated with treatmentAmount for TP application (g/application)2.891.975.78Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Andía","given":"Ana Azparren","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Boletín de Información Farmacoterapéutica de Navarra","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2001"]]},"page":"1–13","title":"Corticoides tópicos [Topical corticosteroids]","type":"article-journal","volume":"9"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/S0190-9622(03)01475-0","ISSN":"01909622","abstract":"Objectives: We sought to determine the safety and efficacy of topical bexarotene (Targretin; Ligand Pharmaceuticals, La Jolla, Calif) gel 1% in patients with refractory or persistent early-stage cutaneous T-cell lymphoma. Methods: We conducted a multinational, open-label, phase III study of 50 patients with stage IA to IIA cutaneous T-cell lymphoma. The primary end point classification was the overall complete and partial response rate by the higher of 2 measures: the Physician's Global Assessment of Clinical Condition or the Composite Assessment of Index Lesion Disease Severity. Results: The overall response rates for the Physician's Global Assessment of Clinical Condition, Composite Assessment of Index Lesion Disease Severity, and primary end point classification were 44%, 46%, and 54%, respectively. The most common adverse events possibly related to study medication were mild to moderate irritant dermatitis, pruritus, pain (ie, primarily burning at application site), and skin disorder (eg, skin inflammation, excoriation, and new lesions). There were no serious treatment-related adverse events. Conclusions: Topical bexarotene gel was generally well tolerated and demonstrated substantial efficacy in patients with refractory or persistent early-stage cutaneous T-cell lymphoma.","author":[{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mehlmauer","given":"Marilyn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Martin","given":"Ann G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Crowley","given":"Constance A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yocum","given":"Richard C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reich","given":"Steven D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Group","given":"Worldwide Bexarotene Study","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Academy of Dermatology","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2003","11"]]},"page":"801–815","publisher":"Elsevier","title":"Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial","type":"article-journal","volume":"49"},"uris":[""]},{"id":"ITEM-3","itemData":{"author":[{"dropping-particle":"","family":"Committee for Medicinal Products for Human Use","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Medicines Agency","id":"ITEM-3","issued":{"date-parts":[["2017"]]},"publisher-place":"Amsterdam","title":"European Public Assessment Report: LEDAGA (EMA/CHMP/13156/2017)","type":"report"},"uris":[""]}],"mendeley":{"formattedCitation":"49,50,71","plainTextFormattedCitation":"49,50,71","previouslyFormattedCitation":"50,51,72"},"properties":{"noteIndex":0},"schema":""}49,50,71Tests and additional visitsCortisol levels (monthly frequency)0.130.080.17Panel of clinical expertsRepresentativeness (%)*33.33%Calcium/vitamin D levels (monthly frequency)0.080.080.08Representativeness (%)*16.67%Abbreviations: TP, topical. Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit.Table S5. Use of resources associated with systemic retinoidsConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUsage distribution (%)Acitretin OR9.15%Panel of clinical experts Alitretinoin OR0.18%Bexarotene OR 90.50%Isotretinoin OR 0.17%Total100.00%Daily dose (mg/day)Acitretin OR31.7510.0048.38Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2009.09037.x","ISSN":"0007-0963","abstract":"Summary Background? Bexarotene (Targretin?) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL). Objectives? To summarize our experience with bexarotene for patients with CTCL with the aim of assessing efficacy and safety. Methods? A retrospective study of 66 patients (44 male, 22 female) with mycosis fungoides (40 patients) or Sézary syndrome (26 patients) who were commenced on bexarotene prior to August 2007 was carried out. Nineteen patients had early-stage (IB?IIA) refractory mycosis fungoides and 47 patients had advanced-stage CTCL (IIB?IVB). Results? Fifty-two out of 66 (79%) patients completed over 1?month of therapy with an intention-to-treat response rate of 44% (29/66). Of the patients, six (9%) had a complete response, 23 (35%) had a partial response, 15 (23%) had stable disease and eight (12%) had progressive disease. Median time to maximal response was 3?months (1?9?months). Median response duration was 8?months (1 to >?48?months). Median time to progression was 9?months (3?44?months). Fourteen patients (21%) did not complete a month of bexarotene therapy. Adverse effects of the whole group included central hypothyroidism in 100% (all grade II and managed with thyroid replacement) and hyperlipidaemia in 100% (all managed with lipid-lowering therapy?±?dose reduction). Responses were seen in all stages and were higher in advanced stages: 26% (five of 19) with early-stage and 51% (24/47) of advanced-stage disease. Responses were seen in skin, blood and lymph nodes. Twenty-eight out of 66 patients were treated with bexarotene monotherapy and the remainder were on one or more additional anti-CTCL therapies. Conclusions? Our data demonstrate that bexarotene is well tolerated in most patients and responses are seen in almost half of patients with all disease stages. However partial responses were not graded and would include any improvement seen in the skin, blood and lymph node.","author":[{"dropping-particle":"","family":"Abbott","given":"R A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morris","given":"S L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Russell-Jones","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hung","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bashir","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scarisbrick","given":"J J","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2009","5"]]},"page":"1299–1307","publisher":"John Wiley & Sons, Ltd","title":"Bexarotene therapy for mycosis fungoides and Sézary syndrome","type":"article-journal","volume":"160"},"uris":[""]},{"id":"ITEM-2","itemData":{"author":[{"dropping-particle":"","family":"Molin","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomsen","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Volden","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aronsson","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hammar","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hellbe","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wantzin","given":"GL","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roupe","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Dermato Venereologica","id":"ITEM-2","issue":"3","issued":{"date-parts":[["1987"]]},"page":"232–236","title":"Oral retinoids in mycosis fungoides and Sézary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group","type":"article-journal","volume":"67"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1365-2133.2009.09475.x","ISSN":"0007-0963","author":[{"dropping-particle":"","family":"Molin","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ruzicka","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-3","issue":"6","issued":{"date-parts":[["2009","11"]]},"page":"1420–1422","publisher":"John Wiley & Sons, Ltd","title":"Possible benefit of oral alitretinoin in T-lymphoproliferative diseases: a report of two patients with palmoplantar hyperkeratotic-rhagadiform skin changes and mycosis fungoides or Sézary syndrome","type":"article-journal","volume":"161"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.5114/pdia.2013.33375","ISSN":"1642-395X","abstract":"Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids' action is unclear. It is based on the presence of specific receptors' families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.","author":[{"dropping-particle":"","family":"Soko?owska-Wojdy?o","given":"Ma?gorzata","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lugowska-Umer","given":"Hanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maciejewska-Radomska","given":"Agata","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Postepy Dermatol Alergol","edition":"2013/02/20","id":"ITEM-4","issue":"1","issued":{"date-parts":[["2013","2"]]},"page":"19–29","publisher":"Termedia Publishing House","title":"Oral retinoids and rexinoids in cutaneous T-cell lymphomas","type":"article-journal","volume":"30"},"uris":[""]}],"mendeley":{"formattedCitation":"72–75","plainTextFormattedCitation":"72–75","previouslyFormattedCitation":"73–76"},"properties":{"noteIndex":0},"schema":""}72–75Alitretinoin OR30.0030.0030.00Bexarotene OR395.33120.00586.78Isotretinoin OR54.6632.7073.50Concomitant treatmentsFenofibrate: Concomitant use (%)75.45%Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2009.09037.x","ISSN":"0007-0963","abstract":"Summary Background? Bexarotene (Targretin?) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL). Objectives? To summarize our experience with bexarotene for patients with CTCL with the aim of assessing efficacy and safety. Methods? A retrospective study of 66 patients (44 male, 22 female) with mycosis fungoides (40 patients) or Sézary syndrome (26 patients) who were commenced on bexarotene prior to August 2007 was carried out. Nineteen patients had early-stage (IB?IIA) refractory mycosis fungoides and 47 patients had advanced-stage CTCL (IIB?IVB). Results? Fifty-two out of 66 (79%) patients completed over 1?month of therapy with an intention-to-treat response rate of 44% (29/66). Of the patients, six (9%) had a complete response, 23 (35%) had a partial response, 15 (23%) had stable disease and eight (12%) had progressive disease. Median time to maximal response was 3?months (1?9?months). Median response duration was 8?months (1 to >?48?months). Median time to progression was 9?months (3?44?months). Fourteen patients (21%) did not complete a month of bexarotene therapy. Adverse effects of the whole group included central hypothyroidism in 100% (all grade II and managed with thyroid replacement) and hyperlipidaemia in 100% (all managed with lipid-lowering therapy?±?dose reduction). Responses were seen in all stages and were higher in advanced stages: 26% (five of 19) with early-stage and 51% (24/47) of advanced-stage disease. Responses were seen in skin, blood and lymph nodes. Twenty-eight out of 66 patients were treated with bexarotene monotherapy and the remainder were on one or more additional anti-CTCL therapies. Conclusions? Our data demonstrate that bexarotene is well tolerated in most patients and responses are seen in almost half of patients with all disease stages. However partial responses were not graded and would include any improvement seen in the skin, blood and lymph node.","author":[{"dropping-particle":"","family":"Abbott","given":"R A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morris","given":"S L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Russell-Jones","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hung","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bashir","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scarisbrick","given":"J J","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2009","5"]]},"page":"1299–1307","publisher":"John Wiley & Sons, Ltd","title":"Bexarotene therapy for mycosis fungoides and Sézary syndrome","type":"article-journal","volume":"160"},"uris":[""]},{"id":"ITEM-2","itemData":{"author":[{"dropping-particle":"","family":"Molin","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomsen","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Volden","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aronsson","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hammar","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hellbe","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wantzin","given":"GL","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roupe","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Dermato Venereologica","id":"ITEM-2","issue":"3","issued":{"date-parts":[["1987"]]},"page":"232–236","title":"Oral retinoids in mycosis fungoides and Sézary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group","type":"article-journal","volume":"67"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1365-2133.2009.09475.x","ISSN":"0007-0963","author":[{"dropping-particle":"","family":"Molin","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ruzicka","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-3","issue":"6","issued":{"date-parts":[["2009","11"]]},"page":"1420–1422","publisher":"John Wiley & Sons, Ltd","title":"Possible benefit of oral alitretinoin in T-lymphoproliferative diseases: a report of two patients with palmoplantar hyperkeratotic-rhagadiform skin changes and mycosis fungoides or Sézary syndrome","type":"article-journal","volume":"161"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.5114/pdia.2013.33375","ISSN":"1642-395X","abstract":"Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids' action is unclear. It is based on the presence of specific receptors' families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.","author":[{"dropping-particle":"","family":"Soko?owska-Wojdy?o","given":"Ma?gorzata","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lugowska-Umer","given":"Hanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maciejewska-Radomska","given":"Agata","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Postepy Dermatol Alergol","edition":"2013/02/20","id":"ITEM-4","issue":"1","issued":{"date-parts":[["2013","2"]]},"page":"19–29","publisher":"Termedia Publishing House","title":"Oral retinoids and rexinoids in cutaneous T-cell lymphomas","type":"article-journal","volume":"30"},"uris":[""]},{"id":"ITEM-5","itemData":{"URL":"","accessed":{"date-parts":[["2018","11","22"]]},"container-title":"Ministerio de Sanidad Consumo y Bienestar Social","id":"ITEM-5","issued":{"date-parts":[["2018"]]},"title":"Centro de información online de medicamentos (Aemps - CIMA) [Medicine online information center of AEMPS - CIMA]","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"70,72–75","plainTextFormattedCitation":"70,72–75","previouslyFormattedCitation":"71,73–76"},"properties":{"noteIndex":0},"schema":""}70,72–75Daily dose (mg/day)160.00 Number of daily tablets (tablets/day)1.00 Levothyroxine: Concomitant use (%)79.21%Daily dose (μg/day)95.83 Number of daily tablets (tablets/day)1.00 Statins: Concomitant use (%)22.67%Daily dose (mg/day)15.00 Number of daily tablets (tablets/day)1.00 Use of resources associated with treatmentMedian duration of treatment (months)4.401.0020.33Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2009.09037.x","ISSN":"0007-0963","abstract":"Summary Background? Bexarotene (Targretin?) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL). Objectives? To summarize our experience with bexarotene for patients with CTCL with the aim of assessing efficacy and safety. Methods? A retrospective study of 66 patients (44 male, 22 female) with mycosis fungoides (40 patients) or Sézary syndrome (26 patients) who were commenced on bexarotene prior to August 2007 was carried out. Nineteen patients had early-stage (IB?IIA) refractory mycosis fungoides and 47 patients had advanced-stage CTCL (IIB?IVB). Results? Fifty-two out of 66 (79%) patients completed over 1?month of therapy with an intention-to-treat response rate of 44% (29/66). Of the patients, six (9%) had a complete response, 23 (35%) had a partial response, 15 (23%) had stable disease and eight (12%) had progressive disease. Median time to maximal response was 3?months (1?9?months). Median response duration was 8?months (1 to >?48?months). Median time to progression was 9?months (3?44?months). Fourteen patients (21%) did not complete a month of bexarotene therapy. Adverse effects of the whole group included central hypothyroidism in 100% (all grade II and managed with thyroid replacement) and hyperlipidaemia in 100% (all managed with lipid-lowering therapy?±?dose reduction). Responses were seen in all stages and were higher in advanced stages: 26% (five of 19) with early-stage and 51% (24/47) of advanced-stage disease. Responses were seen in skin, blood and lymph nodes. Twenty-eight out of 66 patients were treated with bexarotene monotherapy and the remainder were on one or more additional anti-CTCL therapies. Conclusions? Our data demonstrate that bexarotene is well tolerated in most patients and responses are seen in almost half of patients with all disease stages. However partial responses were not graded and would include any improvement seen in the skin, blood and lymph node.","author":[{"dropping-particle":"","family":"Abbott","given":"R A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morris","given":"S L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Russell-Jones","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hung","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bashir","given":"S J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scarisbrick","given":"J J","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2009","5"]]},"page":"1299–1307","publisher":"John Wiley & Sons, Ltd","title":"Bexarotene therapy for mycosis fungoides and Sézary syndrome","type":"article-journal","volume":"160"},"uris":[""]},{"id":"ITEM-2","itemData":{"author":[{"dropping-particle":"","family":"Molin","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomsen","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Volden","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aronsson","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hammar","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hellbe","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wantzin","given":"GL","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roupe","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Dermato Venereologica","id":"ITEM-2","issue":"3","issued":{"date-parts":[["1987"]]},"page":"232–236","title":"Oral retinoids in mycosis fungoides and Sézary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group","type":"article-journal","volume":"67"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1365-2133.2009.09475.x","ISSN":"0007-0963","author":[{"dropping-particle":"","family":"Molin","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ruzicka","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-3","issue":"6","issued":{"date-parts":[["2009","11"]]},"page":"1420–1422","publisher":"John Wiley & Sons, Ltd","title":"Possible benefit of oral alitretinoin in T-lymphoproliferative diseases: a report of two patients with palmoplantar hyperkeratotic-rhagadiform skin changes and mycosis fungoides or Sézary syndrome","type":"article-journal","volume":"161"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.5114/pdia.2013.33375","ISSN":"1642-395X","abstract":"Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids' action is unclear. It is based on the presence of specific receptors' families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.","author":[{"dropping-particle":"","family":"Soko?owska-Wojdy?o","given":"Ma?gorzata","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lugowska-Umer","given":"Hanna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maciejewska-Radomska","given":"Agata","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Postepy Dermatol Alergol","edition":"2013/02/20","id":"ITEM-4","issue":"1","issued":{"date-parts":[["2013","2"]]},"page":"19–29","publisher":"Termedia Publishing House","title":"Oral retinoids and rexinoids in cutaneous T-cell lymphomas","type":"article-journal","volume":"30"},"uris":[""]}],"mendeley":{"formattedCitation":"72–75","plainTextFormattedCitation":"72–75","previouslyFormattedCitation":"73–76"},"properties":{"noteIndex":0},"schema":""}72–75Tests and additional visitsLiver function test (n)3.672.005.00Panel of clinical expertsMonthly frequency after 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Thyroid function test (n)2.502.004.00Monthly frequency after 1st month (n/month)0.700.321.00Representativeness (%)*100.00%Hemogram analysis (n)3.672.005.00Monthly frequency, 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Complete biochemistry (n)3.672.005.00Monthly frequency after 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Triglycerides and cholesterol levels (n)3.332.004.00Monthly frequency after 1st month (n/month)0.700.321.00Representativeness (%)*100.00%Lymphoid phenotype (n)1.001.001.00Monthly frequency after 1st month (n/month)0.170.170.17Representativeness (%)*16.67%Pregnancy test (n)0.160.160.16Representativeness (%)*16.67%Abbreviations: OR, oral. Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit.Table S6. Use of resources associated with systemic retinoids + PUVAConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUse of resources associated with treatment, PUVAPUVA sessions (weekly frequency)1.380.631.88Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2012.11156.x","ISSN":"0007-0963","abstract":"Summary Background? Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective? To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. Methods? EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin?) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results? The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA?+?bexarotene. Total UVA doses received were 107?J?cm?2 (range 1·4?489·9) in the PUVA arm vs. 101·7?J?cm?2 (0·2?529·9) in the combination arm. The safety profile was acceptable with few grade 3?4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combination arm compared with the PUVA-alone arm. The best overall response (CCR?+?PR) rate was 71% for PUVA alone and 77% for the combination arm (P?=?0·57). The median duration of response was 9·7?months for PUVA vs. 5·8?months for the combination arm (P?=?0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P?=?0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P?=?0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8?J?cm?2) compared with the PUVA arm alone (median 117·5?J?cm?2) (P?=?0·5) was observed. Conclusions? No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA?+?bexarotene) but this did not achieve statistical significance due to insufficient power.","author":[{"dropping-particle":"","family":"Whittaker","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasan","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meulemans","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gellrich","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stadler","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karrasch","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012","8"]]},"page":"678–687","publisher":"John Wiley & Sons, Ltd","title":"Efficacy and safety of bexarotene combined with psoralen–ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB–IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial","type":"article-journal","volume":"167"},"uris":[""]}],"mendeley":{"formattedCitation":"76","plainTextFormattedCitation":"76","previouslyFormattedCitation":"77"},"properties":{"noteIndex":0},"schema":""}76PUVA sessions until CR (n)22.0010.0030.00Maximum duration until CR (weeks)16.00Use of resources associated with treatment, systemic retinoidsDose of bexarotene OR (mg/day)476.90433.07495.68Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2012.11156.x","ISSN":"0007-0963","abstract":"Summary Background? Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective? To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. Methods? EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin?) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results? The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA?+?bexarotene. Total UVA doses received were 107?J?cm?2 (range 1·4?489·9) in the PUVA arm vs. 101·7?J?cm?2 (0·2?529·9) in the combination arm. The safety profile was acceptable with few grade 3?4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combination arm compared with the PUVA-alone arm. The best overall response (CCR?+?PR) rate was 71% for PUVA alone and 77% for the combination arm (P?=?0·57). The median duration of response was 9·7?months for PUVA vs. 5·8?months for the combination arm (P?=?0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P?=?0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P?=?0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8?J?cm?2) compared with the PUVA arm alone (median 117·5?J?cm?2) (P?=?0·5) was observed. Conclusions? No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA?+?bexarotene) but this did not achieve statistical significance due to insufficient power.","author":[{"dropping-particle":"","family":"Whittaker","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasan","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meulemans","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gellrich","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stadler","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karrasch","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012","8"]]},"page":"678–687","publisher":"John Wiley & Sons, Ltd","title":"Efficacy and safety of bexarotene combined with psoralen–ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB–IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial","type":"article-journal","volume":"167"},"uris":[""]}],"mendeley":{"formattedCitation":"76","plainTextFormattedCitation":"76","previouslyFormattedCitation":"77"},"properties":{"noteIndex":0},"schema":""}76Concomitant treatmentsFenofibrate: Concomitant use (%)83.33%Panel of clinical expertsDaily dose (mg/day)160.00 Number of daily tablets (tablets/day)1.00 Levothyroxine: Concomitant use (%)87.50%Daily dose (μg/day)95.83 Number of daily tablets (tablets/day)1.00 Statins: Concomitant use (%)25.00%Daily dose (mg/day)15.00 Number of daily tablets (tablets/day)1.00 Tests and additional visitsLiver function test (n)3.672.005.00Panel of clinical experts Monthly frequency after 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Thyroid function test (n)2.502.004.00Monthly frequency after 1st month (n/month)0.700.321.00Representativeness (%)*100.00%Hemogram analysis (n)3.672.005.00Monthly frequency after 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Complete biochemistry (n)3.672.005.00Monthly frequency after 1st month (n/month)0.600.321.00Representativeness (%)*100.00%Triglycerides and cholesterol levels (n)3.332.004.00Monthly frequency after 1st month (n/month)0.700.321.00Representativeness (%)*100.00%Lymphoid phenotype (n)1.001.001.00Monthly frequency after 1st month (n/month)0.170.170.17Representativeness (%)*16.67%Pregnancy test (n)0.160.160.16Representativeness (%)*16.67%Creatinine level (n)2.002.002.00Representativeness (%)*16.67%ANA level (n)1.001.001.00Representativeness (%)*16.67%Ophthalmology review (n)1.001.001.00Representativeness (%)*16.67%Phototest/photopatch (n)1.001.001.00Representativeness (%)*16.67%Abbreviations: ANA, antinuclear antibodies; OR, oral; PUVA, psoralens with ultraviolet A light; TG, triglycerides. Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit.Table S7. Use of resources associated with IFNα + PUVAConceptUse of resourcesSourceBase caseMinimum scenarioMaximum scenarioUse of resources associated with treatment, PUVAPUVA sessions (weekly frequency)2.502.503.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2008.08886.x","ISSN":"0007-0963","abstract":"Summary Background? Interferon (IFN)-α is widely used in the treatment of mycosis fungoides (MF) and when used in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA) both improved response and duration of complete remission have been reported. However, in spite of encouraging results of the initial studies, currently there is no information available on specific prognostic factors enabling prediction of patients? resistance to PUVA?±?IFN-α treatment. Objectives? To identify factors responsible for resistance to PUVA?±?IFN-α treatment in MF patients. Patients/methods? The gene expression profiling of pretreatment samples from 29 patients diagnosed as IA, IB or IIA stage of MF enrolled in a randomized PUVA vs. PUVA?+?IFN-α clinical trial was analysed using cDNA microarrays. A Cox model (SAM) and gene set enrichment analysis (GSEA) were used for identification of genes and biologically significant pathways related to resistance to treatment. Results? Genes involved in NF-?B signalling, T-cell receptor (TCR) signalling, cytokine signalling and proliferation were differentially expressed between responders and nonresponders. Interestingly, expression of markers representative of those pathways was found not only in the tumoral cells, but also in specific subpopulations of macrophages, dendritic cells and other non-neoplastic cell types constituting the tumour microenvironment, likely involved in the promotion of survival and proliferation of cutaneous T-cell lymphoma. Conclusions? Gene expression changes in both the tumour and the tumour microenvironment are an important determinant of treatment outcome in early-stage MF patients. Some proinflammatory factors such as NF-?B, inflammatory cytokines and their receptors in addition to TCR-associated molecules could be promising targets for MF treatment.","author":[{"dropping-particle":"","family":"Wozniak","given":"M B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tracey","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz-Romero","given":"P L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Montes","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fraga","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fernández Herrera","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vidal","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rodriguez-Peralto","given":"J L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Piris","given":"M ?","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Villuendas (deceased)","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2009","12"]]},"page":"92–102","publisher":"John Wiley & Sons, Ltd","title":"Psoralen plus ultraviolet A ± interferon-α treatment resistance in mycosis fungoides: the role of tumour microenvironment, nuclear transcription factor-κB and T-cell receptor pathways","type":"article-journal","volume":"160"},"uris":[""]},{"id":"ITEM-2","itemData":{"abstract":"BACKGROUND AND OBJECTIVE: The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA. DESIGN AND METHODS: Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF). RESULTS: After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%. INTERPRETATION AND CONCLUSIONS: Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF.","author":[{"dropping-particle":"","family":"Rupoli","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barulli","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guiducci","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mozzicafreddo","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Simonacci","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacchetti","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricotti","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brandozzi","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cataldi","given":"I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Serresi","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ceschini","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bugatti","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giangiacomi","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brancorsini","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leoni","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Haematologica","id":"ITEM-2","issue":"9","issued":{"date-parts":[["1999","1"]]},"page":"809–813","title":"Low dose interferon-alpha2b combined with PUVA is an effective treatment of early stage mycosis fungoides: results of a multicenter study. Cutaneous-T Cell Lymphoma Multicenter Study Group","type":"article-journal","volume":"84"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1600-0609.2005.00497.x","ISSN":"0902-4441","abstract":"Abstract:? Objectives:?Combined high-dose Interferon-α and psoralen plus ultraviolet A irradiation (PUVA) have been reported to be effective in the treatment of early mycosis fungoides (MF); however, our study is the first controlled prospective study in the literature exploring the activity and tolerability of the combination with low dosages and evaluating further clinical outcome of early-MF patients. Methods:?We carried out a multicentric prospective Phase II clinical study on 89 patients with early-stage IA to IIA MF treated for 14?months with low-dose IFN-α2b (6?18?MU/wk) and PUVA. Treatment success was analysed in terms of freedom from treatment failure. Results and conclusions:?Complete remission (CR) was achieved in 84% and an overall response rate in 98% of cases: six-month CR was associated with a non-confluent skin infiltrate at histology (P?=?0.044) and 14-month CR with high epidermal CD1a+ dendritic-cell density (P?=?0.030). The combination protocol was successfully tolerated and the most common reason of ?failure? was related to relapse and not to toxicity. Sustained remissions were achieved in 20% of patients. High CD8+ lymphoid T-cell density was associated with a lower relapse rate (P?=?0.002). We think that our combination therapy can be considered an alternative approach compared with other modalities. Good immunological host surveillance in the skin lesions seems to be an optimal basis for the therapeutic success.","author":[{"dropping-particle":"","family":"Rupoli","given":"Serena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goteri","given":"Gaia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pulini","given":"Stefano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"Alessandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tassetti","given":"Angela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"Massimo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"Giorgio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mozzicafreddo","given":"Giorgio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacchetti","given":"Alfredo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brandozzi","given":"Giuliano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cataldi","given":"Ivana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barulli","given":"Sara","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranaldi","given":"Renzo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scortechini","given":"Anna Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Capretti","given":"Roberta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fabris","given":"Guidalberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leoni","given":"Pietro","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Haematology","id":"ITEM-3","issue":"2","issued":{"date-parts":[["2005","7"]]},"page":"136–145","publisher":"John Wiley & Sons, Ltd","title":"Long-term experience with low-dose interferon-α and PUVA in the management of early mycosis fungoides","type":"article-journal","volume":"75"},"uris":[""]}],"mendeley":{"formattedCitation":"77–79","plainTextFormattedCitation":"77–79","previouslyFormattedCitation":"78–80"},"properties":{"noteIndex":0},"schema":""}77–79Maximum duration until CR (weeks)16.00Use of resources associated with treatment, IFNαWeek 1 (MIU/week)18.0018.0018.00Estimated based on ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2133.2008.08886.x","ISSN":"0007-0963","abstract":"Summary Background? Interferon (IFN)-α is widely used in the treatment of mycosis fungoides (MF) and when used in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA) both improved response and duration of complete remission have been reported. However, in spite of encouraging results of the initial studies, currently there is no information available on specific prognostic factors enabling prediction of patients? resistance to PUVA?±?IFN-α treatment. Objectives? To identify factors responsible for resistance to PUVA?±?IFN-α treatment in MF patients. Patients/methods? The gene expression profiling of pretreatment samples from 29 patients diagnosed as IA, IB or IIA stage of MF enrolled in a randomized PUVA vs. PUVA?+?IFN-α clinical trial was analysed using cDNA microarrays. A Cox model (SAM) and gene set enrichment analysis (GSEA) were used for identification of genes and biologically significant pathways related to resistance to treatment. Results? Genes involved in NF-?B signalling, T-cell receptor (TCR) signalling, cytokine signalling and proliferation were differentially expressed between responders and nonresponders. Interestingly, expression of markers representative of those pathways was found not only in the tumoral cells, but also in specific subpopulations of macrophages, dendritic cells and other non-neoplastic cell types constituting the tumour microenvironment, likely involved in the promotion of survival and proliferation of cutaneous T-cell lymphoma. Conclusions? Gene expression changes in both the tumour and the tumour microenvironment are an important determinant of treatment outcome in early-stage MF patients. Some proinflammatory factors such as NF-?B, inflammatory cytokines and their receptors in addition to TCR-associated molecules could be promising targets for MF treatment.","author":[{"dropping-particle":"","family":"Wozniak","given":"M B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tracey","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz-Romero","given":"P L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Montes","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fraga","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fernández Herrera","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vidal","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rodriguez-Peralto","given":"J L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Piris","given":"M ?","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Villuendas (deceased)","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2009","12"]]},"page":"92–102","publisher":"John Wiley & Sons, Ltd","title":"Psoralen plus ultraviolet A ± interferon-α treatment resistance in mycosis fungoides: the role of tumour microenvironment, nuclear transcription factor-κB and T-cell receptor pathways","type":"article-journal","volume":"160"},"uris":[""]},{"id":"ITEM-2","itemData":{"abstract":"BACKGROUND AND OBJECTIVE: The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA. DESIGN AND METHODS: Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF). RESULTS: After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%. INTERPRETATION AND CONCLUSIONS: Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF.","author":[{"dropping-particle":"","family":"Rupoli","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barulli","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guiducci","given":"B","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mozzicafreddo","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Simonacci","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacchetti","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricotti","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brandozzi","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cataldi","given":"I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Serresi","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ceschini","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bugatti","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giangiacomi","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brancorsini","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leoni","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Haematologica","id":"ITEM-2","issue":"9","issued":{"date-parts":[["1999","1"]]},"page":"809–813","title":"Low dose interferon-alpha2b combined with PUVA is an effective treatment of early stage mycosis fungoides: results of a multicenter study. Cutaneous-T Cell Lymphoma Multicenter Study Group","type":"article-journal","volume":"84"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1600-0609.2005.00497.x","ISSN":"0902-4441","abstract":"Abstract:? Objectives:?Combined high-dose Interferon-α and psoralen plus ultraviolet A irradiation (PUVA) have been reported to be effective in the treatment of early mycosis fungoides (MF); however, our study is the first controlled prospective study in the literature exploring the activity and tolerability of the combination with low dosages and evaluating further clinical outcome of early-MF patients. Methods:?We carried out a multicentric prospective Phase II clinical study on 89 patients with early-stage IA to IIA MF treated for 14?months with low-dose IFN-α2b (6?18?MU/wk) and PUVA. Treatment success was analysed in terms of freedom from treatment failure. Results and conclusions:?Complete remission (CR) was achieved in 84% and an overall response rate in 98% of cases: six-month CR was associated with a non-confluent skin infiltrate at histology (P?=?0.044) and 14-month CR with high epidermal CD1a+ dendritic-cell density (P?=?0.030). The combination protocol was successfully tolerated and the most common reason of ?failure? was related to relapse and not to toxicity. Sustained remissions were achieved in 20% of patients. High CD8+ lymphoid T-cell density was associated with a lower relapse rate (P?=?0.002). We think that our combination therapy can be considered an alternative approach compared with other modalities. Good immunological host surveillance in the skin lesions seems to be an optimal basis for the therapeutic success.","author":[{"dropping-particle":"","family":"Rupoli","given":"Serena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goteri","given":"Gaia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pulini","given":"Stefano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"Alessandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tassetti","given":"Angela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Offidani","given":"Massimo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Filosa","given":"Giorgio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mozzicafreddo","given":"Giorgio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacchetti","given":"Alfredo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brandozzi","given":"Giuliano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cataldi","given":"Ivana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barulli","given":"Sara","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranaldi","given":"Renzo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scortechini","given":"Anna Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Capretti","given":"Roberta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fabris","given":"Guidalberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leoni","given":"Pietro","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Haematology","id":"ITEM-3","issue":"2","issued":{"date-parts":[["2005","7"]]},"page":"136–145","publisher":"John Wiley & Sons, Ltd","title":"Long-term experience with low-dose interferon-α and PUVA in the management of early mycosis fungoides","type":"article-journal","volume":"75"},"uris":[""]}],"mendeley":{"formattedCitation":"77–79","plainTextFormattedCitation":"77–79","previouslyFormattedCitation":"78–80"},"properties":{"noteIndex":0},"schema":""}77–79Week 2 (MIU/week)27.0027.0027.00From week 2 (MIU/week)27.0027.0054.00Tests and additional visitsComplete biochemistry (n)1.001.001.00Panel of clinical expertsRepresentativeness (%)*100.00%Liver function test (n)1.171.002.00Representativeness (%)*100.00%Hemogram analysis (n)2.002.002.00Monthly frequency (n/month)1.001.001.00Representativeness (%)*16.67%Creatinine level (n)2.002.002.00Representativeness (%)*16.67%ANA level (n)1.001.001.00Representativeness (%)*16.67%Ophthalmology review (n)1.001.001.00Representativeness (%)*16.67%Phototest/photopatch (n)1.001.001.00Representativeness (%)*16.67%Consultations with psychiatrist, successive (n)---Monthly frequency (n/month)1.001.001.00Representativeness (%)*100.00%Abbreviations: ANA, antinuclear antibodies; IFNα, interferon alfa; MIU, million international units; PUVA, psoralens with ultraviolet A light; CR, complete response.Notes: *Representativeness: Proportion of clinical experts who indicated the said laboratory test and/or follow-up visit. ................
................

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