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1.
J Drugs Dermatol ; 23(6): e154-e155, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38834216

RESUMO

Sunscreen is an essential component of sun protection. The most important characteristics for patient selection of sunscreens have not been evaluated. A cross-sectional survey study was performed at an academic dermatology office. The sunscreen characteristic chosen most frequently was SPF (75.2%). Fewer patients selected broad-spectrum (20.7%) and water-resistance (22.7%). There remains a gap in patient knowledge regarding AAD recommendations for sunscreen characteristics and educational initiatives may be required. J Drugs Dermatol. 2024;23(6):e154-e155.     doi:10.36849/JDD.8324e  .


Assuntos
Protetores Solares , Humanos , Protetores Solares/administração & dosagem , Estudos Transversais , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fator de Proteção Solar , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários/estatística & dados numéricos , Idoso , Queimadura Solar/prevenção & controle , Adulto Jovem
2.
J Drugs Dermatol ; 23(2): 54-60, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306124

RESUMO

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Prognóstico , Transcriptoma , Consenso
3.
J Drugs Dermatol ; 22(1): 101-104, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607754

RESUMO

BACKGROUND: Studies suggest potential heterogeneity in telemedicine adoption with potential to exacerbate healthcare access inequity. METHODS: A pre-validated survey was electronically sent to a proprietary listserv of practicing US-based dermatologists. Results were stratified by when teledermatology was adopted. Chi-square and odds ratios (OR) with 95% confidence intervals (95%CI) were used to analyze categorical data while single-factor ANOVA with posthoc Tukey-Kramer was used for continuous data. RESULTS: 338 practicing US-based dermatologists completed the questionnaire. Academic/Government dermatologists were 4-times more likely (OR 4.08, 95%CI 2.37-7.03) to adopt teledermatology pre-COVID than private-practice dermatologists. Dermatologists with ≤10 years of experience were 1.8-times (OR 1.8, 95%CI 1.01-3.18) and 2.82-times more likely (OR 2.82, 95%CI 0.78-10.25) to adopt teledermatology pre-COVID-19 or at all, respectively, compared to dermatologists with ≥20 years of experience. Teledermatology adopters practiced more medical-dermatology (P<.0001) than non-adopters, who reported practicing more dermatologic surgery (P=.003; Tukey-Kramer α<.05) and dermatopathology (P<.0001; Tukey-Kramer α<.05). Pre-COVID-19 adopters were 4-times more likely (OR 4.69, 95%CI 1.46-15.07) to switch/incorporate live-interactive-only teledermatology (LI) post-COVID-19. Post-COVID-19 adopters were 6-times more likely (OR 6.09, 95%CI 3.36-11.06) to utilize LI than Pre-COVID-19 adopters. Pre-COVID-19 adopters use teledermatology for a larger proportion of patient visits than Post-COVID-19 adopters (19.6% v 10.4%, P<.0001), but also are 3.43-times more likely (OR 3.43, 95%CI 1.82-6.46) to report future decreases in usage. LIMITATIONS: Cross-sectional retrospective survey and potential response bias. CONCLUSION: Current teledermatology usage may be a suitable tool for medical-dermatology-focused practices. Material hurdles still exist for procedurally-oriented practices and future studies should investigate these barriers to maximize equitable access to dermatological care. J Drugs Dermatol. 2023;21(1):101-104. doi:10.36849/JDD.7169.


Assuntos
COVID-19 , Dermatologia , Dermatopatias , Humanos , Estados Unidos/epidemiologia , Dermatologia/métodos , Estudos Transversais , Estudos Retrospectivos , COVID-19/diagnóstico , COVID-19/epidemiologia , Acessibilidade aos Serviços de Saúde , Dermatopatias/diagnóstico , Dermatopatias/epidemiologia , Dermatopatias/terapia
4.
J Drugs Dermatol ; 22(6): 588-593, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37276166

RESUMO

BACKGROUND: Precision medicine utilizes an individual’s genomics to improve diagnosis, prognosis, and therapy. The joint American Academy of Dermatology and National Psoriasis Foundation 2019 guidelines recognized the need to identify biomarkers that can predict the optimal biologic agent for an individual patient. This paper examines the current state of precision medicine in dermatology and how its use can improve outcomes in psoriasis. METHODS: A search of PubMed/MEDLINE using the terms precision medicine, personalized medicine, biomarkers, genomics, and dermatology was performed to identify relevant publications. An expert consensus panel was then convened to assign levels of evidence to each article using strength of recommendation taxonomy and create consensus statements requiring a two-thirds supermajority for agreement utilizing a modified Delphi approach. RESULTS: Thirteen articles met inclusion and exclusion criteria and were assigned levels of evidence. The panel created 10 consensus statements on how precision medicine can improve patient outcomes, all of which received a unanimous (6/6) vote. CONCLUSION: Choosing a biologic medication for psoriasis often relies on patient preference, provider preference, and a trial-and-error approach. Utilizing precision medicine tests such as Mind.Px can help providers identify biomarkers unique to a patient’s pathophysiology and choose the optimal medication through a targeted and evidence-based approach. Zakria D, Brownstone N, Armstrong AW, et al. Integrating precision medicine into medical dermatology clinical practice: an expert consensus panel. J Drugs Dermatol. 2023;22(6):588-593. doi:10.36849/JDD.7432.


Assuntos
Dermatologia , Psoríase , Humanos , Medicina de Precisão , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Consenso
5.
J Drugs Dermatol ; 22(12): 7691, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38051842

RESUMO

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Consenso , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Transcriptoma
6.
J Drugs Dermatol ; 22(11): e4-e8, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37943266

RESUMO

The COVID-19 pandemic has sparked an increase in focus and use of telemedicine in several patient care settings. This survey study was distributed to actively practicing US-based physicians and examines telehealth use 2 years after the beginning of the COVID pandemic from a physician’s perspective. Notable findings include telehealth benefits which include increased patient access and the ability to work from home. A continued drawback in telehealth visits is the limitations on a complete physical examination, a drawback that was emphasized by the dermatology community. While this study sheds light on the developing nature of telehealth, it is limited by its retrospective nature and sample size. Future research with larger sample sizes focusing on economic incentives and telemedicine training may help to overcome barriers to using telehealth.  J Drugs Dermatol. 2023;22(11):e4-e8    doi:10.36849/JDD.7386e.


Assuntos
Médicos , Telemedicina , Humanos , Pandemias , Estudos Retrospectivos , Percepção
7.
BMC Cancer ; 22(1): 38, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986841

RESUMO

BACKGROUND: Melanoma-intrinsic activated ß-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS). METHODS: We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers. RESULTS: In the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated ß-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases. CONCLUSIONS: APC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.


Assuntos
Genes APC , Melanoma/genética , Melanoma/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , beta Catenina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Melanoma Maligno Cutâneo
8.
Dermatol Surg ; 48(12): 1367-1368, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36449885

RESUMO

BACKGROUND: The dermatology residency application process implemented a new system of preference signaling tokens (PSTs) in the 2021-2022 cycle to allow applicants to express a higher level of interest in specific programs. Limited data are available on the utilization and impact of these tokens. OBJECTIVE: To determine the impact of PSTs on the application process and where in the process PSTs had the greatest influence. MATERIALS AND METHODS: A 14-question survey was sent to 62 ACGME-accredited dermatology residency programs. Primary outcomes were PST impact on 2021-2022 applications. Variables were evaluated using open-ended questions, yes/no responses, and importance ratings from 0 to 100. RESULTS: An average of 7.1% of applicants were offered interviews, but 21.1% of applicants that submitted PSTs were interviewed versus 3.7% of nonsubmitters. 22.5% of ranked applicants and 19% of matched applicants submitted a PST to that program. LIMITATIONS: Not all programs responded, and PST submission restrictions could not be assessed. CONCLUSION: The greatest PST impact was on the interview decision but had minimal subsequent impact. Given PSTs cannot be submitted to home programs or in-person away rotations, the actual impact was probably greater than found. Programs will continue to implement PSTs in future cycles.


Assuntos
Dermatologia , Humanos , Transdução de Sinais
14.
Dermatol Ther (Heidelb) ; 14(2): 323-339, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38340237

RESUMO

INTRODUCTION: Psoriasis is a chronic inflammatory condition affecting the skin, joints, and several other organ systems with significant disease burden. Bimekizumab is the first monoclonal antibody targeting both interleukin (IL)-17A and interleukin-17F and has demonstrated efficacy for treating moderate to severe psoriasis. Limited guidelines exist for incorporating this drug into clinical practice. The purpose of this study was for a panel of experts in psoriasis management to synthesize current literature and provide consensus statements with guidance on use of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the use of bimekizumab for moderate to severe psoriasis and psoriatic arthritis. A panel of nine dermatologists with significant expertise in treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 102 articles that met criteria. A thorough screening of the studies for relevance to the research question resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 14 consensus statements and recommendations, 12 of which were given a strength of "A", one of which was given a strength of "B", and one of which was given a strength of "C". CONCLUSION: Bimekizumab results in rapid and long-lasting clinical improvement for patients with moderate to severe plaque psoriasis and psoriatic arthritis. It has demonstrated superior efficacy when compared to several other biologics. The safety profile is consistent with other biologics, except for an increased incidence of oropharyngeal candidiasis.

15.
Dermatol Clin ; 41(4): 611-617, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37718018

RESUMO

The retirement process is an individualized endeavor. Both financial and social aspects are important to consider when making plans for retirement. In this article, we discuss details of retirement planning, including the need to save, how much and when to start saving, and types of retirement plans. We also review key considerations for deciding when to retire as well as aspects of retirement outside of financial planning, such as redefining one's purpose and finding meaningful activities to fill the void of work.


Assuntos
Aposentadoria , Humanos
16.
Melanoma Res ; 33(1): 80-83, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36223289

RESUMO

The purpose of this study was to investigate whether EIS technology can further improve correct biopsy choices beyond clinical and dermoscopic evaluation for melanoma (MM), severe dysplastic nevi (SDN) and benign PSLs. Images of 49 MMs, SDNs and benign PSLs were randomly selected from a prior study and were provided in a reader-type survey study to dermatologists to evaluate for biopsy. A total of 33,957 biopsy decisions were analyzed. Respondents significantly improved on the correct biopsy choice with the addition of dermoscopy versus clinical image alone for melanoma and severely dysplastic nevi. Respondents also showed a statistically significant improvement in correct biopsy choice beyond their dermoscopic evaluation when integrating the EIS score versus dermoscopy with clinical images for MM, SDN and benign lesions. Respondents also made fewer incorrect biopsy choices with the addition of the EIS score versus dermoscopy and clinical image for MM and benign lesions. Sub-analyses of biopsy choices were also conducted based on experience and practice type. The findings from this study demonstrate that the integration of EIS technology into PSL biopsy decisions has the potential to significantly improve the accuracy of lesion selection for biopsy beyond clinical and dermoscopic evaluation alone.


Assuntos
Síndrome do Nevo Displásico , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Dermoscopia/métodos , Espectroscopia Dielétrica , Biópsia , Diagnóstico Diferencial
17.
Melanoma Res ; 32(5): 379-383, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35979668

RESUMO

This study aimed to assess the current management of melanoma from relative to present guidelines and determine changes 5 years ago. An eight-question survey was sent to practicing US dermatologists using the same methodology and questions from our JAAD study. Overall, saucerization/scoop biopsy (48%) was the most commonly used method. The most commonly chosen margin for melanoma in-situ (MMIS) removal was 6-10 mm (51% of respondents). For CMM with a depth greater than 1 mm, the most commonly chosen margins were in the 1.1-1.9 cm range (55% of respondents). More respondents referred cases of MMIS and CMM out for treatment as compared to 2016. Academic dermatologists in 2021 were 8% less likely to treat MMIS as compared to all other practice types in 2021, whereas 7% more likely to treat CMM greater than 1 mm. Academic dermatologists in 2016, as compared to 2021, were 4% more likely to treat MMIS and 19% more likely to treat CMM greater than 1 mm. A total of 91% of respondents reported having some change in their management of CMM. Our study findings suggest that a knowledge gap still exists representing a continued educational opportunity to more effectively distribute and implement CMM management guidelines.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Melanoma/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Inquéritos e Questionários , Melanoma Maligno Cutâneo
18.
Hand (N Y) ; 17(1): 148-154, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32111122

RESUMO

Background: Although intravenous (IV) infiltration is relatively common, data regarding complications and outcomes of this problem remain limited. In addition, there is wide variation in institutional protocols for the management of IV infiltrations. Through retrospective review, we aim to delineate complications and outcomes, and propose an algorithm for the management of these injuries. Methods: We performed a retrospective review of all patients who had an IV infiltration at a tertiary care center's inpatient and outpatient facilities between January 1, 2016, and December 31, 2018. Results: In all, 479 patients with 495 infiltrations were included, with a mean age of 36.7 years. The upper extremity was involved in 89.6% of events. Of all the events, 8.6% led to a superficial soft tissue infection, 3.2% led to necrosis or eschar formation, and 1.9% led to ulceration or full-thickness wound formation. There were zero cases of compartment syndrome. Only 5.1% resulted in any long-term defects; none resulted in a functional defect of the extremity. Patients with vascular disease did not experience worse outcomes compared with healthy individuals. Plastic or orthopedic surgery was consulted in 25.3% of events. No emergent surgical intervention was required, 7 (1.4%) required bedside procedures, and 7 (1.4%) patients underwent nonacute operations. Conclusions: A specialist was consulted in about one-quarter of IV infiltrations, yet none were surgical emergencies. Instead, most complications could be monitored and managed by a primary team. Therefore, we propose algorithms involving nursing staff, wound care teams, and primary physicians with limited specialist consultation to manage these injuries.


Assuntos
Procedimentos Ortopédicos , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Adulto , Humanos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Extremidade Superior/cirurgia
19.
J Dermatolog Treat ; 33(4): 2034-2037, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33760691

RESUMO

BACKGROUND: Corticosteroid injections are a commonly used treatment for dermatologic pathologies. Although the injectable is often prepared with a local anesthetic, we hypothesize that patients receiving an injection with anesthetic will experience no decrease in pain at the time of injection. METHODS: Patients requiring a corticosteroid injection were prospectively randomized into two cohorts to receive a corticosteroid (triamcinolone acetonide) combined with either lidocaine with epinephrine 1:100 000 (anesthetic) or bacteriostatic normal saline. Both patient and clinician were blinded to the treatment arm. The primary outcome was pain associated with the injection measured using a Visual Analog Scale (VAS) immediately following the injection. RESULTS: Thirty-one patients were enrolled with 18 in the saline group and 13 in the lidocaine with epinephrine group. Pain scores were significantly higher for injections containing lidocaine with epinephrine versus saline (VAS 5.0 vs 2.0, p = .0056). CONCLUSIONS: For various dermatologic pathologies, corticosteroid injections are effective and have relatively little associated pain. Counterintuitively, we found that there is more injection-associated pain when lidocaine with epinephrine is included with the corticosteroid. Therefore, clinicians should omit this anesthetic or dilute corticosteroids with normal saline, rather than with lidocaine and epinephrine. This will minimize injection pain as well as decrease the risk of pharmacologic adverse reactions from an unnecessary additional medication. Due to the small sample size, additional research may be necessary for generalization to other indications. Clinicaltrials.gov listing: NCT03630198.


Assuntos
Anestésicos Locais , Solução Salina , Corticosteroides/uso terapêutico , Anestésicos Locais/uso terapêutico , Método Duplo-Cego , Epinefrina , Humanos , Injeções Intralesionais , Lidocaína , Dor/tratamento farmacológico , Dor/etiologia
20.
J Immunother Cancer ; 10(7)2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35798536

RESUMO

BACKGROUND: Patients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF/MEK inhibitors (BRAF/MEKi). METHODS: Patients with V600BRAF mutant metastatic melanoma treated with BRAF/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group. RESULTS: Of 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF/MEKi and PD1±IPI (16 vs 4 days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 (62% vs 44%), AJCC M1C/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1±IPI (34% vs 57%). Median follow-up from PD1±IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1 vs PD1 across most subgroups except for females, those with <10 days between BRAF/MEKi and PD1±IPI, and those with stage III/M1A/M1B melanoma. The combination of ECOG PS=0 and absence of liver metastases identified patients with >3 years OS (area under the curve, AUC=0.74), while ECOG PS ≥1, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67). CONCLUSIONS: IPI+PD1 and PD1 after BRAF/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy.


Assuntos
Neoplasias Encefálicas , Melanoma , Segunda Neoplasia Primária , Inibidores de Proteínas Quinases , Neoplasias Cutâneas , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Humanos , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mutação , Segunda Neoplasia Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Melanoma Maligno Cutâneo
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