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1.
J Invest Dermatol ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610559

RESUMO

Homologous recombination DNA-damage repair (HR-DDR) deficiency has been used to treat patients with various solid tumors with poly(ADP-ribose) polymerase inhibitors (PARPi). However, the clinical characteristics of melanoma patients with HR-DDR gene mutations, and the consequences of PARP inhibition, are poorly understood. We compared commercially-available next-generation sequencing data from 84 melanomas from our institution with a dataset of 1,986 patients, as well as 1,088 patients profiled in cBioportal. 21.4% of patients had ≥1 functional HR-DDR mutation, most commonly involving BRCA1, ARID1A, ATM, ATR, and FANCA. Concurrent NF1, BRAF, and NRAS mutations were found in 39%, 39% and 22% of cases, respectively. HR-DDR gene mutation was associated with high tumor mutational burden (TMB) and clinical response to checkpoint blockade. A higher prevalence of HR-DDR mutations was observed in datasets from Foundation Medicine and TCGA. Treatment of HR-DDR-mutated patient-derived xenograft models of melanoma with PARPi produced significant anti-tumor activity in vivo, and was associated with increased apoptotic activity. RNA sequencing analysis of PARPi-treated tumors indicated alterations in pathways involving extracellular matrix remodeling, cell adhesion and cell cycle progression. Melanomas with HR-DDR mutations represent a unique subset, which are more likely to benefit from checkpoint blockade, and may be targeted with PARPi.

2.
Cancer ; 126(21): 4717-4725, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32780467

RESUMO

BACKGROUND: Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging. METHODS: The prognostic impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer-generated cut points for mitotic rate were constructed to determine its impact on melanoma-associated survival using Kaplan-Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets. RESULTS: Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high-versus-low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm2 vs ≥2 mitoses/mm2 for T1 melanoma, <4 mitoses/mm2 vs ≥4 mitoses/mm2 for T2 melanoma, <6 mitoses/mm2 vs ≥6/mitoses/mm2 for T3 melanoma, and <7 mitoses/mm2 vs ≥7 mitoses/mm2 for T4 melanoma). Using Kaplan-Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration. CONCLUSIONS: The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.

3.
Surgery ; 168(3): 518-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669204

RESUMO

BACKGROUND: It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. METHODS: We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. RESULTS: There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). CONCLUSION: Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Melanoma/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/mortalidade , Pele/patologia , Idoso , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
4.
Ann Surg Oncol ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524460

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. PATIENTS AND METHODS: The Sentinel Lymph Node Working Group database was queried for thick (> 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). RESULTS: There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P < 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas > 4-8 mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P < 0.0001). For melanomas > 8 mm, only SLN metastasis significantly predicted MSS (> 8-12 mm: HR 3.93, 95% CI 2.00-7.73, P < 0.0001; > 12 mm: HR 3.58, 95% CI 1.56-8.22, p < 0.0027). CONCLUSIONS: Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

5.
Br J Cancer ; 122(5): 648-657, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31857724

RESUMO

BACKGROUND: Patient-derived xenograft (PDX) mouse tumour models can predict response to therapy in patients. Predictions made from PDX cultures (PDXC) would allow for more rapid and comprehensive evaluation of potential treatment options for patients, including drug combinations. METHODS: We developed a PDX library of BRAF-mutant metastatic melanoma, and a high-throughput drug-screening (HTDS) platform utilising clinically relevant drug exposures. We then evaluated 34 antitumor agents across eight melanoma PDXCs, compared drug response to BRAF and MEK inhibitors alone or in combination with PDXC and the corresponding PDX, and investigated novel drug combinations targeting BRAF inhibitor-resistant melanoma. RESULTS: The concordance of cancer-driving mutations across patient, matched PDX and subsequent PDX generations increases as variant allele frequency (VAF) increases. There was a high correlation in the magnitude of response to BRAF and MEK inhibitors between PDXCs and corresponding PDXs. PDXCs and corresponding PDXs from metastatic melanoma patients that progressed on standard-of-care therapy demonstrated similar resistance patterns to BRAF and MEK inhibitor therapy. Importantly, HTDS identified novel drug combinations to target BRAF-resistant melanoma. CONCLUSIONS: The biological consistency observed between PDXCs and PDXs suggests that PDXCs may allow for a rapid and comprehensive identification of treatments for aggressive cancers, including combination therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Melanoma/tratamento farmacológico , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Melanoma/enzimologia , Melanoma/genética , Melanoma/patologia , Camundongos , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Ann Surg Oncol ; 26(7): 2254-2262, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31011906

RESUMO

BACKGROUND: Factors that predict melanoma recurrence after a negative sentinel lymph node biopsy (SLNB) are not well-defined. We evaluated melanoma recurrence patterns, factors prognostic for recurrence, and the impact of recurrence on outcomes after a negative SLNB. METHODS: The Sentinel Lymph Node Working Group database was evaluated from 1996 to 2016 for negative SLNB melanoma patients. Clinicopathologic characteristics were correlated with recurrence, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: Median follow-up was 32.1 months. Recurrences developed in 558 of 5351 negative SLN patients (10.4%). First-site of recurrence included a local or in-transit recurrence (LITR) in 221 cases (4.1%), nodal recurrence (NR) in 109 cases (2%), and distant recurrence (DR) in 220 cases (4.1%). On multivariable analysis, age, thickness, head/neck or lower extremity primary, and microsatellitosis significantly predicted for an LITR as first-site. Having an LITR as first-site significantly predicted for a subsequent NR and DR, and significantly predicted for worse OS and MSS. Furthermore, thickness and head/neck or lower extremity primary significantly predicted for an NR as first-site, while a prior LITR significantly predicted for a subsequent NR. Factors significantly predictive for a DR included thickness, head/neck or trunk primary, ulceration, and lymphovascular invasion. Patients with any type of locoregional recurrence were at higher risk for a DR. CONCLUSIONS: Recurrences occur in 10.4% of negative SLN patients, with LITR and DR being the most common types. Importantly, having an LITR significantly predicts for a subsequent NR and DR, and is prognostic for worse survival after a negative SLNB.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Excisão de Linfonodo/mortalidade , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Biópsia de Linfonodo Sentinela/mortalidade , Linfonodo Sentinela/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Linfonodo Sentinela/cirurgia , Taxa de Sobrevida , Adulto Jovem
8.
J Surg Oncol ; 119(8): 1053-1059, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30883771

RESUMO

BACKGROUND: Completion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND). METHODS: Positive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: There were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS (both P < 0.001). CLND was not performed (No-CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow-up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No-CLND (P = 0.084, P = 0.161, respectively) and comparing positive CLND with No-CLND NR patients (P = 0.565, P = 0.998, respectively). Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis. CONCLUSIONS: Performance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.


Assuntos
Excisão de Linfonodo/estatística & dados numéricos , Melanoma/mortalidade , Melanoma/cirurgia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Taxa de Sobrevida
9.
Ann Surg Oncol ; 26(Suppl 3): 883, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30805804

RESUMO

The article "Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery," written by Stanley P. Leong et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on August 13, 2018, without open access.

10.
Ann Surg Oncol ; 26(1): 33-41, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30421045

RESUMO

BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.


Assuntos
Melanoma/patologia , Repetições de Microssatélites , Biópsia de Linfonodo Sentinela/mortalidade , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Taxa de Sobrevida
12.
Ann Surg Oncol ; 25(11): 3326-3333, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30105436

RESUMO

BACKGROUND: Preoperative imaging and intraoperative gamma probe (GP) localization is standard for identifying sentinel lymph nodes (SLNs) in melanoma patients. The aim of this prospective Institutional Review Board-approved study was to investigate whether an intraoperative portable gamma camera (PGC) improves SLN detection over the GP. METHODS: Lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed after injection of 99mTc-Tilmanocept in melanoma patients (≥ 18 years, Breslow thickness ≥ 1.0 mm). A GP was used to localize the SLNs in each basin, which was explored by the GP to ensure that the operative field was < 10% counts of the hottest SLN. The PGC was then used after a negative GP screening. Any residual hotspots identified by the PGC were considered as additional SLNs and were removed following the 10% rule. RESULTS: Preoperative imaging of 100 patients identified 138 SLN basins, with 306 SLNs being identified by conventional surgery. The PGC localized 89 additional SLNs in 54 patients. Thus, the PGC identified an additional 23% of SLNs [95% confidence interval (CI) 18-27%]. Four of these 89 SLNs showed micrometastasis in four patients, in two of whom the only tumor-positive SLN was identified by the PGC, preventing two false-negative cases. Thus, the null hypothesis that the PGC did not detect additional positive SLNs was rejected (p = 0.000). The overall SLN positive rate was 9.9% (39/395, 95% CI 6-12), and the overall patient positive rate was increased using the PGC, from 25 to 27% (27/100). CONCLUSIONS: Intraoperative PGC imaging yielded additional SLNs in a significant number of patients over GP alone. Identification of these additional SLNs resulted in upstaging of four patients with two patients being converted from a negative to a positive status, thus, preventing two false-negative cases.


Assuntos
Câmaras gama , Cuidados Intraoperatórios , Melanoma/cirurgia , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Feminino , Seguimentos , Humanos , Linfocintigrafia , Masculino , Melanoma/diagnóstico por imagem , Melanoma/patologia , Pessoa de Meia-Idade , Micrometástase de Neoplasia , Prognóstico , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/secundário
13.
Clin Exp Metastasis ; 35(5-6): 361-367, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29992410

RESUMO

Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand the cancer microenvironment and host response to cancer growth. Melanoma is an excellent model to study the interaction of cancer initiation and growth in relationship to its microenvironment. Social evolution with cooperative cellular groups within an organism is what gives rise to multicellularity in the first place. Cancer cells evolve to exploit their cellular environment. The foundations of multicellular cooperation break down in cancer because those cells that misbehave have an evolutionary advantage over their normally behaving neighbors. It is important to classify evolutionary and ecological aspects of cancer growth, thus, data for cancer growth and outcomes need to be collected to define these parameters so that accurate predictions of how cancer cells may proliferate and metastasize can be developed.


Assuntos
Carcinogênese/genética , Proliferação de Células/genética , Melanoma/genética , Microambiente Tumoral/genética , Progressão da Doença , Humanos , Melanoma/patologia , Metástase Neoplásica
14.
Clin Exp Metastasis ; 35(5-6): 403-412, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30022365

RESUMO

Cancer microenvironment is the critical battle ground between the cancer cells and host response. Thus, more emphasis is directed to study the relationship between cancer cells and the stromal cells. Multiplex microscopy is an emerging technique in which multiple cell populations within the cancer microenvironment may be stained so that spatial relationship between cancer cells and, in particular, the immune cells may be studied during different stages of cancer development. Recent discovery of mutational burden and neoantigens in cancer has opened new landscapes in the interaction of host immune cells and cancer neoantigens. The emerging role of miRNAs may become an added dimension to study cancer beyond traditional pathway of DNA directed RNA being associated with the malignant behavior of cancer. Circulating tumor cells, cancer markers and ctDNA can be used as markers for circulating cancer cells in the blood. Further studies are needed to validate if liquid biopsy of cancer may become a routine clinical tool to screen cancer or follow patients for recurrence or responses to treatment.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias/sangue , Humanos , Biópsia Líquida , Mutação , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias/genética , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Microambiente Tumoral/genética
15.
Clin Exp Metastasis ; 35(5-6): 559-561, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30039283

RESUMO

The sentinel lymph node (SLN) is the initial metastatic site for the majority of solid cancers. In some cases, cancer cells may bypass the SLNs and enter the vascular channels directly to spread to the systemic sites. Metastatic progression is an orderly process. During the process of metastasis, complex biochemical and molecular mechanisms are involved being subjected to the host influence, in particular, the immune system. With more detailed understanding of the genomic and molecular characteristics of cancer both from the primary site and its metastases, the pathways of cancer growth and spread within the cancer microenvironment may be further elucidated.


Assuntos
Neoplasias/terapia , Linfonodo Sentinela/patologia , Humanos , Metástase Neoplásica , Neoplasias/patologia
16.
Clin Exp Metastasis ; 35(5-6): 359-360, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29796855
17.
BMC Cancer ; 18(1): 490, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703161

RESUMO

BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Melanoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Am J Surg ; 215(4): 699-706, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29502857

RESUMO

BACKGROUND: Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. METHODS: A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01-4.00 mm) who had SLNB, and assessed predictors for positive SLNB. RESULTS: 3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm2 (p = .01), and microsatellitosis (p < .001). Multivariate analysis revealed age, location, and Breslow depth as significant predictors. Patients ≥75 with lesions 1.01-1.49 mm on the head/neck/upper extremity and 1.5-1.99 mm without high-risk features had <5% risk of SLN positivity. CONCLUSIONS: Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.


Assuntos
Metástase Linfática/patologia , Melanoma/patologia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Idoso , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Biópsia de Linfonodo Sentinela
20.
Pain Rep ; 3(6): e689, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30706034

RESUMO

Introduction: After excision of a primary malignant melanoma (MM), treatment of stage IB or higher MM consists of sentinel lymph node biopsy (SLNB). If malignant cells are identified, a complete lymph node dissection (CLND) can be performed. Objective: To determine the natural history of pain and sensory changes after MM surgery. Methods: We prospectively followed 39 patients (29 SLNB-only, 2 CLND-only, and 8 CLND preceded by SLNB) from before inguinal or axillary surgery through 6 months after surgery on measures of pain intensity, sensory symptoms, allodynia, and questionnaires of anxiety, depression, and catastrophizing. Results: No patient had pain preoperatively. Ten days after surgery, 35% had surgical site pain after SLNB-only compared with 90% after CLND (P < 0.003); clinically meaningful pain (Visual Analogue Scale ≥ 30 mm/100 mm) was reported by 3% of patients after SLNB-only compared with 40% after CLND (P < 0.001). At 6 months, all SLNB-only patients were pain-free. By contrast, 4 of 7 in the SLNB + CLND group still had pain (P < 0.002). At 6 months, symptoms of altered sensation or numbness were reported by 32% and 42% of SLNB-only patients, and by 67% and 67% of patients undergoing CLND surgery (both P > 0.05). Conclusion: Acute pain is more common after CLND surgery. Undergoing SLNB followed by more invasive CLND surgery may increase the likelihood of pain at 6 months. Persistent sensory symptoms typical of those associated with nerve injury are more common after CLND. Surgery for MM is a good model for studying the natural history of postsurgical pain and sensory changes.

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