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PURPOSE: The prognosis of patients with NRAS-mutant melanoma is rather poor. Immunotherapy and targeted therapy have revolutionized anti-tumor therapy, especially for melanoma. In this study, we retrospectively summarized the real-world experience of systematic treatment for NRAS-mutant melanoma patients in this new era. PATIENTS AND METHODS: The respective cohort included NRAS-mutant melanoma patients with metastatic or unresectable disease of Sun Yat-sen University Cancer Center (SYSUCC) from January 2018 to July 2022. The data about the clinical features and impact for systemic therapy of NRAS-mutant patients were collected and analyzed. RESULTS: At data cutoff, 44 patients (19, 11, and 14 for acral, cutaneous, and mucosal ones, respectively) with NRAS-mutant were assessed. In addition, the median time of follow-up was 22.0 months. The immunotherapy-based combined treatment not only significantly improved the progression-free survival (PFS) (P = 0.006, HR 0.322), but was also accompanied by a higher objective response rate (ORR) (18.2%), disease control rate (DCR) (72.7%) than those of cytotoxic therapy or immunotherapy alone for advanced patients as first-line treatment. Nab-paclitaxel combined with anti-PD-1 inhibitor tended to produce better clinical benefit for the first-line treatment, especially for patients with acral melanoma. In addition, the tyrosine kinase inhibitor (TKI) combined with anti-PD-1 inhibitor also seemed to provide longer duration of response (DOR) for some patients. But combined therapy did not prolong the overall survival (OS) of NRAS-mutant patients. The combined therapy was well tolerated. Most adverse events were moderate and controllable. CONCLUSION: In conclusion, PD-1 inhibitor-based combined therapy increased clinical benefit for advanced patients with NRAS-mutant melanoma.
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Melanoma , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Pueblos del Este de Asia , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Pronóstico , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genéticaRESUMEN
Objectives: Non-cutaneous malignant melanomas (NCM) are rare malignancies. Due to their nonspecific symptoms, they present later in life. The value of FDG PET/CT in this group of patients is not clear. The aim of this study is to assess the role of FDG PET/CT in the management of NCM and its prognostic implication. Methods: We retrospectively selected twenty-three patients with a diagnosis of NCM evaluated with FDG PET/CT in Shariati hospital between 2019 and 2021. The PET/CT data were reviewed and compared with available conventional imaging findings. Five patients died within five months. The surviving patients were followed within a time interval of 7 to 27.5 months after their PET/CT study, regarding their disease status. Results: Among 23 patients (8 ocular, 5 sinonasal, 3 pharyngeal, 2 anorectal, 2 vulvovaginal, and 3 unknown primaries), PET/CT was able to detect residual primary disease, assess treatment response, and reveal or exclude metastases. Additional lesions compared to conventional imaging were found in five, while in one with brain metastases PET/CT was unable to detect lesions on MRI. Thirteen patients had negative PET/CT finding of which 11 (85%) did not have remarkable finding on follow-up. Metastatic disease was recognized in eight. Patients with extensive metastases on FDG PET/CT had a poorer outcome. Conclusion: Similar to cutaneous melanoma, PET/CT is valuable in the management of NCM patients and is superior to conventional imaging modalities, with the exception of brain metastases. Patients with negative PET/CT findings have a better outcome as opposed to patients with significant positive PET/CT findings.
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Non-cutaneous melanomas (mucosal, uveal, leptomeningeal, unknown primaries) represent around 5-10 % of all melanoma diagnoses. Non-cutaneous melanomas demonstrate differences in tumour biology, generally present with more advanced stages and have an overall poorer prognosis compared to skin melanomas. The cornerstone of their treatment is surgery followed by radiotherapy in some cases. Unfortunately, in many of these patients their melanoma will recur. Adjuvant therapy for non-cutaneous melanomas remains controversial. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit; the two randomised positive trials were criticized for methodological reasons, small sample size and conflicting results. The aim of this review is to assess the current evidence on systemic adjuvant treatments for high-risk resected non-cutaneous melanomas. We also provide a summary table with the currently recruiting clinical trials in these settings and we discuss some strategies to improve trial design in this particularly niche area of oncology.
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Melanoma , Neoplasias Cutáneas , Terapia Combinada , Humanos , Melanoma/tratamiento farmacológico , Membrana Mucosa , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. We describe the characteristics of UM patients at a tertiary referral center in the Mid-Southern United States, and explore associations and predictors of outcomes. This is a retrospective cohort study of patients with UM seen at West Cancer Center, from 07/2006 to 08/2017. Clinical characteristics and their relationship to outcomes (time-to-death and metastasis) were explored using Cox regression analysis. We identified 208 patients, 51% males, 97% Caucasians, 80% were symptomatic, with a median follow-up of 2.34 years, IQR (1.01-3.03), of which 19.2% died during follow-up. Metastases were diagnosed in 19% (4 older patients had metastases at diagnosis), 53% of those by surveillance. Without considering metastases as a time-varying covariate, age (HR = 1.06/year, CI 1.0-1.1; p < 0.001), headaches (HR = 5.7, CI 1.6-20.5; p = 0.03), and tumor stage (T) were significant covariates for time-to-death. Tumor stages T3 versus T1 (HR = 6.4; CI 1.5-27.7; p = 0.01) and T4 versus T1 (HR = 5.98; CI 1.3-27.8; p = 0.02) were associated with worse outcomes. When considering metastases as a time-varying covariate (HR = 35.8, CI 17-75.2; p < 0.001), only age remains in the model (HR = 1.04/year; p < 0.001). However, tumor stage (p < 0.001), headaches (p = 0.008), and age (p < 0.001) are associated with time-to-metastasis. One in five patients developed metastasis which was the most influential factor on mortality. Predictors of mortality were metastasis, age, tumor stage, and headache as a reported symptom. Surveillance successfully diagnosed metastatic disease in most patients. Most patients had symptoms preceding their UM diagnosis highlighting an opportunity for earlier recognition of UM.
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Melanoma , Neoplasias de la Úvea , Adulto , Anciano , Femenino , Humanos , Masculino , Melanoma/epidemiología , Melanoma/mortalidad , Melanoma/patología , Melanoma/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/terapiaRESUMEN
Melanoma is among the most prevalent neoplasms diagnosed annually with the vast majority arising from a cutaneous origin. Though there are described metastases to the gastrointestinal tract, there are only rare descriptions of primary gastrointestinal melanoma. Both diagnosis and management of this unique population can be challenging given the infrequency with which it occurs. To follow is the third reported case of transverse colon primary melanoma with a description of multimodality treatment with surgery, chemotherapy, and immunotherapy.
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The malignant cell in melanoma is the melanocyte. Because melanocytes are located in the basal layer of the epidermis, melanoma is most commonly seen on the skin. However, melanoma can also arise on mucosal surfaces such as the oral cavity, the upper gastrointestinal mucosa, the genital mucosa, as well as the uveal tract of the eye and leptomeninges. Melanomas tend to be pigmented but can also present as pink or red lesions. They can mimic benign or other malignant skin lesions. This chapter presents the spectrum of typical and less typical presentations of melanoma, as well as patterns of spread. It is divided into (1) cutaneous lesions; (2) patterns of regional spread, (3) non-cutaneous lesions; and (4) distant metastases.
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Melanoma/patología , Humanos , Melanoma/inmunología , Melanoma/secundario , Piel/patología , Neoplasias Cutáneas/patología , Neoplasias de la Úvea/patologíaRESUMEN
Antecedentes: Los melanomas no cutáneos representan el 1-7% del total. Su pronóstico es malo, a pesar de lo cual, los avances tecnológicos pueden haber cambiado su evolución. Objetivo: Descubrir factores que permitan determinar los progresos de los últimos 20 años. Diseño: Retrospectivo, observacional. Lugar de aplicación: Hospital Público de atención terciaria. Población: 30/56 pacientes pertenecían al género masculino, con una relación 1.15/1. La edad media fue 61.07 años. El sitio dominante de los mucosos fue paladar con 22 (39.2%) y senos paranasales con 9 (16%). Los oculares con 24/56 representaron el (42.8%) de la muestra. El 94.6% se hallaban en E I. Métodos: La extensión de la cirugía varió desde la simple resección local en 13/56 -23.2%- pacientes, a la enucleación ocular en 14/56 (25%), exenteración orbitaria en 5/56(9%), maxilectomía superior en 20/56 (35.7%), resección craneofacial en 3 y amputación nasal en 1. Resultados: La morbilidad fue 51.7% y la mortalidad 1.7%. El 67.8% desarrolló recurrencias. El análisis univariado para recu-rrencia demostró que los orígenes rinosinusal y conjuntival, influyeron desfavorablemente en el evento recurrencia. Al cierre de la observación 42/56 (75%) habían fallecido, (85.8%) de ellos por causa específica. Solo 2/42 (4.7%) muertes se produjeron después de los 60 meses. La supervivencia libre de enfermedad a 5 años fue 31.9%. El paladar y el E I, fueron las variables que a su favor conservaron significación estadística. Conclusiones: Urgen nuevos paradigmas de tratamiento para esta enfermedad cuya evolución no se ha modificado sustancial-mente en los últimos 20 años.(AU)
Background: Non cutaneous are 1-7% of all melanoma. The prognosis is poor in spite of which, technological progress may change the outcome. Objective: To discover factors which allow to define progress of last 20 years. Design: Retrospective, observational. Setting: Public Hospital of tertiary care. Population: 30/56 male patients with 1.15/1 rate. Mean age 61.07 years old. Priority sites in mucosal melanoma were palate with 22-39.2% and paranasal sinus with 9 (16%). Ocular melanomas were 42.8% of the sample. 94.6% were EI. Methods: Extention of surgery was simple resection in 13/56 (23.2%), ocular enucleation in 14/56 (25%), orbit exenteration in 5/56 (9%) maxilectomy in 20/56 (35.7%), craniofacial resection in 3 and nasal amputation in 1. Results: Morbility was 51.7% and mortality 1.7%. 67.8% of the sample recurred. Multivariate analysis for recurrence showed that rinosinusal and conjuntival sites unfavorably influence on that event. At close of observation 42/56 (75%) was dead, 85.8% of them for specific cause. Only 2 death happened after 60 months. Five years specific survival was 31.9%. Palate and stage I were favorable sites with statistic significance. Conclusions: Other paradigms of treatment are urgently necessary for this disease which outcome was not substantially modified in the last 20 years.(AU)
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Antecedentes: Los melanomas no cutáneos representan el 1-7% del total. Su pronóstico es malo, a pesar de lo cual, los avancestecnológicos pueden haber cambiado su evolución.Objetivo: Descubrir factores que permitan determinar los progresos de los últimos 20 años.Diseño: Retrospectivo, observacional.Lugar de aplicación: Hospital Público de atención terciaria.Población: 30/56 pacientes pertenecían al género masculino, con una relación 1.15/1. La edad media fue 61.07 años. El sitiodominante de los mucosos fue paladar con 22 (39.2%) y senos paranasales con 9 (16%). Los oculares con 24/56 representaron el(42.8%) de la muestra. El 94.6% se hallaban en E I.Métodos: La extensión de la cirugía varió desde la simple resección local en 13/56 -23.2%- pacientes, a la enucleación ocular en14/56 (25%), exenteración orbitaria en 5/56(9%), maxilectomía superior en 20/56 (35.7%), resección craneofacial en 3 y amputaciónnasal en 1.Resultados: La morbilidad fue 51.7% y la mortalidad 1.7%. El 67.8% desarrolló recurrencias. El análisis univariado para recurrenciademostró que los orígenes rinosinusal y conjuntival, influyeron desfavorablemente en el evento recurrencia. Al cierre de laobservación 42/56 (75%) habían fallecido, (85.8%) de ellos por causa específica. Solo 2/42 (4.7%) muertes se produjeron despuésde los 60 meses. La supervivencia libre de enfermedad a 5 años fue 31.9%. El paladar y el E I, fueron las variables que a su favorconservaron significación estadística.Conclusiones: Urgen nuevos paradigmas de tratamiento para esta enfermedad cuya evolución no se ha modificado sustancialmenteen los últimos 20 años.
Background: Non cutaneous are 1-7% of all melanoma. The prognosis is poor in spite of which, technological progress maychange the outcome.Objective: To discover factors which allow to define progress of last 20 years.Design: Retrospective, observational.Setting: Public Hospital of tertiary care.Population: 30/56 male patients with 1.15/1 rate. Mean age 61.07 years old. Priority sites in mucosal melanoma were palate with22-39.2% and paranasal sinus with 9 (16%). Ocular melanomas were 42.8% of the sample. 94.6% were EI.Methods: Extention of surgery was simple resection in 13/56 (23.2%), ocular enucleation in 14/56 (25%), orbit exenteration in 5/56(9%) maxilectomy in 20/56 (35.7%), craniofacial resection in 3 and nasal amputation in 1.Results: Morbility was 51.7% and mortality 1.7%. 67.8% of the sample recurred. Multivariate analysis for recurrence showed thatrinosinusal and conjuntival sites unfavorably influence on that event. At close of observation 42/56 (75%) was dead, 85.8% of themfor specific cause. Only 2 death happened after 60 months. Five years specific survival was 31.9%. Palate and stage I were favorablesites with statistic significance.Conclusions: Other paradigms of treatment are urgently necessary for this disease which outcome was not substantially modifiedin the last 20 years.