RESUMEN
To summarize the current therapies for skin cancers, the Japanese Skin Cancer Society issued the first guidelines for skin cancers, including melanoma, squamous cell carcinoma, basal cell carcinoma (BCC), and extramammary Paget's disease, in 2007. These guidelines were revised in 2015. Herein, we present the English version of the 2021 edition of the Japanese clinical guidelines for BCC. In the latest edition, all procedures were performed according to the Grading of Recommendations, Assessment, Development and Evaluation systems. The clinical questions that could not be answered were selected for further analysis. A comprehensive literature search, systematic review, and recommendations for each clinical question were determined by a multidisciplinary expert panel comprising dermatologists, a plastic and reconstructive surgeon, and a pathologist. Surgical resection is the gold-standard therapy of BCC. Radiotherapy or topical treatments, other than surgical resection, have been used in some cases. Patients with unresectable or metastatic BCC require systemic therapy. Novel agents, such as immune response modifiers or hedgehog pathway inhibitors, are emerging worldwide for the treatment of BCC. Based on these viewpoints, four relevant clinical questions regarding, surgical resection, radiotherapy, topical treatment, and systemic therapy, were raised in this report that aims to help clinicians select suitable therapies for their patients.
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Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Carcinoma Basocelular/terapia , Carcinoma Basocelular/patología , Carcinoma Basocelular/diagnóstico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Japón , Dermatología/normas , Sociedades Médicas/normas , Antineoplásicos/uso terapéutico , Pueblos del Este de AsiaAsunto(s)
Inhibidores de Puntos de Control Inmunológico , Inmunoglobulinas Intravenosas , Metilprednisolona , Ácido Micofenólico , Miocarditis , Humanos , Persona de Mediana Edad , Quimioterapia Combinada/métodos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Metilprednisolona/administración & dosificación , Ácido Micofenólico/administración & dosificación , Miocarditis/inducido químicamente , Miocarditis/inmunología , Miocarditis/tratamiento farmacológico , Miocarditis/diagnóstico , Resultado del TratamientoRESUMEN
Whether sentinel lymph node biopsy status is a prognostic factor or effective in determining treatment strategies in extramammary Paget disease remains unclear. This study aimed to investigate the significance of sentinel lymph node biopsy in extramammary Paget disease. We retrospectively reviewed the clinical information of previously untreated patients with invasive extramammary Paget disease who underwent wide local excision of the primary tumor and sentinel lymph node biopsy at our hospital between April 2008 and March 2021. Clinical data including the baseline neutrophil-to-lymphocyte ratio and recurrence-free survival were analyzed. Sentinel lymph node metastases were classified as macrometastases and micrometastases, with a cut-off value for sentinel lymph node tumor burden of 2 mm. Univariate and multivariate analyses of factors affecting sentinel lymph node biopsy positivity and recurrence-free survival rates were performed. Overall, 85 patients were included in the analysis. Patients in the sentinel lymph node biopsy-positive group (n = 26) had a significantly higher invasion level and neutrophil-to-lymphocyte ratio. According to multivariate analyses, invasion level and a high neutrophil-to-lymphocyte ratio were independent predictive factors for sentinel lymph node biopsy positivity, and the sentinel lymph node biopsy status was an independent prognostic factor for recurrence-free survival. In conclusion, sentinel lymph node biopsy provides an accurate risk classification and clinical indication for postoperative follow-up in patients with invasive extramammary Paget disease.
Asunto(s)
Enfermedad de Paget Extramamaria , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Biopsia del Ganglio Linfático Centinela , Estudios Retrospectivos , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/cirugía , Enfermedad de Paget Extramamaria/patología , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Ganglios Linfáticos/patología , Pronóstico , Escisión del Ganglio Linfático , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/cirugíaRESUMEN
The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic biomarker for many cancer types. However, the prognostic value of NLR in patients with extramammary Paget disease (EMPD) remains unclear. This study aimed to determine whether NLR is associated with overall survival (OS) in patients with EMPD. In this single-center retrospective case series, we analyzed data of 109 patients with previously untreated EMPD who presented to our hospital. Data on age, sex, primary tumor site, invasion level, presence of lymph node and distant metastases, baseline NLR, and OS were analyzed. The enrolled patients were classified into the metastatic or non-metastatic EMPD groups. The metastatic EMPD group had higher invasion level and NLR value (p < 0.001 and p = 0.005, respectively) compared with the non-metastatic EMPD group. Cox proportional hazards model analysis showed invasion level (p = 0.0093) and NLR value (p = 0.019) to be independent prognostic factors for OS. Notably, multivariate analysis revealed that invasion level (p = 0.045) and NLR value (p = 0.036) were independent prognostic factors for OS in the metastatic EMPD group. The limitations of this study include the small number of participants and its retrospective nature. In conclusion, since NLR can be routinely assessed with high feasibility, it might be a useful biomarker for predicting prognosis in patients with EMPD.
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Linfocitos , Neutrófilos , Enfermedad de Paget Extramamaria , Humanos , Linfocitos/patología , Neutrófilos/patología , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/patología , Enfermedad de Paget Extramamaria/terapia , Pronóstico , Estudios Retrospectivos , Recuento de Leucocitos , Recuento de Linfocitos , Biomarcadores de Tumor/sangreRESUMEN
Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.
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Carcinoma Basocelular , Neoplasias de Cabeza y Cuello , Neoplasias Cutáneas , Carcinoma Basocelular/patología , Carcinoma Basocelular/cirugía , Humanos , Japón , Juicio , Márgenes de Escisión , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaAsunto(s)
Melanoma , Humanos , Melanoma/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , SíndromeRESUMEN
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a known prognostic biomarker for survival and is predictive of sentinel lymph node (SLN) positivity in some cancers. However, its usefulness as a prognostic biomarker for cutaneous squamous cell carcinoma (cSCC) has not been fully investigated. OBJECTIVE: Our objective was to investigate the relationship between the NLR and the disease-specific survival and SLN positivity in patients with cSCC. METHODS: In this single-center retrospective case series, we analyzed patients with cSCC who underwent blood tests prior to the initiation of treatment at our oncology hospital. The relationship between the patients' clinical characteristics (including the NLR) and the disease-specific survival and SLN positivity was evaluated using univariate and multivariate analyses. RESULTS: An elevated NLR was an independent prognostic factor for poor disease-specific survival and a predictive factor for SLN positivity. LIMITATIONS: Limitations include the small number of participants and selection bias due to the large proportion of high-risk cases in our patient population. CONCLUSION: NLR is a useful biomarker in cSCC because it is simple to measure and can predict prognosis.
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Carcinoma de Células Escamosas , Ganglio Linfático Centinela , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Humanos , Linfocitos/patología , Neutrófilos/patología , Pronóstico , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patologíaRESUMEN
Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43-85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8-11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).
Asunto(s)
Carcinoma Neuroendocrino/patología , Carcinoma/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/mortalidad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sudoríparas/genética , Neoplasias de las Glándulas Sudoríparas/mortalidadAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ipilimumab/uso terapéutico , Melanoma/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Ipilimumab/efectos adversos , Masculino , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Nivolumab/efectos adversos , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
We report the 5-year follow-up results from a single-arm, open-label, multicenter phase II study (ONO-4538-08) conducted in Japan. Twenty-four patients with treatment-naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5-year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5-year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5-year progression-free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment-related adverse events reported between the 3- and 5-year follow-up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment-related adverse events occurred in this period. In conclusion, first-line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long-term survival. No new safety signals were reported in the studied population.
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Melanoma , Neoplasias Cutáneas , Protocolos de Quimioterapia Combinada Antineoplásica , Supervivencia sin Enfermedad , Humanos , Ipilimumab/uso terapéutico , Japón/epidemiología , Melanoma/tratamiento farmacológico , Nivolumab/efectos adversos , Supervivencia sin Progresión , Neoplasias Cutáneas/tratamiento farmacológicoAsunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnósticoRESUMEN
BACKGROUND: As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations. MATERIAL AND METHODS: Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed. RESULTS: We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia. CONCLUSION: B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Pueblo Asiatico , Femenino , Humanos , Japón/epidemiología , Masculino , Melanoma/enzimología , Melanoma/etnología , Melanoma/mortalidad , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas B-raf/metabolismo , Estudios Retrospectivos , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/mortalidad , Factores de Tiempo , Adulto JovenRESUMEN
Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes. Several reports indicate the association between vitiligo and treatment response in advanced melanoma during immunotherapy. It has not been investigated, however, if an increase of vitiligo while on treatment with anti-programmed death 1 (PD-1) antibodies is associated with more durable responses. The aim of this study is to evaluate the correlation between the vitiligo dynamics and clinical efficacy of anti-PD-1 antibodies. This study included advanced melanoma patients who were treated with nivolumab or pembrolizumab and developed vitiligo thereafter. Correlation between vitiligo expansion (defined as an increase of lesion size at two separate time points at least 4 weeks apart) as well as vitiligo extent (body surface area [BSA] affected) and clinical efficacy based on response rate, progression-free survival and overall survival was assessed. We retrospectively reviewed 29 patients. The median time from the initiation of anti-PD-1 antibody to vitiligo onset was 4.3 months in patients who showed a response and 5.5 months in patients who showed no response (P = 0.31). Twelve patients showed vitiligo expansion, and in nine of these patients, vitiligo increased to grade 2 (covering ≥ 10% BSA). Vitiligo expansion and grade 2 vitiligo showed no improvement in treatment response (P = 0.59 and 0.25) but were associated with prolonged progression-free survival (P = 0.019 and 0.04). Grade 2 vitiligo also showed a trend for prolonged overall survival (P = 0.07). Trend of expansion and larger vitiligo extent may be predictive factors of prolonged survival during anti-PD-1 antibody in melanoma patients.
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Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Vitíligo/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Masculino , Melanoma/diagnóstico , Melanoma/inmunología , Melanoma/mortalidad , Persona de Mediana Edad , Estadificación de Neoplasias , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Vitíligo/inducido químicamente , Vitíligo/inmunologíaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ipilimumab/efectos adversos , Nivolumab/efectos adversos , Pancitopenia/diagnóstico , Anciano de 80 o más Años , Biopsia , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Médula Ósea/patología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Femenino , Humanos , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/secundario , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neoplasias Primarias Desconocidas/inmunología , Pancitopenia/sangre , Pancitopenia/inducido químicamente , Pancitopenia/inmunología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/secundario , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunologíaAsunto(s)
Neoplasias Óseas/secundario , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Masculinos/patología , Neoplasias Infratentoriales/diagnóstico , Enfermedad de Paget Extramamaria/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Femenino , Estudios de Seguimiento , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de los Genitales Masculinos/mortalidad , Neoplasias de los Genitales Masculinos/terapia , Humanos , Neoplasias Infratentoriales/mortalidad , Neoplasias Infratentoriales/secundario , Neoplasias Infratentoriales/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Enfermedad de Paget Extramamaria/mortalidad , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/terapia , PronósticoRESUMEN
Background: There is no standard systemic therapy for unresectable cutaneous squamous cell carcinoma (ucSCC), although various chemotherapy regimens have been reported. In our department, concurrent chemoradiotherapy (CCRT) for ucSCC resulted in a 1-year survival rate similar to that of resectable cutaneous squamous cell carcinoma (cSCC). Treatment involves continued chemotherapy after CCRT. Here, we report the importance of continued chemotherapy after CCRT, based on treatment outcomes. Patients and Methods: We retrospectively evaluated 13 patients with ucSCC, assessing the overall survival, overall response rate (ORR), and disease control rate (DCR). Results: CCRT with continued chemotherapy resulted in an ORR of 84.6%, DCR of 92.3%, and 1-year survival rate of 75%. Of the 13 patients treated with CCRT with continued chemotherapy, 6 had no metastasis. The remaining 7 patients developed metastasis to other organs or lymph nodes beyond the regional lymph nodes, although most sites of metastasis were outside the irradiation area. Conclusion: We conclude that CCRT with continued chemotherapy was effective in treating the irradiation site (primary lesion and regional lymph nodes) and any organ metastasis, although, it is unclear for how long the treatment remains effective.
RESUMEN
Cell adhesion molecule 1 (CADM1) is aberrantly expressed by T-cell neoplasms such as adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides (MF). We studied the expression of CADM1 and its splicing variants in Sézary syndrome (SS), MF, other cutaneous T-cell lymphoma (CTCL), and cell lines derived from T- and B-cell lymphomas. Soluble CADM1 was measured in the patients' sera. CADM1+ cells in the blood and skin lesions were examined by flow cytometry and immunostaining, respectively. Soluble CADM1 was measured by ELISA, and the splicing variants of CADM1 transcripts were determined by reverse transcriptase-polymerase chain reaction, followed by sequencing. As a result, circulating CADM1+ cells were significantly increased in seven out of 10 patients with SS, ranging from 7.9% to 74.5% of the CD3+CD4+ fractions (median 33.7%; cut-off value 6.5%). The percentages of CADM1+ cells were usually less than those of circulating Sézary cells. CADM1 was expressed, to various degrees, in six of nine T-cell lines derived from SS, MF, ATLL, and anaplastic large cell lymphoma (ALCL), but negative in B-cell lymphoma-derived cell lines. CADM1+ cells were present in the skin infiltrates of MF, SS, ATLL and ALCL. Serum levels of soluble CADM1 were not significantly elevated in SS/MF. Three major splicing variants of CADM1 expressed by neoplastic T-cells contained different combinations of the exons 7, 8, 9 and 11, including a putative oncogenic variant composed of exons 7-8-9-11. In conclusion, CADM1 is frequently expressed in Sézary cells and cell lines from CTCL.
Asunto(s)
Molécula 1 de Adhesión Celular/biosíntesis , Linfoma Cutáneo de Células T/metabolismo , Síndrome de Sézary/metabolismo , Neoplasias Cutáneas/metabolismo , Anciano , Anciano de 80 o más Años , Molécula 1 de Adhesión Celular/genética , Línea Celular Tumoral , Femenino , Humanos , Linfoma Cutáneo de Células T/genética , Masculino , Persona de Mediana Edad , Síndrome de Sézary/genética , Síndrome de Sézary/patología , Neoplasias Cutáneas/genéticaRESUMEN
Pyrexia is the most common adverse event in patients with melanoma or other solid organ malignancies that are treated with the combination of dabrafenib and trametinib (combi-DT). Given the expanded indication for combi-DT, management of pyrexia is a high priority. No previous case series has revealed which blood markers reflect the course of pyrexia and there is no consensus on the management strategy for pyrexia. The current case series study describes the utility of neutrophil count (NC), neutrophil ratio (NR) and C-reactive protein (CRP) in 11 patients with metastatic melanoma and BRAF V600 mutations who experienced pyrexia during combi-DT in our department. We also described the clinical course of pyrexia episodes that were managed with the concomitant use of oral prednisolone and immediate withdrawal of combi-DT. Consequently, the analysis of 37 pyrexia episodes in 11 patients showed that the differences in NC, NR and CRP at the onset of pyrexia were significantly different from those at pyretolysis (P = 0.01, 0.006 and 0.03, respectively). Additionally, in the 24 pyrexia episodes treated with the concomitant use of oral prednisolone and the immediate withdrawal of combi-DT, the mean duration of pyrexia and the mean time to restart combi-DT were 3 and 6 days, respectively. Therefore, the blood markers that reflect the course of pyrexia during combi-DT may be helpful for the appropriate management of pyrexia; also, our management strategy for pyrexia successfully reduced the duration of pyrexia and did not require a long-term drug holiday. Further large-scale studies are required to verify our results.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Proteína C-Reactiva/análisis , Fiebre/diagnóstico , Imidazoles/efectos adversos , Neutrófilos , Oximas/efectos adversos , Piridonas/efectos adversos , Pirimidinonas/efectos adversos , Administración Oral , Adulto , Anciano , Biomarcadores/sangre , Estudios de Factibilidad , Femenino , Fiebre/sangre , Fiebre/inducido químicamente , Fiebre/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Prednisolona/administración & dosificación , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.
Asunto(s)
Melanoma/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Intravenosa , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Pueblo Asiatico , Estudios de Seguimiento , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Melanoma/etnología , Melanoma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Prurito/inducido químicamente , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/patología , Vitíligo/inducido químicamente , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. OBJECTIVES: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. METHODS: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. RESULTS: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. CONCLUSIONS: Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.