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1.
Am J Clin Oncol ; 43(9): 607-614, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889829

RESUMO

OBJECTIVE: We aim to develop and validate an effective nomogram prognostic model for patients with typical lung carcinoid tumors using a large patient cohort from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Data from patients with typical lung carcinoid tumors between 2010 and 2015 were selected from the SEER database for retrospective analysis. Univariate and multivariate Cox analysis was performed to clarify independent prognostic factors. Next, a nomogram was formulated to predict the probability of 3- and 5-year overall survival (OS). Concordance indexes (c-index), receiver operating characteristic analysis and calibration curves were used to evaluate the model. RESULTS: The selected patients were randomly divided into a training and a validation cohort. A nomogram was established based on the training cohort. Cox analysis results indicated that age, sex, T stage, N stage, surgery, and bone metastasis were independent variables for OS. All these factors, except surgery, were included in the nomogram model for predicting 3- and 5-year OS. The internally and externally validated c-indexes were 0.787 and 0.817, respectively. For the 3-year survival prediction, receiver operating characteristic analysis showed that the areas under the curve in the training and validation cohorts were 0.824 and 0.795, respectively. For the 5-year survival prediction, the area under the curve in the training and validation cohorts were 0.812 and 0.787, respectively. The calibration plots for probability of survival were in good agreement. CONCLUSION: The nomogram brings us closer to personalized medicine and the maximization of predictive accuracy in the prediction of OS in patients with typical lung carcinoid tumors.


Assuntos
Neoplasias Ósseas/secundário , Tumor Carcinoide/mortalidade , Neoplasias Pulmonares/mortalidade , Nomogramas , Fatores Etários , Idoso , Tumor Carcinoide/secundário , Feminino , Previsões/métodos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Programa de SEER , Fatores Sexuais , Taxa de Sobrevida , Estados Unidos/epidemiologia
2.
Hum Pathol ; 98: 98-109, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145220

RESUMO

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Pulmonares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Gradação de Tumores , Estadiamento de Neoplasias , Pneumonectomia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
3.
Pediatr Pulmonol ; 55(3): 719-722, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31909892

RESUMO

Lung cancers in children under the age of 15 are very uncommon, with a scarcity of literature describing patient characteristics and survival. This study assessed first primary malignant cancers occurring in the trachea, bronchus, or lung (International Classification of Diseases for Oncology, 3rd edition [ICD-O-3] codes C33-C34) for the period 1983-2015, using data from the population-based Australian Childhood Cancer Registry. Variables of interest included morphology, sex, age group, and metastatic status at diagnosis. Mode of treatment was also assessed where possible. The Kaplan-Meier method was used to calculate 5-year observed survival. Of the 53 in-scope patients, almost half (n = 23, 43%) were diagnosed with pleuropulmonary blastoma and a further 8 (15%) had a carcinoid tumor. Few of the patients with details available on stage at diagnosis (n = 7 of 43, 16%) presented with metastatic disease. Surgical excision was the most common treatment (30 of 37 children, 81%), with two-thirds (n = 28 of 43, 65%) receiving chemotherapy. Five-year observed survival was estimated to be 74% (95% CI = 61%-85%). Our results represent one of the largest and most complete population-based cohorts of children with primary malignant lung cancers available to date. Detection of childhood lung cancer can be difficult due to the rarity of this disease and symptoms that are typically nonspecific.


Assuntos
Neoplasias Pulmonares/mortalidade , Adolescente , Austrália/epidemiologia , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Blastoma Pulmonar/mortalidade , Blastoma Pulmonar/patologia , Sistema de Registros , Neoplasias da Traqueia/mortalidade , Neoplasias da Traqueia/patologia , Adulto Jovem
4.
Ann Surg Oncol ; 27(1): 179-187, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31646450

RESUMO

BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is often misclassified and mistreated due to mixed histologic features. In general, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard of care for peritoneal carcinomatosis (PC) from mucinous appendiceal tumors; however, in PC from GCA, data are limited and the role of CRS/HIPEC is controversial. We report outcomes in PC from appendiceal GCA treated with CRS/HIPEC. PATIENTS AND METHODS: A prospective institutional database of 391 CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2018 was reviewed. Twenty-seven patients with GCA were identified. Perioperative variables were described. Survival was estimated using the Kaplan-Meier method. RESULTS: GCA occurred in 7% (27/391) of appendiceal CRS/HIPEC patients. Seven (26%) cases were aborted. Two patients underwent a second CRS/HIPEC for peritoneal recurrence. Median age at diagnosis was 53 years (range 39-72 years), and 12 (60%) were female. All underwent previous surgery. Seven (35%) had prior chemotherapy and received a median of 5 cycles (range 3-8). Median PCI was 6 (range 1-39). Complete cytoreduction was achieved in 95% (19/20). Grade III complications occurred in three (15%) patients, and no perioperative deaths occurred. Median follow-up was 97 months. Overall survival at 1, 3 and 5 years was 100%, 74% and 67%, respectively. Progression-free survival at 1, 3, and 5 years was 94%, 67% and 59%, respectively. CONCLUSION: CRS/HIPEC should be considered as the main treatment option for patients with PC from appendiceal GCA. When performed at a CRS/HIPEC specialty center, 5-year OS of 67% can be achieved.


Assuntos
Adenocarcinoma/terapia , Neoplasias do Apêndice/terapia , Tumor Carcinoide/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Células Caliciformes/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
J Surg Oncol ; 120(7): 1096-1101, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31592538

RESUMO

BACKGROUND: Goblet cell carcinoid (GCC) tumors of the appendix are a rare malignancy. We aim to examine the overall survival per stage and the relationship between different treatment modalities and outcomes for patients with GCC tumors of the appendix. METHODS: We identified patients with GCC tumors of the appendix from the National Cancer Database. The main outcome was overall patient survival and cox proportional hazard models were used to ascertain predictors of survival. RESULTS: There were 2552 patients identified. The median age of diagnosis was 57 (interquartile range: 49-65) and 52.3% of patients were female. The 5-year survival for Stage I disease was 91.1% (95% confidence interval [CI]: 82.2%-95.7%), for Stage II disease was 90.5% (95% CI: 85.8%-93.7%), for Stage III disease was 57.0% (95% CI: 45.0%-67.3%), and for Stage IV disease was 18.9% (95% CI: 9.3%-31.0%). In a Cox proportional hazard model, older age (hazard ratio [HR]: 1.1; 95% CI: 1.03-1.12; P < .001), lymph node metastasis (HR: 6.9; 95% CI: 2.76-17.01; P < .001), and positive surgical margins (HR: 2.9; 95% CI:1.13-7.26; P = .003) were associated with worse overall survival for Stages I to III disease while only older age (HR: 1.03; 95% CI: 1.002-1.06; P = .04) was associated with worse overall survival for Stage IV disease. CONCLUSIONS: Patients with GCC tumors of the appendix who have the nonmetastatic disease have a high 5-year survival. We have identified several prognostic factors for GCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apendicectomia/mortalidade , Neoplasias do Apêndice/mortalidade , Tumor Carcinoide/mortalidade , Recidiva Local de Neoplasia/mortalidade , Idoso , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
6.
Hum Pathol ; 94: 78-85, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31499081

RESUMO

Loss of alpha thalassemia/mental retardation syndrome X-linked (ATRX), a chromatin regulator, is associated with worse prognosis in pancreatic neuroendocrine tumors. We investigated ATRX expression in pulmonary carcinoid tumors (PCT) and its diagnostic and prognostic role in these patients. Resected PCTs (1997-2017) were reviewed. Tumors were staged according to 8th UICC/AJCC system. ATRX nuclear expression was recorded independently by 2 reviewers. A cutoff of ≤5% of nuclear ATRX expression was statistically established as loss of expression. One-hundred-fifteen patients (72 women [63%]; median age of 60.5 years [interquartile range, 50.8-71.5]) harbored 69 (60%) typical and 46 (40%) atypical PCTs. Median tumor size was 2.3 cm (interquartile range, 1.6-3.8 cm). Loss of ATRX expression was associated with atypical PCTs (OR 7.4 [95% CI, 2.6-23, P < .001]), when adjusted for lymphovascular invasion and perineural invasion. ATRX expression predicted atypical PCT with sensitivity of 37% (95% CI, 24%-52%), specificity of 92% (95% CI, 86%-98%), AUC of 0.62 (95% CI, 0.52-0.72). Loss of ATRX expression was associated with shorter disease-specific survival (HR = 11, 95% CI, 1.8-68, P = .01), after adjusting for lymphovascular invasion and presence of metastatic disease at time of diagnosis. Interobserver agreement on ATRX expression by two reviewers was substantial (κ = 0.72 [95% CI, 0.60-0.80]). ATRX expression is more commonly lost in atypical than in typical PCT, and is associated with more aggressive tumor characteristics and shorter disease-specific survival.


Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/enzimologia , Núcleo Celular/enzimologia , Neoplasias Pulmonares/enzimologia , Proteína Nuclear Ligada ao X/análise , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Núcleo Celular/patologia , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores de Tempo
7.
Nat Commun ; 10(1): 3407, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431620

RESUMO

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.


Assuntos
Biomarcadores Tumorais/genética , Tumor Carcinoide/genética , Carcinoma de Células Grandes/genética , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Hibridização Genômica Comparativa , Conjuntos de Dados como Assunto , Feminino , Genômica , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Prognóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Adulto Jovem
8.
Lung Cancer ; 134: 85-95, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31320001

RESUMO

The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial procedures have emerged as a parenchyma sparing alternative for tumors located in the central airways. This review was performed to identify the optimal treatment strategy for pulmonary carcinoid, with a particular focus on the feasibility and outcome of parenchyma sparing techniques versus surgical resection. A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two separate searches of publications in endobronchial and surgical treatment in patients with pulmonary carcinoid, were performed. Outcomes were overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Finally, 43 studies concerning surgical treatment and 9 studies related to endobronchial treatment for pulmonary carcinoid were included. Assessment of included studies showed that lymph node involvement, histological grade, tumor location and tumor diameter were identified as poor prognostic factors and seem to be important for patients with pulmonary carcinoid. For patients with a more favorable prognosis, tumor location and tumor diameter are important factors that can help decide on the optimal treatment strategy. Centrally located small intraluminal pulmonary carcinoids, without signs of metastasis can be treated with minimally invasive alternatives such as endobronchial treatment or parenchyma sparing surgical resection. Patients with parenchyma sparing resections should be followed with long term follow up to exclude recurrence of disease. In a multidisciplinary setting, it should be determined whether individual patients are eligible for parenchyma sparing procedures or anatomical resection. Overall evidence is of low quality and future studies should focus on prospective trials in the treatment of pulmonary carcinoid.


Assuntos
Broncoscopia , Tumor Carcinoide/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Broncoscopia/métodos , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/mortalidade , Custos de Cuidados de Saúde , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Tratamentos com Preservação do Órgão/métodos , Pneumonectomia/métodos , Complicações Pós-Operatórias , Prognóstico , Qualidade de Vida , Recidiva , Resultado do Tratamento
9.
Pathology ; 51(5): 481-486, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230818

RESUMO

Carcinoid classification in the lung is still based on morphological criteria. Although there are many studies investigating the role of Ki-67 proliferation index in the classification of lung neuroendocrine tumours, it is still not used in routine diagnostics. Interestingly, cyclins, which have a crucial role in controlling the cell cycle, have not been thoroughly studied in lung neuroendocrine tumours. The aim of our study was to investigate the correlation of cyclin A2 and B1 expression with prognosis, Ki-67 proliferation index, and carcinoid morphology. A cohort of 134 resected typical and atypical carcinoids was stained with antibodies against Ki-67, cyclin A2 and B1. The positive nuclear reaction was assessed in hot spot areas and expressed as the percentage of tumour cells. Univariate analyses found the highest relative hazard between low and high cyclin A2 expression both with respect to overall survival [hazard ratio (HR)=16; 95% confidence interval (CI) 4.8-51; p=0.0000054], and relapse (HR=8; 95% CI 3.1-21; p=0.00002). In multivariate analysis for overall survival cyclin A2 (HR=10; 95% CI 2.5->100; p=0.0082) and B1 (HR=6.5; 95% CI 1.5-35; p=0.02) remained significant when adjusted for other risk factors, whereas Ki-67 was no longer significant (HR=0.64; 95% CI 0.003-5.5; p=0.65). This suggests that Ki-67 is closer to conventional risk factors for survival than cyclin A2 and B1. Furthermore, the analysis revealed 4 mitoses per 2 mm2 as a more powerful prognostic cut-off than currently accepted 2 mitoses. We have clearly demonstrated that application of cyclin A2 and cyclin B1 might bring additional value regarding the overall and progression-free survival of patients with carcinoids of the lung.


Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/patologia , Ciclina A2/biossíntese , Ciclina B1/biossíntese , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Adulto Jovem
10.
Ann Thorac Surg ; 108(3): 859-865, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31059684

RESUMO

BACKGROUND: The role of sublobar resection in the treatment of pulmonary typical carcinoids is controversial. This study aims to compare long-term outcomes between sublobar and lobar resections in patients with peripheral typical carcinoid. METHODS: We retrospectively compared consecutive patients who underwent curative sublobar resection with patients who underwent lobectomy for cT1-3 N0 M0 peripheral pulmonary typical carcinoid in eight centers between 2000 and 2015. Primary outcomes were rates and patterns of recurrence and overall survival. Cox regression modeling was performed to identify factors influencing overall survival and recurrence. Propensity score analysis was done, and overall survival was compared between the two groups. RESULTS: In all, 177 patients were analyzed, consisting of 74 sublobar resections and 103 lobectomies, with a total of 857 person-years of follow-up. The R1 resection rates were 7% and 1% after sublobar resection and lobectomy, respectively (P = .08). One of 5 patients with sublobar R1 resection had recurrence. Recurrence rate was 0.02 (95% confidence interval [CI]: 0.009 to 0.044) per person-year of follow-up after sublobar resection and 0.008 (95% CI: 0.003 to 0.02) after lobectomy (P = .15). Five-year survival rates were 91.7% (95% CI: 78.5% to 96.9%) and 97.4% (95% CI: 90.1% to 99.4%) after sublobar and lobar resection, respectively (P = .08). Extent of resection was not a predictor of recurrence or survival. Propensity score analysis confirmed a similar survival and freedom from recurrence between the two groups. CONCLUSIONS: Sublobar resection of peripheral cT1-3 N0 M0 pulmonary typical carcinoid was not associated with worse short- or long-term outcomes compared with lobectomy. In select patients, sublobar resection may be considered for treatment of peripheral typical carcinoids if an R0 resection is obtained.


Assuntos
Tumor Carcinoide/mortalidade , Tumor Carcinoide/cirurgia , Causas de Morte , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Idoso , Tumor Carcinoide/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Internacionalidade , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/mortalidade , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
11.
Lung Cancer ; 131: 90-94, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31027704

RESUMO

BACKGROUND: Atypical bronchopulmonary carcinoid tumors are rare but carry high recurrence rates following resection. The role of adjuvant therapy remains unclear owing to a lack of high-volume data. To address this knowledge gap, we examined predictors of adjuvant therapy and effects on outcome. METHODS: We queried the National Cancer Database for patients with resected stage I-III atypical carcinoid. Adjuvant therapy was defined as chest radiation, chemotherapy, or a combination thereof. Multivariable logistic regression identified predictors of adjuvant therapy. Multivariable Cox regression evaluated predictors of survival. Propensity matching accounted for indication biases. RESULTS: Overall, 533 stage I/II and 129 stage III patients were identified. Predictors for adjuvant therapy in stage I/II disease were stage II, positive margins, lymph node ratio (LNR) of 1-25%, and more remote year of treatment. Predictors for adjuvant therapy in stage III were female gender and LNR of 26-50%. Median overall survival in stage I/II and III was 116 months and 61 months, respectively. Predictors for survival in stage I/II were age, margins, comorbidity score, and LNR; factors for stage III disease were LNR and more remote year of treatment. Delivery of adjuvant therapy was not independently associated with survival in either stage I/II or III patients. Furthermore, propensity matched analysis did not reveal a benefit to adjuvant therapy. CONCLUSIONS: This study shows no clear survival benefit with adjuvant radiotherapy and/or chemotherapy, even in stage III disease. Although this implies that adjuvant therapy should not be routinely delivered, individualized judgment is still recommended.


Assuntos
Tumor Carcinoide/terapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Neoplasias Pulmonares/terapia , Radioterapia Adjuvante , Adulto , Fatores Etários , Idoso , Tumor Carcinoide/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Fatores Sexuais , Análise de Sobrevida , Resultado do Tratamento
12.
J BUON ; 24(1): 256-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941978

RESUMO

PURPOSE: Neuroendocrine lung tumors (NET) include typical carcinoids (TC), atypical carcinoids (AC), large cell NE carcinoma (LCNEC) and small-cell carcinoma (SCLC), with different clinicopathological profiles and relative grades of malignancy. Although differences between carcinoids and high grade carcinomas are recognized, precise differences and behavior of TC and AC have not been clearly defined. The aim of this study was to better define the differences in the clinical behavior of TC and AC, and to establish new prognostic factors of overall survival (OS), by determining the levels of genetic expression of IGF1R, ERCC1, Bax, p53, Bcl2 and Bcl2/Bax ratio. METHODS: The histopathological diagnosis of 52 surgically resected pulmonary carcinoid tumors was made according to the WHO classification. Gene expressions were evaluated by quantitative real-time PCR. RESULTS: The confirmed prognostic factors for overall survival (OS) were pTNM T (p<0.01), pTNM N (p<0.05), clinical stage (p<0.05), type of surgery (p<0.01) and histopathological (HP) tumor type (p<0.05). Bcl2 mRNA level and Bcl2/Bax ratio were found to have a potential for discrimination of the HP type of tumor (AC vs TC, Receiver Operating Characteristics (ROC) cut-off values 0.1451 and 0.3015, respectively), but without statistically significant impact on OS. CONCLUSIONS: In patients with NETs, smaller primary tumor, absence of positive lymph nodes, and TC type of tumor predicted longer OS. Type of resection has influence on OS. Bcl2 expression and Bcl2/Bax ratio might be valuable as independent diagnostic parametars in lung carcinoids. Therapeutic approaches using attenuation of Bcl2 or upregulation of Bax might prove useful in lung NETs.


Assuntos
Tumor Carcinoide/mortalidade , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Neoplasias Pulmonares/mortalidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Somatomedina/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Tumor Carcinoide/genética , Tumor Carcinoide/metabolismo , Tumor Carcinoide/patologia , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor IGF Tipo 1 , Receptores de Somatomedina/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Adulto Jovem , Proteína X Associada a bcl-2/genética
13.
Clin Lung Cancer ; 20(3): e284-e290, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30850224

RESUMO

INTRODUCTION: Surgery is the standard of care for pulmonary carcinoid tumors; however, options for inoperable patients are few. We report the outcomes of inoperable pulmonary carcinoid patients treated with stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: From an institutional database, we retrospectively identified patients treated with SBRT for pulmonary carcinoid tumors from 2007 to 2017. Additional inclusion criteria were previous histopathologic diagnosis, age older than 18 years and Karnofsky performance status ≥ 70. RESULTS: Ten patients were treated for 12 pulmonary carcinoid lesions with 5 to 10 fractions of SBRT. Their median age was 66.5 years (range, 40-83 years) and most presented with nonspecific symptoms of cough, shortness of breath, or hemoptysis. Pathology revealed typical carcinoid for 9 patients, with the 10th with atypical histology. The median prescription dose for all patients was 50 Gy in 5 to 10 fractions (range, 40-60 Gy) with SBRT/hypofractionated radiation with daily image-guided radiotherapy (IGRT) delivered using a linear accelerator with respiratory monitoring. Four patients received 10-fraction hypofractionated radiation with daily IGRT and 6 others received 5-fraction SBRT. The follow-up after SBRT/hypofractionated IGRT ranged from 6 to 56 months (median, 25 months). Four patients were alive with stable disease at their last follow-up. Two patients died from disease progression in the mediastinal lymph nodes as well as in the lung. Both opted for palliative treatment. The other 4 patients died from their comorbid medical conditions, but had stable disease at their last follow-up. Median overall survival was 27.1 months (range, 5.5-56 months). CONCLUSION: Pulmonary carcinoid tumors treated with SBRT have a promising tumor control rate and survival.


Assuntos
Tumor Carcinoide/terapia , Neoplasias Pulmonares/terapia , Radiocirurgia , Radioterapia Guiada por Imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tosse , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Future Oncol ; 15(12): 1397-1406, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734573

RESUMO

Aim: Elevated serotonin in patients with neuroendocrine tumors (NETs) may impact heart failure incidence but a quantitative relationship has not been established. Materials & methods: Systematic review and meta-analysis of studies assessing 24-h urinary 5-hydroxyindoleacetic acid (u5-HIAA) and mortality in patients with NETs (2007-2017) with a primary outcome of 1-year mortality risk and 24-h u5-HIAA. Results: We identified 1715 records of which 12 studies including 755 patients (3442 person-years with 376 deaths) were eligible for meta-analysis. Mean u5-HIAA was 149.2 mg/24 h (standard deviation: 96.6) and mortality was 13.0%. The meta-regression equation showed an 11.8% (95% CI: 8.9-17.0%; I2  = 93.0%) increase in 1-year mortality for every ten-unit increase in u5-HIAA. Conclusion: Serotonin measured by its metabolite u5-HIAA is predictive of 1-year all-cause mortality in patients with NETs.


Assuntos
Biomarcadores Tumorais/sangue , Doença Cardíaca Carcinoide/mortalidade , Tumor Carcinoide/mortalidade , Neoplasias Intestinais/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Serotonina/sangue , Neoplasias Gástricas/mortalidade , Doença Cardíaca Carcinoide/sangue , Doença Cardíaca Carcinoide/etiologia , Tumor Carcinoide/sangue , Tumor Carcinoide/complicações , Humanos , Neoplasias Intestinais/sangue , Neoplasias Intestinais/complicações , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/complicações , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/complicações , Valor Preditivo dos Testes , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações
15.
Am J Surg ; 217(5): 937-942, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30686481

RESUMO

BACKGROUND: Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. METHODS: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups. RESULTS: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045). CONCLUSION: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.


Assuntos
Tumor Carcinoide/mortalidade , Tumor Carcinoide/cirurgia , Gastrectomia , Gastroscopia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Tumor Carcinoide/patologia , Feminino , Humanos , Complicações Intraoperatórias , Tempo de Internação/estatística & dados numéricos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias Gástricas/patologia
16.
Oncologist ; 24(8): 1066-1075, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30610008

RESUMO

BACKGROUND: Using data from four tertiary referral centers in the U.S., we assessed real-world treatment patterns and clinical outcomes of patients with advanced lung neuroendocrine tumors (NETs). SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective chart review of adult patients with locally advanced/metastatic (typical/atypical) lung NETs treated between July 2011 and December 2014. Index date was histologically confirmed typical/atypical carcinoid tumor diagnosis date. Data included baseline characteristics, treatment patterns, progression, death, and lung NET-related health care resource use from index date through last contact/death. Time to treatment discontinuation and first progression, time from first to second progression, and overall survival (OS) were estimated using Kaplan-Meier analysis. RESULTS: We identified 83 patients; 19 (23%) had functional NET. First-line treatments included somatostatin analogs (SSAs) alone (56%) or in combination with other therapies (6%), cytotoxic chemotherapy (20%), external beam radiation therapy (EBRT) (9%), liver-directed therapy (LDT) (4%), and everolimus/other (5%). Sixty patients had second-line therapy including SSA alone (18%) or in combination (40%), cytotoxic chemotherapy (17%), everolimus (12%), LDT (7%), EBRT (3%), and other treatments (3%). Median time (months) to first-line discontinuation were as follows: SSAs, 43.3; cytotoxic chemotherapy, 3.6. Overall median time (months) to investigator-assessed progression following treatment initiation was 12.4. Median OS (months) following treatment initiation was 66.4 for all patients and 81.5 for patients receiving SSAs. CONCLUSION: SSAs, alone and in combination, are common treatments for advanced lung NETs. Patients have additional treatment options and relatively long survival compared with patients with other advanced cancers. Treatment pattern assessment following approval of newer treatments is needed. IMPLICATIONS FOR PRACTICE: Somatostatin analogs (SSAs), cytotoxic chemotherapy, EBRT, liver-directed therapy, and targeted therapies are common treatments for locally advanced/metastatic (typical/atypical) lung neuroendocrine tumors (NETs). SSAs alone or in combination with other treatment modalities were the most common first- and second-line therapy, followed by cytotoxic chemotherapy. Patients continued treatment with SSAs long-term with median treatment duration of 43 months. Median overall survival was 66 months following initiation of first-line therapy for all patients. Treatment pattern assessment beyond the time period of this study is needed given recent U.S. Food and Drug Administration approvals for additional treatments for lung NETs that will likely be incorporated in the treatment landscape.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumor Carcinoide/terapia , Neoplasias Pulmonares/terapia , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Quimiorradioterapia/métodos , Quimiorradioterapia/estatística & dados numéricos , Progressão da Doença , Embolização Terapêutica/estatística & dados numéricos , Everolimo/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Registros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Centros de Atenção Terciária/estatística & dados numéricos , Resultado do Tratamento
17.
Adv Anat Pathol ; 26(2): 75-83, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30601149

RESUMO

Goblet cell carcinoid (GCC) or goblet cell carcinoma is a unique mixed endocrine-exocrine neoplasm that is almost exclusively seen in the appendix. The hallmark of GCC is the concentric infiltration of the appendiceal wall by small tight clusters, nests or cords of tumor cells that exhibit a goblet cell morphology with a small compressed nucleus and conspicuous intracytoplasmic mucin. The coexistence of high-grade adenocarcinoma with GCC has been increasingly recognized as a common finding, which has been called adenocarcinoma ex GCC or mixed GCC-adenocarcinoma. A number of studies have shown that it is the high-grade adenocarcinomatous component that dictates the prognosis. Several histologic classification/grading systems have been proposed, which correlate with overall patient survival. Treatment options are primarily based on tumor stage and the presence or absence of a high-grade adenocarcinomatous component.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Células Caliciformes/patologia , Neoplasias Complexas Mistas/patologia , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Neoplasias do Apêndice/química , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/terapia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Tumor Carcinoide/química , Tumor Carcinoide/mortalidade , Tumor Carcinoide/terapia , Células Caliciformes/química , Humanos , Imuno-Histoquímica , Técnicas de Diagnóstico Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/mortalidade , Neoplasias Complexas Mistas/terapia , Resultado do Tratamento
18.
J Clin Endocrinol Metab ; 104(6): 2083-2093, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657933

RESUMO

CONTEXT: Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs. OBJECTIVE: To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data. DESIGN, SETTING, AND PATIENTS: This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients' clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies. MAIN OUTCOME MEASURE: SSTR1 to SSTR5 expression in PC tumors. RESULTS: Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively). CONCLUSION: SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor's metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Pulmonares/patologia , Receptores de Somatostatina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/cirurgia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo , Análise Serial de Tecidos , Adulto Jovem
19.
Cardiovasc Intervent Radiol ; 42(4): 569-576, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30627774

RESUMO

PURPOSE: To evaluate initial response and overall survival of neuroendocrine tumor (NET) liver metastases initially treated with transarterial embolization (TAE) using spherical particles of different sizes. METHODS: A single-institution retrospective review was performed of 160 patients with NET liver metastases initially treated with TAE using < 100 µm (n = 77) or only ≥ 100 µm (n = 83) spherical particles. For each patient, we evaluated: initial response by mRECIST, time to progression, overall survival, complications, primary site, tumor grade and degree of differentiation, volume of liver disease, extrahepatic disease, NET-related symptoms, comorbidities, Child-Pugh score, performance status, lobar versus selective embolization, and arteriovenous shunting. RESULTS: Initial response was higher for TAE using particles < 100 versus TAE using only particles ≥ 100 µm (64 vs 42%, p = 0.007). Multivariate logistic regression showed that use of particles < 100 µm and liver < 50% replaced with tumor were independent predictors of a better initial response rate. There was no difference in major or minor complications between the two particle size groups. Median overall survival after TAE was 55 months for well- to moderately differentiated NET and 13 months for poorly differentiated or undifferentiated NET. There was no significant difference in survival between TAE patients treated with < 100 versus only ≥ 100-µm particles. CONCLUSION: NET patients treated with TAE using particles < 100 µm had better initial response, but the same overall survival, compared to TAE using only particles ≥ 100 µm.


Assuntos
Embolização Terapêutica/métodos , Neoplasias Hepáticas/secundário , Microesferas , Tumores Neuroendócrinos/secundário , Tamanho da Partícula , Adulto , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/terapia , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/terapia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Gastrointest Cancer ; 50(4): 709-715, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29974346

RESUMO

PURPOSE: Adenocarcinoma ex-goblet cell carcinoids (AGCCs) are rare appendiceal tumors with mixed neuroendocrine and glandular features. They tend to behave more aggressively than typical carcinoid tumors, affect younger patients, and have a greater predilection for spreading to the peritoneum. Outcomes of AGCC patients treated with chemotherapy, extrapolated from colon cancer regimens, in the adjuvant or metastatic setting have not been explicitly reported. We sought to explore outcomes of AGCC patients with either local disease treated with adjuvant FOLFOX or metastatic disease treated with FOLFOX/FOLFIRI post-cytoreductive debulking (or CRS plus HIPEC in the peritoneal-limited setting). METHODS: We performed a single-institution retrospective analysis of 23 pathologically identified AGCC patients from Vanderbilt University Medical Center treated with chemotherapy in either the adjuvant or metastatic settings. Each patient's tumor was categorized as group B or group C based on the criteria from Tang et al. Median progression-free survival (PFS) or disease-free survival (DFS) (in the curative setting) and overall survival (OS) were determined for each patient and specified patient subgroup. RESULTS AND CONCLUSION: AGCC patients who were treated with FOLFOX chemotherapy in the adjuvant setting or FOLFOX/FOLFIRI in the metastatic setting experienced prolonged PFS, DFS, and OS. Five patients with peritoneal-limited disease treated with CRS plus HIPEC have not yet reached median PFS or OS. While small sample size, patient selection, and retrospective nature limit the generalizability of findings from our analysis, the efficacy signals we observed suggest prospective evaluation with chemotherapy and CRS plus HIPEC is warranted in AGCC patients.


Assuntos
Neoplasias do Apêndice/terapia , Tumor Carcinoide/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Células Caliciformes/patologia , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Intervalo Livre de Progressão , Estudos Retrospectivos
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