Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features

Iyoda, Akira; Hiroshima, Kenzo; Toyozaki, Tetsuya; Haga, Yukiko; Baba, Masayuki; Fujisawa, Takehiko; Ohwada, Hayato

doi:10.1002/1097-0142(20010901)92:5<1108::aid-cncr1427>3.0.co;2-7

Cited by 81 publications

(65 citation statements)

References 21 publications

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“…31,32 We observed a 24% 5-year overall survival rate and a 31-month median survival in patients with poorly differentiated LCNEC patients, in line with previous studies that demonstrated a 5-year survival rate between 13% and 57%. 3,8,9,11,22,27,28 In the current study, a high mitotic count and a low number of neuroendocrine markers at immunohistochemistry emerged as prognostic factors for survival in patients with poorly differentiated LCNEC. For the first time, we have identified relevant prognostic impact for the mitotic count in poorly differentiated LCNEC: Patients with < 37 mitoses per 10 HPFs had tumors that were characterized by a less aggressive behavior.…”

Section: Discussionmentioning

confidence: 58%

“…10,11,13,[22][23][24] Historic LCNEC series have suggested a natural aggressive course with a median survival < 1 year. 25,26 From a prognostic standpoint, LCNEC stage has been described as a major determinant for survival in most studies [27][28][29] but not in all studies. 21 More recently, the degree of endocrine differentiation, p16 expression, and c-kit expression were proposed as new prognostic parameters for survival.…”

Section: Discussionmentioning

confidence: 99%

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Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Faggiano

Sabourin

Ducreux

et al. 2007

Cancer

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BACKGROUND.Poorly differentiated large cell neuroendocrine carcinomas (LCNEC) comprise a rare and still scarcely known subgroup of neuroendocrine tumors. The objective of this study was to investigate the epidemiology, clinical presentation, prognostic factors, and molecular pathways of patients with poorly differentiated LCNEC.METHODS.Forty‐one patients who had a confirmed diagnosis of poorly differentiated LCNEC according to the criteria of the most recent World Health Organization classification of neuroendocrine tumors of the lung entered the study. The clinicopathologic features of patients with poorly differentiated LCNEC were reviewed, prognostic parameters for their survival were studied, and the prognostic roles of the proteins involved in cell cycle regulation were investigated with tissue array analysis in a subset of patients with LCNEC.RESULTS.Twenty‐four men and 17 women with a median age of 63 years (age range, 26–81 years) who had LCNEC were studied. LCNEC developed after therapy for a first cancer in 14% of patients. Neither a personal or familial history of endocrine tumors nor a primary association that was compatible with an inherited syndrome was observed. The increase of at least 1 serum biologic marker was observed in 93% of patients. A primary tumor was identified in only 63% patients. Thirty‐one patients had distant metastases, and 10 patients had only lymph node metastases at the time of the diagnosis. The 5‐year survival rate was 24%. High mitotic count, low expression of neuroendocrine markers, and a Bcl‐2/Bax ratio > 1 were unfavorable prognostic factors for survival (P < .01). All patients who had isolated peripheral lymph node LCNEC achieved a cure.CONCLUSIONS.The results from this study highlighted distinctive clinical features and prognostic indicators of poorly differentiated LCNEC. Peripheral isolated lymph node clinical presentation is proposed as a new clinical entity. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Faggiano

Sabourin

Ducreux

et al. 2007

Cancer

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“…However, it has been reported that patients with stage I large cell neuroendocrine carcinoma, who were treated with either neoadjuvant or postoperative adjuvant chemotherapy, had significantly higher survival rates than patients treated only with surgery. 9 The aim of this study was to elucidate the morphological, phenotypical, and genetic characteristics of large cell neuroendocrine carcinoma and compare them with those of small cell carcinoma, to determine the biological differences of these two tumors, and to evaluate the utility of these markers for the diagnosis of neureondocrine tumors and the prognosis according to the expression of these proteins.…”

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confidence: 99%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

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“…También hay experiencias con el uso de quimioterapia neoadyuvante, adyuvante y radioterapia 43,45,46 . En la serie de Iyoda, la quimioterapia adyuvante basada en cisplatino, prolongó la supervivencia de los CNCG en estadios iniciales 47 . En nuestra serie (Tabla IV), los dos pacientes tratados con quimioterapia adyuvante tuvieron supervivencias prolongadas.…”

Section: Discussionunclassified

Carcinoma neuroendocrino de células grandes de pulmón: análisis de una serie de once casos en un hospital universitario

et al. 2006

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ResumenPropósito: Los tumores pulmonares con diferenciación neuroendocrina (DN) son un grupo heterogéneo de neoplasias que incluyen tumores carcinoides típicos, carcinoides atípicos, carcinomas neuroendocrinos de células grandes (CNCG) y carcinoma pulmonar de células pequeñas. Los CNCG constituyen menos del 5% de los carcinomas pulmonares no células pequeñas (CPNCP). En este trabajo se describe una serie de CNCG, tratados en un solo centro a lo largo de 10 años. Material y métodos:Se analizan 11 pacientes diagnosticados de CNCG (5 con histologías mixtas).Resultados: La edad media de los pacientes fue de 66 años, 5 fueron varones, 4 tuvieron enfermedad localizada, 5 localmente avanzada y 2 diseminada. Siete pacientes, con tumores localizados, fueron tratados con cirugía radical, 2 de ellos recibieron quimioterapia adyuvante; 1 quimioterapia y radioterapia y los otros 3 solo quimioterapia. La mediana de supervivencia de la serie es de 24 meses, y la supervivencia global a 2 y 5 años del 45% y 27% respectivamente. Conclusión:Los datos de nuestra serie corroboran las recomendaciones de que el manejo de los CNCG debe hacerse de forma similar al del resto de los CPNCP. La cirugía radical es el tratamiento fundamental en los tumores localizados. No hay datos suficientes que indiquen una peor respuesta a los tratamientos de quimioterapia o radioterapia en este tipo de tumores. Palabras clave:Carcinoma pulmonar. Células grandes. Diferenciación neuroendocrina. Oncología, 2006; 29 (8):321-328 IntroducciónLa clasificación histológica de los tumores epiteliales pulmonares, según la Organización Mundial de la Salud, incluye algunas tumoraciones de comportamiento benigno (Papilomas, adenomas, lesiones preinvasivas, etc) y otras, que representan la gran mayoría tanto por número como por incidencia, de desarrollo clínico generalmente maligno (Carcinomas de Células Escamosas, de Células Pequeñas, de Células Grandes, Adenocarcinomas, Carcinosarcomas, etc) 1 . La compleja y heterogénea clasificación, que forman el segundo grupo, se suele simplificar y dividir en dos grandes categorías con evolución, pronóstico y tratamiento diferente 2 : A. Carcinoma de pulmón de no célula pequeña (CPNCP): escamosos, células grandes, adenocarcinomas y combinados. B. Carcinomas de pulmón de células pequeñas (CPCP): "oat cell", células pequeñas/grandes, y combinado.Sin embargo, esta simplificación no satisface plenamente la comprensión y posibilidades terapéuti-cas de un importante subgrupo de tumores malignos, que vienen a denominarse como tumores neuroendocrinos pulmonares (TNP). Los TNP son un grupo heterogéneo de neoplasias cuya clasificación se ha ido estableciendo lo largo de las últimas déca-das, en base a criterios morfológicos por micoscopía óptica 3, 4 , y otros datos de diferenciación neuroendocrina (DN) demostrables por inmunohistoquí-mica o microscopía electrónica 5,6 . Dentro de los TNP se incluyen tumores carcinoides típicos, tumores carcinoides atípicos, carcinomas neuroendocrinos de células grandes (CNCG) y carcinoma pulmonar de célu...

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Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features

Cited by 81 publications

References 21 publications

Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Carcinoma neuroendocrino de células grandes de pulmón: análisis de una serie de once casos en un hospital universitario

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