Carcinoma of unknown primary site: development in a single institution of a prognostic model based on clinical and serum variables.

PURPOSE: To identify clinical and biologic variables with significant impact on survival in patients with carcinomas of an unknown primary site (CUP) and to develop a simple prognostic model. PATIENTS AND METHODS: In this retrospective study, univariate and multivariate prognostic factors analyses were conducted in a population of 100 patients with CUP. Patients with features requiring well defined treatments had previously been excluded. RESULTS: Overall survival (OS) was significantly related to the following pretreatment adverse prognostic clinical factors: a poor performance status (2 or 3), weight loss more than 10% in the last six months, the presence of liver metastases and more than two metastatic sites. Two biological parameters predicted a significantly shorter survival: elevated serum levels of alkaline phosphatase and of lactate dehydrogenase. In the multivariate analysis, only two independent adverse prognostic parameters were retained: a poor performance status and the presence of liver metastases. We developed a prognostic model for OS based on the following subgroups: good prognosis (PS 0 or 1 and absence of liver metastases), intermediate prognosis (PS> or =2 or presence of liver metastases) and poor prognosis (PS> or =2 or presence of liver metastases). Median OS for the three groups was 10.8, 4 and 1.9 months respectively, p<0.0001. CONCLUSION: A simple prognostic model using performance status and presence of liver metastases was developed. It allowed the assignment of patients into three subgroups with different outcomes. Treatment strategies could be adapted for each subgroup. We think that this prognostic model could be useful and should be validated in other patient series.

[Peritoneal mesothelioma: an inusual clinical presentation in a patient without exposure to asbestos]. / Mesotelioma peritoneal: una presentación clínica inusual en un paciente sin exposición al asbesto.

Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium. The predominant cause is inhalation exposure to asbestos. We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy.

[Meningeal myelomatosis as an exclusive form of recurrence in a case of IgA-lambda myeloma in complete systemic remission]. / Mielomatosis meníngea como forma exclusiva de recaída en un caso de mieloma IgA-lambda en remisión completa sistémica.

Meningeal myelomatosis is an extremely rare clinical presentation generally associated to terminal states of the disease and is more frequent in the presence of peripheric plasmocytosis or leukemia of the plasmatic cells. Diagnosis requires its demonstration in the cephalorhachidian liquid and its monoclonal secretion. A case of relapse of meningeal myelomatosis in a patient with multiple IgA-lambda myeloma is presented in which the systemic disease fulfilled the criteria for complete remission.

[Tetracycline pleurodesis for treatment of malignant pleural effusions. Retrospective study of 91 cases]. / Pleurodesis con tetraciclinas en el tratamiento del derrame pleural maligno. Estudio retrospectivo de 91 casos.

BACKGROUND: Malignant pleural effusions (MPE) are a common complication in patients with advanced neoplasms. Even though no large series confirming this exist, tetracycline pleurodesis has become the therapy of choice. The aim of this retrospective study was to evaluate its efficacy, adverse effects and possible factors predicting the success of the method. METHODS: Between 1985 through 1991, 91 patients with cytologically or histologically confirmed MPE were treated with 1,000-1,500 mg tetracycline pleurodesis. There were 49 females and 42 males, with a mean age of 59 years. The most common malignancies were lung, breast and unknown primary carcinomas. 85% patients complained of dyspnea and the volume of the effusion was moderate in half the cases. 12 variables were analyzed in relation with the probability of response through chi 2 test; survival and recurrence times were calculated with Kaplan and Meier's method. RESULTS: 73 patients were evaluable, with a 67% response rate (22 complete, 27 partial). Time to relapse was significantly higher for partial responses (mean 112 days) than for failures (mean 33 days). 37 patients presented mild complications (pain and fever). Karnofsky performance status (70% or greater), size of the effusion (small or moderate), chest radiograph (only effusion) and pleural LDH (600 U/l or less) attained favourable prognostic significance. Median survival was reached at 6 months. CONCLUSIONS: Tetracycline pleurodesis is an effective and well-tolerated paliative treatment for MPE. Along with other known parameters (pleural pH and glucose levels), Karnofsky performance status, size of the effusion, chest radiograph and pleural LDH allow to predict its results and optimize its indications.

[Thymomas]. / Timomas.

Thymomas are non-frequent neoplasias which are interesting because of their special association with the immune system pathology; although the pathogenic relationship has yet to be confirmed. A literature review is carried out on clinical aspects, prognosis and treatment, basically chemotherapy in advanced cases. Although they are classically categorized as benign, they are nevertheless considerably aggressive and maintain a low response to most active oncology treatment.

[Undifferentiated small cell tumor of the thoracopulmonary region]. / Tumor indiferenciado de células pequeñas de la región toracopulmonar.

The group of rounded small-cell tumors include different neoplasias involving different therapies; we can name neuroblastoma, Ewing' sarcoma, embrionary rhabdomyosarcoma, lymphoma and other pathology such as Askin's tumor or small cell tumor of the thorax area. Based on microscopic and immunohistochemistry findings, it is suggested that it originates from the neural crest or pluri-potential cells from the neuroectodermy. This has a very aggressive behaviour and is usually resistant to oncologic therapies.

[Synchronous presentation of thyroid carcinoma and malignant lymphoproliferative disease: report of 3 cases]. / Presentación sincrónica de carcinoma de tiroides y enfermedad linfoproliferativa maligna: a propósito de tres casos.

Multiple primary neoplasms are increasing in clinical practice, which is mainly due to the longer survival of cancer patients. Radiotherapy at an early stage of Hodgkin disease or lymphoma is well known to be associated with the future occurrence of secondary thyroid cancer. Nevertheless, the synchronous presentation of these two types of neoplasms is exceptional. We report here three cases of synchronic diagnosis of thyroid carcinoma and a malignant lymphoproliferative disease in patients who had not previously received radiotherapy nor chemotherapy. In malignant tumours of synchronic presentation, there is usually and underlying genetic predisposition involved in the etiology. In our patients, no carcinogenic environmental factor was demonstrated and, while this neoplastic association might be casual, an investigation on the possible individual predisposing factors would be warranted.

Mesotelioma peritoneal: una presentación clínica inusual en un paciente sin exposición al asbesto / Peritoneal mesothelioma: an inusual clinical presentation in a patient without exposure to asbestos

El mesotelioma maligno es un tumor insidioso que se origina de las superficies mesoteliales de las cavidades pleurales y peritoneales, la túnica vaginal o el pericardio. La principal causa relacionada es la exposición al asbesto. Presentamos el caso de un mesotelioma maligno peritoneal en un varón de 64 años, sin hábitos tóxicos ni exposición al asbesto, que debutó con síndrome constitucional y derrame pleural derecho. La tomografía por emisión de positrones combinada con tomografía axial computerizada (PET-TAC) fue de especial utilidad demostrando un intenso hipermetabolismo en peritoneo con extensión a pared torácica. El paciente inició tratamiento con quimioterapia sistémica, esquema cisplatino-pemetrexed, alcanzando una respuesta parcial tras los 3 ciclos pero con una evolución tórpida secundaria a toxicidad del tratamiento citostático

Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium. The predominant cause is inhalation exposure to asbestos. We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy

Heat shock proteins as targets in oncology

Heat shock proteins are ubiquitous molecular chaperones involved in posttranslational folding, stability, activation and maturation of many proteins that are essential mediators of signal transduction and cell cycle progression. Hsp90 proteins are the best studied proteins of this family. A growing number of Hsp90 client proteins have been shown to be important for the development, proliferation and survival of several types of cancer. Inhibition of Hsp90 leads to the degradation of known oncogene products, such as Her2, BRAF and others, leading to the simultaneous blockade of multiple oncogenic transduction pathways. Hsp90 inhibitors, derived from the natural compound geldanamycin, are attractive targets for anticancer drug development. We will review the clinical data on Hsp90 inhibitors in different malignancies. The best known of them, 17-AAG, has shown significant antitumour activity against a broad variety of cancers in preclinical studies, including breast, myeloma, melanoma, prostate and lung cancers. Hsp90 inhibitors can be used as single agents or in combination with other targeted treatments or chemotherapy and radiotherapy. The results of clinical phase II and III trials evaluating the effi cacy of these drugs in different types of tumours are awaited (AU)

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Biomarkers in bronchopulmonary cancer

Non-small-cell lung cancer (NSCLC) ranks among the neoplasms with the worst prognoses and the highest mortality rates. Several factors, mainly clinical, are known that provide a predictive value on the course of the disease. In the era in which we live, the molecular basis of cancer is studied in depth and several molecular markers have been described that could play a prognostic role or that could predict the probability of responding to the different treatments used. Moreover, some mechanisms have been proposed that could explain primary or acquired resistance to treatment with chemotherapy and to targeted therapies. Knowing all these pathways is very important, as it allows the development of selective therapeutic strategies that minimise toxicity and optimise treatment effectiveness. However, the data obtained yield results that are at times contradictory, prospective studies with biomarkers thus being necessary so that their role can be established with the necessary evidence (AU)

Orbital and myocardial metastases of a primary pulmonary melanotic schwannoma

We present the case of a 60-year-old man with a primary pulmonary melanotic schwannoma treated with surgery and who developed an orbital and myocardial relapse 2 years after the initial diagnosis. Melanotic schwannomas are rare pigmented tumours that tend to arise from the peripheral nerves near the midline. A primary lung presentation, as in our case, is extremely rare. In more than half of cases, the Carney triad of myxomas of the heart, skin and breast, spotty pigmentation and endocrine hyperactivity is present. A thorough pathological study is pivotal for a correct diagnosis. The main differential diagnosis is with metastases of malignant melanoma. The biological behaviour is unpredictable. Treatment should include radical surgery if possible; the role of chemotherapy and radiotherapy is uncertain due to the rarity of the tumour (AU)

Carcinoma of unknown primary site: development in a single institution of a prognostic model based on clinical and serum variables

PURPOSE: To identify clinical and biologic variables with significant impact on survival in patients with carcinomas of an unknown primary site (CUP) and to develop a simple prognostic model. PATIENTS AND METHODS: In this retrospective study, univariate and multivariate prognostic factors analyses were conducted in a population of 100 patients with CUP. Patients with features requiring well defined treatments had previously been excluded. RESULTS: Overall survival (OS) was significantly related to the following pretreatment adverse prognostic clinical factors: a poor performance status (2 or 3), weight loss more than 10% in the last six months, the presence of liver metastases and more than two metastatic sites. Two biological parameters predicted a significantly shorter survival: elevated serum levels of alkaline phosphatase and of lactate dehydrogenase. In the multivariate analysis, only two independent adverse prognostic parameters were retained: a poor performance status and the presence of liver metastases. We developed a prognostic model for OS based on the following subgroups: good prognosis (PS 0 or 1 and absence of liver metastases), intermediate prognosis (PS> or =2 or presence of liver metastases) and poor prognosis (PS> or =2 or presence of liver metastases). Median OS for the three groups was 10.8, 4 and 1.9 months respectively, p<0.0001. CONCLUSION: A simple prognostic model using performance status and presence of liver metastases was developed. It allowed the assignment of patients into three subgroups with different outcomes. Treatment strategies could be adapted for each subgroup. We think that this prognostic model could be useful and should be validated in other patient series (AU)

Tratamiento del cáncer de pulmón no microcítico avanzado y metastático con la combinación de paclitaxel-carboplatino-vinorelbina / Treatment of advanced and metostatic non-small-cell lung cancer with a combination of paclitaxel, carboplatin and vinorelbine

Objetivo: Evaluar efectividad y toxicidad de la combinación de paclitaxel- carboplatino-vinorelbina como tratamiento del cáncer de pulmón no microcítico estadios III-B y IV. Material y método: Entre septiembre de 1999 y diciembre del 2000, 28 pacientes fueron tratados con paclitaxel 150 mg/m2 día 1, carboplatino AUC 5 día 1 y vinorelbina 25 mg/m2 días 1 y 8.Resultados: Fueron administrados 134 ciclos, (mediana: 4 ciclos por paciente). La intensidad de dosis fue del 92 por ciento para el paclitaxel, 100 por ciento para el carboplatino y 84 por ciento para la vinorelbina. La dosis del día 8 fue suspendida en 22 ocasiones. La toxicidad hematológica del esquema fue escasa salvo la anemia (17 por ciento anemia grado 2-3). Las toxicidades extrahematológicas fueron: alopecia grado 2-3 (45 por ciento), emesis grado 2-3 (38 por ciento) y neurotoxicidad grado 2-3 (17 por ciento). Tasa de respuesta objetiva del 36 por ciento. Mediana de supervivencia de 12 meses y mediana de tiempo hasta la progresión de 2.5 meses. Concusiones: La combinación de estos tres fármacos, aunque bien tolerada no mejora los resultados de otras combinaciones. A pesar de la baja tasa de respuesta, la mediana de supervivencia es similar a la obtenida con otros esquemas (AU)

Combinación gemcitabina-cisplatino en el tratamiento del carcinoma broncopulmonar no microcítico estadios III-B y IV. Resultados de un ensayo fase II / Combination therapy with gemcitabine and displatin in stages III-B and IV non-samll cell lung cancer (NOSCLC). Results of a phase II trial

Propósito: La Gemcitabina presenta, como agente único, un índice de respuestas de 20-28 por ciento en el carcinoma no microcítico de pulmón (CPCNP). La asociación Gemcitabina y Cisplatino resulta atractiva para el tratamiento de estas neoplasias. En estudios previos con la combinación se ha objetivado cerca de un 40 por ciento de respuestas. Material y métodos: Ensayo fase II en pacientes afectos de CPCNP, estadios III-B y IV. Esquema de tratamiento: Gemcitabina 1200 mg./m2 (días 1 y 8) y Cisplatino 100 mg/m2 (día 1), cada 21 días. Desde junio 1998 a octubre 1999 se han incluido 26 pacientes, 19 estadios IIIB y 7 estadios IV. Resultados: Se administraron un total de 105 ciclos. La mediana de la intensidad de dosis global fue de 88 por ciento. Efectos secundarios: trombopenia grado 3/4 (37 por ciento de los casos), neutropenia grado 3/4 (31 por ciento) y emesis grado 3 (23 por ciento). Se registraron 14 respuestas parciales (53,8 por ciento, IC 9'5 por ciento: 40 por ciento-80 por ciento). En 18 pacientes (69 por ciento) se administró radioterapia posterior como consolidación. La mediana del tiempo hasta la progresión fue de 5 meses. La supervivencia actuarial a los 18 meses fue de 38 por ciento; mediana de supervivencia de 12 meses. Conclusiones: La combinación es activa en este grupo de pacientes y su toxicidad aceptable (AU)