Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia / Apresentação clínica, resultados do tratamento e fatores relacionados à resistência em mulheres sul-americanas com neoplasia trofoblástica gestacional pós-molar de baixo risco

Abstract Objective There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Methods Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. Results A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p= 0.019). Conclusion 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Resumo Objetivo Existem poucos estudos multinacionais sobre os resultados do tratamento da neoplasia trofoblástica gestacional (NTG) na América do Sul. O objetivo deste estudo foi avaliar a apresentação clínica, os resultados do tratamento e os fatores associados a casos de quimiorresistência em NTG pós-molar de baixo risco tratados com quimioterapia de agente único de primeira linha em três centros sul-americanos. Métodos Estudo multicêntrico de coorte histórica incluindo mulheres com NTG pós-molar de baixo risco com estadiamento International Federation of Gynecology and Obstetrics (FIGO) em centros de atendimento na Argentina, Brasil e Colômbia entre 1990 e 2014. Foram obtidos dados sobre as características do paciente, apresentação da doença e resposta ao tratamento. A regressão logística foi usada para avaliar a relação entre fatores clínicos e resistência ao tratamento de primeira linha com agente único. Foi realizada uma análise multivariada dos fatores clínicos significativos na análise univariada. Resultados Cento e sessenta e três mulheres com NTG de baixo risco foram incluídas na análise. A taxa global de resposta completa à quimioterapia de primeira linha foi de 80% (130/163). As taxas de resposta completa ao metotrexato ou actinomicina-D como tratamento de primeira linha e actinomicina-D como tratamento de segunda linha após falha do metotrexato foram 79% (125/157), 83% (⅚) e 70% (23/33), respectivamente. A mudança para o tratamento de segunda linha por quimiorresistência ocorreu em 20,2% dos casos (33/163). A análise multivariada demonstrou que pacientes com pontuação de risco FIGO de 5 a 6 foram 4,2 vezes mais propensos a desenvolver resistência ao tratamento com agente único de primeira linha (p= 0,019). Conclusão 1) Na apresentação, a maioria das mulheres demonstrou características clínicas favoráveis a um bom resultado, 2) a taxa geral de remissão completa sustentada após o tratamento de primeira linha com agente único foi comparável à de países desenvolvidos, 3) um escore de risco FIGO de 5 ou 6 está associado ao desenvolvimento de resistência à quimioterapia de agente único de primeira linha.

Infección por COVID-19 en pacientes oncológicos y asociación con el tratamiento recibido / COVID-19 infection in cancer patients and association with the antineoplastic treatment

Resumen La evidencia que relaciona la terapia oncológica con la incidencia por COVID-19 varía según el tipo de terapia administrada. La incidencia informada en pacientes que reciben tratamiento oncológico varía entre 1 y 4%. El objetivo del presente estudio fue determinar la incidencia por COVID-19 en pacientes oncológicos en tratamiento activo y evaluar si existe asociación con el esquema recibido. Se utilizó una cohorte retrospectiva que incluyó de forma consecutiva a los pacientes adultos que realizaron tratamiento ambulatorio desde marzo/2020 hasta abril/2021 en un Hospital Público de referencia. El evento principal fue el diagnóstico confirmado de COVID-19. La asociación con los tratamientos oncológicos fue evaluada mediante regresión logís tica multivariada ajustando por edad, sexo, localización del tumor, cobertura de salud y localidad de residencia. Se incluyeron 463 pacientes, mediana de edad 58 años (RIC = 47-66), 73.3% (n = 337) mujeres. La incidencia de COVID-19 fue 5.6% (n = 26) con una tasa de mortalidad del 12% (n = 3). El riesgo de infección fue mayor en los que estaban realizando tratamiento únicamente con anticuerpos monoclonales, 14.3% vs. 4.9% (OR-ajustado = 3.3, p = 0.03) y aquellos en tratamiento con inhibidores de puntos de control inmunológicos, 23.1% vs. 5.1% (OR-ajustado = 5.8, p = 0.03). La quimioterapia citotóxica, sola o en combinación con anticuerpos mo noclonales, no presentó mayor riesgo de infección. La edad, sexo, sitio tumoral, cobertura de salud y localidad de residencia no se asoció con la incidencia de COVID-19. En base a nuestros resultados, el tratamiento con anticuerpos monoclonales o inhibidores de puntos de control inmunológicos se asoció con mayor incidencia de infección por COVID-19.

Abstract Evidence linking anticancer therapy with the incidence of COVID-19 varies according to the type of therapy administered. The reported COVID-19 incidence in patients receiving antineoplastic treatment varies between 1 and 4%. The aim of this study was to determine the incidence of COVID-19 in cancer patients under active treatment and to assess whether there is an association with the received anticancer therapy. It was a retrospective cohort that consecutively included adult outpatients who underwent treatment in a referral center from March 2020 to April 2021. The primary endpoint was the confirmed diagnosis of COVID-19. The association with anticancer treatments was evaluated using multivariate logistic regression adjusting for age, sex, tumor site, health coverage status, and place of residence. The sample included 463 patients, the median age was 58 years (IQR = 47-66), 73.3% (n = 337) were women. The incidence of COVID-19 was 5.6% (n = 26) with a mortality rate of 12% (n = 3). The risk of infection was higher in patients undergoing treatment only with monoclonal antibod ies, 14.3% vs. 4.9% (adjusted OR = 3.3, p = 0.03) and those in treatment with immunotherapy, 23.1% vs. 5.1% (adjusted OR = 5.8, p = 0.03). Cytotoxic chemotherapy, alone or in combination with monoclonal antibodies, did not present an increased risk of infection. Age, sex, tumor site, health coverage, and place of residence did not show association with the incidence of COVID-19. Based on our results, treatment with monoclonal antibodies or immunotherapy was associated with a higher rate of COVID-19 infection while chemotherapy did not modify the incidence of COVID-19.

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia.

OBJECTIVE: There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. METHODS: Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. RESULTS: A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p = 0.019). CONCLUSION: 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

OBJETIVO: Existem poucos estudos multinacionais sobre os resultados do tratamento da neoplasia trofoblástica gestacional (NTG) na América do Sul. O objetivo deste estudo foi avaliar a apresentação clínica, os resultados do tratamento e os fatores associados a casos de quimiorresistência em NTG pós-molar de baixo risco tratados com quimioterapia de agente único de primeira linha em três centros sul-americanos. MéTODOS: Estudo multicêntrico de coorte histórica incluindo mulheres com NTG pós-molar de baixo risco com estadiamento International Federation of Gynecology and Obstetrics (FIGO) em centros de atendimento na Argentina, Brasil e Colômbia entre 1990 e 2014. Foram obtidos dados sobre as características do paciente, apresentação da doença e resposta ao tratamento. A regressão logística foi usada para avaliar a relação entre fatores clínicos e resistência ao tratamento de primeira linha com agente único. Foi realizada uma análise multivariada dos fatores clínicos significativos na análise univariada. RESULTADOS: Cento e sessenta e três mulheres com NTG de baixo risco foram incluídas na análise. A taxa global de resposta completa à quimioterapia de primeira linha foi de 80% (130/163). As taxas de resposta completa ao metotrexato ou actinomicina-D como tratamento de primeira linha e actinomicina-D como tratamento de segunda linha após falha do metotrexato foram 79% (125/157), 83% (⅚) e 70% (23/33), respectivamente. A mudança para o tratamento de segunda linha por quimiorresistência ocorreu em 20,2% dos casos (33/163). A análise multivariada demonstrou que pacientes com pontuação de risco FIGO de 5 a 6 foram 4,2 vezes mais propensos a desenvolver resistência ao tratamento com agente único de primeira linha (p = 0,019). CONCLUSãO: 1) Na apresentação, a maioria das mulheres demonstrou características clínicas favoráveis a um bom resultado, 2) a taxa geral de remissão completa sustentada após o tratamento de primeira linha com agente único foi comparável à de países desenvolvidos, 3) um escore de risco FIGO de 5 ou 6 está associado ao desenvolvimento de resistência à quimioterapia de agente único de primeira linha.

[COVID-19 infection in cancer patients and association with the antineoplastic treatment]. / Infección por COVID-19 en pacientes oncológicos y asociación con el tratamiento recibido.

Evidence linking anticancer therapy with the incidence of COVID-19 varies according to the type of therapy administered. The reported COVID-19 incidence in patients receiving antineoplastic treatment varies between 1 and 4%. The aim of this study was to determine the incidence of COVID-19 in cancer patients under active treatment and to assess whether there is an association with the received anticancer therapy. It was a retrospective cohort that consecutively included adult outpatients who underwent treatment in a referral center from March 2020 to April 2021. The primary endpoint was the confirmed diagnosis of COVID-19. The association with anticancer treatments was evaluated using multivariate logistic regression adjusting for age, sex, tumor site, health coverage status, and place of residence. The sample included 463 patients, the median age was 58 years (IQR = 47-66), 73.3% (n = 337) were women. The incidence of COVID-19 was 5.6% (n = 26) with a mortality rate of 12% (n = 3). The risk of infection was higher in patients undergoing treatment only with monoclonal antibodies, 14.3% vs. 4.9% (adjusted OR = 3.3, p = 0.03) and those in treatment with immunotherapy, 23.1% vs. 5.1% (adjusted OR = 5.8, p = 0.03). Cytotoxic chemotherapy, alone or in combination with monoclonal antibodies, did not present an increased risk of infection. Age, sex, tumor site, health coverage, and place of residence did not show association with the incidence of COVID-19. Based on our results, treatment with monoclonal antibodies or immunotherapy was associated with a higher rate of COVID-19 infection while chemotherapy did not modify the incidence of COVID-19.

La evidencia que relaciona la terapia oncológica con la incidencia por COVID-19 varía según el tipo de terapia administrada. La incidencia informada en pacientes que reciben tratamiento oncológico varía entre 1 y 4%. El objetivo del presente estudio fue determinar la incidencia por COVID-19 en pacientes oncológicos en tratamiento activo y evaluar si existe asociación con el esquema recibido. Se utilizó una cohorte retrospectiva que incluyó de forma consecutiva a los pacientes adultos que realizaron tratamiento ambulatorio desde marzo/2020 hasta abril/2021 en un Hospital Público de referencia. El evento principal fue el diagnóstico confirmado de COVID-19. La asociación con los tratamientos oncológicos fue evaluada mediante regresión logística multivariada ajustando por edad, sexo, localización del tumor, cobertura de salud y localidad de residencia. Se incluyeron 463 pacientes, mediana de edad 58 años (RIC = 47-66), 73.3% (n = 337) mujeres. La incidencia de COVID-19 fue 5.6% (n = 26) con una tasa de mortalidad del 12% (n = 3). El riesgo de infección fue mayor en los que estaban realizando tratamiento únicamente con anticuerpos monoclonales, 14.3% vs. 4.9% (ORajustado = 3.3, p = 0.03) y aquellos en tratamiento con inhibidores de puntos de control inmunológicos, 23.1% vs. 5.1% (OR-ajustado = 5.8, p = 0.03). La quimioterapia citotóxica, sola o en combinación con anticuerpos monoclonales, no presentó mayor riesgo de infección. La edad, sexo, sitio tumoral, cobertura de salud y localidad de residencia no se asoció con la incidencia de COVID-19. En base a nuestros resultados, el tratamiento con anticuerpos monoclonales o inhibidores de puntos de control inmunológicos se asoció con mayor incidencia de infección por COVID-19.

Outcomes in the management of high-risk gestational trophoblastic neoplasia in trophoblastic disease centers in South America.

BACKGROUND: South America has a higher incidence of gestational trophoblastic disease than North America or Europe, but whether this impacts chemotherapy outcomes is unclear. The purpose of this study was to evaluate outcomes among women with high-risk gestational trophoblastic neoplasia (GTN) treated at trophoblastic disease centers in developing South American countries. METHODS: This retrospective cohort study included patients with high-risk GTN treated in three trophoblastic disease centers in South America (Botucatu and Rio de Janeiro, Brazil, and Buenos Aires, Argentina) from January 1990 to December 2014. Data evaluated included demographics, clinical presentation, FIGO stage, WHO prognostic risk score, and treatment-related information. The primary treatment outcome was complete sustained remission by 18 months following completion of therapy or death. RESULTS: Among 1264 patients with GTN, 191 (15.1%) patients had high-risk GTN and 147 were eligible for the study. Complete sustained remission was ultimately achieved in 87.1% of cases overall, including 68.4% of ultra high-risk GTN (score ≥12). Early death (within 4 weeks of initiating therapy) was significantly associated with ultra high-risk GTN, occurring in 13.8% of these patients (p=0.003). By Cox's proportional hazards regression, factors most strongly related to death were non-molar antecedent pregnancy (RR 4.35, 95% CI 1.71 to 11.05), presence of liver, brain, or kidney metastases (RR 4.99, 95% CI 1.96 to 12.71), FIGO stage (RR 3.14, 95% CI 1.52 to 6.53), and an ultra-high-risk prognostic risk score (RR 7.86, 95% CI 2.99 to 20.71). Median follow-up after completion of chemotherapy was 4 years. Among patients followed to that timepoint, the probability of survival was 90% for patients with high-risk GTN (score 7-11) and 60% for patients with ultra-high-risk GTN (score ≥12). CONCLUSION: Trophoblastic disease centers in developing South American countries have achieved high remission rates in high-risk GTN, but early deaths remain an important problem, particularly in ultra-high-risk GTN.

[Pulmonary tumorlet associated with second neoplasia]. / Asociación de tumorlet pulmonar con segundas neoplasias.

Tumorlets are pulmonary neuroendocrine tumors smaller than 0.5 cm. They are benign and usually asymptomatic. Their diagnosis is important so as to differentiate them from other neuroendocrine pathologies that require therapeutic intervention. We report a case of such entity and a discussion on the subject that can contribute to highlight the importance of diagnosing this entity.

Asociación de tumorlet pulmonar con segundas neoplasias / Pulmonary tumorlet associated with second neoplasia

Los tumorlets son tumores neuroendocrinos pulmonares menores a 0.5 cm, de evolución benigna y habitualmente asintomáticos. Su diagnóstico es importante para realizar la diferenciación con otras afecciones neuroendocrinas y enfermedad metastásica de otro origen, que requerirán una intervención terapéutica. Se presenta un caso de dicha entidad asociada a otros tumores.

Tumorlets are pulmonary neuroendocrine tumors smaller than 0.5 cm. They are benign and usually asymptomatic. Their diagnosis is important so as to differentiate them from other neuroendocrine pathologies that require therapeutic intervention. We report a case of such entity and a discussion on the subject that can contribute to highlight the importance of diagnosing this entity.

Low molecular weight hyaluronan induces migration of human choriocarcinoma JEG-3 cells mediated by RHAMM as well as by PI3K and MAPK pathways.

Hyaluronan (HA) is the major glycosaminoglycan present in the extracellular matrix. It is produced by some tumours and promotes proliferation, differentiation and migration among others cellular processes. Gestational trophoblastic disease (GTD) is composed by non-tumour entities, such as hydatidiform mole (HM), which is the most common type of GTD and also malignant entities such as choriocarcinoma (CC) and placental site trophoblastic tumour (PSTT), being CC the most aggressive tumour. Although there is a growing understanding of GTD biology, the role of HA in the pathogenesis of this group of diseases remains largely unknown. The aim of this work was to study the role of HA in the pathogenesis of GTD by defining the expression pattern of HA and its receptors CD44 and RHAMM, as well as to determine if HA can modulate proliferation, differentiation and migration of CC cells. Receptors and signalling pathways involved were also analyzed. We demonstrated that HA and RHAMM are differently expressed among GTD entities and even among trophoblast subtypes. We also showed that HA is able to enhance the expression of extravillous trophoblast markers and also to induce migration of JEG-3 cells, the latter mediated by RHAMM as well as PI3K and MAPK pathways. These findings indicate a novel regulatory mechanism for CC cell biology and also contribute to the understanding of GTD pathophysiology.

Role of Capecitabine in the Management of Gestational Trophoblastic Neoplasia: A Drug for Two Settings.

OBJECTIVE: To evaluate the role of capecitabine in the management of gestational trophoblastic neoplasia (GTN). STUDY DESIGN: The medical records of 155 patients with GTN were reviewed. All patients were treated and followed at our center. RESULTS: All patients were scored and stratified with the FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease. In the low-risk group (118 patients), 4 selected patients received capecitabine as second line of treatment, with a 75% response rate and long-term disease-free survival, and 1 of those patients needed EMA/CO to achieve cure. The cure rate was 100%. In the high-risk group 37 patients were reviewed. Capecitabine was indicated after EMA/CO or EMA/PE failure in the second, third, or sixth line. Six patients received capecitabine, with a 50% response rate, and remain as long-term survivors. Two patients who progressed with capecitabine were cured with TP/TE and EMA/PE regimens. One patient was refractory to all lines of chemotherapy. CONCLUSION: The use of capecitabine avoids multi-ple drug schemes and further toxicity for patients with curative disease, where long-term effects of therapy should be considered a second target. Its convenient oral route of administration and efficacy make capecitabine a drug to be taken into account in future studies of patients with GTN showing progression to standard regimens. Its use as new regimen in these patients must be evaluated. A greater number of cases and ideally a randomized study is needed to confirm our observation.

Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial.

IMPORTANCE: Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein ubiquitously expressed in clear cell renal cell carcinoma (ccRCC). Its safety and activity in phase 2 studies prompted investigation into its use as adjuvant monotherapy in participants with high-risk ccRCC. OBJECTIVE: To evaluate the safety and efficacy of adjuvant girentuximab on disease-free survival (DFS) and overall survival (OS) in patients with localized completely resected high-risk ccRCC. DESIGN, SETTING, AND PARTICIPANTS: The ARISER trial (Adjuvant Rencarex Immunotherapy Phase 3 Trial to Study Efficacy in Nonmetastatic RCC) was a randomized, double-blind, placebo-controlled phase 3 clinical trial that took place between June 10, 2004, and April 2, 2013, at 142 academic medical centers in 15 countries in North and South America and Europe. Eligible adult patients had undergone partial or radical nephrectomy for histologically confirmed ccRCC and fell into 1 of the following high-risk groups: pT3/pT4Nx/N0M0 or pTanyN+M0 or pT1b/pT2Nx/N0M0 with nuclear grade 3 or greater. Patients were assigned via central computerized double-blind 1:1 randomization to receive either a single loading dose of girentuximab, 50 mg (week 1), followed by weekly intravenous infusions of girentuximab, 20 mg (weeks 2-24), or placebo, stratified by risk group and region. The data were analyzed from March 31, 2012, to April 2, 2013. MAIN OUTCOMES AND MEASURES: Co-primary end points were DFS and OS, based on imaging studies assessed by independent radiological review committee. Secondary end points included safety, assessed as the rate and grade of adverse events. RESULTS: A total of 864 patients (66% male; median [interquartile range] age, 58 [51-65] years) were randomized to girentuximab (n = 433) or placebo (n = 431). Compared with placebo, participants treated with girentuximab had no statistically significant DFS (hazard ratio, 0.97; 95% CI, 0.79-1.18) or OS advantage (hazard ratio, 0.99; 95% CI, 0.74-1.32). Median DFS was 71.4 months (interquartile range, 3 months to not reached) for girentuximab and never reached for placebo group. Median OS was never reached regardless of treatment. Drug-related adverse events occurred in 185 patients (21.6%), reported comparably between arms. Serious adverse events occurred in 72 patients (8.4%), reported comparably between arms. One drug-related serious adverse event occurred in a patient receiving placebo. CONCLUSIONS AND RELEVANCE: Girentuximab had no clinical benefit as adjuvant treatment for patients with high-risk ccRCC. The surprisingly long DFS and OS in these patients represent a challenge to adjuvant ccRCC drug development. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00087022.

Inmunoterapia en cáncer / Inmunotherapy in Cancer

Tradicionalmente, el tratamiento de las enfermedades tumorales se basa en la cirugía, el uso de radiaciones ionizantes y la quimioterapia. Este paradigma se consolidó durante el siglo XX y logró un importante paso adelante en la cura y en la calidad de vida de los pacientes...

Gestational trophoblastic disease: a 21-year review of the clinical experience at an Argentinean public hospital.

OBJECTIVE: To analyze the clinical trends of gestational trophoblastic disease (GTD) in a public hospital of Buenos Aires, Argentina. STUDY DESIGN: A review of the clinical records of 358 patients with a diagnosis of GTD admitted to Durand Trophoblastic Disease Center between 1990 and February 2011 was performed. Features of diagnosis, treatment and follow-up were analyzed. RESULTS: A total of 358 cases of GTD were reviewed. Hydatidiform mole was diagnosed in 340 patients; of those 223 (66%) experienced spontaneous remission after evacuation. Of the 135 patients with persistent gestational trophoblastic neoplasia (GTN), 99 (73%) had low-risk GTN, 32 (26%) had high-risk GTN and 4 had either placental site trophoblastic disease or epithelioid trophoblastic tumor. In the low-risk group the first-line treatment was methotrexate and the second-line treatment was actinomycin D, etoposide, cytoxan, and oncovin (EMA/CO), with a complete response rate of 100%. High-risk patients whose WHO prognostic scores were 7-13 were treated initially with EMA/CO. Patients whose scores were >13 were treated with EMA/PE, where platinum and etoposide replaced oncovin and cytoxan. Salvage therapy in patients with relapse or resistant disease were treated with a wide variety of chemotherapy regimens. The complete response rate was 98.2%. Compliance was 100%. Three patients died. In all cases the outcome was related with inadequate initial treatment. CONCLUSION: This protocol is in agreement with international consensus. It was useful, safe and feasible in our population. The compliance with international guidelines allows reach a successful treatment and follow-up in one Latin-American population.

[Hypertension as predictive factor in renal cell cancer treated with antiangiogenic therapy]. / Hipertensión arterial como factor predictivo en pacientes con cáncer renal tratados con antiangiogénicos.

Knowledge of several pathways of oncogenesis has led to the development of novel therapies in the treatment of advanced kidney cancer in the last five years. These have targeted the vascular endothelium-derived factor (VEGF) (angiogenesis) and mammalian target of rapamycin (mTOR). Antiangiogenics are a group of active molecules with a peculiar spectrum of toxicity including the development of hypertension, thyroid dysfunction and hand-foot syndrome. The identification of molecular and clinical predictors would allow to identify those patients who would benefit from such treatment and saveguarding the rest from toxic exposure. The occurrence of hypertension has been correlated with treatment response and clinical efficacy. In our retrospective series, patients treated with antiangiogenic agents who developed high blood pressure showed a higher response rate and disease-free interval compared to those without increased blood pressure. Hypertension should be considered a clinical predictor in the treatment of these patients. These findings should be confirmed in a larger study population.

Hipertensión arterial como factor predictivo en pacientes con cáncer renal tratados con antiangiogénicos / Hypertension as predictive factor in renal cell cancer treated with antiangiogenic therapy

El conocimiento de las diversas vías de oncogénesis ha llevado al desarrollo en los últimos cinco años de nuevas terapias para el tratamiento del cáncer renal avanzado, las que poseen como blanco al factor derivado del endotelio vascular (VEGF) y sus receptores (antiangiogénicos) y al blanco mamífero de la rapamicina (mTOR). Los antiangiogénicos constituyen un grupo de moléculas activas con un espectro de toxicidad peculiar que comprende el desarrollo de hipertensión arterial, disfunción tiroidea y síndrome de mano-pie. La identificación de factores predictivos clínicos y moleculares lograría identificar aquellos pacientes que se beneficiarían con dicho tratamiento, evitando exposición y toxicidad innecesaria al resto. La aparición de hipertensión arterial se ha correlacionado con respuesta al tratamiento y eficacia clínica. En nuestra serie retrospectiva, los pacientes tratados con antiangiogénicos que desarrollaron hipertensión arterial tuvieron aumento de la tasa de respuestas e intervalo libre de enfermedad en comparación con aquellos que, tratados de la misma manera, no manifestaron hipertensión. La hipertensión arterial debería considerarse como un factor predictor clínico en su tratamiento. Dichos hallazgos deberían ser corroborados en forma prospectiva y con un mayor número de pacientes.

Knowledge of several pathways of oncogenesis has led to the development of novel therapies in the treatment of advanced kidney cancer in the last five years. These have targeted the vascular endothelium-derived factor (VEGF) (angiogenesis) and mammalian target of rapamycin (mTOR). Antiangiogenics are a group of active molecules with a peculiar spectrum of toxicity including the development of hypertension, thyroid dysfunction and hand-foot syndrome. The identification of molecular and clinical predictors would allow to identify those patients who would benefit from such treatment and saveguarding the rest from toxic exposure. The occurrence of hypertension has been correlated with treatment response and clinical efficacy. In our retrospective series, patients treated with antiangiogenic agents who developed high blood pressure showed a higher response rate and disease-free interval compared to those without increased blood pressure. Hypertension should be considered a clinical predictor in the treatment of these patients. These findings should be confirmed in a larger study population.

[Adjuvant chemotherapy for non small cell lung cancer]. / Quimioterapia adyuvante en el cáncer de pulmón de células no pequeñas.

Lung cancer is one of the leading causes of death worldwide. Its incidence is directly related to tobacco use. The patients can be classified in three large groups: those with localized or resectable disease; those with locally advanced disease and lastly those with metastatic disease. Except for anecdotal cases, in the first group cure is possible. For these patients surgery is the treatment of choice. However, with the appearance of effective systemic chemotherapy, well designed cooperative studies and a better understanding of the biological behaviour, overall survival has improved for the first time in a hundred years. The role of adjuvant chemotherapy is a true option after a decade of clinical trials. The objective of this article is to perform a review of the available evidence which has made cisplatin based combinations is the treatment of choice after surgery for stages II-IIIA non-small cell lung cancer.

Quimioterapia adyuvante en el cáncer de pulmón de células no pequeñas / Adjuvant chemotherapy for non small cell lung cancer

El cáncer de pulmón constituye una de las principales causas de mortalidad en todo el mundo. Su incidencia se relaciona directamente al uso del tabaco. Puede clasificarse a los pacientes en tres grupos: con enfermedad localizada o resecable, con enfermedad localmente avanzada y con enfermedad metastásica. Excepto algunos casos, el primer grupo es pasible de curación. En ellos la cirugía es el tratamiento de elección. El advenimiento de quimioterapia sistémica efectiva, estudios cooperativos bien diseñados y mejor comprensión del comportamiento biológico han logrado mejorar la sobrevida global por primera vez en una centuria. El rol de la quimioterapia adyuvante encuentra un escenario cierto, luego de una década de estudios clínicos. El objetivo de este artículo es realizar una revisión de la evidencia disponible que ha colocado a las combinaciones basadas en cisplatino como el tratamiento de elección luego de la cirugía en los estadios II-IIIA del cáncer de pulmón de células no pequeñas.

Lung cancer is one of the leading causes of death worldwide. Its incidence is directly related to tobacco use. The patients can be classified in three large groups: those with localized or resectable disease; those with locally advanced disease and lastly those with metastatic disease. Except for anecdotal cases, in the first group cure is possible. For these patients surgery is the treatment of choice. However, with the appearance of effective systemic chemotherapy, well designed cooperative studies and a better understanding of the biological behaviour, overall survival has improved for the first time in a hundred years. The role of adjuvant chemotherapy is a true option after a decade of clinical trials. The objective of this article is to perform a review of the available evidence which has made cisplatin based combinations is the treatment of choice after surgery for stages II-IIIA non-small cell lung cancer.

Resección local endorrectal en el cáncer de recto / Endorrectal local resection in the rectum cancer

Antecedentes: La resección local (RL) transanal de los cánceres de recto fue históricamente catalogada como un procedimiento paliativo. En la actualidad, la RL transanal constituye un procedimiento curativo en pacientes selectos, en especial en aquellos con características favorables. Objetivos: Evaluar los resultados obtenidos con las RL en el tratamiento de cánceres de recto medio e inferior. Lugar de aplicación: Hospital general de agudos, asociado a la Universidad de Buenos Aires y práctica privada. Diseño: Evaluación retrospectiva. Material y Métodos: 28 pacientes (12 hombres) en quienes se realizó una RL. Todos lo cánceres eran bien o moderadamente diferenciados, hasta 4 cm de diámetro y ubicados hasta 7 cm del margen anal. La evaluación incluyó el tacto rectal, fibrocolonoscopia, tomografía computada, ecografía transrectal, radiografía de tórax, laboratorio que incluyó dosaje de antígeno cacinoembrionario y CA 19-9 y exámen cardiológico. En todos los casos la resección fue realizada con un margen macroscópico de 1 cm alrededor del timor, y en profundidad se llegó siempre hasta la grasa perirrectal. La congelación intraoperatoria de la pieza quirúrgica se realizó sistemñaticamente. El cierre de la brecha quirúrgica fue realizado con material reabsorbible. En todos los casos realizados con criterio curativo se realizó radio y quimioterapia postoperatoria. El seguimiento postoperatorio fue estricto y completo en todos los casos. Resultados: El índice de resecabilidad fue del 100%. En 24 casos la resección fue curativa. No hubo mortalidad operatoria. El diámetro promedio de los tumores fue 3,5 cm (2-5cm). Las complicaciones postoperatorias inmediatas observadas: neumoperitoneo (2 casos); alejadas: incontinencia de gases (1 caso), urgencia defecatoria (1 caso) y estenosis rectal (1 caso). Cuatro casos fueron T1 y los restantes T2. Todos los T1 y T2 operados están vivos y libres de enfermedad con un seguimiento promedio de 5 años (1-9 años)...