Gustavo Werutsky

Synchronous gastrointestinal stromal tumors (GIST) and other primary cancers: Case series of a single institution experience

BACKGROUND Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasm affecting the gastrointestinal tract. The incidental occurrence of mesenchymal tumors and other primary tumors has not been well described in literature. OBJECTIVE The aim of this study was to evaluate the clinical and pathologic features of GIST occurring synchronously with other primary tumors. METHODS Forty-three patients with diagnosis of GIST treated surgically with curative intent at our institution from 1998 to 2006 were included. The patient clinical data and pathological reports were reviewed. RESULTS Of the 43 patients, there were 6 (14%) cases of synchronous GIST and other primary tumors discovered as coincidental findings. The synchronous GISTs analyzed were located in the stomach (50%) and small intestine (50%), size ranging from 0.7 to 7.6 cm (median 3.35 cm). Five (83%) of the concurrent primary tumors were from gastrointestinal origin and only one (17%) patient presented with concurrent breast cancer and GIST. The synchronous GISTs immunofenotype shows positivity for CD117 and CD34 (100%), smooth-muscle actin (SMA) (67%), S100 (50%) and desmin (33%). Whereas staining for cytokeratin AE1/AE3 and PDGF were all negative. According to GIST risk category for aggressive behavior three were classified as very low, one intermediate and two high. CONCLUSIONS The synchronous occurrence of GISTs and other primary neoplasm is not an uncommon entity and usually they are discovery incidentally. Epithelial tumors of the gastrointestinal tract are the most associated with concomitant GISTs. Further studies are required to clarify the molecular and genetic mechanisms of carcinogenesis and progression associating GIST and synchronous tumors.

Inequalities in Pap smear screening for cervical cancer in Brazil.

OBJECTIVE To examine the risk factors associated with never being screened for cervical cancer (CC) in Brazil. METHODS Using the National Household Sample Survey 2008 (PNAD), we analyzed data from 102,108 Brazilian women ages 25-64years. The patients were analyzed as having been or never having been screened with a Pap smear (Yes/No). Age-adjusted prevalence of never-screening was analyzed using a Chi-squared test. Crude and adjusted models using Poisson regression were performed. RESULTS The prevalence of never-screened women for CC was 12.9%, 11.5% and 22.2% in Brazil in general, urban and rural areas, respectively. The Brazilian region with the highest prevalence of never-screening was the North (17.4%, 14.7% and 27.3% in general, urban and rural areas, respectively). The factors associated with a higher risk for never being screened were the following: poverty, younger age, lower educational level, non-white skin color, a greater number of children, no supplemental health insurance and not having visited a doctor in the past 12months. CONCLUSION Socioeconomic and demographic conditions lead to inequalities in access to Pap smear screening in Brazil. Public health policy addressing these risk groups is necessary.

Idade como fator prognóstico no câncer de mama em estádio inicial

OBJETIVO: Analisar a idade como fator prognostico no câncer de mama em estadio clinico inicial. METODOS: Estudo retrospectivo que analisou as caracteristicas clinicas e a sobrevida livre de doenca de 280 pacientes entre 25 e 81 anos com câncer de mama estagio clinico I e II com acompanhamento em hospital de Porto Alegre (RS), de 1995 a 2000. Dados clinicos, patologicos, tratamento e desfechos foram extraidos dos prontuarios das pacientes. As pacientes foram divididas em dois grupos conforme a idade ao diagnostico ( 40 anos). Os dois grupos foram comparados quanto ao estagio clinico, histologia, expressao de receptores hormonais, terapia e radioterapia utilizando o teste qui-quadrado e/ou exato de Fisher e para analise de sobrevida, o teste de long-rank e metodo de Kaplan-Meier. RESULTADOS: Do total de 280 mulheres estudadas, 54 (19,3%) tinham ate 40 anos de idade. Ambos os grupos de pacientes eram similares em estagio clinico, histologia e expressao de receptores hormonais. A proporcao de pacientes com sobrevida livre de doenca em seguimento de 56 meses foi significativamente maior nas pacientes acima de 40 anos (84% versus 70%). Proporcionalmente, as pacientes mais jovens receberam mais terapia adjuvante (88,8% versus 77,8%). Houve diferenca significativa na probabilidade das mulheres acima de 40 anos de permanecerem livre de doenca (84%), sendo mais evidente quando comparadas as pacientes com < 40 anos em estagio clinico I. CONCLUSOES: Os achados confirmam que mulheres de ate 40 anos com câncer de mama inicial apresentam um pior prognostico. Entretanto, tal prognostico parece nao estar relacionado a maior numero de casos com receptores hormonais negativos. Pacientes jovens que permaneceram livre de doenca receberam mais terapia adjuvante, sugerindo efeito positivo da quimioterapia e hormonioterapia.OBJECTIVE To analyze age as a prognostic factor in early breast cancer. METHODS Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (< or = 40 years and > 40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fishers exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS Of 280 women studied, 54 (19.3%) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84% versus 70%). Proportionally, younger subjects received more adjuvant therapy (88.8% vs. 77.8%). Those women over 40 years were significantly more likely to remain disease-free (84%), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.

Age as a prognostic factor in early breast cancer

OBJETIVO: Analisar a idade como fator prognostico no câncer de mama em estadio clinico inicial. METODOS: Estudo retrospectivo que analisou as caracteristicas clinicas e a sobrevida livre de doenca de 280 pacientes entre 25 e 81 anos com câncer de mama estagio clinico I e II com acompanhamento em hospital de Porto Alegre (RS), de 1995 a 2000. Dados clinicos, patologicos, tratamento e desfechos foram extraidos dos prontuarios das pacientes. As pacientes foram divididas em dois grupos conforme a idade ao diagnostico ( 40 anos). Os dois grupos foram comparados quanto ao estagio clinico, histologia, expressao de receptores hormonais, terapia e radioterapia utilizando o teste qui-quadrado e/ou exato de Fisher e para analise de sobrevida, o teste de long-rank e metodo de Kaplan-Meier. RESULTADOS: Do total de 280 mulheres estudadas, 54 (19,3%) tinham ate 40 anos de idade. Ambos os grupos de pacientes eram similares em estagio clinico, histologia e expressao de receptores hormonais. A proporcao de pacientes com sobrevida livre de doenca em seguimento de 56 meses foi significativamente maior nas pacientes acima de 40 anos (84% versus 70%). Proporcionalmente, as pacientes mais jovens receberam mais terapia adjuvante (88,8% versus 77,8%). Houve diferenca significativa na probabilidade das mulheres acima de 40 anos de permanecerem livre de doenca (84%), sendo mais evidente quando comparadas as pacientes com < 40 anos em estagio clinico I. CONCLUSOES: Os achados confirmam que mulheres de ate 40 anos com câncer de mama inicial apresentam um pior prognostico. Entretanto, tal prognostico parece nao estar relacionado a maior numero de casos com receptores hormonais negativos. Pacientes jovens que permaneceram livre de doenca receberam mais terapia adjuvante, sugerindo efeito positivo da quimioterapia e hormonioterapia.OBJECTIVE To analyze age as a prognostic factor in early breast cancer. METHODS Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (< or = 40 years and > 40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fishers exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS Of 280 women studied, 54 (19.3%) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84% versus 70%). Proportionally, younger subjects received more adjuvant therapy (88.8% vs. 77.8%). Those women over 40 years were significantly more likely to remain disease-free (84%), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.

A Phase II Randomized Study of Lapatinib Combined with Capecitabine, Vinorelbine, or Gemcitabine in Patients with HER2-Positive Metastatic Breast Cancer with Progression after a Taxane (Latin American Cooperative Oncology Group 0801 Study)

BACKGROUND Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. PATIENTS AND METHODS In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. RESULTS A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. CONCLUSION LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.

AIDS-related sinonasal Burkitt lymphoma successfully treated with intensive chemotherapy regimen and high active antiretroviral therapy

Burkitt lymphoma (BL) is the second most common AIDS-related lymphoma. Primary sinonasal BL in HIV patients is extremely rare and treatment data in this subset of patients is almost nonexistent. Recently, a few studies reported promising results treating HIV-associate BL with an intensive chemotherapy regimen. The use of highly active antiretroviral therapy (HAARTHAART) concomitantly with chemotherapy seems to improve patient outcomes, but this topic is still controversial due to potential drug interactions. We report a case of a 29-year old woman diagnosed with AIDS presenting with symptoms of chronic sinusitis. Subsequent investigation by CT scan and endoscopic biopsy discovered a sinonasal BL in an early stage. The patient was treated with intensive chemotherapy and HAARTHAART and achieved a complete remission and long-term immunologic recovery. This case report describes a rare entity whose natural history, treatment and prognosis is infrequently characterized in the medical literature.

Expressed Gene Fusions as Frequent Drivers of Poor Outcomes in Hormone Receptor–Positive Breast Cancer

We sought to uncover genetic drivers of hormone receptor-positive (HR+) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes, including PIK3CA, AKT3, RAF1, and ESR1, in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three-dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors. Correspondingly, fusions were uncommon (<5%) among 300 patients presenting with primary HR+ breast cancer. Collectively, our findings identify expressed gene fusions as frequent and potentially actionable drivers in HR+ breast cancer.Significance: By using a powerful clinical molecular diagnostic assay, we identified expressed intergenic fusions as frequent contributors to treatment resistance and poor survival in advanced HR+ breast cancer. The prevalence and biological and prognostic significance of these alterations suggests that their detection may alter clinical management and bring to light new therapeutic opportunities. Cancer Discov; 8(3); 336-53. ©2017 AACR.See related commentary by Natrajan et al., p. 272See related article by Liu et al., p. 354This article is highlighted in the In This Issue feature, p. 253.

Edad como factor pronóstico en el cáncer de mama en fase inicial

OBJETIVO: Analisar a idade como fator prognostico no câncer de mama em estadio clinico inicial. METODOS: Estudo retrospectivo que analisou as caracteristicas clinicas e a sobrevida livre de doenca de 280 pacientes entre 25 e 81 anos com câncer de mama estagio clinico I e II com acompanhamento em hospital de Porto Alegre (RS), de 1995 a 2000. Dados clinicos, patologicos, tratamento e desfechos foram extraidos dos prontuarios das pacientes. As pacientes foram divididas em dois grupos conforme a idade ao diagnostico ( 40 anos). Os dois grupos foram comparados quanto ao estagio clinico, histologia, expressao de receptores hormonais, terapia e radioterapia utilizando o teste qui-quadrado e/ou exato de Fisher e para analise de sobrevida, o teste de long-rank e metodo de Kaplan-Meier. RESULTADOS: Do total de 280 mulheres estudadas, 54 (19,3%) tinham ate 40 anos de idade. Ambos os grupos de pacientes eram similares em estagio clinico, histologia e expressao de receptores hormonais. A proporcao de pacientes com sobrevida livre de doenca em seguimento de 56 meses foi significativamente maior nas pacientes acima de 40 anos (84% versus 70%). Proporcionalmente, as pacientes mais jovens receberam mais terapia adjuvante (88,8% versus 77,8%). Houve diferenca significativa na probabilidade das mulheres acima de 40 anos de permanecerem livre de doenca (84%), sendo mais evidente quando comparadas as pacientes com < 40 anos em estagio clinico I. CONCLUSOES: Os achados confirmam que mulheres de ate 40 anos com câncer de mama inicial apresentam um pior prognostico. Entretanto, tal prognostico parece nao estar relacionado a maior numero de casos com receptores hormonais negativos. Pacientes jovens que permaneceram livre de doenca receberam mais terapia adjuvante, sugerindo efeito positivo da quimioterapia e hormonioterapia.OBJECTIVE To analyze age as a prognostic factor in early breast cancer. METHODS Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (< or = 40 years and > 40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fishers exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS Of 280 women studied, 54 (19.3%) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84% versus 70%). Proportionally, younger subjects received more adjuvant therapy (88.8% vs. 77.8%). Those women over 40 years were significantly more likely to remain disease-free (84%), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.