Sandro Martins

Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma

BACKGROUND The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that could play an important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential. METHODS We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage IIIB or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, Cox regression, and conjunctive consolidation. RESULTS The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%; range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio (HR): 1.03, 95% confidence interval (CI): 1.01-1.06; low TTF-1 expression (<40%) - HR: 4.00, 95% CI: 1.75-9.09; and high MMP-9 expression (> or =80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 or high MMP-9; median survival: 39.0 weeks); and high risk (low TTF-1 and high MMP-9; median survival: 16.4 weeks). CONCLUSION TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens.

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

BackgroundAlthough modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients.MethodsIn this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2), and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy.ResultsAnalysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively.ConclusionAge does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

Aspectos clínico-econômicos da quimioterapia adjuvante no câncer de mama HER-2 positivo

PURPOSE: To examine efficacy figures and drug expenditure for adjuvant chemotherapy in human epidermal growth factor receptor 2 (HER-2) positive breast cancer, in the Brazilian supplemental health insurance market. METHODS: We obtained efficacy data (disease free survival at 3-years) and drug cost estimate for current adjuvant strategies in HER-2 positive breast cancer: Finland Herceptin (FinHER), National Surgical Adjuvant Breast and Bowel Project (NSAPB-31), North Central Cancer Treatment Group (N9831), Herceptin Adjuvant (HERA) and Breast Cancer International Research Group (BCIRG-006). We estimated clinical impact measures - number needed to treat (NNT) and absolute risk reduction (ARR) - and total drug cost by protocol to avoid one single cancer recurrence. RESULTS: The largest ARR was 11.7% (95% CI: 2.2% to 21.2%) in the FinHER study, and the smallest in the nonanthracycline arm of the BCIRG trial, 4.9% (95% CI: 1.8% to 8.1%). The NNT was 8 (95% CI: 3 to 28) in the FinHER, 8 (95% CI: 7 to 11) in the NSABP-31/N9831, 12 (95% CI: 9 to 18) in the HERA, 14 (95% CI: 11 to 24) in the BCIRG/Anthracycline, and 17 (CI 95% CI: 12 to 34) in the BCIRG/Nonanthracycline. Drug cost to avoid one single cancer recurrence would be R

Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer

418,285.44 with the FinHER regimen, R

Marcadores morfológicos de prognóstico no mesotelioma maligno: um estudo de 58 casos

1,716,789.44 with the NSABP-31/N9831, R

Extrahepatic biliary cystadenocarcinoma mimicking Klatskin tumor

2,481,891.58 with the HERA, R

CRITICAL EVALUATION OF LONG-TERM RESULTS OF MALIGNANT HEPATIC TUMORS TREATED BY MEANS CURATIVE LAPAROSCOPIC HEPATECTOMY

2,963,634.62 with the BCIRG/Anthracicline, and R

Nuclear and environment morphometric profile in tumor size and nodal metastasis of resected typical pulmonary carcinoid

3,930,520.43 with the BCIRG/Nonanthracycline (exchange rate: R

Thyroid transcription factor-1 and matrix metalloproteinase-9 in the prognostic assessment of patients with lung adenocarcinoma

1.00 = USD 0.56). CONCLUSION: From an economic viewpoint, four to seven times more patients could benefit by using a short-course of trastuzumab at the initial adjuvant chemotherapy cycles (FinHER regimen) than by the prolonged trastuzumab administration as used in other adjuvant schedules.

Epidermal growth factor receptor (EGFR) status and prognosis in gallbladder cancer.

BackgroundMedical oncologists continue to use performance status as a proxy for quality of life (QOL) measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy.MethodsWe enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2).ResultsPatient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival.ConclusionLCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.