Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.

This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.

Outcomes, toxicity profiles, and prognostic factors of unresectable head and neck cancer treated with chemoradiotherapy

Introduction: Head and neck cancer (HNC) is a heterogeneous group of neoplasms that can have a poor prognosis when diagnosed in advanced stages. The optimized treatment for locally advanced and unresectable lesions is mainly based on radiotherapy associated with chemotherapy (cisplatin 100mg/m²), however, at the expense of a high toxicity index. Objective: Evaluate whether chemoradiotherapy (CRT) ­ the goldstandard treatment for locally advanced head and neck cancer (HNC) ­ is effective in the study population. Methods: This is a retrospective study aimed at determining the efficacy of definitive CRT in patients with unresectable HNC treated between the 2012 and 2018 in a single institution. The following outcomes were evaluated: objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: Fifty-two (52) patients diagnosed with HNC between 2012 and 2018 met the inclusion criteria. The ORR was 84.6%, with 50% showing complete response. Median PFS and OS were 35.3 and 52 months, respectively. Analysis of the toxicity profiles revealed that 69.2% of the patients presented grade 3-4 toxicity. Completion of two or more cycles of cisplatin-based therapy (HR 3.57 [95% CI 1.25­10.25]; p p<0.001), grade 3-4 toxicity (HR 0.27 [95% CI 0.09-0.8] ­ p<0.02), and Charlson comorbidity index (CCI) (HR 3.23 [95% CI 1.26­8.29]; p<0.001) were significantly associated with survival. Regarding toxicity, prophylactic low-level laser therapy (HR 0.48 [95% CI 0.27­0.86]; p<0.001 for those without this practice) and body mass index (BMI) (HR 0.27 [95% CI 0.09­0.76]; p<0.01) showed statistical significance. Conclusion: CRT was effective to treat HNC in the study population, with PFS and OS comparable to those reported in larger sample studies and lower toxicity grade. Some clinical characteristics have been identified as prognostic and/or predictive factors.

RELATIONSHIP BETWEEN OBESITY AND BREAST CANCER / Relação entre obesidade e câncer de mama

Obesity is a growing clinical condition around the world, considered a risk factor for numerous diseases such as hypertension, myocardial infarction, diabetes, and cancer. Among the neoplasms related to overweight, breast cancer stands out. Therefore, the objective of this review is to elucidate the impact of obesity on the most prevalent cancer among women, either as a direct risk factor for its onset or as a determinant of survival

A obesidade aponta como condição clínica em ascensão pelo mundo, considerada fator de risco para inúmeras doenças como hipertensão, infarto, diabetes e câncer. Dentre as neoplasias relacionadas com o excesso de peso, destaca-se o câncer de mama. O objetivo desta revisão é, portanto, elucidar o impacto que a obesidade causa no câncer mais prevalente entre as mulheres, seja como fator de risco direto para seu aparecimento, seja como determinante na sobrevida

KRAS mutation associated with CD44/CD166 immunoexpression as predictors of worse outcome in metastatic colon cancer.

INTRODUCTION: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation. OBJECTIVE: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome. MATERIAL AND METHODS: Fifty-eight samples of tumor tissue samples of metastatic colon adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray. RESULTS: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007). CONCLUSION: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis.

Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma.

BACKGROUND: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes. METHODS: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status. RESULTS: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients. CONCLUSION: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.

Tumor neuroendócrino primário de mama: relato de três casos e revisão de literatura / Primary neuroendocrine carcinoma of the breast: case report and literature review

Os tumores neuroendócrinos primários de mama (TNPMs) são incomuns e não há consenso quanto a tratamento e prognóstico. No presente trabalho, foram revisados os diagnósticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP), identificando três casos que preenchiam os critérios de TNPM, segundo classificação estabelecida pela Organização Mundial da Saúde (OMS) em 2003. Foram avaliados os achados clinicopatológicos e imuno-histoquímicos e as terapias realizadas, buscando caracterizar os padrões histopatológicos e de comportamento distintos dos carcinomas convencionais de mama.

Primary neuroendocrine breast carcinomas (NECs) are uncommon. Moreover, there is no consensus as to its treatment and prognosis. In this study, the diagnoses of 1,184 cases of breast cancer treated at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo (HCFMRP/USP) were reviewed. Three among them fulfilled the criteria for primary NEC according to the classification established by the World Health Organization (WHO) in 2003. Clinicopathological, immunohistochemical features and treatments were assessed in order to characterize histopathological and distinct patterns of conventional breast carcinomas.