Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

Filling gaps in experiences religious understanding of people living with cancer in palliative care: a phenomenological qualitative study.

BACKGROUND: According to a phenomenology of contemporary religion, the analysis of religious experiences finds that they are part of an individual's search for something powerful that overcomes him seeking not only a need, but the meaning of all existence. The present study aims to contribute to a deeper understanding of the religious experiences of people living with cancer in palliative care (PC) and fill gaps in access to experience, with regard to how it was properly lived. METHODS: A qualitative, phenomenological, cross-sectional study was conducted with 14 people living with cancer undergoing PC at two outpatient clinics of a public hospital. The experiences were accessed through in-depth interviews and the results were analysed according to the principles of classical phenomenology. RESULTS: The patients confidently surrendered to the divine, attributing to it the power of continuity of life or not, which sustained them and launched them into horizons of hope, directing them to possibilities of achieving meaning in life, which it fed back their faith and to continue living, opening them up to an intense perception of the value of life. CONCLUSIONS: The religious positions of confident surrender to the divine, to his will and a belief in his intervention, regardless of the outcome, opened possibilities to patients for the belief in the continuity of life by the power of faith. This position allowed the patients in this study to visualize achievements in the present and in the future, opening a horizon of hope, meaning and value of living. This study showed how this elements are presented and sustained, providing subsidies to health professionals seeking to provide more holistic care.

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.

Genomic landscapes of ovarian clear cell carcinoma from latin countries reveal aberrations linked to survival and progression.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. METHODS: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations. RESULTS: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. CONCLUSIONS: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.

Hybrid volatilomics in cancer diagnosis by HS-GC-FID fingerprinting.

Assessing volatile organic compounds (VOCs) as cancer signatures is one of the most promising techniques toward developing non-invasive, simple, and affordable diagnosis. Here, we have evaluated the feasibility of employing static headspace extraction (HS) followed by gas chromatography with flame ionization detector (GC-FID) as a screening tool to discriminate between cancer patients (head and neck-HNC,n= 15; and gastrointestinal cancer-GIC,n= 19) and healthy controls (n= 37) on the basis of a non-target (fingerprinting) analysis of oral fluid and urine. We evaluated the discrimination considering a single bodily fluid and adopting the hybrid approach, in which the oral fluid and urinary VOCs profiles were combined through data fusion. We used supervised orthogonal partial least squares discriminant analysis for classification, and we assessed the prediction power of the models by analyzing the values of goodness of prediction (Q2Y), area under the curve (AUC), sensitivity, and specificity. The individual models HNC urine, HNC oral fluid, and GIC oral fluid successfully discriminated between healthy controls and positive samples (Q2Y = 0.560, 0.525, and 0.559; AUC = 0.814, 0.850, and 0.926; sensitivity = 84.8, 70.2, and 78.6%; and specificity = 82.3; 81.5; 87.5%, respectively), whereas GIC urine was not adequate (Q2Y = 0.292, AUC = 0.694, sensitivity = 66.1%, and specificity = 77.0%). Compared to the respective individual models, Q2Y for the hybrid models increased (0.623 for hybrid HNC and 0.562 for hybrid GIC). However, sensitivity was higher for HNC urine and GIC oral fluid than for hybrid HNC (75.6%) and hybrid GIC (69.8%), respectively. These results suggested that HS-GC-FID fingerprinting is suitable and holds great potential for cancer screening. Additionally, the hybrid approach tends to increase the predictive power if the individual models present suitable quality parameter values. Otherwise, it is more advantageous to use a single body fluid for analysis.

COSTS ANALYSIS OF SPINAL COLUMN METASTASES SURGICAL TREATMENT.

Introduction: End-of-life cancer treatment is associated with substantial healthcare costs. Objective: This study aimed to analyze the surgical treatment cost of spinal metastasis and epidural compression patients undergoing surgical treatment. Methods: A retrospective cost analysis of 81 patients with spinal metastasis and epidural compression undergoing surgical treatment. Cost evaluation was defined in the following categories: medications, laboratory and imaging tests, nursery, recovery room, intensive care unit, surgical procedure, and consigned material. The cost of pain improvement, functional activity, and survival was also evaluated. Results: The total cost of surgical treatment for 81 patients was $3,604,334.26, and the average value for each patient was $44,497.95. The highest costs were related to implants (41.1%), followed by hospitalization (27.3%) and surgical procedure (19.7%). Conclusion: The cost of surgical treatment for spinal metastases is one of the most expensive bone complications in cancer patients. The cost of treatment related to outcomes showed differences according to the outcome analyzed. Hospital stay, tests, drugs, and intensive care play an important role in some of the costs related to the specific outcome. Level of Evidence II, Retrospective Study .

Introdução: O tratamento do câncer em fim de vida está associado a custos substanciais em saúde. Objetivo: O objetivo do estudo foi analisar o custo do tratamento cirúrgico de pacientes com metástase espinhal e compressão peridural submetidos ao tratamento cirúrgico. Métodos: Uma análise retrospectiva de custos de 81 pacientes com metástase espinhal e compressão peridural submetidos a tratamento cirúrgico. A avaliação de custos foi definida nas seguintes categorias: medicamentos, exames laboratoriais e de imagem, enfermaria, sala de recuperação, unidade de terapia intensiva, procedimento cirúrgico e material consignado. O custo relacionado à melhora da dor, atividade funcional e sobrevida também foi avaliado. Resultados: O custo total do tratamento cirúrgico de 81 pacientes foi de R $ 3.604.334,26 e o valor médio de cada paciente foi de R $ 44.497,95. Os maiores gastos foram relacionados com implantes (41,1%), seguidos de internação (27,3%) e procedimento cirúrgico (19,7%). Conclusão: O custo do tratamento cirúrgico para metástases espinhais é um dos mais caros entre as complicações ósseas em pacientes com câncer. O custo do tratamento relacionado aos desfechos apresentou diferença de acordo com o desfecho analisado e a permanência hospitalar, exames, medicamentos e terapia intensiva tem papel importante em alguns dos custos relacionados ao desfecho específico. Nível de Evidência II, Estudo retrospectivo .

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.

Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment.

Background: Glioblastoma is an incurable neoplasm. Its hypoxia mechanism associated with cancer stem cells (CSCs) demonstrates hypoxia-inducible factor 1α (HIF-1α) expression regulation, which is directly related to tumor malignancy. The aim of this study was to identify a possible tumor malignancy signature associated with regulation of HIF-1α by microRNAs miR-21 and miR-326 in the subpopulation of tumor stem cells which were irradiated by ion in primary culture of patients diagnosed with glioblastoma. Materials and methods: We used cellular cultures from surgery biopsies of ten patients with glioblastoma. MicroRNA expressions were analyzed through real-time polymerase chain reaction (PCR ) and correlated with mortality and recurrence. The ROC curve displayed the cutoff point of the respective microRNAs in relation to the clinical prognosis, separating them by group. Results: The miR-21 addressed high level of expression in the irradiated neurosphere group (p = 0.0028). However, miR-21 was not associated with recurrence and mortality. miR-326 can be associated with tumoral recurrence (p = 0.032) in both groups; every 0.5 units of miR-326 increased the chances of recurrence by 1,024 (2.4%). Conclusion: The high expression of miR-21 in the irradiated group suggests its role in the regulation of HIF-1α and in the radioresistant neurospheres. miR-326 increased the chances of recurrence in both groups, also demonstrating that positive regulation from miR-326 does not depend on ionizing radiation treatment.

Personal positioning of oncology patients in palliative care: a mixed-methods study.

BACKGROUND: Advanced oncological disease requires comprehensive health care, although attention is predominantly paid to the physical dimension of care. The consideration of personal positioning encompasses other dimensions of patients' management of their illness, such as existential management and expanding forms of care. The objective of this study was to understand the personal positioning of cancer patients in palliative care. METHODS: This was a cross-sectional study using the mixed convergent parallel method. The sample consisted of 71 cancer patients in palliative care, of whom 14 participated in the qualitative and quantitative portions and 57 participated in only the quantitative portion. Phenomenological interviews were performed, and qualitative and quantitative methods were used to collect meaning of life (PIL-Test), quality of life (EORTC QLQ C-30), anxiety and depression (HADS) and sociodemographic data. The interview results were analysed according to the principles of classical phenomenology, and the quantitative data were analysed using the generalized structural equations model. RESULTS: The results showed that the patients turned to living, focusing on their possibilities and distancing themselves from the impact of the illness and the factuality of death, which the patients themselves associated with not succumbing to depression, a condition whose signs were exhibited by 21% of the sample. Sustaining this positioning required a tenacious fight, which feeds on sensitivity to life. Linked to this position was the belief in the continuation of life through religious faith, together with the patients' realization of the meaning of their lives. In this same direction, there was a direct association between awareness of the meaning of life and increased scores on the functional scales (p <  0.01) and decreased scores for symptoms (p <  0.01), anxiety (p = 0.02) and depression (p < 0.01). The last element that emerged and structured this experience was the intense will to live and a sense of the value of life. CONCLUSIONS: Through the use of mixed methods, the present study recognized the existential positioning of cancer patients in palliative care. This understanding can aid in the realization of more comprehensive and meaningful treatment plans and can contribute to the goal of achieving humanization in this area of treatment.

Costs analysis of spinal column metastases surgical treatment / Análise dos custos do tratamento cirúrgico das metástases da coluna vertebral

ABSTRACT Introduction End-of-life cancer treatment is associated with substantial healthcare costs. Objective This study aimed to analyze the surgical treatment cost of spinal metastasis and epidural compression patients undergoing surgical treatment. Methods A retrospective cost analysis of 81 patients with spinal metastasis and epidural compression undergoing surgical treatment. Cost evaluation was defined in the following categories: medications, laboratory and imaging tests, nursery, recovery room, intensive care unit, surgical procedure, and consigned material. The cost of pain improvement, functional activity, and survival was also evaluated. Results The total cost of surgical treatment for 81 patients was $3,604,334.26, and the average value for each patient was $44,497.95. The highest costs were related to implants (41.1%), followed by hospitalization (27.3%) and surgical procedure (19.7%). Conclusion The cost of surgical treatment for spinal metastases is one of the most expensive bone complications in cancer patients. The cost of treatment related to outcomes showed differences according to the outcome analyzed. Hospital stay, tests, drugs, and intensive care play an important role in some of the costs related to the specific outcome. Level of Evidence II, Retrospective Study.

RESUMO Introdução O tratamento do câncer em fim de vida está associado a custos substanciais em saúde. Objetivo O objetivo do estudo foi analisar o custo do tratamento cirúrgico de pacientes com metástase espinhal e compressão peridural submetidos ao tratamento cirúrgico. Métodos Uma análise retrospectiva de custos de 81 pacientes com metástase espinhal e compressão peridural submetidos a tratamento cirúrgico. A avaliação de custos foi definida nas seguintes categorias: medicamentos, exames laboratoriais e de imagem, enfermaria, sala de recuperação, unidade de terapia intensiva, procedimento cirúrgico e material consignado. O custo relacionado à melhora da dor, atividade funcional e sobrevida também foi avaliado. Resultados O custo total do tratamento cirúrgico de 81 pacientes foi de R $ 3.604.334,26 e o valor médio de cada paciente foi de R $ 44.497,95. Os maiores gastos foram relacionados com implantes (41,1%), seguidos de internação (27,3%) e procedimento cirúrgico (19,7%). Conclusão O custo do tratamento cirúrgico para metástases espinhais é um dos mais caros entre as complicações ósseas em pacientes com câncer. O custo do tratamento relacionado aos desfechos apresentou diferença de acordo com o desfecho analisado e a permanência hospitalar, exames, medicamentos e terapia intensiva tem papel importante em alguns dos custos relacionados ao desfecho específico. Nível de Evidência II, Estudo retrospectivo.

Complications of surgical treatment of spinal metastases / Complicações do tratamento cirúrgico das metástases vertebrais / Complicaciones del tratamiento quirúrgico de las metástasis vertebrales

ABSTRACT Objectives: To evaluate the complications of surgical treatment in a group of patients with spinal metastasis with epidural compression, undergoing surgical treatment. Methods: This is a comparative retrospective study (level of evidence III), which evaluated 96 patients with spinal metastases undergoing surgical treatment. Intra- and postoperative complications were obtained from the patients' medical records and correlated with the following clinical characteristics: tumor type, tumor location, neurological deficit, age, number of affected vertebrae, Tokuhashi scale, Tomita scale, Karnofsky performance scale, and type of approach. Results: Complications of surgical treatment were observed in 29 (30.20%) patients. Surgical wound infection was the most frequent complication, observed in 15% of patients. Conclusions: Surgical treatment of spinal metastases presents complications in about 30% of patients and their occurrence should be considered in the treatment planning, weighing the risks and benefits for achieving the treatment goals. Level III evidence; Retrospective Study.

RESUMO Objetivo: Avaliar as complicações do tratamento cirúrgico em grupo de pacientes com metástase da coluna vertebral, compressão epidural e submetidos ao tratamento cirúrgico. Métodos: Trata-se de estudo retrospectivo comparativo (nível de evidência III), que avaliou 96 pacientes com metástase da coluna vertebral, submetidos ao tratamento cirúrgico. As complicações intra e pós-operatórias foram obtidas dos prontuários dos pacientes e correlacionadas com características clínicas: tipo de tumor, localização do tumor, déficit neurológico, idade, número de vértebras acometidas, escala de Tokuhashi, escala de Tomita, escala de performance de Karnofsky e tipo de acesso. Resultados: As complicações do tratamento cirúrgico foram observadas em 29 (30,20%) pacientes. A infecção da ferida operatória foi a complicação mais frequente e observada em 15% dos pacientes. Conclusões: O tratamento cirúrgico das metástases da coluna vertebral apresenta complicações em cerca de 30% dos pacientes, e a sua ocorrência deve ser considerada na elaboração do tratamento frente aos riscos e benefícios para a obtenção dos objetivos do tratamento. Evidência nível III; Estudo Retrospectivo.

RESUMEN Objetivos: Evaluar las complicaciones del tratamiento quirúrgico en un grupo de pacientes con metástasis vertebrales, compresión epidural y sometidos a tratamiento quirúrgico. Métodos: Se trata de un estudio comparativo retrospectivo (nivel de evidencia III), que evaluó a 96 pacientes con metástasis en la columna vertebral sometidos a tratamiento quirúrgico. Las complicaciones intra y postoperatorias se obtuvieron de la historia clínica de los pacientes y se correlacionaron con las características clínicas: tipo de tumor, localización del tumor, déficit neurológico, edad, número de vértebras afectadas, escala de Tokuhashi, escala de Tomita, escala de rendimiento de Karnofsky y tipo de acceso. Resultados: Se observaron complicaciones del tratamiento quirúrgico en 29 (30,20%) pacientes. La infección de la herida quirúrgica fue la complicación más frecuente y se observó en el 15% de los pacientes. Conclusiones: El tratamiento quirúrgico de las metástasis de columna vertebral presenta complicaciones en aproximadamente el 30% de los pacientes, y su ocurrencia debe ser considerada en la elaboración del tratamiento, considerando los riesgos y beneficios para lograr los objetivos del mismo. Evidencia de nivel III; Estudio retrospectivo.

Outcomes and survival of spinal metastasis with epidural compression.

OBJECTIVE: The goal of the study was to retrospectively evaluate the demographics, clinical manifestation, outcomes, treatment result, and survival of patients with spinal metastasis with epidural metastasis who underwent surgical treatment. MATERIALS AND METHODS: A retrospective evaluation of 103 patients with spinal metastasis and epidural compression who underwent surgical treatment between 2009 and 2015 was performed. The recorded parameters selected for the study were general demographic data (gender, age, and educational level) and clinical data (primary tumor, performance status according to Karnofsky score, neurological status according to Frankel scale, pain, surgical treatment outcomes, and patient survival). RESULTS: The mean age of the patients was 55.28 ± 15.79 years, and spinal metastasis was more frequent in males (61.7%). The two most frequent tumors were malignant breast cancer (26.21%) and prostate cancer (22.33%). Preoperative pain was presented in 96 (94.12%) patients and improvement was observed in 44 (47.31%) patients. Symptoms of spinal cord compression were the initial clinical manifestation of the primary tumor in 35 (33.98%) patients. Neurological deficit was observed in 66 (64.07%) patients, and improvement was observed in 43 (41.74%) patients. Improvement of functional outcome and pain was observed in 34 (37.38%) patients. The mean survival was 12.26 months. Longer survival (mean 19.13 months) was observed in patients who showed improvement in their ability to walk or kept it preserved (Frankel D or E). CONCLUSIONS: Surgical treatment of spinal metastasis can improve pain and functional activities. Longer survival was observed in patients that keep or recovery the walking ability.

ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. METHODS: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. RESULTS: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples. CONCLUSION: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

Unknown primary tumor sites in spinal metastasis / Metástase vertebral em tumor primário de localização desconhecida / Metástasis vertebral en tumor primario de localización desconocida

ABSTRACT Objective: The goal of the study was to report the prevalence of spinal metastasis with unknown primary tumor, clinical features, treatment results and patient survival. Methods: A retrospective evaluation of 103 patients with spinal metastasis and epidural compression, who underwent surgical treatment between March 2009 and August 2015. The prevalence of metastatic spinal tumor with unknown primary tumor was evaluated, as well clinical features, survival and treatment results. Results: Of 103 patients with spinal metastasis and epidural compression, seven patients (6.8%) with unknown primary tumor site were identified; five (71.4%) male and two (28.6%) female, with ages ranging from 37 to 67 years (50.7 years). The metastasis was located in the thoracic spine in six of the patients (85.7%) and in the cervical spine in one (14.3%). The mean survival time was 44.8 days. Conclusion: Spinal metastasis with unknown primary tumor was found in 6.8% of patients. The prognosis and outcomes were poor, and patients had poor survival rates. Level of evidence III; Experimental study.

RESUMO Objetivo: O objetivo deste estudo foi relatar a prevalência de metástases vertebrais em tumores primários desconhecidos, suas características clínicas, resultados do tratamento e sobrevida dos pacientes. Métodos: Avaliação retrospectiva de 103 pacientes com metástase da coluna vertebral e compressão epidural, submetidos a tratamento cirúrgico entre março de 2009 e agosto de 2015. Avaliou-se a prevalência de tumores metastáticos vertebrais com tumor primário desconhecido, assim como as características clínicas, a sobrevida e os resultados do tratamento. Resultados: Dos 103 pacientes com metástase vertebral e compressão epidural, foram identificados sete pacientes (6,8%) com tumor primário de origem desconhecida; cinco pacientes (71,4%) eram do sexo masculino e dois pacientes (28,6%) do sexo feminino, com idades variando de 37 a 67 anos (50,7 anos). A localização da metástase vertebral era na coluna torácica em seis pacientes (85,7%) e na coluna cervical em um paciente (14,3%). A média de sobrevida dos pacientes foi de 44,8 dias. Conclusões: As metástases vertebrais com tumor primário de origem desconhecida foram observadas em 6,8% dos pacientes. O prognóstico e os resultados foram ruins, e os pacientes tiveram sobrevida bastante baixa. Nível de evidencia III; Estudo Comparativo Retrospectivo.

RESUMEN Objetivo: El objetivo de este estudio fue relatar la prevalencia de metástasis vertebrales en tumores primarios desconocidos, sus características clínicas, resultados del tratamiento y sobrevida de los pacientes. Métodos: Evaluación retrospectiva de 103 pacientes con metástasis de la columna vertebral y compresión epidural, sometidos a tratamiento quirúrgico entre marzo de 2009 y agosto de 2015. Se evaluó la prevalencia de tumores metastásicos con tumor primario desconocido, así como las características clínicas, la sobrevida y los resultados del tratamiento. Resultados: De los 103 pacientes con metástasis vertebral y compresión epidural, fueron identificados siete pacientes (6,8%) con tumor primario de origen desconocido; cinco pacientes (71,4 %%) eran del sexo masculino y dos (28,6%) del sexo femenino, con edades variando de 37 a 67 años (50,7 años). La localización de la metástasis vertebral era en la columna torácica en seis pacientes (85,7%) y en la columna cervical en un paciente (14,3%). El promedio de sobrevida de los pacientes fue de 44,8 días. Conclusiones: Las metástasis vertebrales con tumor primario de origen desconocido fueron observadas en 6,8% de los pacientes. El pronóstico y los resultados fueron malos y los pacientes tuvieron sobrevida bastante baja. Nivel de evidencia III; Estudio Comparativo Retrospectivo.

Apoptosis related microRNAs and MGMT in glioblastoma cell lines submitted to treatments with ionizing radiation and temozolomide.

AIM: To evaluate the effect of radiotherapy and temozolomide on the expression of miRNAs apoptotic (miRNAs-21, -221, -222 (anti-apoptotic) and miRNAs-15a, -16 (pro-apoptotic)) and the gene MGMT in glioblastoma cell lines. BACKGROUND: The limited knowledge of the molecular biology of malignant gliomas may hinder the development of therapeutic modalities. In this scenario, one of the greatest advances of recent years was the identification of microRNAs. These molecules have an important role in biological processes involving cancer, including glioblastoma. MATERIALS AND METHODS: Trypan blue was used to verify the cell viability, and real time PCR to quantify the expression of microRNAs and gene 24, 48 and 120 h after exposure to treatments. RESULTS: There was a statistically significant decrease of expression of miR-15a between 48 and 120 h in line T98 G treated with radiation, increased expression of miR-15a between 24 and 120 h in line U251 treated with radiation and temozolomide, and increased expression of miR-16 between 24 and 120 h in line U251 treated with radiation alone and when combined with temozolomide. There was a decrease in MGMT gene expression, between 24 and 48 h in U343 cells treated with temozolomide. CONCLUSIONS: Ionizing radiation and temozolomide modified the expression of miRNAs studied and MGMT.

Investigation of sweat VOC profiles in assessment of cancer biomarkers using HS-GC-MS.

Volatile organic compounds (VOCs) have been studied in biological samples in order to be related to the presence of diseases. Sweat can represent substances existing in blood, has less complex composition (compared with other biological matrices) and can be obtained in a non-invasive way. In this work, sweat patches were collected from healthy controls and volunteers with cancer. Static Headspace was used for VOCs extraction, analysis was performed by gas chromatography coupled with mass spectrometry. Principal Components Analysis was used to investigate data distribution. Random Forest was employed to develop classificatory models. Controls and positive cases could be distinguished with maximum sensitivity and specificity (100% of accuracy) in a model based on the incidence of 2-ethyl-1-hexanol, hexanal and octanal. Discrimination between controls, primary tumors and metastasis was achieved using a panel with 11 VOCs. Balanced accuracy of more than 70% was obtained for the classification of a neoplasm site. Total n-aldehydes presented to be strongly correlated with staging of adenocarcinomas, while phenol and 2,6-dimethyl-7-octen-2-ol were correlated with Gleason score. These findings corroborate with the development of accessible screening tools based on VOC analysis and highlight sweat as a promising matrix to be studied in a clinical context for cancer diagnosis.

Recognition of taste in patients during antineoplastic therapy with platinum drugs.

Taste changes caused by the use of platinum drugs have been described. However, few studies qualify the impaired tastes and whether these changes are derived exclusively from chemotherapy (QTx). AIMS: Evaluation of changes in sweet, sour, salty, bitter, and umami tastes in patients receiving QTx with platinum drugs was the aim of this study. METHODS: A total of 43 subjects, 21 from the study group and 22 from the control, were studied in two time periods, one before the start of QTx (T0) and another after two cycles of QTx (T1). The usual dietary intake, body mass index (BMI), handgrip strength and fatigue (through the fatigue pictogram) were evaluated to characterize the group studied. Taste Strips tests were performed for all 4 tastes and umami was studied by comparing Likert's scale using monosodium glutamate (GMS) food. Statistical analysis was performed using repeated measures (ANOVA), mixed model, with significance level p≤0.05. RESULTS: Salty and sour were the most affected tastes in the study group (p = 0.001 and 0.05); as well as the ionotropic receptors (p = 0.02) responsible for identifying these tastes. There was a difference between the times for BMI, dynamometry and impact in daily activities, by the fatigue pictogram (p = 0.008, 0.009 and 0.006 respectively). CONCLUSION: These findings suggest an important role in altering taste recognition, mainly in salty and sour tastes, identified by ionotropic receptors, which seems to be related to dietary changes. QTx has demonstrated a contribution to impairment of functionality and fatigue.

microRNA-181d associated with the methylation status of the MGMT gene in Glioblastoma multiforme cancer stem cells submitted to treatments with ionizing radiation and temozolomide.

Despite the increased understanding of the oncological mechanisms underlying Glioblastoma multiforme (GBM) pathophysiology, and recent advances in therapeutic strategies such as maximal surgical resection and post-operative radiotherapy with concomitant and adjuvant temozolomide chemotherapy, the prognosis for patients with brain tumors remains limited. Evidences indicate that the assessment of DNA methylation status in cancer stem cells would allow identifying molecules expressed in these cells, to lead to targeted elimination of this critical population from brain tumors, making the glioblastoma treatment more effective. This study aimed to analyze the role of microRNA-181d associated with the methylation status of the O6-methylguanine methyl transferase (MGMT) gene in Glioblastoma multiforme cancer stem cells subjected to treatment with temozolomide and ionizing radiation. Such responses were analyzed in terms of cell survival, evaluation of the MGMT gene methylation status by MS-HRM (Methylation-Sensitive High Resolution Melting), and analysis of miRNA-181d and MGMT gene expression by relative quantification of mRNA levels in cancer stem cells subjected to treatment with temozolomide and ionizing radiation, isolated or combined. We showed that ionizing radiation and temozolomide reduced the viability of cancer stem cells from GBM patients, as well as modified MGMT gene and miRNA-181d expression in cancer stem cells, suggesting that miRNA-181d interferes in the glioblastoma cancer stem cell response to treatment with temozolomide and ionizing radiation.

Weight Gain during Systemic Oncologic Therapy for Breast Cancer: Changes in Food Intake and Physical Activity / Ganho Ponderal durante o Tratamento Oncológico Sistêmico para Câncer de Mama: Mudanças na Ingestão Alimentar e na Atividade Física / Aumento de Peso durante el Tratamiento Oncológico Sistémico para Cáncer de Mama: Cambios en la Ingestión de Alimentos y Actividad Física

Introduction: Weight gain frequently occurs during treatment for breast cancer. Objective: To evaluate changes in dietary intake and physical activity in the weight evolution of women on systemic oncologic treatment for breast cancer. Method: The prospective and comparative study included 89 women submitted to systemic oncologic treatment for breast cancer, grouped according to the occurrence of weight gain in relation to body weight documented before beginning treatment. Patients were classified as 1) Group with weight gain (those with an increase in body weight greater than or equal to 2% over pre-treatment weight); 2) Group without weight gain (those who maintained or lost weight during treatment). We calculated body mass index (BMI) of patients and analyzed their body composition by bioelectrical impedance (BIA). Changes in food intake, gastrointestinal symptoms, and physical activity level, as well as reductions in muscle and fat mass, were documented. Results:Tumor staging (p=0.24), use of antineoplastic drugs (p=0.23) and intention of treatment (p=0.61) were no different between the weight gain group (n=36) and no weight gain group (n=53). No difference was found in anthropometric and BIA data between the groups during oncologic treatment. Frequency of gastrointestinal symptoms was not different between the groups. However, increased food intake and bed rest, and a decrease in physical activity level were more frequent among women who gained weight during therapy. Conclusions: Weight gain in women undergoing systemic oncologic therapy for breast cancer may be, at least in part, caused by higher energy intake and lower physical activity.

Introdução: O ganho ponderal ocorre com frequência durante o tratamento oncológico para o câncer de mama. Objetivo: Avaliar as mudanças da ingestão alimentar e da atividade física na evolução ponderal de mulheres sob tratamento oncológico sistêmico para câncer de mama. Método: Estudo prospectivo e comparativo que incluiu 89 mulheres submetidas a tratamento oncológico sistêmico para neoplasia mamária, agrupadas de acordo com a ocorrência de aumento ponderal em relação ao peso corporal documentado antes do início do tratamento. As pacientes foram classificadas em 1) Grupo com ganho ponderal (aumento ≥2% em relação ao peso pré-tratamento); 2) Grupo sem ganho ponderal (ganho ou manutenção do peso durante o tratamento). O índice de massa corporal foi calculado e a composição corporal foi determinada por impedância bioelétrica. Foram documentadas mudanças na ingestão de alimentos e no padrão de atividade física, queixas digestivas e alterações da massa corporal muscular e adiposa. Resultados: Os grupos com ganho ponderal (n=36) e sem ganho ponderal (n=53) foram semelhantes quanto ao estadiamento tumoral (p=0,24), emprego das classes de drogas antineoplásicas (p=0,23) e modalidade de tratamento oncológico (p=0,61). Durante o tratamento oncológico sistêmico, a composição corporal foi semelhante entre os grupos de estudo. Comparadas com o grupo sem ganho de peso, houve maior proporção de aumento na ingestão alimentar e de restrição na atividade física entre as mulheres que ganharam peso. Conclusão: O ganho ponderal em mulheres com neoplasia mamária em tratamento oncológico sistêmico pode ser atribuído à maior ingestão energética e à redução na atividade física.

Introducción: El aumento de peso es frecuente durante el tratamiento oncológico para el cáncer de mama. Objetivo: Evaluar los cambios de la ingesta alimentaria y de la actividad física en la evolución ponderal de las mujeres en tratamiento oncológico sistémico para el cáncer de mama. Método: El estudio prospectivo y comparativo incluyó 89 mujeres sometidas a tratamiento sistémico oncológico por neoplasia mamaria, agrupadas de acuerdo con la ocurrencia de aumento ponderal en relación al peso corporal al início del tratamiento. Las pacientes fueron clasificadas en 1) Grupo con ganancia ponderal (≥2% en relación al peso pretratamiento); 2) Grupo sin ganancia ponderal (mantenimiento o pérdida de peso durante el tratamiento). El índice de masa corporal fue calculado y la composición corporal fue determinada por impedancia bioeléctrica. Fueron documentadas las variaciones en la ingestión de alimentos y el patrón de actividad física, quejas digestivas y redución en la masa corporal. Resultados: Los grupos con ganancia ponderal (n=36) y sin ganancia ponderal (n=53) fueron semejantes cuanto a estadificación tumoral (p=0,24), empleo de medicamentos antineoplásicos (p=0,23) y modalidad del tratamiento oncológico (p=0,61). Durante el tratamiento oncológico, la composición corporal fue semejante entre los grupos de estudio. Comparados con el grupo sin aumento de peso, se observó aumento en la ingestión de alimentos y restricción en la actividad física entre las mujeres que ganaron peso. Conclusión: El aumento de peso en mujeres sometidas a tratamiento oncológico para cáncer de mama, puede ser atribuido a mayor ingestión energética y reducción de actividad física.

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