The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases.

BACKGROUND: Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. METHODS: Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan-Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant. RESULTS: A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%. CONCLUSIONS: This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.

BACKGROUND: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. METHODS AND FINDINGS: The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). CONCLUSION: The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Sociodemographic, Clinical, and Pathological Factors Influencing Outcomes in Locally Advanced Triple Negative Breast Cancer: A Brazilian Cohort.

OBJECTIVE: To evaluate the association of sociodemographic, clinical, and pathological factors with response and survival in triple negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NACT). METHODS: Clinical-pathological and sociodemographic data were obtained from medical records of 235 eligible women with TNBC diagnosed between 2010 and 2014 undergoing NACT and surgery at the Brazilian National Cancer Institute. They have been assessed for pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Both univariate and multivariate Cox regression analyses were performed. RESULTS: The median follow-up was 64.3 months. Most patients had advanced clinical stage (III: 85.1%; cT3/T4: 86.4%; cN1-3: 74.4%) and high-grade tumors (72.1%). Clinical staging (III vs II, adjusted hazard ratio [HR] = 2.95, P = .012) significantly influenced the pCR rate. Alcohol intake negatively influenced EFS (adjusted HR = 1.67, P = .006) and OS (adjusted HR = 1.89, P = .005). Women with pCR showed better EFS (crude HR = 0.15, P < .001) and OS (crude HR = 0.12, P < .001) compared with non-pCR. The ypT (<0.001) and ypN (<0.001) gradually influenced survival outcomes. CONCLUSION: Clinical stage III were associated with lower response rate and worse survival. Alcohol intake, pCR, and burden of post-NACT residual disease have shown considerable influence on survival outcomes.

Adjuvant therapy for non-small cell lung cancer.

OBJECTIVE: Adjuvant chemotherapy is recommended for most patients submitted to resection due to non-small cell lung cancer (NSCLC) staged as II or IIIA. However, although various chemotherapy regimens that include cisplatin have been used in phase III trials, the best choice remains unclear. The objective of this study was to describe the experience of the Instituto Nacional do Câncer (INCA, Brazilian National Cancer Institute), located in the city of Rio de Janeiro, Brazil, with the use of the cisplatin-etoposide combination in such patients, with a special focus on survival data. METHODS: We retrospectively evaluated the medical charts of the patients receiving adjuvant therapy for NSCLC at the INCA between 2004 and 2008. RESULTS: We included 51 patients, all of whom were treated with the cisplatin-etoposide combination. The median follow-up period was 31 months, and the median overall survival was 57 months. In the univariate analysis, median survival was lower in the patients submitted to chemotherapy plus radiotherapy than in those submitted to chemotherapy alone (19 vs. 57 months; p < 0.001), and there was a trend toward lower median survival in stage III patients than in stage I-II patients (34 vs. 57 months; p = 0.22). Overall survival was not significantly associated with gender (p = 0.70), histological pattern (p = 0.33), or cisplatin dose (p = 0.13). CONCLUSIONS: Our results support the use of adjuvant chemotherapy, and our survival data are similar to those reported in major randomized clinical trials. However, long-term follow-up is warranted in this population.

Tratamento adjuvante em câncer de pulmão de células não pequenas / Adjuvant therapy for non-small cell lung cancer

OBJETIVO: A quimioterapia adjuvante é recomendada na maioria dos casos de câncer de pulmão de células não pequenas (CPCNP) ressecados em pacientes nos estádios II ou IIIA. No entanto, diferentes esquemas quimioterápicos contendo cisplatina foram utilizados em estudos de fase III, e a melhor escolha permanece obscura. O objetivo deste estudo foi descrever a experiência do Instituto Nacional de Câncer (INCA), localizado na cidade do Rio de Janeiro (RJ), com o uso da combinação de cisplatina e etoposídeo nessa situação, com especial foco para os dados de sobrevida. MÉTODOS: Foram avaliados retrospectivamente os prontuários dos pacientes com diagnóstico de CPCNP que receberam terapia adjuvante no INCA entre 2004 e 2008. RESULTADOS: Foram incluídos 51 pacientes, e todos foram tratados com a combinação de cisplatina e etoposídeo. A mediana de tempo de seguimento foi de 31 meses de seguimento, e a mediana de sobrevida global foi de 57 meses. Na análise univariada, a sobrevida foi inferior nos pacientes submetidos a radioterapia + quimioterapia do que aqueles somente submetidos a quimioterapia (mediana de 19 vs. 57 meses; p < 0,001), e houve uma tendência a menor sobrevida nos pacientes em estádio III em relação àqueles em estádios I-II (mediana de 34 vs. 57 meses, respectivamente; p = 0,22). Não houve associações significativas entre a sobrevida global e gênero (p = 0,70), padrão histológico (p = 0,33) ou dose de cisplatina (p = 0,13). CONCLUSÕES: Nossos resultados corroboram a utilização da quimioterapia adjuvante, e os resultados de sobrevida se aproximam daqueles descritos nos principais ensaios clínicos randomizados. Contudo, é importante o acompanhamento a longo prazo nessa população.

OBJECTIVE: Adjuvant chemotherapy is recommended for most patients submitted to resection due to non-small cell lung cancer (NSCLC) staged as II or IIIA. However, although various chemotherapy regimens that include cisplatin have been used in phase III trials, the best choice remains unclear. The objective of this study was to describe the experience of the Instituto Nacional do Câncer (INCA, Brazilian National Cancer Institute), located in the city of Rio de Janeiro, Brazil, with the use of the cisplatin-etoposide combination in such patients, with a special focus on survival data. METHODS: We retrospectively evaluated the medical charts of the patients receiving adjuvant therapy for NSCLC at the INCA between 2004 and 2008. RESULTS: We included 51 patients, all of whom were treated with the cisplatin-etoposide combination. The median follow-up period was 31 months, and the median overall survival was 57 months. In the univariate analysis, median survival was lower in the patients submitted to chemotherapy plus radiotherapy than in those submitted to chemotherapy alone (19 vs. 57 months; p < 0.001), and there was a trend toward lower median survival in stage III patients than in stage I-II patients (34 vs. 57 months; p = 0.22). Overall survival was not significantly associated with gender (p = 0.70), histological pattern (p = 0.33), or cisplatin dose (p = 0.13). CONCLUSIONS: Our results support the use of adjuvant chemotherapy, and our survival data are similar to those reported in major randomized clinical trials. However, long-term follow-up is warranted in this population.

Prognostic relevance of KIT and PDGFRA mutations in gastrointestinal stromal tumors.

BACKGROUND: Prediction of biological behavior is crucial for selection of new therapeutic modalities in GIST. Here, we aimed to assess whether KIT and PDGFRA mutations have survival impact in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: Fifty-five Brazilian patients with completely resected GIST were examined for KIT and PDGFRA mutations. The 5-year disease-free survival (DFS) was analyzed. RESULTS: KIT and PDGFRA mutations were identified in 74.5% and 7.3% of patients, respectively. The 5-year DFS rate for all patients was 52.8%. The 5-year DFS rate was lower in patients with tumors having in-frame deletions or concomitant in-frame deletions and insertions affecting codons 557-558 than in patients with tumors having other exon 11 KIT mutations (p=0.023). Conversely, when the patients with concomitant deletion-insertion mutations affecting codons 557-558 were excluded from the analysis, deletions involving codons 557-558 had no influence on 5-year DFS rates. CONCLUSION: Our findings indicate that a specific KIT mutation may be associated with unfavorable behavior in GIST. This finding may have implications on selecting patients for adjuvant therapy.

Streptococcal bacteraemia in patients submitted to hematopoietic stem cell transplantation: the role of tooth brushing and use of chlorhexidine.

A retrospective evaluation of 73 consecutive recipients of hematopoietic stem cell transplantation (HSCT) was conducted to investigated the role of oral care and incidence of streptococcal bacteremia in patients submitted to hematopoietic stem cell transplantation. Patients were retrospectively evaluated and divided into group A (GA=38) and group B (GB=35). During hospitalization patients from GA performed oral hygiene daily with extra soft toothbrush and toothpaste besides performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solution tree times a day. In contrast GB patients performed mouth cleaning with extra soft toothbrush and toothpaste, but no chlorhexidine was used. Using the Chi square test it was observed that all patients from GA presented negative blood culture for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1 patient without oral mucositis from GB presented positive blood cultures for Streptococcus intermedius (p=0.48). The results indicate that methodology used for oral care before the HSCT and the practice of tooth brushing during the period were effective in preventing streptococcal bacteremia. Moreover, our data suggest that the mouth cleaning with chlorhexidine during HSCT may be not mandatory.

Gastrostomia endoscópica percutânea ambulatorial em pacientes com de câncer de cabeça e pescoço / Outpatient percutaneous endoscopic gastrostomy in head and neck cancer patients

Introdução: A gastrostomia endoscópica percutanea (GEP) é um método relativamente simples e seguro para fornecimento de nutrição enteral, sendo normalmente realizado em pacientes hospitalizados. A utilização da GEP como procedimento ambulatorial ainda não está bem estabelecida. Objetivo: Investigar a viabilidade e a segurança da GEP como procedimento ambulatorial em pacientes com câncer de cabeça e pescoço. Métodos: Em estudo de coorte prospectivo, pacientes com câncer de cabeça e pescoço em bom estado geral foram selecionados e incluídos em um protocolo de acompanhamento de GEP ambulatorial. Resultados: 136 pacientes foram selecionados para realização de GEP ambulatorial. Destes, 129 (94,8%) receberam alta hospitalar três horas após o procedimento. Três pacientes foram excluídos do estudo no pré-operatório e quatro foram hospitalizados pós-procedimento. A taxa de complicações menores foi de 17,6% (dor local 7,4%; infecção de ferida 6,6%; dor abdominal 2,9%; hematoma 0,7%). Complicações maiores ocorreram em 2,2% dos procedimentos. Não houve óbito. Conclusão: A realização ambulatorial de GEPs é viável e segura em pacientes com câncer de cabeça e pescoço em boas condições clinicas. As taxas de complicações precoces são semelhantes às descritas para pacientes hospitalizados. Internações desnecessárias são evitadas e os custos hospitalares são reduzidos.

Introduction: Percutaneous endoscopic gastrostomy (PEG) is a relatively simple and safe method of providing access for enteral feeding, being usually performed in hospitalized patients. The feasibility of PEG as an outpatient procedure has not been well established. Objective: To investigate the feasibility and safety of PEG as an outpatient procedure in a selected group of head and neck cancer patients. Methods: In this prospective cohort study, head and neck cancer subjects in good clinical condition were selected and enrolled in a close follow-up protocol of outpatient PEG. Results: Out of a total of 136 PEG patients, 129 (94.8%) were discharged 3 hours after the procedure. Three were excluded from the study and four were hospitalized. The rate of minor complications was 17.6% (local pain, 7.4%; wound infection, 6.6%; abdominal pain, 2.9%; hematoma, 0.7%). Major complications occurred in 2.2% of the procedures (buried bumper syndrome, 1.5%; early tube displacement, 0.7%). There was no mortality. Conclusion: Ambulatory placement of gastrostomy tubes is viable and safe in head and neck cancer patients in good clinical condition. The early complication rates are similar to those described for hospitalized patients. Unnecessary admissions are avoided and costs of hospitalization are reduced.

Outpatient percutaneous endoscopic gastrostomy in selected head and neck cancer patients.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a relatively simple and safe method of providing access for enteral feeding. The procedure is usually performed in hospitalized patients. The feasibility of PEG as an outpatient procedure has not been well estabilished in the medical literature. The main objective of this study was to investigate the feasibility and safety of PEG as an outpatient procedure in a selected group of head and neck cancer patients. PATIENTS AND METHODS: In this prospective cohort study, head and neck cancer subjects in good clinical condition were selected and enrolled in a close follow-up protocol of outpatient PEG. The clinical and demographic variables evaluated were age, gender, early complications, and timing of PEG. RESULTS: Of a total of 136 PEG patients, 129 (94.8%) were discharged 3 h after the procedure. Three were excluded from the study and four were hospitalized because of moderate abdominal pain. The rate of minor complications was 17.6% (local pain, 7.4%; wound infection, 6.6%; abdominal pain, 2.9%; hematoma, 0.7%). Major complications occurred in 2.2% of the procedures (buried bumper syndrome, 1.5%; early tube displacement, 0.7%). There was no mortality. CONCLUSION: Ambulatory placement of gastrostomy tubes is viable and safe in head and neck cancer patients in good clinical condition. The early complication rates are similar to those described for hospitalized patients. Unnecessary admissions are avoided and costs of hospitalization are reduced.

Palliative percutaneous nephrostomy in recurrent cervical cancer: a retrospective analysis of 50 consecutive cases.

Cervical cancer is a public health problem in Brazil, with annual incidence rates of 20-40 cases/100,000 women. Most patients with recurrent disease have symptoms from locoregional disease and may develop renal failure. This study aims to evaluate the outcome of patients with recurrent cervical cancer who underwent percutaneous nephrostomy (PN). We reviewed the medical records of 50 such patients who were referred to the Palliative Care Unit of the Brazilian National Cancer Institute from January 2002 to October 2006. Median age was 44 years (range, 26-67 years). Half the patients had improvement in pain or uremic symptoms, and seven (14%) had improved performance status (PS) after the procedure. Thirty patients (60%) had improvement of renal function; median creatinine levels before and after PN were 6.4 and 3.7mg/dL, respectively (P<0.05). Median overall survival after PN was 8.9 weeks (95% confidence interval [CI]: 7.4-10.3). Median survival was 9.9 weeks (95% CI: 8.7-11.0) in 40 patients with baseline PS 1-3 and one week (95% CI: 0.1-1.9) in 10 patients with PS 4 (log rank, P<0.0001). Median survival in patients with and without improvement of renal function after PN was 10.0 weeks (95% CI: 8.6-11.3) and 2.6 weeks (95% CI: 0-11.3), respectively (log rank, P=0.01). Twenty-nine patients (58%) died from renal failure. Complications were mainly urinary tract infection (n=10), catheter loss (n=9), and bleeding (n=1). These data suggest that PN can be of clinical benefit for carefully selected patients with recurrent cervical cancer.

Uso de topotecan no tratamento do tumor epitelial de óvario refratório à platina: experiência do INCA / Topotecan for tratment of platinum-resistant epithelial ovarian cancer: the experience at the Brazilian National Cancer Institute

Introdução: O câncer de ovário é a principal causa de morte entre os tumores malignos ginecológicos nos Estados Unidos. Apesar dos avanços da terapia inicial, a maioria das pacientes apresentará recaída e necessitará de tratamento adicional. Topotecan é um agente quimioterápico estabelecido para o tratamento de câncer de ovário refratário à platina e foi utilizado como droga de escolha no Instituto Nacional de Câncer (INCA) para essas pacientes. O presente estudo tem como objetivo descrever estes casos. Metodologia: Estudo de seguimento, retrospectivo edescritivo realizado através de revisão dos prontuários das pacientes, com diagnóstico de câncer epitelial de ováriorefratário à platina, que receberam tratamento com topotecan no INCA, no período de janeiro de 2003 a dezembrode 2005. Resultados: Trinta e uma pacientes preencheram critérios para inclusão no estudo. Com seguimentomediano de 12 meses (3-36), o tempo mediano livre de progressão foi de quatro meses (IC 95%; 2,1-5,8) e amediana estimada de sobrevida global foi de 14 meses (IC 95%; 5,1-22,8). A progressão locorregional foi a maiscomum, descrita em 22 (81,5%). Foram encontradas: taxas de resposta clínica de 22,6%, resposta bioquímica de25,8% e resposta radiológica de 20%. Conclusão: O presente estudo evidencia o benefício do tratamento comtopotecan na população estudada, com taxa de resposta, tempo livre de progressão e sobrevida global, que estão de acordo com os da literatura

Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial.

We investigated the clinical effects of low-power laser therapy (LPLT) on prevention and reduction of severity of conditioning-induced oral mucositis (OM) for hematopoietic stem cell transplantation (HSCT). We randomized 38 patients who underwent autologous (AT) or allogeneic (AL) HSCT. A diode InGaAlP was used, emitting light at 660 nm, 50 mW, and 4 J/cm2, measured at the fiberoptic end with 0.196 cm2 of section area. The evaluation of OM was done using the Oral Mucositis Assessment Scale (OMAS) and the World Health Organization (WHO) scale. In the LPLT group, 94.7% of patients had an OM grade (WHO) lower than or equal to grade 2, including 63.2% with grade 0 and 1, whereas in the controls group, 31.5% of patients had an OM grade lower than or equal to grade 2 (P < .001). Remarkably, the hazard ratio (HR) for grades 2, 3, and 4 OM was 0.41 (range, 0.22-0.75; P = .002) and for grades 3 and 4 it was 0.07 (range, 0.11-0.53; P < .001). Using OMAS by the calculation of ulcerous area, 5.3% of the laser group presented with ulcers of 9.1 cm2 to 18 cm2, whereas 73.6% of the control group presented with ulcers from 9.1 cm2 to 18 cm2 (P = .003). Our results indicate that the use of upfront LPLT in patients who have undergone HSCT is a powerful instrument in reducing the incidence of OM and is now standard in our center.