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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.
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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, â§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.
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Carcinossarcoma , Molécula L1 de Adesão de Célula Nervosa , Neoplasias Uterinas , Humanos , Feminino , Idoso , Prognóstico , Proteína Supressora de Tumor p53/genética , Estudos Retrospectivos , Neoplasias Uterinas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Fator de Transcrição CDX2/genéticaRESUMO
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.
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BACKGROUND: Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, there is no biological rationale that justifies this current standard of care. We compared a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting. PATIENTS AND METHODS: In a randomized, open-label, single-center phase II trial, women with inoperable, locally advanced, HER2-negative breast cancer were stratified by hormone receptor status and randomized to three cycles of docetaxel (T) followed by three cycles of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus three cycles of FAC followed by three cycles of docetaxel. Surgery, radiotherapy, and adjuvant hormonal therapy were administered as per local guidelines. The primary endpoint was pathological complete response (pCR), and secondary endpoints included toxicity, event-free survival (EFS), and overall survival (OS). RESULTS: Treatment sequence did not improve pCR, which was 7% with T-FAC and 3% with FAC-T. However, after a median follow-up of 79 months, the 5-year EFS rate was 75.7% (95% confidence interval [CI], 65.4%-87.7%) with T-FAC and 48.2% (95% CI, 37.0%-62.7%) with FAC-T (hazard ratio [HR], 0.46; 95% CI, 0.26-0.81; log-rank p = .0054), and the 5-year OS rate was 89.7% (95% CI, 82.2%-97.8%) with T-FAC and 64.7% (95% CI, 53.6%-78.1%) with FAC-T (HR, 0.41; 95% CI, 0.22-0.78; p = .0052). There were no unexpected toxicities. CONCLUSION: We showed for the first time an improvement in EFS and OS with taxane-first compared with anthracycline-first sequencing chemotherapy in HER2-negative, locally advanced breast cancer. Confirmation of these results may have implications for clinical practice. This trial was registered with Clinicatrials.gov identifier NCT01270373. IMPLICATIONS FOR PRACTICE: The NeoSAMBA trial showed a benefit for taxane-first sequencing chemotherapy consistent with the systematic review of the literature as well as the larger Neo-tAnGo study. Many recent and current ongoing clinical trials have already followed this treatment strategy. As a taxane-before-anthracycline sequence carries neither an incremental cost nor an increased toxicity, and given the available literature on this issue, reinforced that taxane-first regimen can be easily incorporated into daily clinical practice while awaiting confirmation of these findings from larger trials.
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Antraciclinas , Neoplasias da Mama , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Taxoides/uso terapêuticoRESUMO
"Patients with germ cell tumors (GCT) that relapse after first-line platinum-based chemotherapy can still be successfully rescued with second-line regimens. High-dose chemotherapy has shown favorable outcomes, and is a preferred option in most instances. Herein, we argued if conventional-dose chemotherapy (CDCT) could also be an alternative in selected patients"
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Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Platina , Recidiva , Neoplasias Testiculares/patologia , Neoplasias Embrionárias de Células Germinativas , Tratamento Farmacológico , Recidiva Local de Neoplasia , Pacientes , Papel (figurativo) , Análise de Sobrevida , Seminoma , População Negra , Dosagem , Metástase Neoplásica/patologiaRESUMO
BACKGROUND: Preclinical evidence suggests that zoledronic acid (ZOL) works synergistically with chemotherapy by enhancing anti-tumor activity. ZOL blocks the mevalonate pathway and may indirectly interact with human epidermal growth factor receptor 2 (HER2) pathway activation. The clinical efficacy and biological rationale of chemotherapy plus anti-HER2 therapy and ZOL as a part of neoadjuvant therapy has not been previously tested. PATIENTS AND METHODS: We conducted a phase II clinical trial to evaluate the efficacy and safety of ZOL as part of a neoadjuvant treatment in patients with HER2-positive breast cancer (BC). The protocol consisted of four cycles of doxorubicin/cyclophosphamide with ZOL, followed by four cycles of docetaxel with trastuzumab and ZOL prior to surgery. The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints were safety and the identification of clinicopathological characteristics associated with pCR. RESULTS: A total of 71 patients with stage IIA to IIIB BC were included, with 60 eligible for the safety assessment and 58 for the efficacy analysis. Overall, the pCR rate was 42%, with higher rates in hormone receptor (HR)-positive tumors (40%), which contrasts with the results of pivotal trials. The most commonly observed grade 3 and 4 events were febrile neutropenia (grade 3, 20%; grade 4, 3%) and diarrhea (grade 3, 12%). CONCLUSIONS: The addition of ZOL as a repositioning drug in neoadjuvant treatment was an effective and well-tolerated therapy. This drug combination might overcome endocrine and anti-HER2 resistance. The higher pCR rates in the HR-positive subgroup deserve further translational investigation.
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BACKGROUND: Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. METHODS: From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. RESULTS: From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. CONCLUSIONS: Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. CLINICAL TRIAL INFORMATION: NCT01439724.
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Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Análise Custo-Benefício , Neoplasias de Cabeça e Pescoço/terapia , Terapia com Luz de Baixa Intensidade/economia , Mucosite/prevenção & controle , Idoso , Brasil , Carcinoma de Células Escamosas/economia , Quimiorradioterapia/economia , Método Duplo-Cego , Feminino , Neoplasias de Cabeça e Pescoço/economia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/economia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cisplatin-based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin-based CRT (E + CRT) recommended a phase 2 erlotinib dose of 150 mg/day. METHODS: Eligibility criteria included International Federation of Gynecology and Obstetrics stage IIB to IIIB epidermoid cervical cancer, no prior therapy, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received erlotinib at a dose of 150 mg/day 1 week before and in combination with cisplatin (40 mg/m(2) administered weekly for 5 cycles) and radiotherapy (4500 centigrays in 25 fractions), followed by brachytherapy (4 fractions at a dose of 600 centigrays weekly). RESULTS: A total of 36 patients completed treatment with E + CRT. The median duration of therapy was 77 days and the median follow-up period was 59.3 months. The therapy was well tolerated overall, and 34 patients (94.4%) achieved a complete response. The 2-year and 3-year cumulative overall and progression-free survival rates were 91.7% and 80.6% and 80% and 73.8%, respectively. CONCLUSIONS: Treatment with E + CRT appears to be safe and exerts significant activity against locally advanced cervical cancer. To the best of the authors' knowledge, this is the first study to date to demonstrate that a target agent has promising activity against locally advanced cervical cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Receptores ErbB/antagonistas & inibidores , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cloridrato de Erlotinib , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
Imatinib therapy has undoubtedly contributed to the treatment of metastatic gastrointestinal stromal (GIST) tumors that were previously untreatable. However, disease progression during treatment with tyrosine kinase inhibitors remains an issue in clinical practice not fully explained by KIT and PDGFRA mutation status. We investigated the role of three important signaling molecules (insulin-like growth factor 1 receptor [IGF1R], protein kinase C-θ [PKCθ], and Raf kinase inhibitor protein [RKIP]) that have been implicated in GIST pathogenesis as potential biomarkers for prediction of response to imatinib treatment. We retrospectively reviewed 76 patients with metastatic GIST submitted to imatinib treatment between 2002 and 2007, and analyzed 63 of them. Insulin-like growth factor 1, total PKCθ, phosphorylated PKCθ, and RKIP immunohistochemical expression were correlated with objective response to imatinib treatment and progression-free and overall survival. Median follow-up was 31.2 mo (95% confidence interval, 26.3-36.1 mo). There was a statistically significant association between IGF1R expression and type of response to imatinib treatment (P = 0.05)-that is, higher IGF1R expression was related to lower objective response. However, IGF1R higher expression did not affect progression-free and overall survival. Insulin-like growth factor 1, but not PKCθ and RKIP, emerges as a potential biomarker for prediction of response to imatinib treatment in metastatic GISTs. Validation studies are warranted.
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Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Feminino , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/secundário , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Valor Preditivo dos Testes , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptor Cross-Talk/efeitos dos fármacos , Receptor Cross-Talk/fisiologia , Receptor IGF Tipo 1/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Transdução de Sinais/fisiologiaRESUMO
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Métodos Epidemiológicos , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/administração & dosagem , Métodos Epidemiológicos , Etoposídeo/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapiaRESUMO
PURPOSE: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. METHODS AND MATERIALS: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Câncer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m(2) 120-hour infusion or 1,000 mg/m(2) 96-hour infusion) plus CP (100 mg/m(2)) on the first day of each cycle or MMC (10-15 mg/m(2)) on the first day of Cycle 1 was administered concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Câncer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. RESULTS: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. CONCLUSION: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Adulto , Idoso , Análise de Variância , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Cisplatino/administração & dosagem , Colostomia/estatística & dados numéricos , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Terapia de Salvação , Fatores SexuaisRESUMO
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.
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Tumores do Estroma Gastrointestinal/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Idoso , Códon , Éxons , Feminino , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Completion lymph node dissection (CLND) is the standard procedure for patients with positive sentinel lymph nodes (SLN). With extensive pathological workup, increased numbers of small metastatic deposits are detected in SLN. This study evaluated the prognostic significance of SLN metastatic deposits < or = 0.2 mm in patients treated in a referral cancer center in Brazil. METHODS: Patients with stage I/II melanoma, consecutively submitted to a SLN procedure by the same surgeon from 2000 to 2006, were evaluated. All positive SLN and randomly selected negative cases were reviewed by two pathologists. Different prognostic factors and SLN tumor burden were recorded. Additional positive non-SLN after CLND, and disease outcome were evaluated. RESULTS: Of 381 patients who underwent SLN biopsy, 103 (27%) were positive. The mean/median Breslow tumor thickness in the overall group was 3.4/2.0 mm and in the SLN positive patients was 5.72/4.0 mm. Among these patients, 48 (47%) had metastatic deposits >2 mm (macrometastasis), 49 (47%) had metastatic deposits < or =2 mm but >0.2 mm (micrometastasis), and 6 (6%) had metastatic deposits < or =0.2 mm (submicrometastasis). Additional positive non-SLN were detected in 29% of patients with macrometastasis, in 25% of patients with micrometastasis, and in 0% of patients with submicrometastases. At median follow-up of 35 months, the estimated 3-year overall survival was 92% for negative SLN, 64% for micrometastases, 53% for macrometastases, and 100% for submicrometastases (P < 0.001). CONCLUSION: In the present study, patients with SLN metastatic deposits < or =0.2 mm had no additional positive non-SLNs, and no recurrences or deaths were recorded, suggesting that their prognosis is equivalent to that of patients with negative SLN.
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Melanoma/mortalidade , Melanoma/secundário , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
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.
Assuntos
Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Clorexidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antissépticos Bucais/uso terapêutico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Escovação Dentária , Adolescente , Adulto , Bacteriemia/etiologia , Bacteriemia/microbiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estreptocócicas/etiologia , Adulto JovemRESUMO
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.
RESUMO
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.
Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Transtornos de Deglutição/cirurgia , Endoscopia/métodos , Nutrição Enteral/métodos , Gastrostomia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Estudos de Coortes , Transtornos de Deglutição/etiologia , Nutrição Enteral/instrumentação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to investigate whether mRNA expression of the apoptosis-associated genes, XAF1 and XIAP, in bladder cancer patients correlates with response to neoadjuvant treatment. METHODS: Gene expression was analyzed by a real-time quantitative PCR method in paired samples from 14 bladder cancer patients treated with a combination of neoadjuvant gemcitabine and cisplatin. The prognostic significance of XAF1 and XIAP mRNA expression as well as the correlation with several clinical and pathological findings were evaluated. RESULTS: The clinical response in the XAF1-high subset (n = 5) was remarkably higher compared with the XAF1-low subset (n = 9) (100% vs. 44.4%; P = 0.038). These results translated into a notably improvement of progression-free survival (PFS) in the XAF1-high subset (log-rank P = 0.012). In addition, patients in the XAF1-high subset had a 3.9-fold decreased chance of dying from the disease (hazard ratio for death (HR), 0.257; (CI 95%), 0.043-1.536, P = 0.036). When we evaluated the expression of XIAP, although an inverse correlation was found between expression and pathological response, there were no statistically significant associations with the clinical response, the length of PFS, and OS. CONCLUSIONS: This is one of the few studies to address the role of XAF1 in a clinical setting. The data presented here identify XAF1 as a novel predictive and prognostic factor in bladder cancer patients. Furthermore, our observations are in line with previous studies, which point towards XAF1 as a tumor-suppressor gene. Nonetheless, additional studies, both mechanistic and translational, are warranted and may help not only in corroborating the role of XAF1 as a prognostic marker, but also as a potential target for anticancer therapy.
Assuntos
Quimioterapia Adjuvante/métodos , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/fisiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , GencitabinaRESUMO
HYPOTHESIS: The combination of chemotherapy and radiotherapy is a standard nonsurgical treatment for locally advanced laryngeal cancer. Nevertheless, there are no validated markers to predict the outcome of nonsurgical therapies. The impact of previous tracheotomy is not clear in patients submitted to concomitant chemoradiotherapy. STUDY DESIGN: A non-randomized prospective study. Prognostic factors such as stage, age, performance status, number of chemotherapy cycles, radiotherapy dose, stage VIb disease, and previous tracheotomy were analyzed using the Cox's proportional hazard model. The Kaplan-Meier and log rank tests were used to evaluate the progression-free and overall survival. PATIENTS AND METHODS: Patients with stage III/IV laryngeal carcinoma were prospectively selected. Treatment consisted of cisplatin 100 mg/m(2) every 3 weeks for 3 cycles, radiotherapy to a total dose of 70.2 Gy and salvage surgery. RESULTS: Forty-nine patients were analyzed; tracheotomy was performed in 12 patients (24.5%) before therapy. Patients who had previous tracheotomy had a lower rate of complete response (41.7 vs. 75%, p = 0.034, HR 0.55, CI 95% 0.27-1.11), shorter progression free-survival (HR 2.83, CI 95% 1.60-4.88, p < 0.001), and median overall survival (12 vs. 56 months, HR 2.37, CI 95% 1.43-3.93, p < 0.001), in comparison to those without a tracheotomy. Moreover a significant difference was observed in 3-year survival rates (6 vs. 61%, p = 0.001), in favor of the group without tracheotomy. Interestingly, the impact of previous tracheotomy was not altered when adjusted by other prognostic factors (HR 8.7, CI 95% 3.1-24.0, p < 0.001). CONCLUSIONS: Previous tracheotomy is a negative prognostic factor for patients submitted to chemotherapy combined with radiotherapy and should be considered as a negative clinical prognostic factor in the selection of patients for more aggressive treatment strategies.
Assuntos
Obstrução das Vias Respiratórias/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/terapia , Traqueotomia/métodos , Adulto , Idoso , Obstrução das Vias Respiratórias/mortalidade , Obstrução das Vias Respiratórias/patologia , Análise de Variância , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radioterapia Adjuvante , Medição de Risco , Análise de Sobrevida , Traqueotomia/efeitos adversosRESUMO
PURPOSE: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer. EXPERIMENTAL DESIGN: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m(2), weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB. RESULTS: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 at DL 150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity. CONCLUSIONS: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated. The maximum tolerated dose has been defined as 150 mg. To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.