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PURPOSE: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. METHOD: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. RESULTS: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. CONCLUSION: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.
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INTRODUCTION: Information regarding HER2-low tumors in metastatic gastric cancer is sparse. Our aim here was to determine the frequency of low HER2 expression in metastatic gastric cancer and to compare the clinicopathological characteristics, survival, and treatment response of HER2-low patients with HER2-zero patients. METHODS: All the data were collected retrospectively from computerized system of the hospital. We categorized the patients according to clinicopathological features, treatment responses, and survival in terms of HER2-low tumors and HER2-zero tumors. RESULTS: Of 226 patients, 71 (31.4%) had low HER2 expression and 155 (68.6%) had zero HER2 expression. HER2-low tumors were detected more frequently in older patients and in low-grade tumors than HER2-zero tumors (69% vs 47.7%, P = 0.003, 16.9% vs 3.8%, P < 0.001). All patients received a first-line chemotherapy regimen. The disease control rate was not statistically different between both groups (40% vs 46.4%, P=0.11). The median survival was 12.05 (95% CI, 8.09-16.02) months in HER2-low patients, and 10.41 (95% CI, 8.52-12.3) months in HER20-zero patients with no statistical difference (P=0.73). CONCLUSION: HER2-low metastatic gastric cancer has a higher rate of being low-grade than HER2-zero tumors. HER2-low metastatic gastric cancer is similar to HER2-zero in terms of chemotherapy response and survival.
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BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.
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Neoplasias da Mama , Humanos , Feminino , Everolimo , Receptor ErbB-2/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Fulvestranto/uso terapêutico , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.
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Neoplasias da Mama , Humanos , Feminino , Letrozol/uso terapêutico , Neoplasias da Mama/patologia , Estudos Retrospectivos , Aminopiridinas/uso terapêutico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2RESUMO
5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40 years, induces grade III-IV toxicities in up to 15% of patients with polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot syndrome, and rare ocular adverse effects. Here, we present the case of a female patient with rectal cancer who received 5-FU-based chemotherapy and developed grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic analysis revealed that the patient had an 85T>C mutation in the DPYD gene resulting in a DPYD*9A allele. The clinical and molecular observations indicate that DPYD deficiency may be responsible for the severe ocular adverse effects observed in 5-FU-treated patients. Application of personalized therapy based on molecular testing should help clinicians provide the most effective chemotherapy agents and dose modifications for each patient, although further population-based pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to minimize adverse effects and enhance clinical outcomes.
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Antimetabólitos Antineoplásicos/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/genética , Oftalmopatias/induzido quimicamente , Fluoruracila/efeitos adversos , Alelos , Antimetabólitos Antineoplásicos/efeitos adversos , Oftalmopatias/genética , Feminino , Fluoruracila/uso terapêutico , Síndrome Mão-Pé/etiologia , Humanos , Pessoa de Meia-Idade , Mutação , Farmacogenética , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/etiologiaRESUMO
BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.
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BACKGROUND: Surgical excision constitutes an important part of the treatment of local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high-dose interferon therapy is still the only therapy used in stage IIB and III high-risk melanoma patients. METHODS: One hundred two high-risk malignant melanoma patients who received high-dose interferon-α-2b therapy were evaluated retrospectively. The clinicopathological features, survival times, and prognostic factors of the patients were determined. RESULTS: The median disease-free and overall survival times were 25.2 and 60.8 months, respectively. Our findings revealed that male gender, advanced disease stage, lymph node involvement, lymphatic invasion, the presence of ulceration, and a high Clark level were significant negative prognostic factors. CONCLUSION: In light of the favorable survival results obtained in this study, high-dose interferon treatment as adjuvant therapy for high-risk melanoma is still an efficient treatment and its possible side effects can be prevented by taking the necessary precautions.
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Antineoplásicos/administração & dosagem , Interferons/administração & dosagem , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante/mortalidade , Quimioterapia Adjuvante/tendências , Terapia Combinada/mortalidade , Terapia Combinada/tendências , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
Biomarkers such as hormone receptors (HR) and human epidermal growth factor receptor2 (HER2) may change after neoadjuvant chemotherapy (NAC) in breast cancer patients. The aim of this study was to investigate the rates of receptor change after NAC and to evaluate the prognostic impact of change. Patients with breast cancer who received NAC were included in the study. Changes in pathological findings (ER, PR, HER-2, Ki-67, grade) before and after NAC were examined. In addition, the effect of receptor exchange on prognosis was evaluated. Kaplan Meier analysis was used for survival analyses. Study was approved by Ethics Board of Tepecik Training and Research Hospital (Decision number 2021/10-02). We confirm that all methods were performed in accordance with relevant named guidelines and regulations. The study included 203 female patients. When pathological findings before and after NAC were compared, significant regression was found in grade and Ki-67 values (p = 0.003, p < 0.001). ER change rate was 11.8%, PR change rate was 24.6% and HER-2 change rate was 12.5%. No significant correlation was found between ER, PR and HER-2 changes and prognosis. The pathological T stage after NAC being 1 or 2, no lymph nodes detected, and the tumor grade being 1 or 2 were independent variables related to survival (p: 0.002, p: 0.014, p < 0.001). In patients with breast cancer, it would be appropriate to re-evaluate the HER-2 and HR status of the surgical specimen following NAC, especially in initially negative patients. The correlation of receptor discordance with prognosis is not clear and more extensive studies are needed.
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Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/metabolismo , Adulto , Receptor ErbB-2/metabolismo , Idoso , Receptores de Progesterona/metabolismo , Imuno-Histoquímica , Receptores de Estrogênio/metabolismo , Antígeno Ki-67/metabolismo , Estimativa de Kaplan-Meier , Quimioterapia AdjuvanteRESUMO
Background & aims: Prognostic factors of metastatic rectal cancer are not well known. We aim to determine prognostic factors affecting survival for metastatic rectal cancer patients and also to investigate the effect of tumor localization on overall survival. Methods: Metastatic rectal cancer patients who received treatment in 5 different centers between 2012 and 2022 were included. Prognostic factors for survival were evaluated using univariate and multivariate analysis. The statistical methods included Pearson's chi-square test, Fisher exact test, Log-rank test, and Cox regression model. Results: A total of 283 patients with metastatic rectal cancer were included in the study. The median OS was not significantly different among the three groups (upper rectum 30.1 months, middle rectum 28.3 months, and low rectum cancer 24.8 months; log-rank p = 0.25). In univariate analysis, Grade 3, ECOG performance status 2, the presence of multiple metastatic sites, the presence of KRAS mutation, the presence of liver metastases, the presence of nonregional lymph node metastases, and the presence of bone metastases were significant predictors of poor survival. In multivariate analysis, Grade 3, ECOG performance status 2, and the presence of multiple metastatic sites were determined as indicators of worse prognosis. Conclusion: Our findings, primary tumor location did not affect survival in metastatic rectal cancer. The most important factors affecting survival were multiple metastatic sites, tumor grade, and ECOG performance status.
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To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, Pâ =â .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (Pâ =â .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.
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Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas , Crizotinibe , Neoplasias Pulmonares , Humanos , Crizotinibe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico/genética , Adulto , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) is an effective but highly toxic regimen for the treatment of advanced gastric cancer. To improve tolerability while maintaining the efficacy of the DCF regimen, we developed a modified DCF regimen including an infusional 5-fluorouracil administration according to the de Gramont regimen. METHODS: In this study, 70 patients with advanced gastric cancer were treated. Each 2-week cycle consisted of docetaxel (60 mg/m(2)), cisplatin (50 mg/m(2)), a 5-fluorouracil (400 mg/m(2)) i.v. bolus, and 5-fluorouracil (2,400 mg/m(2)) i.v. over 46 h plus leucovorin (400 mg/m(2)) i.v. over 2 h. RESULTS: The median progression-free survival and overall survival were 9.0 months (95% CI, 7.1-10.9) and 10.8 months (95% CI, 7.4-14.2), respectively; the 1-year and 2-year overall survival rates were 46.3 and 18.4%, respectively. Twenty-nine (41.4%) partial responses, 19 (27.1%) stable disease, and 22 (31.4%) progression of disease were observed. Grade 3-4 toxicities included neutropenia (37.1%), febrile neutropenia (15.7%), thrombocytopenia (10.0%), anemia (8.6%), nausea and vomiting (10.0%), stomatitis (5.7%), infection (8.6%), and diarrhea (2.9%). CONCLUSIONS: Our results show that a de Gramont-based DCF regimen may have tolerable toxicities and be an effective and convenient palliative treatment for advanced gastric cancer.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
AIM: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). PATIENTS AND METHODS: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. RESULTS: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. CONCLUSION: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.
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Leiomiossarcoma , Segunda Neoplasia Primária , Sarcoma Sinovial , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Turquia/epidemiologia , Sarcoma/patologia , IndazóisRESUMO
The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Feminino , Humanos , Masculino , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Estudos Retrospectivos , Turquia/epidemiologia , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. METHODS: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. RESULTS: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). CONCLUSIONS: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.
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Neoplasias Encefálicas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Análise Multivariada , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/uso terapêutico , Trastuzumab , TurquiaRESUMO
BACKGROUND/AIMS: The efficacy and tolerability of oxaliplatin in combination with either folinic acid, fluoro-uracil (5-FU) (FOLFOX4 regimen) or capecitabine (XE-LOX regimen) was evaluated in advanced pancreatic cancer. METHODOLOGY: In this study, eighty-five patients with advanced pancreatic cancer were enrolled after failing to gemcitabine-based chemotherapy between November 2005 and August 2011. FOLFOX4 was repeated every two weeks and XELOX regimen was repeated every three weeks until either disease progression or unacceptable toxicity occurred. RESULTS: Eighty-five patients were evaluated for tumor response.Seven patients (18%) achieved a partial response with XELOX and stable disease was observed in 16 patients (41%). Eight patients (17%) achieved a partial response with FOLFOX4 and stable disease was observed in 12 patients (26%). Disease control rates were 59%in the XELOX arm and 43% in the FOLFOX4 arm. The median time to progression was 16 weeks in both arms.The median overall survival was 21 weeks with XELOX and 25 weeks with FOLFOX4. CONCLUSIONS: Oxaliplatin-based combination therapy showed moderate clinical activity with acceptable toxicity in patients who had progressive disease after receiving gemcitabine-based chemotherapy for advanced and/or metastatic pancreatic cancer. We conclude that XELOX is similar in terms of efficacy and toxicity profile to FOLFOX4 in the sec-ond-line treatment of metastatic pancreatic cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaloacetatos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Turquia , GencitabinaRESUMO
Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect of dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) polymorphisms in colorectal cancer patients. Eighty-five patients who were administered fluoropyrimidine-based treatment were included in the study. The DPYD, TYMS and MTHFR polymorphisms were scanned by a next generation Sequenom MassARRAY. Fluoropyrimidine toxicities were observed in 92% of all patients. The following polymorphisms were detected: DPYD 85T>C (29.4% heterozygote mutants, 7.1% homozygote mutants), DPYD IVS 14+1G>A (1.2% heterozygote mutants), TYMS 1494del TTAAAG (38.4% heterozygote mutants, 24.7% homozygote mutants), MTHFR 677C>T (43.5% heterozygote mutants, 9.4% homozygote mutants) and MTHFR 1298A>C (8.2% heterozygote mutants, 2.4% homozygote mutants). A statistically significant association was demonstrated between MTHFR 677C>T and fluoropyrimidine-related toxicity. Furthermore, MTHFR 1298A>C was associated with hematopoietic toxicity. MTHFR polymorphisms may be considered as related factors of fluoropyrimidine toxicity and may be useful as predictive biomarkers for the determination of the colorectal cancer patients who can receive the greatest benefit from fluoropyrimidine-based treatments.
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BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Adenocarcinoma/mortalidade , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Intestino Delgado/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
Data regarding the prognostic importance of BRAFV600 tumor mutations in high-risk, non-metastatic, stage 2 and 3 malignant melanoma (MM) patients are controversial. There is not sufficient information in the medical literature regarding the reliability of BRAF mutations as a predictive factor in prognosis and adjuvant treatment decision issues in this patient group. The data of 50 operated high-risk, non-metastatic, stage 2B/2C and 3 MM patients who received high-dose interferon alfa-2b therapy were evaluated retrospectively. BRAF mutations were analyzed by using microarray-based molecular methods. The associations between BRAF mutations and both clinicopathological characteristics and survival were assessed. Of the 50 patients, 52 % was female and 48 % was male, and the median age was 51.5 years. Twenty-three (46 %) and 27 (54 %) patients had stage 2B/2C and stage 3 disease, respectively. BRAF mutation was detected in 21 patients. The median overall survival (OS) was 58.1 months, whereas the median disease-free survival (DFS) was 22.7 months. When the OS and DFS were compared according to the BRAF mutation status, no difference was detected between the two groups. BRAF mutations were detected more frequently in tumors with mitosis and ulceration; however, no statistically significant difference was observed in other clinicopathological parameters. In conclusion, it is not appropriate to use BRAF mutations as a prognostic and predictive marker for selecting the treatment and assessing its outcomes in patients with early stage, high-risk MM.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Melanoma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Interferon alfa-2 , Estimativa de Kaplan-Meier , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidadeRESUMO
BACKGROUND: Soft tissue sarcomas (STSs) are rare malignant tumors of embryogenic mesoderm origin. Primary thoracic STSs account for a small percentage of all STSs and limited published information is available. This study aimed to identify the prognostic factors for thoracic STSs and evaluate the disease's clinical outcomes. METHODS: The medical records of 109 patients with thoracic STSs who were treated between 2003 and 2013 were retrospectively reviewed. Patients' survival rates were analyzed and potential prognostic factors evaluated. RESULTS: The median follow-up period was 29 months (range: 1-121 months). STSs were most frequently localized on the chest wall (n = 42; 38.5%) and lungs (n = 42; 38.5%). The most common histological types were malignant fibrous histiocytoma (n = 23; 21.1%), liposarcoma (n = 17; 15.6%), and leiomyosarcoma (n = 16; 14.7%). The median survival time of all patients was 40.3 months (95% confidence interval, 14.22-66.37 months), with one and five-year survival rates of 93.4% and 63.5%, respectively. Univariate analysis of all groups revealed that metastatic stage, unresectability, tumor diameter of >10 cm, tumor location other than the chest wall, and grade 3 diseases were predictable of poor survival. However, only grade 3 diseases and tumor location other than the chest wall were confirmed by multivariate analysis as poor prognostic factors. CONCLUSIONS: Primary thoracic STSs are rarely seen malignant tumors. Our results indicated that patients with low-grade tumors and those localized on the chest wall often experienced better survival outcomes.