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1.
Medicine (Baltimore) ; 103(21): e37972, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787994

RESUMO

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%, P = .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 (P = .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.


Assuntos
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 Tratamento
2.
J Clin Oncol ; : JCO2400144, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771995

RESUMO

PURPOSE: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). PATIENTS AND METHODS: In this open-label, multi-center, randomized phase 2 trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3-weeks-on, 1-week-off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS). RESULTS: Among 222 patients randomized to ribociclib plus ET (n=112) or combination CT (n=110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. Median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4-26.7 months) and 12.8 months (combination CT; 95% CI, 10.1-18.4 months); hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P=.003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (HR, 0.76; 95% CI, 0.55-1.06). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSIONS: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

3.
Vaccines (Basel) ; 11(10)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37896948

RESUMO

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common types of cancer with high mortality rates. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with a personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

4.
J Cancer Res Clin Oncol ; 149(14): 13271-13277, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37480524

RESUMO

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

5.
Cancers (Basel) ; 15(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36980554

RESUMO

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

7.
Vaccines (Basel) ; 10(8)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-36016150

RESUMO

mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment. Nevertheless, further research is required to optimize RNA stabilization, delivery platforms, and improve clinical efficacy by interacting with the tumor microenvironment to induce a long-term antitumor response. This review provides a comprehensive summary of the available evidence on the recent advances and efforts to overcome existing challenges of mRNA-based treatment strategies, and how these efforts play key roles in offering perceptive insights into future considerations for clinical application.

8.
J Thorac Oncol ; 17(5): 651-660, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35183774

RESUMO

INTRODUCTION: To evaluate the effects of the global coronavirus disease 2019 (COVID-19) pandemic on lung cancer trials, we surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before and during the pandemic. METHODS: A Data Collection Survey collected aggregate monthly enrollment numbers from 294 global lung cancer trials for 2019 to 2020. A 64-question Action Survey evaluated the impact of COVID-19 on clinical trials and identified mitigation strategies implemented. RESULTS: Clinical trial enrollment declined from 2019 to 2020 by 14% globally. Most reductions in enrollment occurred in April to June where we found significant decreases in individual site enrollment (p = 0.0309). Enrollment was not significantly different in October 2019 to December of 2019 versus 2020 (p = 0.25). The most frequent challenges identified by the Action Survey (N = 172) were fewer eligible patients (63%), decrease in protocol compliance (56%), and suspension of trials (54%). Patient-specific challenges included access to trial site (49%), ability to travel (54%), and willingness to visit the site (59%). The most frequent mitigation strategies included modified monitoring requirements (47%), telehealth visits (45%), modified required visits (25%), mail-order medications (25%), and laboratory (27%) and radiology (21%) tests at nonstudy facilities. Sites that felt the most effective mitigation strategies were telehealth visits (85%), remote patient-reported symptom collection (85%), off-site procedures (85%), and remote consenting (89%). CONCLUSIONS: The COVID-19 pandemic created many challenges for lung cancer clinical trials conduct and enrollment. Mitigation strategies were used and, although the pandemic worsened, trial enrollment improved. A more flexible approach may improve enrollment and access to clinical trials, even beyond the pandemic.


Assuntos
COVID-19 , Neoplasias Pulmonares , COVID-19/epidemiologia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Pandemias
9.
J BUON ; 26(3): 819-829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268941

RESUMO

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga Tumoral , Turquia , Adulto Jovem
10.
BMC Cancer ; 21(1): 357, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823818

RESUMO

BACKGROUND: The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). METHODS: Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs. RESULTS: The median age was 49 (24-76) years. The majority of patients were clinically T3-4 (n = 31, 50.8%) and clinically N1-3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9-70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066-0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12-0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07-0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17-0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15-0.78, p = 0.01) were found to be associated with improved survival. CONCLUSIONS: These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
11.
Turk Gogus Kalp Damar Cerrahisi Derg ; 29(4): 487-495, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35096446

RESUMO

BACKGROUND: In this study, we aimed to evaluate the factors that contribute to survival outcomes in patients with thymoma treated with multimodal approaches. METHODS: A total of 203 patients (105 males, 98 females; median age: 49 years; range, 17 to 77 years) with Masaoka-Koga Stage II-IV thymoma between January 2002 and December 2018 were retrospectively analyzed. Data including diagnosis of myasthenia gravis, diagnosis of diabetes mellitus, disease stage, histological type of tumor, capsule invasion and surgical margin status, lymphadenectomy, adjuvant radiotherapy or chemotherapy, time from surgery to the first day of adjuvant treatment, length of hospital stay, and overall and disease-free survival rates were recorded. RESULTS: Of the patients, 91 had Stage II, 67 had Stage III, and 45 had Stage IV disease. A total of 123 patients (61%) had myasthenia gravis. Seventy-six patients received adjuvant radiotherapy and 48 patients received either neoadjuvant (n=35) or adjuvant (n=25) chemotherapy. Higher disease stage, presence of R1 resection, and treatment with chemotherapy were significant factors for decreased disease-free survival time. Older age, higher disease stage, longer postoperative hospital stay, chemotherapy, and disease recurrence were effective contributors to decreased overall survival time. Adjuvant radiotherapy had a statistically significant positive effect on overall survival only in patients with completely resected Stage IV disease (five-year overall survival: 94.7% vs. 79.1%, respectively; p=0.015). In the multivariate analysis, older age (hazard ratio: 4.26), higher disease stage (hazard ratio: 2.95), and longer hospitalization time (hazard ratio: 3.81) were significant prognostic factors for overall survival. Patients with local recurrence who underwent complete resection had a survival time comparable to non-recurrent patients (p=0.753). CONCLUSION: For patients with thymoma, higher disease stage, age ≥50 years, longer hospitalization, and need for chemotherapy are associated with worse survival rates. Adjuvant chemotherapy has a positive impact on Stage IV disease. Resection of recurrent lesions has a valuable impact on survival.

12.
Turk J Surg ; 36(2): 147-163, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33015560

RESUMO

OBJECTIVES: Cancer care is excessively influenced by the COVID-19 outbreak for various reasons. One of the major concerns is the tendency for delayed surgical treatment of breast cancer patients. The outbreak has urged clinicians to find alternative treatments until surgery is deemed to be feasible and safe. Here in this paper, we report the results of a consensus procedure which aimed to provide an expert opinion-led guideline for breast cancer management during the COVID-19 outbreak in Turkey. MATERIAL AND METHODS: We used the Delphi method with a 9-scale Likert scale on two rounds of voting from 51 experienced surgeons and medical oncologists who had the necessary skills and experience in breast cancer management. Voting was done electronically in which a questionnaire-formatted form was used. RESULTS: Overall, 46 statements on 28 different case scenarios were voted. In the first round, 37 statements reached a consensus as either endorsement or rejection, nine were put into voting in the second round since they did not reach the necessary decision threshold. At the end of two rounds, for 14 cases scenarios, a statement was endorsed as a recommendation for each. Thirty-two statements for the remaining 14 were rejected. CONCLUSION: There was a general consensus for administering neoadjuvant systemic therapy in patients with node-negative, small-size triple negative, HER2-positive and luminal A-like tumors until conditions are improved for due surgical treatment. Panelists also reached a consensus to extend the systemic treatment for patients with HER2-positive and luminal B-like tumors who had clinical complete response after neoadjuvant systemic therapy.

13.
Lung Cancer ; 148: 48-54, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32799090

RESUMO

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.


Assuntos
Neoplasias Pulmonares , Proteínas Tirosina Quinases , Aminopiridinas , Feminino , Humanos , Lactamas , Lactamas Macrocíclicas , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Proteínas Proto-Oncogênicas , Pirazóis , Receptores Proteína Tirosina Quinases/genética , Estudos Retrospectivos
14.
Balkan Med J ; 37(2): 104-107, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31970972

RESUMO

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Hormônios/normas , Piperazinas/normas , Piridinas/normas , Receptor ErbB-2/metabolismo , Adulto , Estudos de Coortes , Feminino , Hormônios/uso terapêutico , Humanos , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Estudos Retrospectivos
15.
PLoS One ; 14(12): e0226853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860648

RESUMO

BACKGROUND: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. METHODS: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. RESULTS: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. CONCLUSIONS: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomada de Decisão Clínica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Medicina de Precisão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Éxons/genética , Estudos de Viabilidade , Feminino , Humanos , Biópsia Líquida , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
16.
Eur J Breast Health ; 14(3): 173-179, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30123884

RESUMO

OBJECTIVE: In this retrospective study, chemotherapy induced amenorrhea in patients with early stage breast cancer and its effects on survival were investigated. MATERIALS AND METHODS: Two hundred fifty-two patients received adjuvant chemotherapy without ovarian suppression treatment (OST) from 600 premenopausal patients were included in the study. Patients were divided into two groups; with amenorrhea and without, and compared with clinicopathologic features and survival. SPSS version 17 was used. RESULTS: Chemotherapy-induced amenorrhea (CIA) was observed in 145 (57.5%) of 252 patients who received no OST during follow-up. The 5-year OS rate of patients with CIA was significantly higher than patients without CIA (p= 0.042, 95.9% vs. 89.7% vs. 158.88 vs. 135.33 months, respectively). In the subgroup analysis, the OS in patients with hormone receptor (+) was significantly higher than in those receptor (-) in patients with CIA (p=0.011, 97.5% vs. 90.9% vs. 162.13 vs. 126.16 months, respectively). The OS was significantly longer in the luminal A molecular subtype than in those with luminal B molecular subtype, in patients with CIA, but the difference was not significant in patients without CIA (p=0.027 vs. p=0.074, respectively). CONCLUSION: As a conclusion; survival advantage of the chemotherapy induced amenorrhea more pronounced with hormone receptor positivity, lymph node involvement, and advanced disease over patients who do not develop amenorrhea. This advantage of amenorrhea development further prolongs survival compared with luminal B in the luminal A molecular subtype.

17.
Eur J Breast Health ; 14(2): 105-111, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29774319

RESUMO

OBJECTIVE: The aim of this study was to investigate the impacts of personality traits, anxiety, depression and hopelessness levels on quality of life in the patients with breast cancer. MATERIALS AND METHODS: The study was performed on 90 patients diagnosed with breast cancer and 90 healthy women. Sociodemographic and Clinical Data Collection Form designed by us, Beck Hopelessness Scale (BHS), Beck Anxiety Scale (BAS), Beck Depression Scale (BDS), Eysenck Personality Inventory (EPI) and Quality of Life Scale-Short Form (SF-36) were administered to patients and to control group. RESULTS: The patients with breast cancer were found to indicate higher levels of anxiety and depression, lower levels of quality of life, and higher scores of personality inventory subscales as compared to the healthy control group. In the patient group, it was identified that the quality of life subscale scores were found to be negatively correlated with anxiety, depression, hopelessness and neurotic personality scores; there was a positive correlation between neurotic personality scores and depression, anxiety and hopelessness scores. CONCLUSIONS: It can be concluded that the breast cancer patients with extraversion personality traits have lower levels of anxiety and depression, keeping their quality of life better, whereas the patients with higher neuroticism scores may have more impaired quality of life. Therefore, the psychiatric evaluation of the breast cancer patients during and after the treatment cannot be ruled out.

18.
Int J Psychiatry Med ; 53(3): 207-220, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29292669

RESUMO

Objective The aim of the present study was to investigate the possibility of the effect of life long stressful events, along with coping method used, perception of social support, and life style on the development of breast cancer. Methods In this hospital-based case control study, the study group comprised 250 women with breast cancer who were followed by Florence Nightingale Breast Study Group. Control group included 250 women, who had similar sociodemographic characteristics to the study group. Data were collected with semi-structured interview form, Healthy Life Style Behavior Scale, Coping Strategy Indicator, and Stress Evaluation Form developed by us. Results In multivariate analysis, family history of cancer (OR: 1.55, 95% CI: 2.29-1.05), inadequate social support (OR: 1.83, 95% CI: 1.23-2.73), and loss of father during childhood (OR: 2.68, 95% CI: 5.52-1.30) and serious stressor within the last five years (OR: 4.72, 95% CI: 7.03-3.18) were found to be risk factors increasing the risk of breast cancer. When family history of cancer was excluded from the model, the presence of psychiatric disorder history (OR: 1.95, 95% CI: 3.26-1.17) and major life events (OR: 2.24, 95% CI: 4.07-1.24) were added to the model as risk factors. Conclusion The present study indicates that especially the stressful events experienced within the last five years plays an undeniable role in the risk of breast cancer. Social support may be as important in the period before the diagnosis as in the period after diagnosis.


Assuntos
Adaptação Psicológica/fisiologia , Neoplasias da Mama/etiologia , Acontecimentos que Mudam a Vida , Estilo de Vida , Estresse Psicológico/complicações , Adulto , Neoplasias da Mama/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Apoio Social , Estresse Psicológico/psicologia
19.
Lymphat Res Biol ; 16(1): 28-35, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28346852

RESUMO

BACKGROUND: Prolongation of survival in patients with breast cancer due to early diagnosis and modern methods of treatment has turned the attention on lymphedema, which is the most important morbidity secondary to the treatment of the disease. Determination of lymphedema and related risk factors in patients before a surgical intervention may provide protection for patients and early treatment. The aim of this study was to determine the presence of lymphedema before surgery by bioimpedance analysis in patients with breast cancer and to establish risk factors associated with lymphedema. PATIENTS AND METHODS: A total of 277 patients who were diagnosed as having breast cancer, were planned to undergo a surgical intervention, and had no clinical lymphedema were included in the study. The presence of lymphedema was evaluated with clinical examination, measurement of arm circumference, and bioimpedance analysis. RESULTS: Lymphedema was found in 59 (21.3%) patients with no detected differences in arm circumferences. A significant relationship was found between the presence of lymphedema and body mass index (BMI), number of positive lymph nodes, and capsule invasion of the tumor (p = 0.001, p = 0.003, p = 0.002, respectively). Multiple regression analysis revealed that BMI and the number of positive lymph nodes were independent variables (p = 0.024, p = 0.002). ROC curve analysis resulted in an increased risk of preoperative lymphedema when the number of positive lymph nodes was ≥8. Correlation analysis revealed a positive correlation between the number of positive lymph nodes and L-dex score (p = 0.001, r = 0.219). CONCLUSION: Preoperative bioimpedance analysis demonstrated that ∼1/5 of the patients had subclinical lymphedema. Preoperative subclinical lymphedema is associated with obesity and the number of positive lymph nodes, and thus, treatment of the axilla in patients who are preoperatively detected to have subclinical lymphedema should be revised.


Assuntos
Linfedema Relacionado a Câncer de Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Linfonodos/patologia , Obesidade/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/diagnóstico por imagem , Axila/patologia , Índice de Massa Corporal , Linfedema Relacionado a Câncer de Mama/etiologia , Linfedema Relacionado a Câncer de Mama/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Diagnóstico Precoce , Impedância Elétrica , Feminino , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/diagnóstico por imagem , Obesidade/patologia , Curva ROC , Fatores de Risco , Biópsia de Linfonodo Sentinela
20.
Eur J Breast Health ; 13(4): 206-212, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29082379

RESUMO

OBJECTIVE: The aim of this study was to determine the roles of biopsychosocial risk factors in the development of breast cancer. MATERIALS AND METHODS: This hospital-based case-control study included 491 women with breast cancer (study group) and 512 women who did not have cancer or other serious diseases (control group). Biological, psychological, and social risk factors were compared between the two groups. Data were collected using the semi-structured interview, the Stress Assessment Form, and the Coping Strategy Indicator to assess these factors. RESULTS: When the significantly different biopsychosocial variables between the study and the control groups were evaluated together, independent breast cancer risk factors were found as follows: a stressor experienced in the last 5 years, age 40 years and older, inadequate social support perception, use of avoidance coping strategy, being a housewife, having a family history of cancer, and having a body mass index ≥25. CONCLUSION: This study showed a relationship between breast cancer risk and manageable variables (obesity, stressor and coping strategy, social support, and employment status), age and family history of cancer, which are biopsychosocial factors. Biopsychosocial aspects are becoming a greater part of many different healthcare systems.

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