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1.
Mod Pathol ; 37(9): 100552, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38942115

RESUMO

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name "PLAG1-rearranged uterine sarcoma."


Assuntos
Proteínas de Ligação a DNA , Rearranjo Gênico , Leiomiossarcoma , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Adulto , Idoso , Proteínas de Ligação a DNA/genética , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Sarcoma/genética , Sarcoma/patologia , Fenótipo , Biomarcadores Tumorais/genética , Imuno-Histoquímica
2.
Strahlenther Onkol ; 198(9): 783-791, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35059759

RESUMO

PURPOSE: Image-guided adaptive brachytherapy (IGABT) is currently state of the art in the comprehensive treatment of patients with cervical cancer. Here, we report mature clinical data regarding IGABT of cervical cancer in a large patient sample, examining clinical outcomes, manifestations of late toxicities, and dosimetric findings. METHODS: Between May 2012 and October 2020, we performed a total of 544 uterovaginal IGABT applications in 131 consecutive patients with biopsy-proven cervical carcinoma not suitable for surgery. The median duration of follow-up was 43 months. RESULTS: The estimated 3­, 4­, and 5­year LC rates were 88.3% (95% confidence interval [CI] 81.1-95.5), 86.9% (95% CI 78.5-95.3), and 85.5% (95% CI 76-95%), respectively. The 3­, 4­, and 5­year OS estimates were 72.66% (95% CI 63.64-81.69%), 68.9% (95% CI 59.15-78.66%), and 63.96% (95% CI 52.94-74.97%), respectively. Patients who received ≥ 5 cycles of chemotherapy had statistically significantly better 3­year recurrence-free survival (RFS) compared to patients who completed <5 cycles (79.07% [95% CI 60.81-97.34] vs. 58.10% [95% CI 47.22-68.98]; p = 0.0185). We recorded manifestations of genitourinary and gastrointestinal toxicity grade ≥3 in 6.9% and 5.3%, respectively. CONCLUSION: Our mature long-term data on the treatment patients with locally advanced cervical cancer show that excellent treatment outcomes can be achieved with MRI-based IGABT, as well as acceptable late morbidity.


Assuntos
Braquiterapia , Radioterapia Guiada por Imagem , Neoplasias do Colo do Útero , Braquiterapia/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
3.
Strahlenther Onkol ; 197(9): 847-853, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34160632

RESUMO

Carcinoma showing thymus-like elements (CASTLE) is an extremely rare malignant tumor of the thyroid gland and soft tissues of the neck with favorable prognosis. Histological features of the CASTLE are similar to thymic carcinoma, and it is assumed that it arises from the ectopic thymic tissue or the remnants of branchial pouches. The optimal treatment strategy is still uncertain because of the rarity of the tumor. The mainstay of treatment is surgery. The role of other modalities is unclear. We present a case report of a patient with locally advanced CASTLE of the thyroid gland who was not suitable for surgery and underwent radical radiotherapy with subsequent achievement of complete remission. We also present a literature review.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Neoplasias da Glândula Tireoide , Humanos , Prognóstico , Neoplasias do Timo/patologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia
4.
Strahlenther Onkol ; 197(6): 494-504, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33492444

RESUMO

PURPOSE: We aimed to find metabolic, functional or morphological characteristics of the tumor predicting failure to achieve complete metabolic remission (CMR) by the midtreatment PET/MRI (positron emission tomography/magnetic resonance imaging) in cervical cancer patients. METHODS: We evaluated 66 patients treated between August 2015 and November 2019 who underwent pretreatment staging, subsequent midtreatment evaluation, and definitive restaging 3 months after completing the whole treatment, all using PET/MRI. The pretreatment parameters (pre-SUVmax, pre-SUVmean, pre-MTV, pre-MTV­S, pre-TLG, pre-TLG­S [SUV: standard uptake value, MTV: metabolic tumor volume, TLG: total lesion glycolysis]), and the midtreatment parameters at week 5 during chemoradiotherapy (mid-SUVmax, mid-SUVmean, mid-MTV, mid-MTV­S, mid-TLG and mid-TLG-S) were recorded. The value of ADC (apparent diffusion coefficient) was also measured. Furthermore, we recorded absolute and relative changes in all parameters-∆ and ∆%. We divided the whole group of patients into "responders" (CMR) and "non-responders" (non-CMR), and compared them on the basis of the parameters from pre-PET/MRI and mid-PET/MRI. RESULTS: A statistically significant difference in the evaluated parameters between responders and non-responders was found for the following parameters: mid-MTV, mid-TLG, mid-TLG­S, mid-MTV­S, mid-tumor size, and ∆%SUVmax. According to the ROC (receiver operating characteristic) analysis, mid-MTV­S showed the best albeit moderate discrimination ability for the prediction of non-CMR. Significant mutual correlations of all variables, in particular between mid-MTV­S and mid-TLG­S and between mid-MTV and mid-TLG, were found (all p < 0.05). CONCLUSION: Our study confirmed that when using the midtreatment PET/MRI we are able to identify metabolic parameters having the discrimination ability for the prediction of non-CMR. In particular mid-MTV­S, mid-MTV, mid-tumor size, mid-TLG­S, mid-TLG and ∆%SUVmax.


Assuntos
Quimiorradioterapia , Imageamento por Ressonância Magnética , Imagem Multimodal , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Área Sob a Curva , Braquiterapia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Irradiação Linfática , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Radioterapia de Intensidade Modulada , Resultado do Tratamento , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
5.
Ceska Gynekol ; 86(4): 264-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34493052

RESUMO

Molecular classification of endometrial carcinoma is becoming an important part of the dia-gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard dia-gnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia-gnostic practice in the Czech Republic.


Assuntos
Neoplasias do Endométrio , Radioterapia (Especialidade) , Biologia , República Tcheca , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Patologistas , Física
6.
Cesk Patol ; 57(3): 147-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551562

RESUMO

Molecular testing of tumor tissue for the detection of somatic aberrations using NGS is increasingly gaining significance in routine practice. The technical aspects of testing are standardized and currently do not pose a problem. However, the situation is evolving very rapidly regarding the indication of testing, which depends on the sometimes rapidly developing medical knowledge and needs in clinical practice. In order to implement NGS testing in practice and arrange its reimbursement by the health care system, first it is necessary to reach an agreement on the level of professional societies concerning the definition of priority and medically clearly justified areas in which molecular testing has a clear impact on therapeutical choices. The next step is to reach an agreement with the health insurance companies regarding NGS testing. The aim of this article is to provide an overview of the issue of routine tumor tissue testing using the NGS method covered by public health insurance, with a summary of the current situation in the Czech Republic. Only the testing of somatic aberrations in solid tumors performed at pathology departments is discussed. The issue of testing in haemato-oncological centres is not the subject of this review.


Assuntos
Técnicas de Diagnóstico Molecular , Neoplasias , República Tcheca/epidemiologia , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/genética
7.
Cesk Patol ; 57(3): 181-187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551568

RESUMO

Molecular classification of endometrial carcinoma is becoming an important part of the diagnostic process with direct therapeutic implications. Recent international guidelines, including the joint ESGO-ESTRO-ESP recommendation, include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th) edition of the WHO classification of Female Genital Tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of Czech Medical Association of J. E. Purkyně (Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. The result of this meeting is a joint recommendation for molecular testing of endometrial carcinoma in routine diagnostic practice in the Czech Republic.


Assuntos
Neoplasias do Endométrio , Radioterapia (Especialidade) , Biologia , República Tcheca , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Patologistas , Física
8.
Rep Pract Oncol Radiother ; 25(6): 882-885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982594

RESUMO

Thymomas are the most common mediastinal tumors. Systemic therapy for patients with unresectable or recurrent thymomas is a challenging field in the current oncology research. There is some evidence that somatostatin analogs combined with corticosteroids may have a role in the treatment of advanced malignant thymoma; however, the role of these agents have not been fully evaluated. CASE REPORT: A 39-year-old man with metastatic thymoma was administered long-acting depot injection form of octreotide. Octreotide scan before the treatment initiation revealed low uptake. CT control after three months of the treatment revealed marked regression of pleural metastases, while the primary tumor mass remained stable. The treatment response was lasting for 9 months. CONCLUSION: We describe an interesting case of marked clinical and radiological response of advanced malignant thymoma to the treatment with octreotide in a heavily pre-treated patient, even though octreotide scan revealed low uptake.

9.
Rep Pract Oncol Radiother ; 25(6): 934-938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088229

RESUMO

Lymphangiosarcoma, or Stewart-Treves Syndrome (STS), is a very rare skin angiosarcoma with poor prognosis, which usually affects the upper limbs of patients who underwent breast cancer surgery, including axillary dissection followed by radiotherapy (RT). Cutaneous lymphangiosarcomas, which account for approximately 5% of all angiosarcomas, usually originate in the limb with chronic lymphedema. Lymphatic blockade is involved in the onset of STS. RT contributes indirectly to an increased risk of developing STS by causing axillary-node sclerosis and resulting in a lymphatic blockade and lymphedema. Chronic lymphedema causes local immunodeficiency, which indirectly leads to oncogenesis. Currently, axillary nodes are no longer routinely irradiated after axillary dissection, which is associated with a reduction in the incidence of chronic lymphedema from 40% to 4%. The use of sentinel lymph node biopsy technique is also widespread and the associated risk of lymphedema is further reduced. Thus, the incidence of STS decreased significantly with improved surgical and radiation techniques. The overall prognosis of STS patients is very poor. Only early radical surgical removal, including amputation or disarticulation of the affected limb, or wide excision at an early stage offers the greatest chance of long-term survival. Only a few case reports and series with a small number of patients with lymphangiosarcoma can be found in the literature. We present a case report of the first diagnosed STS at our department in an effort to highlight the need of the consideration of developing lymphangiosarcoma in patients with chronic lymphedema.

10.
Strahlenther Onkol ; 195(11): 972-981, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309266

RESUMO

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.


Assuntos
Braquiterapia/efeitos adversos , Imageamento por Ressonância Magnética , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Neoplasias do Colo do Útero/radioterapia , Colo Sigmoide/efeitos da radiação , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Neoplasias do Colo do Útero/patologia
11.
Tumour Biol ; 39(7): 1010428317709283, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28714375

RESUMO

MicroRNAs regulate the expression of genes involved in several important cancer-related processes including cell adhesion, proliferation, and tumour angiogenesis. Bevacizumab is routinely used in the treatment of patients with metastatic colorectal cancer, but, so far, no reliable biomarker predicting response to bevacizumab has been established. The aim of our retrospective study was to evaluate the association of miR-126-3p, miR-126-5p and miR-664-3p tumour expression levels with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. The study included 63 patients. For the assessment of microRNA expression, gene-specific TaqMan assays were used. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-3p were 8.8 and 20.6 months versus 13.5 months and median overall survival was not reached for patients with high expression ( p = 0.0064 and p = 0.0027), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-5p were 9.0 and 22.2 months versus 12.0 and 23.4 months for patients with high expression ( p = 0.2113 and 0.6858), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-664-3p were 9.1 and 22.5 months versus 8.8 and 23.4 months for patients with high expression ( p = 0.2542 and p = 0.1922), respectively. The multivariable Cox proportional hazards model revealed that miR-126-3p expression was significantly associated with progression-free survival (hazard ratio = 0.28, p = 0.0053) and also with overall survival (hazard ratio = 0.18, p = 0.0046). In conclusion, the results of this study suggest that the expression of miR-126-3p in the tumour tissue was associated with outcome of metastatic colorectal cancer patients treated with bevacizumab.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/genética , Adulto , Idoso , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
12.
Tumour Biol ; 39(2): 1010428317691186, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28218046

RESUMO

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ligação a DNA/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Transcrição , Adulto Jovem
13.
BMC Cancer ; 17(1): 880, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29268716

RESUMO

BACKGROUND: It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). METHODS: This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. RESULTS: The median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5-19.5 months), 17.1 months (95% CI 14.5-19.8), and 15.4 months (95% CI 11.0-19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus. CONCLUSIONS: In this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Papilar/secundário , Carcinoma de Células Renais/patologia , Neoplasias Renais/secundário , Terapia de Alvo Molecular , Sistema de Registros/estatística & dados numéricos , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Seguimentos , Humanos , Neoplasias Renais/tratamento farmacológico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Rep Pract Oncol Radiother ; 22(4): 265-276, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28507455

RESUMO

AIM: To figure out how to correlate the findings on functional MRI and carried out after neoadjuvant CRT of rectal carcinoma with final histology after surgery. BACKGROUND: Neoadjuvant CRT is the standard treatment of locally advanced rectal carcinoma. Its use leads to the downstaging of the disease and in 15-42% of patients even to the detection of pCR after TME. The use of functional MRI improves the sensitivity and specificity of pCR detection up to 52-64% and 89-98%, respectively. MATERIALS AND METHODS: Between January 2013 and June 2016, 67 patients suffering from histologically proven locally advanced rectal cancer underwent neoadjuvant RT or CRT. We selected for further investigation only patients (33 patients) who underwent pelvic staging and restaging using multiparametric imaging on 3T MRI scanner. We compared the findings on functional MRI after neoadjuvant CRT with final histology after surgery. RESULTS: In 15 patients pathologic staging of primary tumor differed from expected staging assessed according to preoperative MRI. In 5 patients pathologic complete remission was achieved. In none of these 5 patients pCR was predicted using preoperative MRI. Sensitivity and specificity of MRI in predicting pCR were 0% and 96%. Accuracy of MRI in predicting pT and pN was 79% and 74%. CONCLUSIONS: We have verified that the use of neoadjuvant CRT in the treatment of locally advanced rectal carcinoma leads to a possible achievement of pCR. But in our group of patients this was not predictable nor was it with the use of multiparametric 3T MRI.

15.
Tumour Biol ; 37(5): 6823-30, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26662311

RESUMO

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.


Assuntos
Alelos , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Mutação , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Códon , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Retratamento , Resultado do Tratamento
17.
Tumour Biol ; 36(8): 5801-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25702091

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent novel effective agents approved for the treatment of patients with advanced-stage NSCLC. KRAS mutations have been reported as a negative prognostic and predictive factor in patients with NSCLC treated with EGFR-TKIs. Several studies have recently shown that statins can block tumour cell growth, invasion and metastatic potential. We analysed clinical data of 67 patients with locally advanced (IIIB) or metastatic stage (IV) NSCLC harbouring Kirsten rat sarcoma viral oncogene (KRAS) mutation treated with erlotinib or gefitinib. Twelve patients were treated with combination of EGFR-TKI and statin and 55 patients were treated with EGFR-TKI alone. Comparison of patients' survival (progression-free survival (PFS) and overall survival (OS)) according to the treatment used was performed using the Gehan-Wilcoxon test. The median of PFS and OS for patients treated with EGFR-TKI alone was 1.0 and 5.4 months compared to 2.0 and 14.0 months for patients treated with combination of EGFR-TKI and statin (p = 0.025, p = 0.130). In conclusion, the study results suggest significant improvement of PFS for patients treated with combination of statin and EGFR-TKI, and the difference in OS was not significant.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas p21(ras) , Quinazolinas/administração & dosagem
18.
Tumour Biol ; 36(12): 9215-22, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26088452

RESUMO

Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Cloridrato de Erlotinib/administração & dosagem , Adulto , Idoso , Biomarcadores Tumorais/genética , Proteína C-Reativa/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Resultado do Tratamento
19.
Rep Pract Oncol Radiother ; 20(3): 210-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25949225

RESUMO

AIM: The aim of our study was to compare the staging of the disease declared before anticancer treatment was begun with the staging that was found after the planning PET/CT scanning with (18)F-FLT was performed. BACKGROUND: PET/CT in radiotherapy planning of head and neck cancers can facilitate the contouring of the primary tumour and the definition of metastatic lymph nodes. MATERIALS AND METHODS: Between November 2010 and November 2013, 26 patients suffering from head and neck carcinomas underwent planning PET/CT examination with (18)F-FLT. We compared the staging of the disease and the treatment strategy declared before and after (18)F-FLT-PET/CT was performed. RESULTS: The findings from (18)FLT-PET/CT led in 22 patients to a change of staging: in 19 patients it led to upstaging of the disease and in 3 patients it led to downstaging of the disease. In one patient, a secondary malignancy was found. CONCLUSIONS: We have confirmed in this study that the use of (18)F-FLT-PET/CT scanning in radiotherapy planning of squamous cell head and neck carcinomas has a great potential in the precise evaluation of disease staging and consequently in the precise determination of target volumes.

20.
BMC Gastroenterol ; 14: 53, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24666582

RESUMO

BACKGROUND: Patients aged 65 years and older represent the majority of patients with metastatic colorectal cancer (mCRC). However, this patient population is often underrepresented in clinical trials and probably undertreated in the clinical practice. METHODS: We have analysed the outcomes of 3,187 mCRC patients treated with first-line bevacizumab based on data from the Czech national registry of mCRC patients aiming to compare the treatment efficacy and safety according to the age categories. RESULTS: In total, 2,126 (66.7%), 932 (29.2%), and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years, respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73). Using multivariable Cox model for both PFS and OS, the patient age was not significantly associated with either PFS or OS. No increase in bevacizumab-related toxicity was observed among the elderly mCRC patients with the exception of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%) patients aged <65 years, 65 to 75 years, and 75+ years, respectively. CONCLUSIONS: The results of the present study suggest similar outcome in terms of OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for chemotherapy combined with targeted therapy compared to younger patients. Thus, chronological age should not be considered to represent a limitation in prescribing bevacizumab-containing therapy in mCRC patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fatores Etários , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Capecitabina , República Tcheca , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Hipertensão/induzido quimicamente , Estimativa de Kaplan-Meier , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaloacetatos , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Tromboembolia/induzido quimicamente
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