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1.
Mod Pathol ; 37(9): 100552, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942115

ABSTRACT

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."

2.
Cancer Med ; 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38164124

ABSTRACT

BACKGROUND: The introduction of novel hormonal therapies represented by enzalutamide (ENZ) and abiraterone acetate (ABI) has reached a great progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The majority of mCRPC patients are elderly suffering from chronic co-morbidities requiring use of various concomitant medications. In the present study, we focused on impact of concomitant antihypertensive medication on the outcomes of mCRPC patients treated with ENZ or ABI. METHODS: In total, 300 patients were included and their clinical data were retrospectively analyzed. RESULTS: Angiotensin-converting enzyme inhibitors (ACEIs) represented the only concomitant medication significantly associated with survival. The median radiographic progression-free survival (rPFS) and overall survival (OS) for patients using ACEIs were 15.5 and 32.3 months compared to 10.7 and 24.0 months for those not using ACEIs (p = 0.0053 and p = 0.0238, respectively). Cox multivariable analysis revealed the use of ACEIs a significant predictive factor for both rPFS (HR = 0.704, p = 0.0364) and OS (HR = 0.592, p = 0.0185). CONCLUSION: The findings of this study suggest an association between the concomitant use of ACEIs and longer survival of mCRPC patients receiving ENZ or ABI therapy.

3.
Anticancer Res ; 43(1): 463-471, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36585174

ABSTRACT

BACKGROUND/AIM: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. PATIENTS AND METHODS: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. RESULTS: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre-chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. CONCLUSION: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.


Subject(s)
Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Abiraterone Acetate/therapeutic use , Prednisone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Nitriles , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome
4.
Cancer Genomics Proteomics ; 19(2): 270-281, 2022.
Article in English | MEDLINE | ID: mdl-35181593

ABSTRACT

BACKGROUND/AIM: Circulating tumour DNA (ctDNA) represents an emerging biomarker in non-small cell lung cancer (NSCLC). We focused on the combination of ctDNA and positron emission tomography/computed tomography (PET/CT) in the follow-up monitoring of advanced-stage NSCLC patients treated with chemotherapy. PATIENTS AND METHODS: Eighty-four patients were enrolled in this study. 18F-fluorodeoxyglucose PET/CT and ctDNA assessments were performed at baseline and after two cycles of chemotherapy (follow-up). RESULTS: There was a correlation of ctDNA with metabolic tumour volume (MTV), total lesion glycolysis (TLG), and iodine concentration (IC) at baseline (p=0.001, p=0.001, p=0.003) and at follow-up (p=0.006, p=0.002, p=0.001). The objective response was associated with follow-up ctDNA (p<0.001) and the change of all PET/CT parameters. ROC analyses showed that the combination of follow-up ctDNA with changes in SUVmax is very promising for the estimation of objective response and progression-free survival. CONCLUSION: The combination of ctDNA assessment with PET/CT is a promising approach for the follow-up monitoring of therapy response and prognosis estimation of advanced-stage NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Circulating Tumor DNA/genetics , Fluorodeoxyglucose F18/metabolism , Fluorodeoxyglucose F18/therapeutic use , Glycolysis , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Positron Emission Tomography Computed Tomography/methods , Prognosis , Prospective Studies , Radiopharmaceuticals/therapeutic use , Retrospective Studies , Tumor Burden
5.
Strahlenther Onkol ; 198(9): 783-791, 2022 09.
Article in English | MEDLINE | ID: mdl-35059759

ABSTRACT

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.


Subject(s)
Brachytherapy , Radiotherapy, Image-Guided , Uterine Cervical Neoplasms , Brachytherapy/adverse effects , Chemoradiotherapy/adverse effects , Female , Humans , Magnetic Resonance Imaging , Neoplasm Staging , Radiotherapy Dosage , Radiotherapy, Image-Guided/adverse effects , Treatment Outcome , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/radiotherapy
6.
Cesk Patol ; 57(3): 147-149, 2021.
Article in English | MEDLINE | ID: mdl-34551562

ABSTRACT

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.


Subject(s)
Molecular Diagnostic Techniques , Neoplasms , Czech Republic/epidemiology , Humans , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/genetics
7.
Cesk Patol ; 57(3): 181-187, 2021.
Article in English | MEDLINE | ID: mdl-34551568

ABSTRACT

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.


Subject(s)
Endometrial Neoplasms , Radiation Oncology , Biology , Czech Republic , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Female , Humans , Molecular Diagnostic Techniques , Pathologists , Physics
8.
Ceska Gynekol ; 86(4): 264-272, 2021.
Article in English | MEDLINE | ID: mdl-34493052

ABSTRACT

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.


Subject(s)
Endometrial Neoplasms , Radiation Oncology , Biology , Czech Republic , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Female , Humans , Molecular Diagnostic Techniques , Pathologists , Physics
9.
Target Oncol ; 16(5): 643-652, 2021 09.
Article in English | MEDLINE | ID: mdl-34363554

ABSTRACT

BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) are often elderly and have various comorbidities, including cardiovascular diseases. Although these patients have extensive co-exposure to targeted therapy and cardiovascular drugs, the impact of this co-exposure on outcomes for patients with mRCC remains unclear. OBJECTIVE: Our objective was to evaluate the association between the use of cardiovascular medication and survival of patients with mRCC. METHODS: The study included 343 consecutive patients with mRCC treated with sunitinib or pazopanib in the first line. Clinical data obtained from the Renal Cell Carcinoma Information System (RENIS) clinical registry and hospital information systems were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of common medications, including antihypertensives (i.e., ß-blockers [BBs], angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics), acetylsalicylic acid (aspirin), statins, and proton pump inhibitors. RESULTS: The univariate Cox analysis evaluating the impact of the assessed comedications on patient survival revealed that only BBs were significantly associated with PFS (hazard ratio [HR] 0.533, p < 0.001) and OS (HR 0.641, p = 0.006). The median PFS and OS for users of BBs was 18.39 and 37.60 months versus 8.16 and 20.4 months for patients not using BBs (p < 0.001 and p < 0.001, respectively). The Cox multivariate analysis showed that the use of BBs was a significant factor for both PFS (HR 0.428, p = 0.001) and OS (HR 0.518, p = 0.001). CONCLUSIONS: The results of this retrospective study suggest that the use of BBs is associated with favorable outcomes for patients with mRCC treated with sunitinib or pazopanib in the first line.


Subject(s)
Carcinoma, Renal Cell , Cardiovascular Agents , Kidney Neoplasms , Aged , Carcinoma, Renal Cell/drug therapy , Disease-Free Survival , Humans , Indazoles , Indoles/pharmacology , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Pyrimidines , Pyrroles , Retrospective Studies , Sulfonamides , Sunitinib/pharmacology , Sunitinib/therapeutic use , Treatment Outcome
11.
Strahlenther Onkol ; 197(9): 847-853, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34160632

ABSTRACT

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.


Subject(s)
Neoplasms, Glandular and Epithelial , Thymus Neoplasms , Thyroid Neoplasms , Humans , Prognosis , Thymus Neoplasms/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery
12.
Cancer Manag Res ; 13: 4077-4086, 2021.
Article in English | MEDLINE | ID: mdl-34054309

ABSTRACT

BACKGROUND: The anticancer properties of metformin have been suggested in numerous experimental studies and several retrospective clinical studies show that its use is associated with improved outcome of patients with cancer. However, limited data are available for patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. The aim of this retrospective study was to assess the impact of the metformin use on survival of mRCC patients treated with sunitinib or pazopanib. METHODS: Clinical data from 343 patients with mRCC treated with sunitinib or pazopanib in the first line were analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of metformin. RESULTS: The median PFS and OS for patients using metformin was 31.1 (95% CI 20.6-35.1) and 51.6 (95% CI 44.7-NR) months compared to 9.3 (95% CI 8.0-12.0) and 22.4 (95% CI 19.4-26.8) months for patients not using metformin (p<0.0001 and p=0.0002, respectively). Cox multivariate analysis shows that the use of metformin remains a significant factor for PFS (HR=0.55 [95% CI 0.343-0.883], p=0.013) and also for OS (HR=0.45 [95% CI 0.256-0.794], p=0.006). CONCLUSION: The present study results suggest that the use of metformin was associated with favorable outcome of mRCC patients treated with sunitinib or pazopanib.

13.
Strahlenther Onkol ; 197(6): 494-504, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33492444

ABSTRACT

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.


Subject(s)
Chemoradiotherapy , Magnetic Resonance Imaging , Multimodal Imaging , Neoplasm Staging/methods , Positron-Emission Tomography , Uterine Cervical Neoplasms/therapy , Adult , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Area Under Curve , Brachytherapy , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Cisplatin/therapeutic use , Female , Humans , Image Processing, Computer-Assisted , Lymphatic Irradiation , Lymphatic Metastasis , Middle Aged , Prognosis , ROC Curve , Radiotherapy, Intensity-Modulated , Treatment Outcome , Tumor Burden , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
14.
Rep Pract Oncol Radiother ; 25(6): 934-938, 2020.
Article in English | MEDLINE | ID: mdl-33088229

ABSTRACT

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.

15.
Rep Pract Oncol Radiother ; 25(6): 882-885, 2020.
Article in English | MEDLINE | ID: mdl-32982594

ABSTRACT

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.

16.
Cancer Genomics Proteomics ; 17(5): 605-613, 2020.
Article in English | MEDLINE | ID: mdl-32859639

ABSTRACT

BACKGROUND/AIM: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR. RESULTS: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006). CONCLUSION: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/drug therapy , MicroRNAs/metabolism , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab/pharmacology , Cetuximab/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Down-Regulation , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Panitumumab/pharmacology , Panitumumab/therapeutic use , Progression-Free Survival , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Up-Regulation
17.
Cancer Manag Res ; 12: 5365-5372, 2020.
Article in English | MEDLINE | ID: mdl-32753954

ABSTRACT

PURPOSE: Regorafenib is an oral multikinase inhibitor approved for the therapy of previously treated metastatic colorectal carcinoma (mCRC). The aim of the present study was to analyze the outcomes of treatment with regorafenib in real-world clinical practice based on data from a national registry. METHODS: The CORECT registry, the Czech non-interventional database of patients with mCRC treated with targeted agents, searched for patients with metastatic CRC treated with regorafenib. In total, 555 evaluable patients were identified. RESULTS: The median age at diagnosis was 61.7 years. All patients had disease progression on or after previous systemic treatment. Most patients were treated with an initial dose of 160 mg daily (n = 463; 83.6%). The median duration of treatment was 2.7 months (range 0.0-23.4 months). By the data cut-off date, 472 patients (85%) had completed treatment with regorafenib and were evaluable for treatment response evaluation. Partial response was reported in 13 patients (2.8%) and disease stabilization in 130 patients (27.5%). Median progression-free survival (PFS) and overall survival (OS) were 3.5 months (95% confidence interval [CI] 3.2-3.7 months) and 9.3 months (95% CI 8.3-10.3 months), respectively. The 6-month OS rate was 67.7% (95% CI 63.4-72.1%). Multivariable analysis showed that female gender, longer interval from diagnosis of metastatic disease, M0 stage at diagnosis, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 were associated with longer PFS, while higher body-mass index (BMI), longer interval from diagnosis of metastatic disease, and ECOG PS of 0 were associated with longer OS. CONCLUSION: OS of patients treated with regorafenib in the real-world clinical practice in this cohort exceeded that reported in randomized trials. Regorafenib is a safe and active treatment option for a subgroup of patients with mCRC who are progressing after other systemic therapies and maintain good performance status.

18.
Cancers (Basel) ; 12(4)2020 Mar 27.
Article in English | MEDLINE | ID: mdl-32230921

ABSTRACT

BACKGROUND: The Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model has been widely used for the prediction of the outcome of metastatic renal cell carcinoma (mRCC) patients treated with systemic therapies, however, data from large studies are limited. This study aimed at the evaluation of the impact of the MSKCC score on the outcomes in mRCC patients treated with first-line sunitinib, with a focus on the intermediate-risk group. METHODS: Clinical data from 2390 mRCC patients were analysed retrospectively. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analysed according to the MSKCC risk score. RESULTS: ORR, median PFS, and OS for patients with one risk factor were 26.7%, 10.1, and 28.2 months versus 18.7%, 6.2, and 16.2 months, respectively, for those with two risk factors (ORR: p = 0.001, PFS: p < 0.001, OS: p < 0.001). ORR, median PFS, and OS were 33.0%, 17.0, and 44.7 months versus 24.1%, 9.0, and 24.1 months versus 13.4%, 4.5, and 9.5 months in the favourable-, intermediate-, and poor-risk groups, respectively (ORR: p < 0.001, PFS: p < 0.001, OS: p < 0.001). CONCLUSIONS: The results of the present retrospective study demonstrate the suitability of the MSKCC model in mRCC patients treated with first-line sunitinib and suggest different outcomes between patients with one or two risk factors.

19.
Anticancer Res ; 40(3): 1219-1227, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32132018

ABSTRACT

Immunotherapy based on immune checkpoint inhibitors (ICIs) represents a novel anticancer treatment strategy. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA4), programmed cell death-1 receptor (PD1) and programmed cell death-1 ligand (PD-L1) have shown efficacy and safety in the treatment of various malignancies. Some of them have recently found their place in a routine clinical practice, while others are at different phases of clinical trials. Treatment with ICIs may be accompanied by undesirable impairment of immunotolerance to non-tumoural tissues, leading to a specific side-effect also called immune-related adverse events (irAE). There is an increasing body of evidence that the development of irAEs is associated with a beneficial effect of immunotherapy, thus it has become a hot topic in the field of clinical oncology. This review is focused on data from recently published studies evaluating the association between irAEs and outcome of patients with cancer treated with ICIs.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/drug therapy , Immunotherapy/methods , Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Humans , Treatment Outcome
20.
Target Oncol ; 15(2): 193-201, 2020 04.
Article in English | MEDLINE | ID: mdl-32052341

ABSTRACT

BACKGROUND: Bevacizumab and aflibercept are currently the mainstay of antiangiogenic therapy for metastatic colorectal carcinoma (mCRC). They are often used in sequence with first- and second-line chemotherapy, especially in patients with RAS-mutated tumours. OBJECTIVE: The aim of the present study was to investigate the outcomes of patients with mCRC treated with the bevacizumab-aflibercept sequence in real-world clinical practice. PATIENTS AND METHODS: Data from a national clinical registry of targeted therapies for mCRC were analysed retrospectively. Overall, there were 366 patients with valid data who received first-line treatment with bevacizumab and chemotherapy followed by aflibercept with chemotherapy. The majority of the patients (n = 296, 80.8%) had RAS mutated tumours. RESULTS: Median cumulative progression-free survival (PFS) from the start of the bevacizumab-containing regimen to progression on aflibercept was 18.2 months (95% CI 16.8-19.5). Median PFS for bevacizumab and aflibercept was 10.6 months (95% CI 9.5-11.7) and 5.6 months (95% CI 5.1-6.1), respectively. Longer PFS on aflibercept was associated with metachronous metastatic disease and longer PFS on bevacizumab. Median overall survival (OS) from the start of first-line bevacizumab was 32.0 months (95% CI 26.6-37.5). The presence of metastatic disease at diagnosis was associated with worse OS. CONCLUSIONS: Patients treated with aflibercept in real-world clinical practice achieved similar survival outcomes as those treated within randomised trials. Cumulative survival data provide a benchmark for future studies and enable indirect comparisons with other treatment sequences used in mCRC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Colorectal Neoplasms/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bevacizumab/pharmacology , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Progression-Free Survival , Recombinant Fusion Proteins/pharmacology
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