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Sequential intra-arterial infusion of 90Y-resin microspheres and mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study

Abstract

Background

The aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients.

Patients and methods

The prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of 90Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0.

Results

Sixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed.

Conclusions

Sequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients.

Open access
Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab – real-world experience

Abstract

Background

Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials.

Patients and methods

This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019.

Results

The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6–35.6) and the median progression-free survival (PFS) was 10.7 months (95% CI, 5.9–15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3–4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment.

Conclusions

Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.

Open access
Three-dimensional MRI evaluation of the effect of bladder volume on prostate translocation and distortion

Abstract

Background

The accuracy of any radiation therapy delivery is limited by target organ translocation and distortion. Bladder filling is one of the recognised factors affecting prostate translocation and distortion. The purpose of our study was to evaluate the effect of bladder volume on prostate translocation and distortion by using detailed three-dimensional prostate delineation on MRI.

Patients and methods

Fifteen healthy male volunteers were recruited in this prospective, institutional review board-approved study. Each volunteer underwent 4 different drinking preparations prior to imaging, with MR images acquired pre- and post-void. MR images were co-registered by using bony landmarks and three-dimensional contouring was performed in order to assess the degree of prostate translocation and distortion. According to changes in bladder or rectum distention, subdivisions were made into bladder and rectal groups. Studies with concomitant change in both bladder and rectal volume were excluded.

Results

Forty studies were included in the bladder volume study group and 8 in the rectal volume study group. The differences in rectal volumes yielded higher levels of translocation (p < 0.01) and distortion (p = 0.02) than differences in bladder volume. Moderate correlation of prostate translocation with bladder filling was shown (r = 0.64, p < 0.01). There was no important prostate translocation when bladder volume change was < 2-fold (p < 0.01). Moderate correlation of prostate distortion with bladder filling was shown (r = 0.61, p < 0.01).

Conclusions

Bladder volume has a minimal effect on prostate translocation and effect on prostate distortion is negligible. Prostate translocation may be minimalised if there is < 2-fold increase in the bladder volume.

Open access
Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

Abstract

Background

Aim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of “Sapienza” University of Rome for BSI calculation.

Patients and methods

127 mCRPC patients bone scan images were processed with DASciS software, and BSI was tested as OS predictor.

Results

546 bone scans were analyzed revealing that the extension of disease is a predictor of OS (0–3% = 28 months of median survival (MoMS]; 3%–5% = 11 MoMS, > 5% = 5 MoMS). BSI has been analyzed as a single parameter for OS, determining an 88% AUC. Moreover, the composition between the BSI and the 3-PS (3-variable prognostic score) determines a remarkable improvement of the AUC (91%), defining these two parameters as the best OS predictors.

Conclusions

This study suggests that OS is inversely correlated with the load of bone disease in mCRPC Ra-223-treated subjects. DASciS software appears a promising tool in identifying mCRPC patients that more likely take advantage from Ra-223 treatment. BSI is proposed as a predictive variable for OS and included to a multidimensional clinical evaluation permits to approach the patients’ enrollment in a rational way, allowing to enhance the treatment effectiveness together with cost optimization.

Open access
Budget Impact of Intravenous Iron Therapy with Ferric Carboxymaltose in Patients with Chronic Heart Failure and Iron Deficiency in Romania

Abstract

Background: Ferric carboxymaltose (FCM) treatment in case of iron deficient (ID) patients with chronic heart failure (CHF) has shown great promise according to the findings of recent studies in improvement of symptoms and quality of life, New York Heart Association (NYHA) classification, and exercise capacity.

Aim of the study: The purpose of the current study is to assess the budget impact of treating CHF patients with FCM in a sample of Romanian hospitals.

Material and methods: Calculations have been based on the budget impact model developed by Theidel et al. The assumptions and clinical outcomes of the current study were based on a multivariate statistical approach used in the same German study. The predicted outcomes were based on data pooled from four double-blind randomized controlled trials. The time horizon of the model was 1 year. Budget impact calculations were performed from the public payer perspective. Two scenarios have been handled: one without applying the Clawback tax and one with applying the tax to the cost of medication.

Results: The yearly budget impact of FCM vs. no iron-replacement treatment without applying the tax ranged between €678,383 and €641,588 for 1,000 patients, resulting in €37 of additional costs per patient per year. The yearly budget impact of FCM vs. no iron-replacement treatment with applying the tax ranged between €616,934 and €641,588 for 1,000 patients, resulting in €9 of cost reduction per patient per year. Key cost drivers included the cost of outpatient visits and the cost of hospitalization due to HF worsening. Sensitivity analysis for both scenarios proved the robustness of the results.

Conclusions: The FCM treatment of CHF patients has a moderate budget impact. Moreover, this budget impact/saving translates into a reduction of the rate and length of hospitalization stay and a better symptomatic profile of the patients.

Open access
Large-vessel Giant Cell Arteritis: A Rare Cause of Acute Upper Limb Ischemia – Case Presentation and Review of the Literature

Abstract

Introduction: Acute upper extremity ischemia is an uncommon vascular emergency due to a relatively rich collateral network and low workload of the upper limb. Its consequences depend on the site and etiology of the arterial occlusion.

Case presentation: Aiming to emphasize the emerging role of Doppler ultrasound in the diagnosis of acute upper limb ischemia, we report the case of a 70-year-old female, with severe left arm resting pain and digital cyanosis. Due to the patient’s age and the presence of cardiovascular risk factors, cardioembolic or thrombotic arterial occlusion would have been the most likely diagnosis in this case, but the color Doppler ultrasound revealed severe left axillary arterial stenosis with hypoechoic wall swelling, being highly suggestive for arteritis. Temporal artery biopsy was performed, which confirmed giant cell arteritis. An excellent clinical response was obtained after initiation of treatment.

Conclusion: In acute upper limb ischemia, color duplex ultrasound provides quick information about the etiology and localization of arterial lesions, offering characteristic findings in case of large-vessel giant cell arteritis.

Open access
Modern Management of Hypertensive Emergencies

Abstract

Hypertensive emergencies (HE) represent critical conditions in which extremely high blood pressure values are accompanied by acute hypertension-mediated organ damage. In this clinical setting, the main therapeutic goal is represented by the immediate reduction of blood pressure, in order to limit the extension or promote the regression of target organ damage. At present, HE are classified according to the condition or target organ involved, into: (1) malignant hypertension with or without thrombotic microangiopathy; (2) coronary ischemia or acute cardiogenic pulmonary edema; (3) acute stroke or hypertensive encephalopathy; (4) acute aortic dissection or aneurysm; and (5) eclampsia or severe preeclampsia/HELLP syndrome. The management of these conditions is different in relation to the complex pathophysiology involved in each of these types. This mini-review presents the main characteristics and management strategy for different forms of HE, revealing the particularities of management strategy for each of them.

Open access
Predictors for In-hospital Mortality in Pediatric Patients with Acute Myocarditis – a Retrospective Study

Abstract

Background: Acute myocarditis, a primary inflammatory cardiac disease commonly caused by viral infection, is an important cause of morbidity and mortality in children. Data obtained from forensic studies found an incidence of 15–33% for acute myocarditis in sudden deaths in the pediatric age group. Currently, there is a lack of data regarding the incidence and factors associated with short-term outcomes in pediatric patients admitted for acute myocarditis.

The aim of the study was to identify predictors for in-hospital mortality in a pediatric population admitted with acute myocarditis.

Material and methods: We conducted a retrospective observational cohort study that included 21 patients admitted for acute myocarditis. Clinical, laboratory, ECG, and imaging data acquired via 2D transthoracic echocardiography and cardiac magnetic resonance imaging were collected from the medical charts of each included patient. The primary end-point of the study was all-cause mortality occurring during hospitalization (period ranging from 10 to 14 days). The study population was divided into 2 groups according to the occurrence of the primary end-point.

Results: The mean age of the study population was 99.62 ± 77.25 months, and 61.90% (n = 13) of the patients were males. The in-hospital mortality rate was 23.9% (n = 5). Patients in the deceased group were significantly younger than the survivors (55.60 ± 56.18 months vs. 113.4 ± 78.50 months, p = 0.039). Patients that had deceased presented a significantly higher level of LDH (365 ± 21.38 U/L vs. 234.4 ± 63.30 U/L, p = 0.0002) and a significantly higher rate of ventricular extrasystolic dysrhythmias (60% vs. 6.25%, p = 0.02, OR: 22.5, 95% CI: 1.5–335) compared to survivors. The 2D echocardiography showed that patients that had deceased presented more frequently an impaired left ventricular ejection fraction (<30%) (p = 0.001) and a significantly higher rate of severe mitral regurgitation (p = 0.001) compared to survivors.

Conclusions: The most powerful predictors for in-hospital mortality in pediatric patients admitted for acute myocarditis were the presence of ventricular extrasystolic dysrhythmias on the 24h Holter ECG monitoring, impaired left ventricular systolic function (LVEF <30%), the presence of severe mitral regurgitation, and confirmed infection with Mycoplasma pneumoniae.

Open access
Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme

Abstract

Background

Glioblastoma is the most frequent and aggressive brain tumour in humans with median survival from 12 to 15 months after the diagnosis. This is mostly due to therapy resistant glioblastoma stem cells in addition to intertumour heterogeneity that is due to infiltration of a plethora of host cells. Besides endothelial cells, mesenchymal stem cells and their differentiated progenies, immune cells of various differentiation states, including monocytes, comprise resident, brain tumour microenvironment. There are compelling evidence for CCL5/CCR5 in the invasive and metastatic behaviour of many cancer types. CCR5, a G-protein coupled receptor, known to function as an essential co-receptor for HIV entry, is now known to participate in driving tumour heterogeneity, the formation of cancer stem cells and the promotion of cancer invasion and metastasis. Clinical trials have recently opened targeting CCR5 using a humanized monoclonal antibody (leronlimab) for metastatic triple negative breast cancer (TNBC) or a small molecule inhibitor (maraviroc) for metastatic colon cancer. There are important CCL5 and CCR5 structure and signalling mechanisms in glioblastoma. In addition, the CCL5/CCR5 axis directs infiltration and interactions with monocytes/macrophages and mesenchymal stem cells, comprising glioblastoma stem cell niches.

Conclusions

CCR5 is highly expressed in glioblastoma and is associated with poor prognosis of patients. CCL5/CCR5 is suggested to be an excellent new target for glioblastoma therapy. The molecular mechanisms, by which chemoattractant and receptor respond within the complex tissue microenvironment to promote cancer stem cells and tumour heterogeneity, should be considered in forthcoming studies.

Open access