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Δευτέρα 4 Ιανουαρίου 2021

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Αυστραλία
Ιαπωνία
Νέα Ζηλανδία
Ρουάντα
Σιγκαπούρη
Νότια Κορέα
Ταϊλάνδη
Κίνα, με την επιφύλαξη επιβεβαίωσης αμοιβαιότητας



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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,

Predictors of five-year survival among patients with hepatocellular carcinoma

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Abstract

Background

Most patients with hepatocellular carcinoma (HCC) are ≥ 65 years old at diagnosis and ~ 20% present with disease amenable to curative intent surgical therapy. The aim of this study was to examine whether treatment, the demographic variables, and clinical factors could predict 5-year survival among HCC patients.

Methods

We included patients, 66 years or older, diagnosed with a first primary HCC from 1994 through 2007 in the SEER-Medicare database, and followed up until death or 31 December 2012. Curative intent treatment was defined as liver transplantation, surgery resection, or ablation. We estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with 5-year survival using logistic regression.

Results

We identified 10,826 patients with HCC with mean age 75.3 (standard deviation, 6.4) years. Most were male (62.2%) and non-Hispanic white (59.7%). Overall, only 8.1% of patients were alive 5 years post-HCC diagnosis date. Among all patients that survived ≥ 5 years, 69.8% received potentially curative treatment. Conversely, patients who received potentially curative treatment represented only 15.7% of patients who survived < 5 years. Curative intent treatment was the strongest predictor for surviving ≥ 5 years (vs. none/palliative treatment; adjusted OR 8.12, 95% CI 6.90–9.64). While stage at diagnosis and comorbidities were also independently associated with ≥ 5-year survival in HCC patients, these factors did not improve discrimination between short- and long-term survivors.

Conclusions

Curative intent treatment was the strongest predictor for survival ≥ 5 years among HCC patients. Given the limited availability of liver transplant and limited eligibility for surgical resection, finding curative intent HCC therapies remain critically important.

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Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

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Cancer Gene Therapy, Published online: 04 January 2021; doi:10.1038/s41417-020-00283-4

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas
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LONG-TERM RESULTS OF DOSE-INTENSIFIED FRACTIONATED STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR PAINFUL SPINAL METASTASES

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Publication date: Available online 4 January 2021

Source: International Journal of Radiation Oncology*Biology*Physics

Author(s): Matthias Guckenberger, Frederick Mantel, Reinhart A. Sweeney, Maria Hawkins, José Belderbos, Merina Ahmed, Nicolaus Andratschke, Indira Madani, Michael Flentje

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Brain stem gliomas and current landscape

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Abstract

Purpose

CNS malignancies are currently the most common cause of disease related deaths in children. Although brainstem gliomas are invariably fatal cancers in children, clinical studies against this disease are limited. This review is to lead to a succinct collection of knowledge of known biological mechanisms of this disease and discuss available therapeutics.

Methods

A hallmark of brainstem gliomas are mutations in the histone H3.3 with the majority of cases expressing the mutation K27M on histone 3.3. Recent studies using whole genome sequencing have revealed other mutations associated with disease. Current standard clinical practice may merely involve radiation and/or chemotherapy with little hope for long term survival. Here we discuss the potential of new therapies.

Conclusion

Despite the lack of treatment options using frequently practiced clinical techniques, immunotherapeutic strategies have recently been developed to target brainstem gliomas. To target brainstem gliomas, investigators are evaluating the use of broad non-targeted therapy with immune checkpoint inhibitors. Alternatively, others have begun to explore adoptive T cell strategies against these fatal malignancies.

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Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

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Abstract

Background

Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM.

Main body

In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis.

Conclusion

Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

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Clear cell histology portends a worse prognosis than other WHO grade II histologies

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Abstract

Purpose

Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas.

Methods

A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival.

Results

We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14–3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97–3.94), though this was not statistically significant.

Conclusion

This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

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Relapsed and refractory primary CNS lymphoma

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Abstract

Background

Relapsed or refractory primary CNS lymphoma (rrPCNSL) is a rare and challenging malignancy for which better evidence is needed to guide management.

Methods

We present a retrospective cohort of 66 consecutive patients with rrPCNSL treated at the University of Washington between 2000 and 2020. Immunosuppressed and secondary CNS lymphoma patients were excluded.

Results

During a median follow-up of 40.5 months from initial diagnosis, median OS for relapsed disease was 14.1 (0.2–88.5) months and median PFS was 11.0 (0.2–73.9) months. At diagnosis (r2 = 0.85, p < 0.001), first relapse (r2 = 0.69, p < 0.001), multiple relapses (r2 = 0.97, p < 0.001) PFS was highly correlated with OS. In contrast, there was no correlation between the duration of subsequent progression-free intervals. No difference in PFS or OS was seen between CSF or intraocular relapse and parenchymal relapse. Patients reinduced with high-dose methotrexate-based (HD-MTX) regimens had an overall response rate (ORR) of 86.7%. Consolidation with autologous stem cell transplant (ASCT) was associated with longer PFS compared to either no consolidation (p = 0.01) and trended to longer PFS when compared to other consolidation strategies (p =  ;0.06). OS was similarly improved in patients consolidated with ASCT compared with no consolidation (p = 0.04), but not compared with other consolidation (p = 0.22). Although patients receiving ASCT were younger, KPS, sex, and number of recurrences were similar between consolidation groups. A multivariate analysis confirmed an independent effect of consolidation group on PFS (p = 0.01), but not OS.

Conclusions

PFS may be a useful surrogate endpoint which predicts OS in PCNSL. Consolidation with ASCT was associated with improved PFS in rrPCNSL.

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MRI-guided stereotactic radiation therapy for hepatocellular carcinoma: a feasible and safe innovative treatment approach

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Abstract

Purpose

Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors.

Methods

We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment–response assessment.

Results

Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1–25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child–Pugh before and after treatment remained unchanged in all but one patient.

Conclusion

MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.

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Efficacy of clobazam as add-on therapy in brain tumor-related epilepsy

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Abstract

Purpose

Brain tumor-related epilepsy (TRE) is often resistant to currently available antiepileptic medications (AEDs). Clobazam was initially approved as adjunctive AED for patients with Lennox Gastaut syndrome but has been used in TRE, despite limited evidence in this context. This observational study aims to examine the effect of clobazam on seizure frequency on patients who have a primary CNS tumor and continued seizures despite their current AEDs.

Methods

A retrospective review of patients with histologically-confirmed primary brain tumors seen in the neuro-oncology interdisciplinary clinic from April 2016–2019 was completed, and patients on clobazam were identified. Response to clobazam was defined as a greater than 50% reduction in seizure frequency. Additional data including patient and tumor characteristics, treatment course, tolerability, AEDs used prior to addition of clobazam, and AEDs concomitantly used with clobazam were collected.

Results

A total of 35 patients with TRE on clobazam were identified, with 2 patients unable to tolerate the medication due to side effects. Of the 33 remaining patients, a total of 31 (93.9%) of patients were deemed responders. Ten patients (30.3%) were seizure free within 6 months of clobazam initiation and 21 (63.6%) reported a significant reduction in seizure frequency. This reduction also allowed several patients to modify concurrent AEDs.

Conclusions

Clobazam is an effective agent to use as add-on AED in TRE, with 94% of patients showing a significant response within 6 months. Furthermore, the addition of clobazam may yield a reduction in polypharmacy, as concomitant AEDs can be reduced and potentially withdrawn.

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Motor deficits at presentation and predictors of overall survival in central nervous system lymphomas

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Abstract

Purpose

Central nervous system lymphomas (CNSL) can present with motor and non-motor symptoms. In many central nervous system tumors, motor deficits are associated with significant morbidity and functional impairment, and correlate with worse prognosis. CNSLs however, often exhibit remarkable response to chemotherapy and radiotherapy with corresponding symptom improvement. We investigate the survival outcomes and trajectories of motor and functional recovery in a cohort of patients presenting with and without initial motor deficits.

Methods

Patients who underwent biopsy and with a histologically confirmed CNSL between 2008 and 2019 were retrospectively identified. Baseline demographic variables, comorbidities, presenting symptoms, histological type, neuroimaging features (location and number of lesions), and treatment administered (pre- and post-operative steroid use and chemotherapy regime) were recorded. Dates of death were obtained from the National Registry of Births and Deaths. Motor power and performance status at admission, 1 month and 6 months were determined.

Results

We identified 119 patients, of whom 34% presented with focal motor deficits. The median overall survival (OS) was 26.6 months. Those with focal motor deficits had longer OS (median 42.4 months) than those without (median 23.3 months; p = 0.047). In multivariate Cox analysis, age (HR 1.04 per year; p = 0.003), CCI (HR 1.31 per point; p < 0.001), leptomeningeal/ependymal involvement (HR 2.53; p = 0.016), thalamus involvement (HR 0.34; p = 0.019), neutrophil:lymphocyte ratio (HR 1.06 per point; p = 0.034), positive HIV status (HR 5.31; p = 0.003), preoperative steroids use (HR 0.49; p = 0.018), postoperative high-dose steroids (HR 0.26; p < 0.001) and postoperative low-dose steroids (HR 0.28; p = 0.010) were significant predictors of OS. By one month, 43% of surviving patients had full power, increasing to 61% by six months.

Conclusion

A significant proportion of patients with initial motor deficits recovered in motor strength by six months. In our population, those presenting with motor deficits had paradoxically better overall survival.

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Parasympathetic influences in cancer pathogenesis: further insights

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