Δευτέρα 18 Ιανουαρίου 2021

Broadening treatment options for patients with non-small-cell lung cancer

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The use of immune-checkpoint inhibitors targeting the CTLA-4, PD-1, or PD-L1 signalling axis in the modulation of anti-tumour T-cell activity has revolutionised the treatment of lung cancer in different settings.1 In patients with PD-L1 expression of at least 50%, pembrolizumab (anti PD-1) and atezolizumab (anti PD-L1) have been approved by the US Food and Drug Administration as first-line single-agent treatments because they significantly prolong overall survival compared with platinum-based chemotherapy, in patients with both squamous and non-squamous tumours without sensitising EGFR mutations or ALK rearrangements.
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First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

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Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk–benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC.
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Longitudinal study of intravenous versus subcutaneous immunoglobulin replacement therapy in hematological malignancy

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Longitudinal study of intravenous versus subcutaneous immunoglobulin replacement therapy in hematological malignancy

First longitudinal study on the clinical impact and patient perception of intravenous versus subcutaneous immunoglobulin replacement therapy in patients with acquired hypogammaglobulinemia secondary to hematological malignancy.


Abstract

Aim

To present findings from a longitudinal study on infection risk, mortality, and patient perspective of intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment for patients with hypogammaglobulinemia secondary to hematological malignancy or its treatment (abbreviated as SID).

Methods

Observational study period included final year of IVIg (13 patients) and of the first 3 years of SCIg (17 patients) with SID. Data were collected on clinical outcomes from medical records and patient perception via study specific questionnaire.

Results

The median age was 63 years (53‐76 years), and for 82.4% of patients their hematological malignancy was in complete remission. The annual mean serum IgG trough levels remained stable over the 4 years and were 7.0 g/L (±2.77 g/L) with IVIg, and 8.0 g/L (±1.75 g/L), 8.7 g/L (±2.75 g/L), and 7.6 g/L (±2.89 g/L) (year 1, 2, and 3, respectively) with SCIg. While the annual infection rate was similar, the rate of hospitalization due to infection fluctuated, with 37%, 9%, 15%, and 32% in year 1, 2, 3, and 4 respectively. There were no systemic adverse events with IVIg or SCIg. Patients reported a strong preference for SCIg. One patient died due to progression of underlying disease and infection within the study period.

Conclusion

SCIg was the preferred treatment mode over IVIg in our cohort, but both were well tolerated without any systemic adverse events in 4‐year follow up. The dosage and serum IgG levels were stable throughout. However, the number of infections requiring hospitalization fluctuated. It is anticipated that these findings encourage more hospitals to offer SCIg for SID patients.

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To betray or to fight? The dual identity of the mitochondria in cancer

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Future Oncology, Ahead of Print.
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Correlations between serum cetuximab and EGFR-related markers, and skin disorders in head and neck cancer patients

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Abstract

Purpose

Cetuximab inhibits epidermal growth factor receptor (EGFR) signaling in cancer and skin cells, thereby inducing anti-cancer effects and skin disorders. The present study aimed to evaluate the relationships between serum cetuximab and EGFR-related markers, and adverse effects in head and neck cancer patients.

Methods

Thirty-four head and neck cancer patients receiving weekly intravenous cetuximab were enrolled. Serum cetuximab levels were determined just before dosing. Blood samples for determination of serum EGFR-related markers including soluble epidermal growth factor receptor (sEGFR) and interleukin-6 (IL-6) were obtained. The severities of skin disorders, their medications, and hypomagnesemia treatment were also assessed.

Results

Serum levels of cetuximab and sEGFR were negatively and positively correlated with that of IL-6, respectively. The serum cetuximab level was twofold higher in the patients with a grade 2–3 skin rash than with a grade 0–1 rash. The serum cetuximab cutoff value related to severe skin rash was 71 μg/mL (sensitivity, 59%; and specificity, 94%). The use of a strong topical corticosteroid for skin rash was also associated with a higher serum cetuximab level. Serum levels of sEGFR and IL-6 had no correlations with the skin disorder severities or their medications. Hypomagnesemia treatment using intravenous magnesium sulfate was not related to serum cetuximab and EGFR-related markers.

Conclusions

Head and neck cancer patients with a higher serum IL-6 level tended to have a lower serum cetuximab level. Serum cetuximab had positive correlations to skin rash severity and its medication in the study population.

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Κυριακή 17 Ιανουαρίου 2021

Herpes simplex laryngitis: Comparison between pediatric and adult patients.

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Herpes simplex laryngitis: Comparison between pediatric and adult patients.

Int J Pediatr Otorhinolaryngol. 2020 Dec 24;142:110596

Authors: Bachrach K, Levi JR, Tracy LF

Abstract
OBJECTIVES: Infection with herpes simplex virus (HSV) typically causes limited oral and genital symptoms, however HSV can also affect the larynx and result in severe aerodigestive symptoms. Due to the rarity of HSV laryngitis, the symptoms and clinical course of are not well understood. This study aims to more completely characterize HSV laryngitis in order to aid clinicians in understanding and recognition of HSV laryngitis.
METHODS: Comprehensive literature search of MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews to identify articles relating to HSV laryngitis. Patient demographics, presenting signs and symptoms, treatment and clinical course were extracted from the selected manuscripts.
RESULTS: There were 31 studies on HSV laryngitis that identified 36 patients (17 pediatric, 19 adult). The average age for pediatric patients was 11 months (9 M, 8F) and 52 years for adults (11 M, 8F). In the pediatric population, stridor was more common at presentation in comparison to the adult population (p < .01). Adults more commonly presented with dysphagia (p = .03) and dysphonia (p < .01) Adult patients were significantly more likely to undergo tracheotomy than pediatric patients (p = .047). The mean length of inpatient hospital stay was 21.2 days in pediatric patients and 15.8 days for adult patients.
CONCLUSION: HSV laryngitis has a unique presentation in pediatrics and adults, but is nonspecific in both populations leading to delays in diagnosis and treatment. HSV laryngitis is associated with significant morbidity including multi-week hospital stay and risk for needing tracheostomy in both adults and pediatric population which demonstrates need for clinical awareness of this complication of HSV infection.

PMID: 33434698 [PubMed - as supplied by publisher]

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DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review

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journal.pone.0244101.g001&size=inline

by Christian Sander Danstrup, Mette Marcussen, Inge Søkilde Pedersen, Henrik Jacobsen, Karen Dybkær, Michael Gaihede

Background

Head and neck squamous cell carcinomas (HNSCC) are often diagnosed in advanced stages. In search of new diagnostic tools, focus has shifted towards the biological properties of the HNSCC, and the number of different biomarkers under investigation is rapidly growing.

Objectives

The objective was to review the current literature regarding aberrantly methylated DNA found in peripheral blood plasma or serum in patients with HNSCC and to evaluate the diagnostic accuracy of these changes.

Methods

The inclusion criteria were clinical studies involving patients with verified HNSCC that reported findings of aberrantly methylated DNA in peripheral blood serum or plasma. We systematically searched PubMed, OVID Embase and Cochrane Library. In addition to the search, we performed forward and backward chaining in references and Web of Science. The protocol was registered in PROSPERO: CRD42019135406. Two authors independently extracted data. The quality and the risk of b ias of the included studies were assessed by the QUADAS-2 tool.

Results

A total of 1,743 studies were found eligible for screening, while ultimately seven studies were included. All studies were found to have methodological weaknesses, mainly concerning patient selection bias. The best individual marker of HNSCC was Septin 9 in plasma with a sensitivity of 57% and a specificity of 95%.

Conclusions

None of the aberrantly methylated genes found in the retrieved studies are applicable as single diagnostic markers for HNSCC and the best gene-panels still lack diagnostic accuracy. Future studies may benefit from newer sequencing techniques but validation studies with well-designed cohorts are also needed in the process of developing epigenetic based diagnostic tests for HNSCC.

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