Factors predicting poor survival after resection of stage IA non–small cell lung cancer

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clinical benefit and risk of death with endocrine therapy in ovarian cancer a comprehensive review and meta analysis

Abstract Background Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. Methods Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose. Results Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34–0.48) for any endocrine treatment, 43% (95%CI, 0.30–0.56) for tamoxifen, 39% (95%CI, 0.29–0.50) for aromatase inhibitors and 37% (95%CI, 0.26–0.48) for progestins. The SCBR for ER + and/or PgR + tumors was 46% (95%CI, 0.34–0.57) versus 37% (95%CI, 0.27–0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28–0.80) versus 40% (95%CI, 0.29–0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR = 0.69, 95%CI, 0.50–0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low. Conclusions The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC

Kaposi's Sarcoma and HIV-Tat: Challenges to Antiangiogenesis Research

Kaposi's sarcoma (KS) is characterized by an abnormal growth of blood vessels. KS was found mainly in older men of Mediterranean or African origin (classic KS) or in patients after organ transplantation (iatrogenic KS). However, in the early 1980s, an aggressive epidemic form, linked to AIDS, was noticed and was one of the first clues to the existence of HIV-1 pandemy. The link between KS occurrence and HIV has raised multiple hypotheses. The drastic reduction of KS after the introduction of HAART, suggests HIV as a powerful co-factor for KS progression. We and others have contributed to the elucidation of KS cell nature and the possible involvement of extracellular HIV Tat. Tat is proangiogenic and is a true promoter of KS lesions acting as a VEGFR2 ligand both on KS and endothelial cells, in addition Tat is able to bind and activate chemokine receptors on monocytes and granulocytes causing a pro-inflammatory status. Evaluation of the effects of extracellular Tat on KS cells by microarray analysis after 24 h of incubation shows an interesting clustering of gene products involved in signal transduction, especially GTP-ase, Kinase and cAMP activity, confirming that Tat acts extracellularly by ways that are probably unrelated to its nuclear activity. KS occurrence is reduced by HAART but still present and in Africa is one of the most frequent oncologic disease. To find suitable drugs with low toxic impact on KS patients, we have tested several drugs and gene therapy approaches in in vivo models. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 200

Economic Impact of Inter-Regional Health Mobility In The Oldest European Administrative Region: A Starting Point For Changing Organizational Model?

Objectives: The aim of this study is to evaluate the inter-regional mobility expenditures, with particular reference to oncology, in Liguria Region. Study design: A descriptive analysis of inter-regional mobility expenditures from 2008 to 2015 was carried out. Methods: The analysis involved a detailed assessment of global balance of interregional health mobility by means the DRGs; the flow of specialist outpatient and pharmaceutical was also used. Results: Since 2008 until 2012 an increase of negative balance of global healthcare expenditure in Liguria Region was observed [34.7 \u20ac mill (2008) and 62.3 \u20ac mill (2012)]; subsequently a quite stable trend was recorded between 2012 and 2015 [ranging between 59.8 \u20ac mill (2013) and 63.2 \u20ac mill (2014)]. The passive mobility was 15.1% on the total spending for hospital acute care in 2012 and a similar value was detected in 2015 (15.2%). The higher costs for passive mobility were attributable to the surgical DRGs (69.4% in 2012 and 69.8% in 2015) with a double estimate of the expenditure in comparison with medical ones (2012: 99.4 \u20ac mill vs 43.8 \u20ac mill, \u394= 55.6 \u20ac mill; 2015: 96.6 \u20ac mill vs 41.9 \u20ac mill, \u394= 54.7 \u20ac mill). The highest cost sources in the process of passive mobility are the surgical areas, particularly the surgical hospitalizations for orthopaedic and cardiologic interventions. The spending analysis for oncologic DRG, divided into surgical and medical for passive and active mobility, showed that the surgical DRG determined a negative balance of 3.8 \u20ac mill in 2012 and 4.3 \u20ac mill in 2015, while the medical DRG showed a positive balance of 0.5 \u20ac mill in 2012 and 0.7 \u20ac mill in 2015. Conclusions: Our evaluation highlights that the inter-regional mobility for hospital acute care is the most relevant issue for the economic regional balance and reveals an important flow of patients moving from Liguria Region to neighbouring regions. As the equity of access and distribution of the supply of care remains a priority of Regional Health System, the active mobility in oncologic field could be a marker of quality health planning

The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 × 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients

Background: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin can reduce colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin has also been associated with decreased colon adenoma recurrence in clinical trials and lower CRC incidence and mortality in epidemiological studies in diabetics. While both drugs have been tested as single agents, their combination has not been tested in cancer prevention trials. Methods/design: This is a randomized, placebo-controlled, double-blind, 2 × 2 biomarker trial of aspirin and metformin to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery, 160 patients with stage I-III CRC are randomly assigned in a four-arm trial to either aspirin (100 mg day), metformin (850 mg bis in die), their combination, or placebo for one year. The primary endpoint biomarker is the change of IHC expression of nuclear factor kappa-B (NFκB) in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the measurement of circulating IL-6, CRP and VEGF; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of genetic markers with treatment response as assessed by next generation sequencing of primary tumors; 4) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; and 5) the evaluation of adenoma occurrence at 1 year. Discussion: A favorable biomarker modulation by aspirin and metformin may provide important clues for a subsequent phase III adjuvant trial aimed at preventing second primary cancer, delaying recurrence and improving prognosis in patients with CRC. Trial registration: EudraCT Number: 2015–004824-77; ClinicalTrial.gov Identifier: NCT03047837. Registered on February 1, 2017

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

New Strategies for Endometrial Cancer Detection and Management

With 400,000 new cases and over 80,000 deaths a year worldwide, endometrial cancer (EC) holds a rather unfortunate record, namely, that of the tumour with the highest increase in incidence, a unique trend among gynaecological cancers [...

Cancer Prevention with Molecular Targeted Therapies

Today, the oncologist is like a detective of the human body who, instead of a magnifying glass, uses the new tools of molecular pathology to search not only for genes or molecular targets, to be targeted with innovative anticancer therapies, but also molecular alterations that allow the identification of population groups at risk of developing tumors for preventive purposes [...