42 research outputs found
High postoperative risk after pneumonectomy in elderly patients with right-sided lung cancer
The present study investigated postoperative mortality (POM), its
predictors and relationship with long-term survival in patients who
underwent surgery for lung cancer. The 30-day mortality after thoracotomy
in 1,830 patients from the Flemish multicentre hospital-based lung cancer
registry was analysed according to patient, tumour, treatment and hospital
characteristics and compared with 5-yr survival figures for the same
patients. Overall POM was 4.4%. In univariate analysis age, extent of
surgery and low hospital volume were associated with a higher POM. In
multiple regression analysis age, extent of surgery and side of the
pneumonectomy proved to be independent predictors of POM. In patients aged
>70 yrs who underwent right-sided pneumonectomy POM was 17.8%. Overall,
mortality was comparable to published series from referral centres. Age
and extent of resection are the main predictors of postoperative mortality
in lung-cancer patients. In the operable elderly patient, age alone does
not justify denying the survival benefit experienced by resection of lung
cancer. The high mortality after right-sided pneumonectomy in elderly
patients warrants caution, as the treatment benefit may become marginal
A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer
Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of
STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma
Background: Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment
approved for glioblastoma utilizes low intensity, alternating electric fields delivered
non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields.
Methods: The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included
ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was
overall survival (OS). A visual analog scale was used to assess EOCG performance status
and cancer-related pain assessed until disease progression. The sample size provided
80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5
months compared to historical controls (Vogelzang, JCO 2003).
Results: All 80 patients had a minimum follow up of 12 months. Median age was 67
(range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53
patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2
months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS
for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable
during the first year of follow up. Median time to deterioration in performance status
was 13.1 months. Average score of pain was lower compared to baseline during the first
7 months of the treatment and was higher later on the study, with a median time to a
clinical significant 33% increase in pain of 8.4 months. No device-related serious
adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported
in 46% (37 patients). Four patients (5%) had grade 3 dermatitis.
Conclusions: The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with
a decrease in performance status or an increase in pain for the duration of TTFields use.
TTFields in combinati
Large-scale copy number analysis reveals variations in genes not previously associated with malignant pleural mesothelioma
Malignant pleural mesothelioma (MPM) is an aggressive tumor that is often causally associated with asbestos exposure. Comparative genomic hybridization techniques and arrays demonstrated a complex set of copy number variations (CNVs) in the MPM-genome. These techniques however have a limited resolution, throughput and flexibility compared to next-generation sequencing platforms. In this study, the presence of CNVs in the MPM-genome was investigated using an MPM-cohort (N = 85) for which genomic microarray data are available through 'The Cancer Genome Atlas' (TCGA). To validate these results, the genomes of MPMs and matched normal samples (N = 21) were analyzed using low-pass whole genome sequencing on an 'Illumina HiSeq' platform. CNVs were detected using in-house developed analysis pipelines and frequencies of copy number loss and gain were calculated. In both datasets, losses on chromosomes 1, 3, 4, 6, 9, 13 and 22 and gains on chromosomes 1, 5, 7 and 17 were found in at least 25% and 15% of MPMs, respectively. Besides the well-known MPM-associated genes, CDKN2A, NF2 and BAP1, other interesting cancer-associated genes were listed as frequently involved in a copy number loss (e.g. EP300, SETD2 and PBRM1). Moreover, four cancer-associated genes showed a high frequency of copy number gain in
Recommendations for implementing lung cancer screening with low-dose computed tomography in Europe
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was
demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease.
European mortality data has recently become available from the Nelson randomised controlled
trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women.
Recent studies in Europe and the USA also showed positive results in screening workers exposed to
asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a
large international group of physicians and other experts concerned with lung cancer—agreed that
LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and
guidelines for its effective and safe implementation still need to be formulated. To this purpose, the
IELS was asked to prepare recommendations to implement LCS and examine outstanding issues.
A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at
a meeting held in Milan in November 2018. The present recommendations reflect that consensus
was reached
Bringing onco‐innovation to Europe’s healthcare systems: The potential of biomarker testing, real world evidence, tumour agnostic therapies to empower personalised medicine
Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre‐eminently in many cancers, but also in an ever‐wider range of conditions— notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country‐related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval—and the role of real‐world evidence in the process—and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe’s industrial competitiveness and innovation require an appropriate policy framework—starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients
Recommendations for implementing lung cancer screening with low-dose computed tomography in Europe
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached