PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge ...with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.
•PRECISION is a national program involving academia, regulatory authorities, and the pharmaceutical industry.•It promotes molecular testing, data storage and sharing, and treatment access via trials and a national molecular tumor board.•The multistakeholder collaboration is the stepping stone to broader next-generation sequencing reimbursement and for access to targeted therapies.
An elevated pre-treatment Neutrophil to Lymphocytes Ratio (NLR) is associated with poor prognosis in various malignancies. As optimal cut-off is highly variable and few data have been reported in ...patients treated with anti-PD-1, we investigated the association between NLR kinetics with outcomes in patients receiving anti-PD-1.
We performed a retrospective study including successive patients with mRCC and NSCLC treated with anti PD-1 N monotherapy in second-line setting or later, between March 2013 and December 2018. NLR were prospectively collected before study entry and before every nivolumab administration. Main clinical and biological characteristics were recorded including IMDC prognostic groups for mRCC cohort. We analysed associations between baseline NLR, NLR kinetics (any increase or decrease) and survival outcomes, including PFS, OS and objective response rate (ORR).
161 patients (86 mRCC and 75 NSCLC) were included in our study. With a median follow-up of 25 months, median PFS and OS were respectively 4.6 and 24.7 months for mRCC cohort and 4.4 and 16.8 months for NSCLC cohort. Between the first and the fourth N administration, 55 and 45% of the overall cohort had a decreased or an increased NLR. Survival outcomes according to NLR variations between the first and the fourth N administration are summarized in the Table. In multivariate analysis, NLR increase was associated with worse PFS (HR=2.6; p=0.000004) and OS (HR=2.3; p=0.001) for the overall cohort but also for the two cohorts when analysed separately. Association between NLR kinetics and response rate, IMDC groups and adverse events in the mRCC will be presented at the meeting.Table1255P Survival outcomesTableAll patientsNLR increaseNLR decreasepPFS (months, 95% IC)3.7 (2.9-4.4)11 (9-15.3)<0.0001OS (months, 95% CI)18 (10.6-28.2)28.5 (27;4-NR)0.01
We report the largest multi-cohort analysis of NLR kinetic in N treated patients supporting that early NLR increase is associated with worse survival outcomes in two distinct cohort of mRCC and NSCLC patients.
The authors.
Has not received any funding.
D. Borchiellini: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Janssen Cilag; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Astellas. C. Thibault: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: bms; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. P. Barthelemy: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Novartis. Y. Vano: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Janssen Cilag; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Astellas. All other authors have declared no conflicts of interest.
The aim of this study was to find molecular markers (RAPD and SCAR) for the wheat leaf rust resistance gene Lr24. A backcross line, RL 6064, possessing a single resistance gene to leaf rust (Lr24) ...and its recurrent parent 'Thatcher' were used to find RAPD markers linked to the Lr24 gene. Among 125 RAPD primers tested, only one (OP-H5) detected an additional band in the resistant line RL 6064. The genetic linkage of this molecular marker to Lr24 was tested on a segregating F2 population derived from a cross between the leaf rust resistant line RL 6064 and the susceptible line 'Chinese Spring'. This marker showed complete linkage to the Lr24 resistance gene. A more reliable and specific marker for this resistance gene was made by converting it into a sequence characterized amplified region (SCAR). The presence of a single amplification product allowed direct detection of the gene in the test tube by the addition of ethidium bromide. This SCAR marker linked to the leaf rust resistance gene Lr24 could be used easily in a practical breeding program.
PDF
