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M. Sandelin
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-022 - Establishing Reflex NGS Testing in NSCLC in a Regional Network of County Hospitals in Central Sweden (ID 4759)
14:30 - 14:30 | Author(s): M. Sandelin
- Abstract
Background:
Extended genetic testing of NSCLC tumor samples provides a foundation for personalized cancer treatment and use of new targeted medication. Testing with Next Generation Sequencing (NGS), mostly performed at university hospitals, has not been available for all patients due to geographic and economic reasons. Many lung cancer patients carry a heavy burden of disease and extensive travelling can negatively impact quality of life. The ability to perform a modern state-of the art work-up at local hospitals, without compromising on diagnostic quality, will enable equal access to personalized treatment for lung cancer patients.
Methods:
In Gävle County hospital routine diagnostic immunohistochemistry (IHC) on biopsies is performed at the local pathology lab. In the case of NSCLC the formalin-fixed, paraffin embedded (FFPE) tissue samples are sent to Uppsala University hospital for further molecular pathology and NGS testing. A targeted NGS test (18 gene panel) was established for mutation screening of small biopsies and cytology specimens (Moens et al., J Mol Diagn, 2015). Fusion genes - ALK, ROS1 and RET - are analysed by IHC, FISH and nanoString. Structured biobanking of surplus biopsies and blood samples during treatment, for explorative biomarker testing and research, was set up as a regional extension of the UCAN infrastructure, including detailed registration of clinical baseline and real-time follow-up data in a dedicated database.
Results:
Inclusion of patients in the biobanking cohort started gradually during 2015 in Uppsala, and in February 2016 in Gävle. The cumulative inclusion in the UCAN biobank is updated at www.u-can.uu.se (see Statistics). To date (July 2016) 70 patients have been included at Gävle County hospital covering 95% of the newly diagnosed NSCLC patients. So, far 242 patients from the region were tested by NGS yielding 23 EGFR+ (9.5%), 75 KRAS+ (31%), 5 BRAF+ (2.1%, codon 600), 2 MET (0.8%, exon 14 skipping), 1 ERBB2 (0.4%, exon 20 insertion), and 6 PIK3CA (2.5%, exon 9/20) cases. Fusion gene analysis resulted in 5 ALK+ (2.1%), 1 ROS1 and 1 RET patients.
Conclusion:
Decentralised local patient care, tissue/blood sampling and biobanking in combination with centralised molecular testing allows advanced lung cancer diagnostics and clinical research in networks of county hospitals. Survival benefits from modern targeted drugs, for national lung cancer cohorts, can only be achieved and evaluated in population-based settings without bias related to selective referral to major cancer centers.
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P1.02-063 - Mutation Profiling by Targeted Next-Generation Sequencing of an Unselected NSCLC Cohort (ID 4147)
14:30 - 14:30 | Author(s): M. Sandelin
- Abstract
Background:
Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with a wide diversity when it comes to molecular variations. In the non-squamous subset a large variety of altered driver genes have been identified.
Methods:
The mutational status was evaluated in a consecutive Swedish NSCLC cohort consisting of 354 patients, who underwent surgical resection between 2006 and 2010. DNA was prepared from either fresh frozen or formalin fixed paraffin embedded tissue (FFPE) and used for library preparation using a Haloplex gene panel and subsequently sequenced on an Illumina Hiseq instrument. The gene panel covers all exons of 82 genes, previously identified in NSCLC. The panel design utilizes two strand capture and reduced target fragment length compatible with degraded FFPE samples (Moens et al., J Mol Diagn, 2015).
Results:
All previously known hotspot alterations in the driver genes KRAS, EGFR, HER2 (exon 20 insertions), NRAS, BRAF, MET (exon 14-skipping) and PIK3CA (exon 9 and 20) were analyzed in the 252 non-squamous cases, see figure. KRAS mutations were found in 98 patients (39%) whereas EGFR alterations were present in 33 (13%). The prevalence of KRAS mutations is higher than normally reported and could be due to the large fraction of smokers included in this cohort. The EGFR prevalence is a bit higher than previously demonstrated (Sandelin et al. Anitcancer Res, 2015). Mutations in the other driver genes were detected at low frequencies (HER2(3%), BRAF(2%), NRAS(1%), MET(1%) and PIK3CA(1%)). Figure 1
Conclusion:
The preliminary analysis of mutational status in this large unselected Swedish NSCLC cohort reveals mutation frequencies in the common driver genes resembling previous reports on western populations with a high smoking rate. Ongoing analysis of the remaining genes will be used for pathway analysis and could provide a more complete picture of the lung cancer pathogenesis.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-041 - Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study (ID 5141)
14:30 - 14:30 | Author(s): M. Sandelin
- Abstract
Background:
The past decade has seen several advances in the field of non-small cell lung cancer (NSCLC), with improved tools for tumor characterization as well as novel targeted and immune therapies. It is important to understand the current treatment landscape including treatment outcomes, in order to maximize patient benefits from these advances. SCAN-LEAF is a Scandinavian retrospective cohort study with prospective annual data cuts, providing a unique opportunity for insights into real-world clinical NSCLC practice over more than a decade. It includes clinical practice patterns of tissue biopsy, pathological diagnosis and tumor biomarker status testing, and their relationship to treatment choices and outcomes. Here, we present intermediate and survival outcomes by disease stage and histology subtype, and factors associated with survival.
Methods:
SCAN-LEAF consists of a registry-based cohort including all diagnosed NSCLC patients in Denmark, Norway and Sweden (Cohort 1), and a Swedish sub-cohort (Cohort 2) supplemented with data from electronic medical records (EMRs). Based on the first data collection including data from NSCLC patients diagnosed 2005-2013, overall survival (OS; Cohort 1 & 2) and progression-free survival (PFS; Cohort 2) will be estimated using Kaplan-Meier analysis and reported as cumulative incidences (with 95% CI) by disease stage at diagnosis, histological subtype, biomarker status, presence of metastases, age and gender. Response rates (Cohort 2) will be described by treatment line in addition to stage and histology subtype. Association of stage with survival (Cohort 1 & 2) and treatment response (Cohort 2) will be analyzed by Cox regression with time to event (death or response) as outcome variable and disease stage category at diagnosis, follow-up time, and therapy line as stratification variables. In addition, the relationship between OS and intermediate outcomes, as well as predictors of OS (e.g. smoking and biomarker status, lesion location, metastasis at diagnosis), will be explored by Cox regression (Cohort 2).
Results:
Intermediate and survival outcomes for Scandinavian NSCLC patients diagnosed between 2005 and 2013, as well as any association between overall survival and factors such as patient characteristics and treatment patterns, will be presented.
Conclusion:
The SCAN-LEAF study, expected to include >115,000 Scandinavian NSCLC patients and >2,000 sub-cohort patients diagnosed between 2005 and 2018 during the full duration of the study, will give valuable insights into current care, changing treatment patterns and patient outcomes in a real-world setting. A better understanding of factors associated with survival and intermediate outcomes among NSCLC patients will inform clinical decision-making.
