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G.J. Tsongalis
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MINI 01 - Pathology (ID 93)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:W.A. Franklin, A.G. Nicholson
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 2c-3c
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MINI01.12 - Implementation of a Molecular Tumor Board: The Impact on Treatment Decisions for NSCLC Patients Evaluated at Dartmouth-Hitchcock in One Year (ID 2719)
11:50 - 11:55 | Author(s): G.J. Tsongalis
- Abstract
- Presentation
Background:
Genetic profiling of tumors is a powerful approach to predict drug sensitivity and resistance. Definitive interpretation of the clinical significance of somatic mutations is possible for only a few well studied mutations. For the majority, prediction of clinical significance is challenging. We established a Molecular Tumor Board (MTB) at our Cancer Center to interpret individual patients’ tumor genetic profiles and provide treatment recommendations.
Methods:
DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory to identify coding mutations in a 50-gene panel. Cases were evaluated by a MTB composed of molecular and anatomic pathologists, medical oncologists, basic research scientists, and genetic counselors.
Results:
35 cases were evaluated in 1 year by the MTB including 8 metastatic NSCLC cases. The most common reason for MTB referral was for recommendations on targeted therapies (91.9%), and for potential germline mutations. Tumors exhibited genetic heterogeneity: 71 different mutations were found across 300 genes (for NSCLC 18 mutations across 10 genes). In 18/32 of advanced/metastatic cases, MTB recommended non-standard therapy with a specific targeted agent (11 clinical trials; 7 off-label use), 4 of the 18 patients were subsequently treated with a MTB-recommended targeted therapy. The remaining 14 patients continued on current therapy because disease was stable (n=4), were treated with non-MTB-recommended standard therapy (n=4), declined conventional therapy (n=5), or died prior to receiving further therapy (n=1). For 4 out of the 8 NSCLC cases MTB recommended a BRAF inhibitor (1), RET inhibitor (1), or MET inhibitor (2). One patient received a BRAF inhibitor, 6 continued on current standard of care therapy, one declined therapy.
Conclusion:
Case evaluation by a multidisciplinary group of individuals in the context of a MTB frequently shapes treatment options and decisions. Importantly, anticipated obstacles to capitalizing on the benefits of a MTB such as access to drugs were rarely encountered in the entire cohort and in the NSCLC patients. Instead, the most commonly encountered reasons that MTB-recommended therapy was not administered stemmed from patient preferences, and genetic profiling at a very late stage of disease.
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MINI 13 - Genetic Alterations and Testing (ID 120)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:Y. Koh, R.K. Thomas
- Coordinates: 9/08/2015, 10:45 - 12:15, 205+207
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MINI13.11 - Detection of Rare Clinically Actionable Mutations in NSCLC Metastatic to the Brain by Targeted Next Generation Sequencing (ID 1004)
11:45 - 11:50 | Author(s): G.J. Tsongalis
- Abstract
- Presentation
Background:
Genotyping of non-small cell lung cancers (NSCLC) is important for directing patient care, particularly in adenocarcinomas (ADC) where targeted therapeutics are available. There is emerging evidence of efficacy of targeted therapy in the treatment and prevention of brain metastases. With recent adoption of next-generation sequencing technologies it is possible to test individual tumors simultaneously for somatic mutations in multiple genes. Here, we present the mutational spectrum of NSCLC brain metastases in our institution over a three year period.
Methods:
The department of pathology archives was searched to identify cases of NSCLC metastatic to brain that underwent surgical resections during 2012-2014. Clinicopathologic information was recorded from the pathology reports and the medical records. Molecular genotyping analysis was performed for EGFR/KRAS mutations using single gene analysis (prior to 2013) or by next generation sequencing (NGS) using the AmpliSeq Cancer Hotspot Panel v2. FISH was used to test for ALK rearrangements.
Results:
During 2012-2014, 31 NSCLC patients underwent surgical resection for brain metastases. Eighteen patients were female (58%) and 13 were male. The median age was 70 years (range 51-89). Tumor histology included 24 ADC and 7 squamous cell carcinomas (SCC). Twenty-three cases had molecular genotyping studies performed on the metastatic disease or the primary lung cancer. These included 3 SCC and 20 ADC. Of the ADC, 12 were tested with the NGS panel; 8 had been tested prior to 2013. The most frequently mutated genes were KRAS (8/20; 40%) and TP53 (7/12; 58%). Of the patients with KRAS mutations 7/8 were female (p = 0.085). The NGS assay detected clinically actionable mutations that would have not been detected with prior single gene assays including an EGFR exon 20 insertion, an ERBB2 exon 20 insertion, and two PIK3CA mutations. Additional mutations were detected in JAK3, FLT3, FBXW7, ATM, STK11, VHL and RB1.
Conclusion:
We found that 40% of the genotyped ADC metastases harbored KRAS mutations more frequently in females (although not significant), similar to prior reports. In addition, with NGS we were able to detect additional clinically significant targetable mutations. In summary, NSCLC genotyping can potentially help guide treatment and prevention of brain metastases.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
