Tracy Stockley

Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC)

BACKGROUND Genomic alterations that activate the MAPK signaling pathway frequently occur in Type I Epithelial Ovarian Cancers (EOCs). We evaluated therapeutic response outcomes in patients with type I EOC treated with genotype-matched therapy on clinical trials enrolled in a prospective molecular profiling program. MATERIAL AND METHODS Formalin fixed paraffin embedded tumor tissues were prospectively screened for genomic alterations using MALDI-ToF mass-spectrometry platform or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel. Treatment outcomes on genotype-matched trials were retrospectively reviewed using RECIST version 1.1 and Gynecological Cancer Intergroup CA125 related-response criteria RESULTS: 55 patients with type I EOC underwent molecular profiling, 41 (75%) low grade serous (LGS), 9 (16%) clear cell (CC), and 5 (9%) mucinous (MC) histologies. Thirty-five patients (64%) were found to have ≥1 somatic mutations: 23 KRAS, 6 NRAS, 5 PIK3CA, 2 PTEN, 1 BRAF, 1 AKT, 1 TP53, and 1 CTNNB1. Fifteen patients were subsequently enrolled in genotype-matched phase I or II trials, including 14 patients with KRAS/NRAS mutations treated with MEK inhibitor targeted combinations. Among 14 RECIST evaluable patients, there were 7 partial responses (PR), 7 stable disease (SD) and 1 disease progression (PD). CA125 responses were observed in 10/10 evaluable KRAS/NRAS mutant patients treated with MEK inhibitor combinations CONCLUSIONS: Genotyping and targeted sequencing of Type I EOCs frequently identifies actionable mutations. Matched treatment with MEK-based combination therapy in KRAS and/or NRAS mutant type I EOC patients is an active therapeutic strategy.

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had ≥3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies.

Abstract PR03: Molecular profiling of advanced solid tumors at Princess Margaret Cancer Centre and patient outcomes with genotype-matched clinical trials

Background: IMPACT and COMPACT are ongoing clinical trials at Princess Margaret (PM) to match advanced solid tumor patients with actionable somatic mutations to clinical trials with investigational therapies [NCT01505400]. We compared the outcome of patients profiled at PM treated on genotype-matched versus genotype-unmatched clinical trials. Methods: Patients with advanced solid tumors treated at PM or collaborating local institutions with available formalin fixed paraffin-embedded (FFPE) tumor tissue were prospectively consented for molecular profiling during standard treatment. Only patients with ECOG performance status ≤1 who were considered therapeutic trial candidates by their treating oncologist were eligible. Following pathology review, tumor DNA from FFPE blocks or unstained slides was extracted and genotyped using a customized Sequenom SNP genotyping panel (23 genes, 279 mutations) or a targeted next generation sequencing (NGS) panel, either the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons) or the Ion Proton Ampliseq Cancer Hotspot Panel version 2 (50 genes, 207 amplicons) with ≤500x coverage in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. An annotated molecular profiling report with somatic variants classified according to clinical actionability was included in the patient9s electronic medical record. Oncologists were provided with regular summary tables of their patients9 molecular profiling results and mutation-specific clinical trial listings to facilitate genotype-matched trial enrolment. Results: From March 2012 to July 2014, 1893 patients were enrolled with gynaecological (22%), breast (18%), lung (18%) colorectal (17%), pancreatobiliary (8%), upper aerodigestive (6%), genitourinary (5%), and other (5%) cancers. Patients had received a median of 4 prior systemic treatments (range 1-23). Of 253 (13%) screen failures, 10% were for insufficient tissue and 3% for clinical deterioration or other reasons. Patients were more likely to have one or more somatic mutations identified by NGS testing [597/813 (73%); average 1.23 mutations/patient; range 0-9 mutations/patient] compared with SNP genotyping [341/827 (41%); average 0.46 mutations/patient; range 0-2 mutations/patient; p Conclusions: Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling program were subsequently treated on genotype-matched therapeutic trials. Compared with SNP genotyping, profiling with a broader NGS panel did not increase the likelihood of receiving treatment on a genotype-matched trial. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate. Greater efforts should be made to expand opportunities for genotype-trial matching and further studies are needed to evaluate the clinical utility of targeted NGS profiling. This abstract is also presented as Poster 18. Citation Format: Philippe L. Bedard, Amit Oza, Blaise Clarke, Ming-Sound Tsao, Natasha B. Leighl, Eric X. Chen, Albiruni Razak, Hal K. Berman, Stefano Serra, Michael Roehrl, Nadia Califaretti, Mateya Trinkaus, Tong Zhang, Mahadeo A. Sukhai, Anca Milea, Aaron R. Hansen, Trevor J. Pugh, Tracy Stockley, Suzanne Kamel-Reid, Lillian L. Siu. Molecular profiling of advanced solid tumors at Princess Margaret Cancer Centre and patient outcomes with genotype-matched clinical trials. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR03.

Abstract 02: Pan-cancer analysis of hotspot mutations in genes encoding the members of mitogen activated protein kinase (MAPK) and phosphoinosidtide-3 kinase (PI3K) pathways among smokers and non-smokers

Background: In lung cancer, the MAPK pathway is activated mainly by KRAS and EGFR mutations in smokers and non-smokers, respectively. It is relatively unknown how smoking affects MAPK and PI3K pathways across multiple cancers. Methods: Mutation data and smoking status were available from 854 solid tumor patients whose tumors were profiled by NGS with Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons) in the Princess Margaret Cancer Centre Integrated Molecular Profiling in Advanced Cancer Trial (IMPACT). The panel included hotspot exons of EGFR, ERBB2, KRAS, NRAS, BRAF, PIK3CA, PTEN and AKT1. Mutation frequencies between smokers and non-smokers (never smoker + former light smoker [ Results: Lung cancers (N=101) from smokers contained more KRAS mutations (38% vs.12%, P=0.004) while those from non-smokers had more EGFR mutations (34% vs. 10%, P=0.003). In contrast, non-lung cancers (N=753) had no difference in KRAS mutation frequencies between smokers and non-smokers (19% vs.17%, P=0.47). Too few EGFR and NRAS mutations were found in this cohort for meaningful analysis. Across the cohorts, there was no difference in BRAF, PIK3CA, or PTEN mutation frequency between smokers and non-smokers (BRAF, 5% vs. 4.5%, P=0.6; PIK3CA, 14% vs.15%, P=0.8; PTEN, 4.5% vs. 3.6%, P=0.6). Five non-lung cancers (4 non-smokers, 1 smoker) had AKT1 mutations. All nine cases with ERBB2 mutations (2 lung and 7 non-lung cancers) were non-smokers. No difference in KRAS, BRAF, PIK3CA and PTEN mutation frequencies between smokers and non-smokers was observed within specific cancers; breast, cervix, colorectal, endometrium, ovarian, pancreatobiliary and upper aerodigestive (P values>0.05, N= 107, 36, 126, 55, 167, 70, 81 respectively). Conclusions: Our data suggest that, with the exception of lung cancer, there is no difference in frequencies of hotspot mutations in critical genes encoding MAPK and PI3K pathways members between smokers and non-smokers across multiple cancers analysed. ERBB2 hotspot mutations (N=9) were exclusively found in non-smokers. Citation Format: Kyaw L. Aung, Trevor J. Pugh, Tracy Stockley, Lisa Wang, Greg Korpanty, Stefano Serra, Patricia Shaw, Ming S. Tsao, Neesha Dhani, Helen Mackay, Frances A. Shepherd, Suzanne Kamel-Reid, Lillian L. Siu, Philippe L. Bedard. Pan-cancer analysis of hotspot mutations in genes encoding the members of mitogen activated protein kinase (MAPK) and phosphoinosidtide-3 kinase (PI3K) pathways among smokers and non-smokers. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 02.

Minimally Invasive Real-Time Detection of Actionable Mutations in Patients With Metastatic Solid Tumors Using Fine-Needle and Liquid Biopsies

PurposeFine-needle biopsy (FNB) and liquid biopsy are minimally invasive methods of tumor sampling that provide feasible means to assess tumor genotypes in real time. However, more data are needed to establish the strength of these methods by benchmarking against the current gold standard methods, core-needle biopsy (CNB) or surgical excision of the tumor.Patients and MethodsEligible patients with advanced solid tumors were prospectively recruited. We performed mutation profiling using matched tumor DNA obtained by CNB, FNB and liquid biopsy, and matrix-assisted laser desorption/ionization time-of-flight custom mass-spectrometry or targeted next-generation DNA sequencing. The actionability of detected mutations was determined using the OncoKB Web tool. Agreement between mutations detected in CNBs, FNBs, and circulating tumor DNA (ctDNA) was examined.ResultsForty-one patients underwent tumor biopsy. Thirty CNBs (73%) and 34 FNBs (83%) had sufficient tumor and DNA for mutation profiling. Median DNA yield fr...

Abstract P3-09-05: Clinical outcome of patients with advanced triple negative breast cancer with germline and somatic variants in homologous recombination gene

Background: Variants in homologous recombination (HR) genes other than BRCA1/2 may cause a BRCA -like phenotype triple negative breast cancer (TNBC), which includes the sensitivity to platinums and DNA repair inhibitors. Evaluation of HR proficiency may influence the clinical management of TNBC. Our aim was to evaluate germline and somatic HR gene variants in advanced TNBC patients (pts) and clinical outcome. Methods: Our cohort included advanced TNBC pts unselected for family history or age at diagnosis, enrolled in an institutional molecular screening program (NCT01505400). DNA from matched blood and FFPE tumor samples was assessed using a lab developed next generation sequencing Hereditary Cancer Panel (NGS-HCP) that includes all exons of 52 cancer predisposition genes, with 20 HR genes (Illumina MiSeq/NextSeq, germline coverage 100x, somatic coverage 500x). Medical records were reviewed for clinical outcome, pathology and prior germline BRCA1/2 testing results. All pts consented for research on banked samples and return of pathogenic germline variants was optional. Log rank test was used to determine time from surgery with curative intent to relapse (TTR) and overall survival from diagnosis to death (OS) differences based on presence of HR variants. Results: We included 32 pts who consented for return of pathogenic germline variants and had sufficient DNA for NGS-HCP analysis. Median age at diagnosis was 45 years (range 21-80). Initial stages at diagnosis were: I (12.5%), II (62.5%), III (19%) and IV (6%). Germline HR variants were detected in 17 pts (53%) with a median number of variants per patient of 1 (range 0-6). Five pts had likely pathogenic or pathogenic variants in HR genes: BRCA1 (2), BRCA2 (1) FANCC (1) and FANCC + BML (1). Another patient had a BRCA1 pathogenic variant previously detected by Multiplex Ligation-dependent Probe Amplification but was not detected by NGS-HCP. 26 variants of unknown significance (VUS) were identified in 13 HR genes, including FANCA (6), FANCF (3) and BRCA1 (3). Only one patient had a somatic HR variant in FANCA not found in the germline. 30 pts (94%) had somatic TP53 variants. Sporadic somatic BRCA1/2 variants were not seen. BRCA1/2 variants present in the tumor were equivalent to those detected in blood of BRCA1/2 carriers. Median (m) TTR was 17 months (range 1-119) and mOS was 49 months (range 8-123). Presence of likely pathogenic or pathogenic germline variants was not associated with TTR (p=0.78) and OS (p=0.23). Presence of germline VUS, likely pathogenic or pathogenic variants also did not correlate with TTR (p=0.72) and OS (p=0.47) Conclusions: In our cohort of pts with advanced TNBC, 12% had germline pathogenic variants in BRCA1/2 , similar to the previously reported rate in early stage TNBC pts. Prevalence of likely pathogenic or pathogenic variants in non- BRCA HR genes was 6%. The presence of germline variants in HR genes was not associated with clinical outcome, however, the number of patients included was small and we had limited power to detect survival differences. Background: Variants in homologous recombination (HR) genes other than BRCA1/2 may cause a BRCA -like phenotype triple negative breast cancer (TNBC), which includes the sensitivity to platinums and DNA repair inhibitors. Evaluation of HR proficiency may influence the clinical management of TNBC. Our aim was to evaluate germline and somatic HR gene variants in advanced TNBC patients (pts) and clinical outcome. Methods: Our cohort included advanced TNBC pts unselected for family history or age at diagnosis, enrolled in an institutional molecular screening program (NCT01505400). DNA from matched blood and FFPE tumor samples was assessed using a lab developed next generation sequencing Hereditary Cancer Panel (NGS-HCP) that includes all exons of 52 cancer predisposition genes, with 20 HR genes (Illumina MiSeq/NextSeq, germline coverage 100x, somatic coverage 500x). Medical records were reviewed for clinical outcome, pathology and prior germline BRCA1/2 testing results. All pts consented for research on banked samples and return of pathogenic germline variants was optional. Log rank test was used to determine time from surgery with curative intent to relapse (TTR) and overall survival from diagnosis to death (OS) differences based on presence of HR variants. Results: We included 32 pts who consented for return of pathogenic germline variants and had sufficient DNA for NGS-HCP analysis. Median age at diagnosis was 45 years (range 21-80). Initial stages at diagnosis were: I (12.5%), II (62.5%), III (19%) and IV (6%). Germline HR variants were detected in 17 pts (53%) with a median number of variants per patient of 1 (range 0-6). Five pts had likely pathogenic or pathogenic variants in HR genes: BRCA1 (2), BRCA2 (1) FANCC (1) and FANCC + BML (1). Another patient had a BRCA1 pathogenic variant previously detected by Multiplex Ligation-dependent Probe Amplification but was not detected by NGS-HCP. 26 variants of unknown significance (VUS) were identified in 13 HR genes, including FANCA (6), FANCF (3) and BRCA1 (3). Only one patient had a somatic HR variant in FANCA not found in the germline. 30 pts (94%) had somatic TP53 variants. Sporadic somatic BRCA1/2 variants were not seen. BRCA1/2 variants present in the tumor were equivalent to those detected in blood of BRCA1/2 carriers. Median (m) TTR was 17 months (range 1-119) and mOS was 49 months (range 8-123). Presence of likely pathogenic or pathogenic germline variants was not associated with TTR (p=0.78) and OS (p=0.23). Presence of germline VUS, likely pathogenic or pathogenic variants also did not correlate with TTR (p=0.72) and OS (p=0.47) Conclusions: In our cohort of pts with advanced TNBC, 12% had germline pathogenic variants in BRCA1/2 , similar to the previously reported rate in early stage TNBC pts. Prevalence of likely pathogenic or pathogenic variants in non- BRCA HR genes was 6%. The presence of germline variants in HR genes was not associated with clinical outcome, however, the number of patients included was small and we had limited power to detect survival differences. Citation Format: Stjepanovic N, Kim RH, Wilson M, Mandilaras V, Berman H, Amir E, Cescon D, Elser C, Randall Armel S, McCuaig J, Volenik A, Demsky R, Chow H, Misyura M, Wang L, Oza AM, Kamel-Reid S, Stockley T, Bedard PL. Clinical outcome of patients with advanced triple negative breast cancer with germline and somatic variants in homologous recombination gene [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-09-05.

Abstract 4765: Impact of TP53 status and functional classification on molecular profiles in breast cancer subtypes

Breast cancer is a multifaceted disease with several clinical, pathological and molecular attributes contributing to disease prognosis or treatment outcome. Treatment measures in breast cancer are based on hormone/growth factor receptor -estrogen/progesterone receptor (ER/PR) or human epidermal growth factor receptor 2 (Her2) status. TP53 pathway inactivation in breast cancer is well-established. Although TP539s therapeutic relevance is well-recognized, it remains under-utilized in patient-management, since all TP53 mutants are treated equally in the diagnostic context. In reality, enormous heterogeneity exists in nature, type and functional impact of TP53 variants. Therefore, understanding the diversity of TP53 variants in breast cancer subtypes may enhance its diagnostic utility in this cancer. We utilized clinical NGS data, obtained using commercially available targeted panels, TruSeq Amplicon Cancer Panel (Illumina) and Ion AmpliSeq Cancer Hotspot Panel v2 (Thermofisher) to analyze tumor DNAs from cancer patients at the Advanced Molecular Diagnostic Laboratory (Princess Margaret Cancer Centre, Toronto, Canada). We focused on data from 105 advanced breast cancer patients. We consolidated several schemes proposed in the literature to classify TP53 variants, and evaluated patient molecular profiling and pathology data based on: (1) presence of TP53 variants; (b) coding effect; and (c) transcriptional activity. We further investigated whether TP53 variants were associated with reportable variant load, co-occurrence with other molecular changes and hormone/growth-factor receptor status. In our study group, 70.4% cases carried one or more variants. TP53 alterations were prevalent (40.9%) in our cohort, followed by PIK3CA variants (36.2%). 15/105 cases (14.3%) carried variants in both genes. Unlike in other cancer types, where missense TP53 variants predominate (e.g., colorectal, 72.6%), missense (49%) and nonsense/frameshift (42%) variants were similarly distributed in breast cancers. Gain-of-Function (GOF) and Loss-of-Function (LOF) TP53 variants were also equally distributed (32% vs. 33%). However, TP53mut PIK3CAmut breast cancer cases were more likely to carry missense and/or LOF variants (10/15 cases). TP53 variants were also associated with hormone/growth-factor receptor status. A greater proportion of ER- vs ER+, PR- vs PR+, and ER-PR-Her2- vs ER+PR+Her2- breast cancer cases carried missense GOF TP53 variants respectively when compared to missense LOF and variants of unknown significance taken together(80-85% vs 50-55%; p Taken together, we define a stratification strategy for TP53 that takes into account the diversity of TP53 variants, and demonstrate its application to molecular profiling and clinico-pathological data in breast cancer. Citation Format: Swati Garg, Mahadeo A. Sukhai, Maksym Misyura, Mariam Thomas, Tong Zhang, Lillian L. Siu, Philippe L. Bedard, Tracy L. Stockley, Suzanne Kamel-Reid. Impact of TP53 status and functional classification on molecular profiles in breast cancer subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4765.

Abstract 4260: Clinical testing and implementation of the TruSight Myeloid Next Generation Sequencing (NGS) panel for identification of clinically relevant variants in hematological malignancies

Recent cancer genome profiling studies have increased our understanding of the somatic mutation landscape of myeloid malignancies. A number of genes and variants are known to have prognostic/predictive utility in several myeloid malignancies, allowing for more accurate stratification, and enhanced patient management. This has led to consideration of NGS for detection of somatic mutations in myeloid malignancies in the clinical diagnostic setting, to supplant single-gene molecular testing assays in current use. Building on our prior work establishing a novel mass spectrometry-based high throughput mutation detection assay for hematologic malignancies, we investigated the application of NGS to myeloid malignancy diagnostics. To do this, we validated the Illumina TruSight Myeloid Sequencing Panel (54 genes, 568 amplicons) on 71 acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN) patient samples, alongside relevant controls. NGS Libraries were prepared using standard protocols, and sequencing performed on the Illumina MiSeq platform. Concordance among NGS calls, single gene tests, and Sanger verification was tested as part of the clinical validation process. Analysis of 41 cases tested in our previously developed mass spectrometry assay indicated 100% concordance (70/70) for reportable variants mutually covered in both assays. Single nucleotide variations detectable in lab-standard single gene assays were all found by NGS (100% concordance). 58/71 (82%) cases had at least one additional potentially clinically relevant variant that would not have been identified in the existing assay (mean 1.95 additional variants/case; range 1-9). Additionally, we determined that AMLs carrying IDH1, IDH2 or TET2 mutations had a higher mutation burden (mean 4.6 mutations/case, range 2-7), compared to AMLs wild-type for these three genes (mean 3.1 mutations/case, range 2-4; p = 0.008). Clinically relevant insertions (up to 33 bp) and deletions (up to 52 bp) associated with AML and MPN, including FLT3 ITD and CALR deletions, were detected in known positive cases. In these cases, our analysis was supplemented with a custom bioinformatics algorithm allowing for alignment against an artificial reference sequence to detect larger indels. Due to low coverage of the clinically actionable CEBPA, we supplemented the NGS assay with Sanger sequencing for this locus. Therefore, we report the validation of an NGS panel for high throughput detection of mutations in myeloid malignancies, and the development of a wet-bench and informatics workflow enabling maximal information benefit in the diagnostic setting. This pipeline allows the detection of variants that impact diagnosis and patient management, with significantly improved information benefit over current tests. Citation Format: Mariam Thomas, Mahadeo Sukhai, Tong Zhang, Djamel Harbi, Justin De Souza, Katherine MacDonald, Trevor Pugh, Mark Minden, Andre Schuh, Tracy L. Stockley, Suzanne Kamel-Reid. Clinical testing and implementation of the TruSight Myeloid Next Generation Sequencing (NGS) panel for identification of clinically relevant variants in hematological malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4260. doi:10.1158/1538-7445.AM2015-4260

Abstract 3708: Filling the void of Canadian T-cell lymphoma epidemiology: Data from the canadian institute for health information discharge abstract database

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Introduction Epidemiological data for rare malignancies can be difficult to obtain; population-based data sets are often abridged to group disparate rare malignancies into larger more manageable clusters. These problems are acute in Canada, where such epidemiological data are often estimated from “second-hand” US data (e.g. Surveillance, Epidemiology and End-Results (SEER) data). Recently, the Canadian Institute of Health Information (CIHI) has set out to make epidemiological data more readily accessible, permitting University-affiliated researchers to access the anonymized and codified CIHI Discharge Abstract Database (DAD). Methods We undertook to estimate the incidence, demographics, and outcome data relating to the various subtypes of peripheral T-cell lymphomas (PTCLs) in Canada (excluding Quebec and British Columbia, for which data was not collected). The CIHI DAD consists of a two fiscal-year anonymized 10% random sample of all hospital discharge abstracts in Canada. The DAD is indexed by a unique anonymous patient identifiers and includes relative date metrics, by which all dates originally present on the abstract are standardized to a unique but confidential CIHI DAD reference date. From these data we were able to identify all hematolymphoid diagnoses, isolate the PTCLs, separate new from historical diagnoses, and identify patient age range, gender and disposition data. When the disposition data were combined with the relative date metrics, a gross estimate of T-cell lymphoma overall survival (relative to all other hematolymphoid diagnoses) was generated. Population normalization was achieved using inter-censal estimates obtained from Statistics Canada. Results PTCL incidence was estimated at 0.72 cases per 100,000 per annum (comparable to recently published SEER data). We also estimated a prevalence of 21 PTCLs per 100,000 healthcare encounters. Most cases of PTCL originated from males (63%) and the distribution of age ranges was skewed toward older adults (median age by number of cases = 60 years). The most frequent diagnosis was PTCL, NOS (46%). By the Cox-proportional hazards method, there was a statistically significant difference in survival between the T-cell lymphomas and non T-cell hematolymphoid malignancies (regression co-efficient for PTCL vs. non-PTCL diagnosis p = 0.003) in favor of the latter; not surprisingly, age was also predictive of overall survival, regardless of the subtype of malignancy (regression co-efficient p = 0.004). Conclusions To our knowledge, the above is the first attempt to estimate the epidemiology of PTCLs in Canada. In addition, we present a unique approach to obtaining high-quality (albeit geographically incomplete) Canadian epidemiological data via the CIHI DAD database; this dataset may serve as a valuable resource in the context of rare diseases whose epidemiological data may not be widely or publicly available. Citation Format: Etienne R. Mahe, Princess Margaret Cancer Centre Advanced MolecularDiagnostics Laboratory, Trevor Pugh, Tracy Stockley, Suzanne Kamel-Reid. Filling the void of Canadian T-cell lymphoma epidemiology: Data from the canadian institute for health information discharge abstract database. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3708. doi:10.1158/1538-7445.AM2015-3708

1612PFINE NEEDLE BIOPSIES ARE FEASIBLE AS A MINIMALLY INVASIVE MEANS FOR TARGETED NEXT GENERATION SEQUENCING IN ADVANCED SOLID TUMORS

ABSTRACT Aim: Core needle biopsies (CNB) are used routinely to obtain metastatic tumor tissue for genotyping and to aid clinical decision-making. Fine needle biopsies (FNB) are a less invasive method to procure tumor cells. This ongoing study aims to compare the success and concordance of clinical genotyping using CNB and FNB of the same metastasis. Methods: Patients (pts) with advanced melanoma, breast, colorectal and gynecological cancers with no contraindication to biopsy were eligible. FNB were performed first (≤3 passes) followed by 3 CNB, using 25 and 18 gauge needles respectively. FNB underwent rapid onsite evaluation to ensure lesion sampling and both rinse and smear were used for profiling. CNB were formalin fixed and paraffin embedded. Following pathology review, tumor DNA was extracted and profiling was performed in a CLIA-certified laboratory using the Illumina MiSeq TruSeq panel (48 genes, 212 amplicons) or a customized solid tumor genotyping panel on the Sequenom MassArray (23 genes, 279 mutations). If available, genomic concordance between the archival specimen of the primary tumor and metastasis was assessed. Results: 35 pts (21 breast, 5 gynecological, 5 colorectal and 4 melanoma) were enrolled. 31 pts underwent a single biopsy, 3 pts were considered unsuitable and 1 pt had 2 biopsies separated by a line of systemic therapy. Liver was the most common biopsy site (15 pts [48%]). No biopsy related severe adverse events occurred. 26 biopsies have been reported, 5 CNB-FNB pairs had no tumor and another 4 CNB had no tumor with malignant cells seen on FNB only. There was no difference in DNA yield from CNB and FNB (mean 660ng vs 900ng, p=0.24). 29 mutations in 12 genes were identified from 22 biopsies (TP53 9, PIK3CA 5, APC 3, BRAF 2, ERBB2 2, KRAS 2, AKT1 1, ATM 1, CTNNB1 1, JAK2 1, KIT 1, NRAS 1). Two of the 20 pts with available primary tissue showed discordance with the biopsy of the metastasis (involving ATM and TP53 variants). Conclusions: Genotyping or targeted sequencing of FNB is feasible. CNB and FNB show high concordance for genotype. Few genotype differences were detected between the primary tumor and metastasis, although broader genomic testing may be required to identify clonal evolution. Disclosure: L.L. Siu: Research funding: Roche, Pfizer, Bristol-Myer Squibb, Boerhinger-Ingelheim. All other authors have declared no conflicts of interest.