Genomic Tumor Board Research Articles

Remote genomic consultation to support uptake of a multi-gene genomic tumor panel (MGTP) by community oncologists (COs): Results of a pilot study.

1587 Background: MGTP use in routine cancer (CA) care is likely to increase w/lower costs for NGS-based testing and growing numbers of actionable targets coupled with targeted therapeutics. Early MGPT uptake has been slow among community oncologists (COs) due to their lower confidence to order, interpret, and act upon results of MGTP. This study evaluated the provision of telephone genomic consultation (GC) via an academic clinician link to an institutional genomic tumor board to support MGTP testing of CA patients (PTs) by COs. Methods: 4 practices of COs participated: 9 COs recruited 25 PTs w/metastatic CA. All PTs/COs completed baseline and follow-up (FU) assessments. Tumor blocks were evaluated at Fox Chase Cancer Center (FCCC) and tested w/a 50-gene MGTP. 12% blocks were inadequate. MGTP results were presented when appropriate at FCCC’s Genomic Tumor Board. All MGTP yielded > 1 variant (Var) [range 1-6]: 13/22 (59%) pts tested had a clinically relevant V; 6 other Vars were potentially actionable w/ approved therapy, while 3 Vars have novel therapies in Phase I/II studies. MGTP were called out to COs (by MJH) < 2 wks of resulting. A tailored summary was provided to COs. Results: At baseline, COs (n = 9) had limited experience w/MGTP (78%, < 5 ordered). Barriers for COs were: poor understanding of MGTPs (67%), cost (89%), uncertain benefit (44%), and poor access to targeted therapies (67%). At FU, 4/8 (50%) COs found GC “very useful”, and 63% reported MGPT paired w/GC would “probably/definitely” increase their use of MGTPs. Most (88%) felt MGPTs should be offered to PTs w/incurable CA. Among PTs at baseline (n = 25), awareness of MGTP was moderate (50%), but 79% reported it would help doctors take better care of their PTs. Valuation of MGTP was mixed—30% would pay $0 out of pocket, yet 30% also said they would travel “any distance” for an MGT-targeted experimental therapy. At FU (n = 14), 86% PTs felt MGPT was valuable, yet only 46% would “definitely” retest, and only 31% would pay > $100 to retest, even for 500+ genes. Conclusions: GC can be effective to support COs to use MGTPs. PTs w/CA have high expectations of MGTPs to improve their care, and yet attribute modest value to retest or to have a larger MGTP.

Feasibility of collaborative precision medicine oncology between academic- and community-based hospitals.

e18015 Background: The Rutgers Cancer Institute of New Jersey (CINJ) is conducting an ongoing, prospective, observational clinical trial that is evaluating use of comprehensive genomic profiling (CGP) and molecular tumor board (MTB) review to assist in caring for patients with rare or refractory cancers. As part of this precision medicine approach to cancer care, CINJ has formed a partnership with community hospitals (Meridian Health) to enroll patients in this study, and to actively participate in MTB meetings. The purpose of this cohort analysis is to evaluate the feasibility of using CGP to identify clinically-relevant genomic alterations as an aid to guiding point-of-care management in a community hospital setting. Methods: Meridian Health staff was trained in patient selection, enrollment, and follow-up. CGP was performed by Foundation Medicine, Inc. The patient case’s clinical history, pathology, and CGP results were presented at an MTB meeting. The enrolling physicians (n = 11) were invited to attend the MTB in person or through web-accessible video conferencing. A letter listing MTB consensus recommendations on potential treatment options was sent to the referring physician, and patient follow-up was scheduled at regular intervals. Results: 35 patients were enrolled by Meridian Health. Gyn and GI cancers were the most common types at enrollment (each 26%, 9 out of 35), followed by breast cancer (20%, 7 out of 35). At study enrollment, the mean KPS was 91%, and 23 patients (66%) had stage IV disease. The median duration between study enrollment and MTB presentation was 44 days. 3 patients were excluded because of deteriorated clinical status at the time of the MTB. MTB-based treatment options were implemented in 9 of 32 patients (28%). This result is similar to those reported in published analyses of patients enrolled at CINJ. Conclusions: Collaborations between an academic cancer center and a community hospital is a feasible approach to facilitating access to precision medicine for cancer patients treated in the community. A larger cohort is needed to determine the impact on patient’s outcomes.

Precision oncology experience at a tertiary care center.

e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery.

BackgroundThe ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM).ResultsPrior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding. Standard of care (SOC) options were continued by 15% (14/92) of patients tested before exhausting SOC options, with 71% (10/14) responding to treatment. Over 35% (34/92) of patients with actionable targets were not treated with 65% (22/34) choosing comfort measures or passing away.Materials and MethodsPatients (N = 165) were referred to the CIM Clinic between October 2012 and December 2015. All patients received clinical genomic panel testing with selected subsets receiving array comparative genomic hybridization and clinical whole exome sequencing to complement and validate panel findings. A genomic tumor board (GTB) reviewed results and, when possible, developed treatment recommendations.ConclusionsTreatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in a minority of patients. The success of genomically driven therapy depends both on access to drugs and robustness of bioinformatics analysis. While novel clinical trial designs are increasing the utility of genomic testing, robust data sharing of outcomes is needed to optimize clinical benefit for all patients.

Abstract OT3-04-01: BRE12-158: A phase II randomized controlled trial of genomically directed therapy after preoperative chemotherapy in patients with triple negative breast cancer (TNBC)

Abstract Background: About 1/3 of patients with TNBC who receive preoperative therapy will experience a pathological complete response (pCR). Patients with residual disease have a markedly inferior overall survival (OS) compared to those who experience pCR. Recently, the CREATE-X trial demonstrated an improvement in disease free survival (DFS) and OS for post-neoadjuvant capecitebine; although the addition of capecitebine to standard therapy has not previously improved outcome across other non-selected adjuvant or neo-adjuvant trials. Prior data have also demonstrated that the residual tumors are genomically diverse and that these genetic changes are reflected at time of relapse. Trial Design: This trial is a randomized phase II trial to determine whether a genomically guided therapy in the setting of incomplete response to standard neoadjuvant therapy will improve outcomes compared to standard of care. DNA from archived tumor samples collected at the time of surgery will be extracted and sequenced. The sequencing data will be interrogated for known genomic drivers of sensitivity or resistance to existing FDA approved agents. A cancer genomic tumor board (CGTB) will consider the genomic data along with the patient's prior treatment history, toxicities, and comorbidities and select the optimal therapy. Participants with a CGTB recommendation will be randomized to Experimental Arm A (genomically directed monotherapy) or Control Arm B (standard of care). Participants may have no CGTB recommendation either because sequencing did not identify a matched drug or because the drug was contraindicated and will be assigned to Control Arm B. Eligibility criteria: Patients must have histologically confirmed TNBC with completion of all definitive local therapy and no evidence of metastatic disease. There must be significant residual disease characterized by >2cm primary tumor, or lymph node positivity or RCB classification II or III. An FFPE tumor block with tumor cellularity >20% is required. All patients must have completed preoperative chemotherapy including a taxane or anthracycline or both. Specific aims: The Primary Aim is to compare 2-year DFS with a genomically directed therapy vs. standard of care. Secondary Aims include 1-year DFS, 5-year OS, collection of archival specimens for correlative studies, and to describe toxicities. Exploratory Aims are to describe the evolution of genomically directed therapies during the course of the study and to evaluate the drug specific effect on efficacy and toxicity. Statistical methods: In order to detect an improvement in the fraction of patients free from disease at 2-year from 40% in the control Arm B to 63.2% in the genomically directed Experimental Arm A (corresponding to an HR=0.5), 136 participants will have 80% power to detect a difference in DFS using a two-side log-rank test with 0.05 level of significance. Present accrual/target accrual: 38 accrued of 136 to be randomized. Citation Format: Schneider B, Miller KD, Badve S, O'Neil B, Helft P, Chitambar C, Falkson C, Nanda R, McCormick M, Danso M, Blaya M, Langdon R, Lippman M, Paplomata E, Walling R, Thompson M, Robin E, Aggarwal L, Shalaby I, Canfield V, Adesunloye B, Lee T, Daily K, Ma C, Erban J, Radhakrishnan N, Bruetman D, Graham M, Reddy NA, Lynce FC, Radovich M. BRE12-158: A phase II randomized controlled trial of genomically directed therapy after preoperative chemotherapy in patients with triple negative breast cancer (TNBC) [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 OT3-04-01.

"A rising tide lifts all boats": establishing a multidisciplinary genomic tumor board for breast cancer patients with advanced disease.

BackgroundResearch suggests that multidisciplinary genomic tumor boards (MGTB) can inform cancer patient care, though little is known about factors influencing how MGTBs interpret genomic test results, make recommendations, and perceive the utility of this approach. This study’s objective was to observe, describe, and assess the establishment of the Breast Multidisciplinary Genomic Tumor Board, the first MGTB focused on interpreting genomic test results for breast cancer patients with advanced disease.MethodsWe conducted a qualitative case study involving participant observation at monthly MGTB meetings from October 2013 through November 2014 and interviews with 12 MGTB members. We analyzed social dynamics and interactions within the MGTB regarding interpretation of genomic findings and participants’ views on effectiveness of the MGTB in using genomics to inform patient care.ResultsTwenty-two physicians, physician-scientists, basic scientists, bioethicists, and allied care professionals comprised the MGTB. The MGTB reviewed FoundationOne™ results for 40 metastatic breast cancer patients. Based on findings, the board mostly recommended referring patients to clinical trials (34) and medical genetics (15), and Food and Drug Administration-approved (FDA) breast cancer therapies (13). Though multidisciplinary, recommendations were driven by medical oncologists. Interviewees described providing more precise care recommendations and professional development as advantages and the limited actionability of genomic test results as a challenge for the MGTB.ConclusionsFindings suggest both feasibility and desirability of pooling professional expertise in genomically-guided breast cancer care and challenges to institutionalizing a Breast MGTB, specifically in promoting interdisciplinary contributions and managing limited actionability of genomic test results for patients with advanced disease.

The findings and recommendations of a breast Multidisciplinary Genomic Tumor Board.

e23138Background: Advancements in precision medicine and genomic sequencing are evolving rapidly. To apply the results of complex genomic assays to breast cancer patient (pt) care, University Hospi...

Tumor genomic profiling (TGP) in metastatic colorectal cancer (CRC): Bridging the community and the tertiary cancer center through genomic consultation (GC).

538 Background: TGP of cancers is increasingly accessible to oncologists (MDs) and patients (pts). Despite efforts to provide clinical interpretation and decision support within TGP reports, results are complex and their interpretation remains fraught with uncertainty. In an ongoing pilot, we provide community MDs access to a 50-gene next generation sequencing (NGS)-based TGP assay and expert guidance through remote access to genomic tumor board (GTB) resources via telephone-based GC. Our goal is to explore how access to GTB expertise impacts community patterns of care. In parallel, we examine MDs and pts perceptions of TGP with a focus on awareness and expectations. Methods: MDs from 4 community practices participated. Participating MDs and their pts with metastatic unresectable CRC receiving 2nd line or beyond chemotherapy provide informed consent and complete baseline and follow-up surveys. Adequate tumor samples are tested with the Fox Chase 50-gene NGS-based TGP assay. All results are presented at a bi-monthly GTB or are reviewed with the GTB chair. MDs have a ~10 min GC by telephone with the PI to summarize findings and convey GTB recommendations. Results: 9 MDs have enrolled 22 pts and TGP has been completed on 15 samples (4 additional in process and 3 insufficient for TGP). Pts report diverse ancestry (24% Hispanic or non-White) and SES (33% income < $25K). To date, all completed TGPs have reported > 1 mutation. Of 11 pts who have received TGP results, 1 has sought consultation at a tertiary center for a clinical trial. Pts with higher education were more aware of TGP (p = 0.05). Most (80%) pts felt TGP would improve their MD’s ability to treat their cancer. Male sex and higher education were associated with stronger belief that TGP will improve life expectancy. Conclusions: A partnership with community MDs to provide TGP and GTB expertise through GC is feasible. Pts exhibit high expectations of TGP, despite limited data to support improved outcomes from TGP-guided treatment. Further research into optimizing partnership between community MDs and tertiary centers is valuable to guide treatment and clinical trial participation based on TGP results.

Prospective Next-Generation Sequencing Molecular Profiling of Myeloid Malignancies: Assessment of Information Benefit and Impact on Patient Care

Introduction. Recent genome profiling studies have increased our understanding of the mutation landscapes of myeloid malignancies. Molecular testing of AMLs (NPM1, FLT3-ITD, KIT) and MPNs (JAK2, CALR) constitute current diagnostic standard-of-care. Evidence for the diagnostic, prognostic and/or therapeutic impact of a growing set of genes and variants in myeloid malignancies allows for more accurate patient stratification and enhanced patient management. This has led to consideration of next-generation sequencing (NGS) approaches to simultaneously detect multiple variants in myeloid malignancies for use in the clinical diagnostic setting, to supplant single-gene molecular assays. We designed the Princess Margaret Advanced Genomics in Leukemia (AGILE) trial to prospectively assess the utility of NGS molecular profiling in the management of patients with myeloid malignancies.Methods. Patients for the AGILE trial are consented at the time of diagnosis using an REB approved written consent. Bone marrow or peripheral blood samples are collected at consent, accessioned within CoPath, and DNA extracted for NGS testing. NGS molecular profiling was performed using the TruSight Myeloid Sequencing Panel (TMSP; Illumina) on the MiSeq benchtop genome sequencer (Illumina) by the University Health Network Advanced Molecular Diagnostics Laboratory. The TMSP enables profiling of 54 genes (39 hotspot region; 15 complete coding region coverage) using amplicon-based library preparation and sequencing by synthesis. The TMSP detects the CALR 52 base pair deletion relevant to myelofibrosis, but not FLT3 internal tandem duplications greater than 30 base pair in size. Data were analyzed by NextGENe (v.2.3.1, SoftGenetics) and MiSeq Reporter v2.4.60. A specific script enabling alignment and calling of CALR deletions was added to the analysis to ensure there were no false negative calls. Additional testing and verification of CEBPA variants was performed by Sanger sequencing. Variants were interpreted according to Sukhai et al (Genetics in Medicine, 2015), reviewed by lab directors and reported in the Electronic Patient Record. Impact on patient care was defined as: potential for post-consolidation clinical trials; changes to frequency of monitoring; and, changes to transplant management. Cases were discussed in an interdisciplinary Genomic Tumor Board setting, at which NGS profiling data were reviewed in the context of all other diagnostic information for the patient, to determine impact on patient care.Results. Between February 11 and July 24, 2015, 162 patients were consented for AGILE; 148/162 were profiled by NGS, and to date 124/148 have been reviewed and interpreted. 62/124 (50%) of interpreted cases had a diagnosis of acute myeloid leukemia (AML); 21/124 (20%) with myeloproliferative neoplasms (MPNs); 13/124 (10%) with myelodysplastic syndromes (MDS); 6/124 (5%) with MDS/MPN; and, 15% with other hematologic malignancies. 90% of all cases profiled were informative for at least one variant (range 1-9 variants, average 3.1 variants/case). AML, MDS and MDS/MPN cases exhibited slightly more variants (3.4-4.4 variants/case) than did MPN cases (2.6 variants/case). Overall, 69% of variants were potentially actionable (Sukhai et al, 2015: 23% class 1; 8% class 2; 38% class 3), with a large fraction of cases (90/124, 72.6%) demonstrating at least one class 1 or class 3 variant. Additionally, 73/124 (58.9%) of patients exhibited actionable, class 1, variants not currently being identified by routine molecular diagnostics. In AMLs and MPNs, 88-90% of cases exhibited at least one potentially actionable variant; NGS profiling was more informative in AMLs (62% of cases exhibiting potentially actionable variants not profiled in standard of care testing, compared to 12% of MPN cases).Conclusions. We report the results of a prospective analysis of integrated NGS profiling in the context of diagnosis and management of patients with myeloid malignancies. Using a targeted NGS panel, molecular profiling of patients yielded significant information benefit over current standard approaches in 58.9% of cases analyzed, enabling potential impact on patient management. These data highlight the utility of NGS profiling to complement the initial diagnostic evaluation of myeloid malignancies. DisclosuresGupta:Incyte: Honoraria, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract 1114: Genomics in cancer patient care: Bench to bedside and beyond

Abstract Burgeoning sequencing technologies and the slow pace to use genomics data clinically has been largely hampered by lack of unestablished clinical utilities. There is an immediate need to store, analyze and retrieve meaningful clinical information from high throughput genomics data. At Intermountain Cancer Genomics (ICG) we created a complete translational pipeline that integrates these major core aspects: a clinical laboratory that generates data targeted within our gene panel, a bioinformatics pipeline that accounts for the quality of the data and further generates a set of variants that can be interpreted and targeted clinically to improve the quality of a patient's life. At the ICG clinical laboratory we have developed a comprehensive ICG100 targeted sequencing panel under CLIA-CAP guidelines. DNA extracted from patient's tumor specimen gets sequenced for the entire coding region of 96 cancer-related genes which are often altered in cancer. These targeted regions are sequenced on Illumina's MiSeq sequencing platform using an in-solution, oligo-capture sequencing method. This test offers high coverage (>100X) and detects all classes of genomic alterations, including indels, translocations, copy number alterations (CNAs), and point mutations across the exons of 96 genes. This approach is viable and well-suited for all sample types including FFPE, fresh tissue and plasma. We have developed a comprehensive bio-analytics pipeline that accommodates the diverse variants generated by the unique sequencing chemistry. Comparison of ICG100 to a commercially available CLIA-certified sequencing test that also detects copy number alterations, reveals high concordance across the spectrum of variant types. In addition, the ICG100 test detected 10 additional CNAs across 6 separate samples that were not identified in the commercially available test, suggesting an increased sensitivity with ICG100. This integrated service utilizes a collaborative molecular tumor board that consist of subject expert scientists and physicians. Interdisciplinary tumor board suggests effective treatment options based on genomics data and clinical relevance. ‘Actionable’ genomic alterations are categorized as such if linked to an approved therapy in the solid tumor examined or another solid tumor. This test can be ordered by oncologist through a simple web-based interface where genomic results and molecular tumor board interpretation can be viewed. Additionally, oncologists can make a treatment selection and order drug at their convenience. The ICG100 test therefore not only is cost-effective but offers higher sensitivity, coverage, superior ability for clinical management with identification of actionable CNAs, genomics-driven personalized treatment and precision cancer care. Citation Format: Sharanya Raghunath, David Loughmiller, Aimee Shamo, Jackie Wayne, Patrick Bradley, Jason Gillman, Gary Stone, Derrick Haslem, Lincoln Nadauld, Pravin J. Mishra. Genomics in cancer patient care: Bench to bedside and beyond. [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 1114. doi:10.1158/1538-7445.AM2015-1114

Abstract LB-109: Exome sequencing identifies common somatic mutations in an adult patient with a concurrent germ cell tumor (GCT) and acute myeloid leukemia (AML) suggesting a single clonal origin

Abstract The Genomics Tumor Board at Washington University was established to increase knowledge, competence, and performance in the application of genomic testing in cancer care. Here we report the findings from a Tumor Board case of concurrent germ cell tumor and acute myeloid leukemia. A 33-year old male presented with generalized weakness, weight loss, and dyspnea on exertion. Initial workup was notable for a platelet count of 5,000 platelets/μL, hemoglobin of 13.1g/dl, and a white count of 9,200 cells/μL with a normal differential. His AFP was 237 (ULN 8.1 ng/ml), LDH was 6760 U/L (ULN 250 U/L) and β-hCG <5 (normal <5 IU/L). Chest CT scan revealed an anterior mediastinal mass. A bone marrow biopsy and aspirate showed a cellularity of 70%, with the core biopsy showing a fibrotic marrow with a population of larger mononuclear cells. The hemodilute aspirate showed 15% large blasts, and a subset of the larger cells expressed CD61 and weak CD117. These findings were consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7). The patient underwent incisional biopsy of the mediastinal mass with pathology showing necrotic fragments of tissue with scattered foci of moderately to poorly differentiated adenocarcinoma. Immunostaining was consistent with a nonseminomatous germ cell tumor. Multiple prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous germ cell tumors, and a recent study identified a patient with a concurrent AML and GCT that shared several mutations including PTEN, TP53, and chromosome 12 abnormalities, suggesting that a common founding clone initiated both cancers (Oshrine, B. R., et al. Cancer Genet 2014). To investigate the clonal relationship in our samples, we studied the GCT (whole genome amplification was performed on 2 ng of DNA isolated by laser capture microdissection of viable cells from the FFPE tumor specimen) and the M7 AML (cryopreserved cells from the diagnostic bone marrow biopsy were flow-sorted using the above markers) by whole exome sequencing. We found both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). Both the mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. A copy number comparison between the 2 samples revealed similar amplifications of chromosome 12p. In addition, we detected a heterozygous germline variant in FANCA (R858D), which is known to be associated with Fanconi anemia and is of uncertain significance here. In conclusion, the data not only support a common clonal ancestor for these cancers but also suggest that a specific set of distinct genomic alterations drives the rare association between GCT and AML, and likely underlies the poor outcome of these patients. Citation Format: Charles Lu, Peter Riedell, Peter Westervelt, Christopher Miller, Ian S. Hagemann, Eric J. Duncavage, Elaine R. Mardis, Richard K. Wilson, Bradley A. Ozenberger, Lukas D. Wartman. Exome sequencing identifies common somatic mutations in an adult patient with a concurrent germ cell tumor (GCT) and acute myeloid leukemia (AML) suggesting a single clonal origin. [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 LB-109. doi:10.1158/1538-7445.AM2015-LB-109

Molecular profiling (MP) programs to increase access to targeted therapies in a rural setting.

e17576 Background: Nearly 85% of cancer patients (pts) are treated in the community. In order to advance our understanding of cancer genomics and the impact of targeted therapy, this research needs to expand in the community. Community-based MP programs can improve access to targeted therapies and support genomic research. Methods: From June 1st, 2014 through January 15th, 2015 we instituted a prospective MP study at Sanford Health. Sanford Health is a multi-center, predominantly rural health system centered in the Dakotas. Patients with incurable, advanced solid tumors who had progressed after exhausting standard treatment options were offered enrollment in a MP program. All patients enrolled had MP performed on a recent tumor biopsy ( < 14 weeks from enrollment) using the Foundation One targeted sequencing panel. Results were reviewed at a multi-center, video-conferenced, weekly genomic tumor board. Treatment options were offered based on actionable alterations (AA) identified through MP. FDA approved o...

Abstract P2-03-12: An academic cancer center's experience in establishing a breast cancer-focused multidisciplinary genomic tumor board

Abstract Background. Clinically, it is becoming increasingly important to assess genomic alterations in breast cancers using Next Generation Sequencing to find potential targets for personalized treatment. However, care paths for using such results to guide treatment have not yet been established. Previously reported studies suggest that developing an interdisciplinary review board to evaluate genomic findings can help to guide patient care. We report on a prospective qualitative study of a multidisciplinary genomic tumor board (MGTB) developed to discuss breast cancer patients’ genomic test results in the context of the clinical history and current practice guidelines. Our goal was to observe and describe the establishment of the MGTB and its members’ perceptions of a tumor board approach to interpreting genomic test results. Materials and Methods. After IRB approval, we used qualitative case study methodology to study the MGTB and its participants, which include medical, surgical, and radiation oncologists, pathologists, geneticists, epidemiologists, bioinformaticians, pharmacologists, nurses, and bioethicists. MGTB meets on a monthly basis. Cases are anonymously presented by the treating physician. Genomic tumor findings from commercial vendors and in-house studies are discussed. Treatment recommendations are made by consensus, with level of evidence assigned based on Simon-Paik-Hayes biomarker guidelines. After obtaining consent from MGTB members, MGTB proceedings and interviews were recorded and transcribed for thematic analysis. Social dynamics within the MGTB, which includes interaction among MGTB members regarding interpretation and communication of genomic findings, were analyzed. Results. MGTB began meeting monthly in 10/2013. As of 6/2014, 24 cases have been presented. All were female with metastatic breast cancer; 16/24 (67%) hormone receptor positive (ER or PR &amp;gt;1%), 7/24 (29%) triple negative, and 2/24 (9%) her2 positive. Analysis of meeting and interview transcripts revealed that though inherently multidisciplinary, the MGTB’s recommendations seem to be driven by medical oncologists with input from geneticists and pharmacologists when present. MGTB recommendations have become increasingly consistent over time. Based on genomic findings, the board often recommends referring patients to clinical trials (18/24, 75%) and to Medical Genetics (9/24, 38%) for evaluation of suspected germline abnormalities over other options such as drug therapies approved by the FDA for use in other tumor types. Discussion and Conclusion. MGTB is a unique forum to discuss genomic test results and departs from typical tumor boards by involving non-clinicians. This case study suggests the feasibility of standardizing interdisciplinary evaluation and level of evidence recommendations for genomic results. The findings of this qualitative case study reveal MGTB members’ discomfort with recommending off-label use of FDA-approved therapies. Hence, on an institutional level, team dynamics will determine how testing and recommendations are established. Further study is required to assess institutional and professional variability in offering genomic testing and making treatment recommendations on the basis of genomic findings. Citation Format: Michelle McGowan, Shaveta Vinayak, Steven Maximuk, Roselle Ponsaran, Patricia Marshall, Lyndsay Harris, Paula Silverman. An academic cancer center's experience in establishing a breast cancer-focused multidisciplinary genomic tumor board [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-12.

Genomic testing to enhance treatment choices and clinical trial accrual in metastatic colorectal cancer: Results of a prospective cohort study.

593 Background: Tumor genome sequencing is being used widely in clinical settings but its value to individual patients has not been well-studied. A prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and their impact on management decisions was conducted. Methods: Eligibility requirements included pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥18 years, and an ECOG PS of 0-2. Data for the colorectal cancer (CRC) subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes using FoundationOne (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 45 patients with CRC were analyzed. Median age was 60 years; 23 (51%) were female; 38 (84%) were white. Median time from consent to result was 25 (range, 7-75) days. One (2%) sample had inadequate tissue. A median of 5 (range, 2-19) mutations were detected per sample; APC (89%), TP53 (73%) and KRAS (66%) were most common. A therapy targeting an actionable alteration was recommended in 22 (51%) patients; 88% of these recommendations were for clinical trials. To date, 6 (33%) of 18 patients who switched management after test results received genomics-driven therapies (Table). Previously unknown RAS (KRAS Q61H, NRAS) mutations were detected in an additional 3 patients, influencing EGFR antibody use decisions. The commonest reason for non-receipt of therapy based on the test result was non-availability of clinical trials. Conclusions: Routine tumor genome profiling in CRC patients is feasible and influenced treatment decisions in a third of patients. A genomics tumor board for the interpretation of rapidly evolving information, and improved access to clinical trials of targeted agents are critical to the success of precision oncology. [Table: see text]

Challenges with genomic testing in pancreaticobiliary cancers: Results of a prospective cohort study.

314 Background: Therapeutic options for advanced pancreaticobiliary (PB) malignancies may be improved by genomics-driven therapies. We conducted a prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and therapeutic impact of such testing in PB cancers. Methods: Eligibility requirements included confirmed pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and an ECOG performance status of 0-2. Data for the PB cancer subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes in collaboration with Foundation Medicine, Inc. (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 228 patients were analyzed; 24 (11%) had PB cancers. For the latter subgroup, median age was 60 years; 14 (58%) were male; 20 (83%) were white. Twelve (50%) tumors were pancreatic, 11 (46%) from biliary tract/gallbladder, and 1 (4%) periampullary. Median time from consent to result was 24 (range, 3-84) days. Eight (33%) samples had inadequate tissue compared with 6/174 (3%) non-PB samples (p&lt;0.001). Among patients with adequate tissue (n=16), a median of 3 (1-7) mutations were detected per sample; TP53 (50%), CDKN2A/p16 (44%) and KRAS (38%) were most common. A targeted therapy was recommended in 7 (44%) patients. Of these, 78% of recommendations were for specific clinical trials. To date, no patient with PB cancer has received a targeted therapy, compared with 6/45 (13%) patients with colorectal cancer (p=0.18). The most common reason for non-receipt of recommended targeted therapy was non-availability of clinical trials. Conclusions: Compared with other common solid tumors, genomic profiling in pancreaticobiliary cancers is challenged by paucity of diagnostic tissue collected during routine clinical care. Targeted therapy options (on-study or off-label) are few at this time. Precision oncology in pancreaticobiliary cancers will remain under-utilized until access to clinical trials is enhanced.