Evolving Landscape of Molecular Prescreening Strategies for Oncology Early Clinical Trials

Most academic precision oncology programs have been designed to facilitate enrollment of patients in early clinical trials with matched targeted agents. Over the last decade, major changes were seen both in the targetable molecular alteration landscape and in drug development trends. In this article, we describe how the Vall d’Hebron Institute of Oncology molecular prescreening program adapted to a dynamic model of biomarker-drug codevelopment. We started with a tumor-agnostic hotspot mutation panel plus in situ hybridization and immunohistochemistry of selected markers and subsequently transitioned to tumor-specific amplicon-based next-generation sequencing (NGS) tests together with custom copy number, fusion, and outlier gene expression panels. All assays are optimized for archived formalin-fixed paraffin-embedded tumor tissues without matched germline sequencing. In parallel, biomarker-matched trials evolved from a scenario of few targets and large populations (such as PI3K inhibitors in PIK3CA mutants) to a complex situation with many targets and small populations (such as multiple targetable fusion events). Recruitment rates in clinical trials with mandatory biomarkers decreased over the last 3 years. Molecular tumor board meetings proved critical to guide oncologists on emerging biomarkers for clinical testing and interpretation of NGS results. The substantial increase of immunotherapy trials had a major impact in target prioritization and guided clinical implementation of new markers, such as tumor mutational burden, with larger exon-based NGS assays and gene expression signatures to capture microenvironment infiltration patterns. This new multiomics era of precision oncology is expected to increase the opportunities for early clinical trial matching.

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.593 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 593-593

Author(s):

Davendra Sohal ◽

Brian I. Rini ◽

Robert James Pelley ◽

Bassam N. Estfan ◽

Dale Randall Shepard ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trials ◽

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Cleveland Clinic ◽

Tumor Board ◽

Genomic Testing ◽

Precision Oncology ◽

Tumor Genome

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]

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Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

JCO Precision Oncology ◽

10.1200/po.20.00261 ◽

2021 ◽

pp. 859-875

Author(s):

Amanda O. L. Seet ◽

Aaron C. Tan ◽

Tira J. Tan ◽

Matthew C. H. Ng ◽

David W. M. Tai ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Tumor Tissue ◽

Molecular Profiling ◽

Tumor Board ◽

Cancer Center ◽

Precision Oncology ◽

Molecular Tumor Board ◽

Tumor Types ◽

Tertiary Cancer Center

PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

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Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board

JCO Precision Oncology ◽

10.1200/po.16.00022 ◽

2017 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Mark E. Burkard ◽

Dustin A. Deming ◽

Benjamin M. Parsons ◽

Paraic A. Kenny ◽

Marissa R. Schuh ◽

...

Keyword(s):

Clinical Trials ◽

Precision Medicine ◽

Clinical Utility ◽

Journal Club ◽

Academic Community ◽

Tumor Board ◽

Observational Research ◽

Evidence Based ◽

Precision Oncology ◽

Molecular Tumor Board

Purpose Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

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Precision oncology experience at a tertiary care center.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18118 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18118-e18118

Author(s):

Meena Sadaps ◽

Pauline Funchain ◽

Petros Grivas ◽

Bassam N. Estfan ◽

Jame Abraham ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Real World ◽

Care Center ◽

Tertiary Care ◽

Cleveland Clinic ◽

Tumor Board ◽

Genomic Testing ◽

Precision Oncology ◽

Genomic Profiling

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.

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Präzisionsonkologie und molekulare Tumorboards – Konzepte, Chancen und Herausforderungen

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-0042-120717 ◽

2017 ◽

Vol 142 (22) ◽

pp. 1676-1684 ◽

Cited By ~ 2

Author(s):

Julian Holch ◽

Christoph Westphalen ◽

Wolfgang Hiddemann ◽

Volker Heinemann ◽

Andreas Jung ◽

...

Keyword(s):

Clinical Trials ◽

Genetic Analysis ◽

Treatment Strategies ◽

Standard Of Care ◽

Tumor Board ◽

Precision Oncology ◽

Current Standard ◽

Recent Developments ◽

Tumor Types ◽

New Strategies

AbstractRecent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, “precision oncology” also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for “universal genetic testing” in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that “precision oncology” approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary “molecular tumor board”, and preferably within clinical trials.

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Precision oncology in pancreatobiliary cancers: A longitudinal study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.399 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 399-399

Author(s):

Meena Sadaps ◽

Bassam N. Estfan ◽

Davendra Sohal ◽

Alok A. Khorana

Keyword(s):

Clinical Trials ◽

Solid Tumor ◽

Performance Status ◽

Cleveland Clinic ◽

Poor Performance ◽

Tumor Board ◽

Poor Performance Status ◽

Precision Oncology ◽

Advanced Cancer Patients ◽

Off Label

399 Background: Precision oncology – the use of next-generation sequencing (NGS) to identify therapeutic options for advanced cancer patients – is being used widely, but its utility in patients with pancreatobiliary (PB) cancers has not been studied systematically. We evaluated the prevalence of actionable alterations and their impact on therapeutic decision-making in patients with PB cancers. Methods: We conducted a retrospective cohort study of consecutive patients seen at the Cleveland Clinic between 2013 and 2016 with incurable solid tumor malignancies, in whom FoundationOne™ (Cambridge, MA) NGS was ordered. All results were reviewed at a multidisciplinary genomics tumor board (GTB), which determined actionability and made therapeutic recommendations. Treatment decisions (on label, off label, or clinical trials) based on said recommendations were reviewed. Results: The study population was 600 patients, of whom 53 had PB cancers. For these 53, median age was 59.6 years; 62.2% (33/53) were female; 86.8% (46/53) were Caucasian. Eight samples (15.1%) had inadequate tissue; of 45 resulted cases, 21 (46.7%) were recommended treatment, including clinical trials (n = 19) and off-label drugs (n = 2). The most common targets for therapy were FGFR (5/21) and CDKN2 (3/21). Of 21 patients with recommendations, only two (9.5%) received genomics-driven therapy, compared with 31.7% (86/271) of patients with other solid tumor malignancies (p = 0.03). One received an IDH1 inhibitor, and one received dabrafenib and trametinib for a BRAF alteration; both on clinical trials. At time of last follow-up, best responses were unknown and partial response, respectively. Unavailability of clinical trials in the vicinity (9.5%), and clinical trial ineligibility, mainly due to poor performance status (9.5%), were common reasons for lack of actionability. Conclusions: Benefit from precision oncology in the PB population is low, with only 4.4% (2/45) of patients with NGS results eventually receiving genomics-driven therapy. Benefit to patients will not improve until access to clinical trials is enhanced and patients are evaluated for these trials earlier in the course of their disease, when their performance status is likely to be higher.

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Genomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.571 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 571-571 ◽

Cited By ~ 2

Author(s):

Aranzazu Fernandez-Martinez ◽

Maki Tanioka ◽

Cheng Fan ◽

Joel S. Parker ◽

Katherine A. Hoadley ◽

...

Keyword(s):

Gene Expression ◽

Clinical Trials ◽

Predictive Biomarkers ◽

Specific Gene ◽

Mrna Levels ◽

Clinical Implementation ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Erbb2 Mrna

571 Background: In HER2-positive breast cancer, new biomarkers of response are needed in order to direct multi-agent anti-HER2 combinations towards patients in whom they are truly needed. CALGB 40601 and PAMELA trials tested neoadjuvant dual HER2 blockade and included gene expression analysis aimed to evaluate different genomic biomarkers of trastuzumab and/or lapatinib benefit. Methods: Gene expression by mRNA sequencing (RNAseq) was performed on 265 and 142 pre-treatment tumors of the CALGB 40601 and the PAMELA clinical trials respectively. Intrinsic subtypes were determined by nCounter PAM50-predictor on the PAMELA samples. A new HER2-positive specific gene-centering method was trained on the PAMELA RNAseq data, and showed a higher concordance with PAM50 predictions obtained from nCounter platform. This method was then applied to CALGB 40601 samples. Results: In the combined cohort, the subtype distribution was 10% Luminal A, 8% Luminal B, 62% HER2-enriched (HER2-E), 10% Basal and 10% Normal-like. The pCR rate was significantly higher in HER2-E vs. not HER2-E subtypes (48.6% vs. 20.7%; P < 0.001). HER2-E subtype correlation, ERBB2 amplicon and B-cell genomic signatures were associated with pCR, while luminal signatures were associated with non-responders. In multivariate analysis HER2-E subtype, ERBB2 mRNA and IgG signature expression were independent predictors of response to paclitaxel + trastuzumab +/-lapatinib (OR = 1.98, OR = 1.51, OR = 1.48, respectively, P <0.05). The event free survival analysis at 5 years in the CALGB 40601 cohort showed a benefit of dual vs single anti-HER2-blockade (HR 0.35, P <0.05). Within the HER2-E, ERBB2-high and IgG–high subpopulations, there were also a benefit of dual vs. single anti-HER2 treatment (HR = 0.32, HR = 0.15, HR =0.15, respectively, P <0.05). Conclusions: Intrinsic subtype, ERBB2 mRNA levels, and IgG genomic signature are independent predictive biomarkers of response in the combined cohort. The clinical implementation of these biomarkers could help to design future escalation/de-escalation clinical trials in the HER2-positive neoadjuvant setting. Support: U10CA180821, U10CA180882, U24CA196171, P50-CA58223, GSK, SPORE, BCRF and SEOM. https://acknowledgments.alliancefound.org .

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Mutational landscape of endometrial cancer identified by prospective clinical sequencing in a nationwide cancer network.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17123 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17123-e17123

Author(s):

Julian C. Schink ◽

Ricardo H. Alvarez ◽

Julia Andrea Elvin ◽

Amber Moran ◽

Rebecca Rollins ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Endometrial Cancer ◽

Large Series ◽

Tumor Board ◽

Precision Oncology ◽

Genomic Profiling ◽

Genomic Alterations ◽

Cancer Network ◽

Matched Treatment

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

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Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19266 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19266-e19266

Author(s):

Igor I. Rybkin ◽

Nadia Z Haque ◽

Kristen Collins ◽

Louisa Laidlaw ◽

Tom Mikkelsen

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Performance Status ◽

Tumor Board ◽

Molecular Testing ◽

Precision Oncology ◽

Ecog Performance Status ◽

Off Label ◽

Molecular Tumor Board ◽

The Impact

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

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Toward Improving Practices for Submission of Diagnostic Tissue Blocks for National Cancer Institute Clinical Trials

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz141 ◽

2019 ◽

Vol 153 (2) ◽

pp. 149-155 ◽

Cited By ~ 1

Author(s):

Hala Makhlouf ◽

Mark A Watson ◽

Heather A Lankes ◽

Carol Weil ◽

Maura Dickler ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

National Cancer Institute ◽

Limited Resource ◽

Standard Of Care ◽

Precision Oncology ◽

Formalin Fixed Paraffin ◽

Diagnostic Block ◽

Formalin Fixed Paraffin Embedded ◽

Patient Advocates

Abstract Objectives The National Cancer Institute (NCI) National Clinical Trials Network performs phase II and III clinical trials, which increasingly rely on the submission of diagnostic formalin-fixed, paraffin-embedded tissue blocks for biomarker assessment. Simultaneously, advances in precision oncology require that clinical centers maintain diagnostic specimens for ancillary, standard-of-care diagnostics. This has caused tissue blocks to become a limited resource for advancing the NCI clinical trial enterprise and the practice of modern molecular pathology. Methods The NCI convened a 1-day workshop of multidisciplined experts to discuss barriers and strategic solutions to facilitate diagnostic block submission for clinical trial science, from the perspective of patient advocates, legal experts, pathologists, and clinical oncologists. Results The expert views and opinions were carefully noted and reported. Conclusions Recommendations were proposed to reduce institutional barriers and to assist organizations in developing clear policies regarding diagnostic block submission for clinical trials.

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