Precision oncology for the treatment of salivary gland tumors.

e17577 Background: Salivary gland tumors (SGT) represent a rare and heterogeneous group of malignancies. No standard treatment exists in the advanced situation and the prognosis is poor. We here report characteristics and clinical outcomes of patients with SGT discussed at the Charité molecular tumor board (MTB). Methods: Patients with advanced cancer and no curative treatment option were discussed at the Charité MTB. Eligible patients underwent fresh tissue sampling and subsequent whole exome (WES) and RNA sequencing (RNA-seq) and immunohistochemical analyses (EGFR, HER2, AR as well as validation tests) or panel sequencing. Results from molecular testing were discussed at the MTB and patients were followed-up after recommendations were made. Results: 24 patients (median age 56 years, 13 male, 11 female) with advanced SGT were presented at the MTB between 2016 and 2019 (9 adenoidcystic carcinomas, 5 adenocarcinomas, 3 mucoepidermoid, 2 carcinosarcoma, 5 miscellaneous). WES/RNA sequencing was performed on tumor tissue from 16 patients. 2 patients were not included in the sequencing program and WES/RNA-Seq was ongoing for another 4 patients at the time of analysis. For another 2 patients, panel sequencing and IHC analysis, respectively was done. Results from analyses were discussed and a median of 2 recommendations, ranked by priority according to prespecified evidence levels, were made for 17 patients, each. Most commonly proposed treatment options by the MTB were FGFR inhibitors in 6 patients, mTOR or PARP inhibitors in 5 each, EGFR, HDAC inhibitors or antiandrogen therapy in 4, each. Treatments following MTB recommendations were initiated in 8 patients, 1 of which received a second recommended therapy after progression (antiandrogen therapy in 4, EGFR inhibitor in 2, a PDGFR, mTOR and PARP inhibitor in 1, each). A clinical benefit (CR = 1; Mixed Response = 1, SD = 3) was achieved in 5 patients, including a complete response in a patient with a metastatic adenocarcinoma of the parotid gland, treated with antiandrogen therapy. Conclusions: Precision oncology represents a feasible treatment strategy in patients with advanced SGT and shows early evidence of activity in a subset of patients. These results suggest further exploration of personalized therapy in these hard-to-treat tumors.

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Precision Genomic Practice in Oncology: Pharmacist Role and Experience in an Ambulatory Care Clinic

Pharmacy ◽

10.3390/pharmacy8010032 ◽

2020 ◽

Vol 8 (1) ◽

pp. 32 ◽

Cited By ~ 1

Author(s):

Farah Raheem ◽

Pauline Kim ◽

Meagan Grove ◽

Patrick J. Kiel

Keyword(s):

Clinical Trial Design ◽

Cost Effective ◽

Standard Of Care ◽

The United States ◽

Tumor Board ◽

Patient Specific ◽

Cancer Center ◽

Molecular Testing ◽

Precision Oncology ◽

Care Clinic

Recent advancements in molecular testing, the availability of cost-effective technology, and novel approaches to clinical trial design have facilitated the implementation of tumor genome sequencing into standard of care oncology practices. Current models of precision oncology practice include specialized clinics or consultation services based on a molecular tumor board (MTB) approach. MTBs are comprised of interprofessional teams of clinicians and scientists who evaluate tumors at the molecular level to guide patient-specific targeted therapy. The practice of precision oncology utilizing MTB-based models is an emerging approach, transforming precision genomics from a novel concept into clinical practice. This rapid shift in practice from cytotoxic therapy to targeted medicine poses challenges, yet brings exciting opportunities to clinical pharmacists practicing in hematology and oncology. Only a few precision genomics programs in the United States have a strong pharmacy presence with oncology pharmacists serving in leadership roles in research, interpreting genomic sequencing, making treatment recommendations, and facilitating off-label drug procurement. This article describes the experience of the precision medicine clinic at the Indiana University Health Simon Cancer Center, with emphasis on the role of the pharmacist in the precision oncology initiative.

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A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients

JAMIA Open ◽

10.1093/jamiaopen/ooz045 ◽

2019 ◽

Vol 2 (4) ◽

pp. 505-515 ◽

Cited By ~ 11

Author(s):

Michael J Pishvaian ◽

Edik M Blais ◽

R Joseph Bender ◽

Shruti Rao ◽

Simina M Boca ◽

...

Keyword(s):

Treatment Plan ◽

Critical Role ◽

Tumor Board ◽

Care Process ◽

Molecular Profile ◽

Molecular Testing ◽

Precision Oncology ◽

Therapy Options ◽

Scoring Model ◽

Molecular Tumor Board

Abstract Objectives Scalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings. Materials and Methods We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. Results The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. Discussion VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. Conclusion Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

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Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT2): Challenges and Opportunities in Conducting an MD Anderson Randomized Study in Precision Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3140 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3140-3140

Author(s):

Henry Hiep Vo ◽

Siqing Fu ◽

David S. Hong ◽

Daniel D. Karp ◽

Sarina Anne Anne Piha-Paul ◽

...

Keyword(s):

Clinical Trial ◽

Advanced Cancer ◽

Patient Preference ◽

Randomized Study ◽

Tumor Board ◽

Molecular Testing ◽

Precision Oncology ◽

Phase I Clinical Trials ◽

Metastatic Setting ◽

Patient Resources

3140 Background: Precision oncology is associated with favorable outcomes in selected patients with cancer. Our first IMPACT trial (IMPACT1) demonstrated that in sequential patients with advanced cancer who had tumor molecular testing and participated in phase I clinical trials, matched targeted therapy (MTT) was associated with superior rates of response, progression-free survival (PFS) and overall survival compared with those of patients who received non-MTT. Despite the statistical significance for these outcomes, the study was non-randomized. Recognizing that it would be difficult to randomize patients we nonetheless undertook IMPACT2, a phase 2 randomized study to determine whether patients treated on the basis of tumor genomic alterations have longer PFS compared to those whose treatment is not selected on the basis of molecular alteration analysis. Methods: Patients with metastatic cancer undergo a tumor biopsy and genomic profiling. Patients are presented at tumor board and are offered to be randomized between two arms: MTT or non-MTT, when criteria (biomarker present, available clinical trial, eligibility criteria met, insurance approval) are met. In April 2019, we amended the trial to include a “patient-preference” cohort for each arm. Patients who decline randomization are offered choice of arm (ClinicalTrials.gov: NCT02152254). The primary analysis will use both randomized and patient-preference cohorts based on a Bayesian hierarchical model that “borrows” from the patient-preference cohorts to the extent to which its PFS agrees with that in the randomization cohort. Results: The key barriers randomizing patients with actionable molecular alterations are patient-related (advanced, metastatic setting requiring immediate intervening therapy; decline in performance status, organ function; or death); drug-related (FDA-approved drug available; or unavailable MTT against key driver biomarker) or financial (no insurance coverage of MTT; lack of patient resources to participate in trials). As the study spans over a few years, some investigational agents that were considered non-MTT at the time of treatment assignment were later proven to be MTT (e.g., immunotherapeutic agents targeting high tumor mutational burden); and/or were approved by the FDA. Conclusions: Although randomized trials have been considered the gold standard in drug development, such studies in the advanced metastatic setting are complicated. The benefit of Precision Oncology has been exemplified in individual patients who were treated with biomarker-selected therapy. The adaptive design of IMPACT2 enables patient randomization despite the evolving tumor biomarkers and the plethora of investigational drugs. IMPACT2 provides insights for the development of cancer genome-based medicine. Outcomesfor randomized patients are awaited. Clinical trial information: NCT02152254.

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An Update on Molecular Diagnostics of Squamous and Salivary Gland Tumors of the Head and Neck

Archives of Pathology & Laboratory Medicine ◽

10.5858/2010-0655-rair.1 ◽

2011 ◽

Vol 135 (5) ◽

pp. 602-609 ◽

Cited By ~ 2

Author(s):

Jennifer L. Hunt

Keyword(s):

Salivary Gland ◽

Head And Neck ◽

Salivary Gland Tumors ◽

Molecular Testing ◽

Prognostic Information ◽

Papilloma Virus ◽

Molecular Alterations ◽

Current State ◽

Polymerase Chain

Abstract Context.—Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations. Objective.—To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck. Data Sources.—Published literature on squamous and salivary gland tumors of the head and neck. Conclusions.—The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets.

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Advancing precision medicine in clinical oncology: Whole exome paired tumor-normal DNA and RNA sequencing at a single-institution cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14006 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14006-e14006

Author(s):

Kevin McDonnell ◽

Amit Kulkarni ◽

Melissa Woodhouse ◽

Sidney A Smith ◽

Christine Hong ◽

...

Keyword(s):

Clinical Trial ◽

Precision Medicine ◽

Rna Sequencing ◽

Clinical Oncology ◽

Tumor Board ◽

Cancer Center ◽

Rna Seq ◽

Dna And Rna ◽

Whole Exome ◽

Board Review

e14006 Background: Next generation sequencing (NGS) allows for reliable, comprehensive and cost-effective identification of clinically actionable genetic and genomic alterations. The increasing adoption of NGS in clinical oncology has increased our ability to identify germline alterations predisposing to cancer development as well as somatic changes enabling prescription of individualized cancer treatment and enhanced clinical trial participation. Here we summarize implementation of an NGS-based precision medicine initiative involving oncology patients from a single institution cancer center. Methods: IRB-approved NGS matched whole exome (WES) germline and solid tumor somatic tumor sequencing together with somatic tumor RNA sequencing (RNA-seq) were performed using germline DNA extracted from peripheral blood lymphocytes and nucleic acids for tumor DNA and RNA sequencing obtained from formalin-fixed, paraffin-embedded tumor specimens. Results of sequencing and analyses were presented to a multi-disciplinary tumor board to establish recommendations for management of germline pathogenic variation, therapeutic drug matching, clinical trials eligibility and molecularly informed patient prognosis. Results: A total of 1,005 patients completed sequencing. Germline and somatic WES exceeded 100X and 250X mean target coverage, respectively; somatic RNA-seq exceeded 200 million mean reads. Patients ranged in age from 17 to 90 years. The study cohort comprised comparable numbers of female (51%) and male (49%) patients. Ethnicities and races were broadly represented with 22% of participants identifying as Hispanic, 14% as Asian, 4% as Black, 55% as Non-Hispanic White and 5% as other. The most common solid tumor histological classification was colorectal (18%), followed by breast (16%), prostate (7%), head and neck (7%), sarcoma (7%), ovarian (5%), melanoma (4%) and lung (3%). Bioinformatic analyses and precision medicine tumor board review established that 12% of patients harbored a germline pathogenic variant and 43% carried clinically actionable genetic/genomic alterations; a majority of patients met molecular requirements for participation in a clinical trial. Conclusions: This study confirms the feasibility and utility of clinical NGS and precision medicine tumor board review in clinical oncology to identify germline genetic pathology, deliver personalized cancer therapeutics, increase clinical trial enrollment and clarify diagnosis and prognosis.

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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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Targeted RNA Sequencing in the Routine Clinical Detection of Fusion Genes in Salivary Gland Tumors

Genes Chromosomes and Cancer ◽

10.1002/gcc.22979 ◽

2021 ◽

Author(s):

Justin Bubola ◽

Christina M. MacMillan ◽

Elizabeth G. Demicco ◽

Rose A. Chami ◽

Catherine T‐S Chung ◽

...

Keyword(s):

Salivary Gland ◽

Rna Sequencing ◽

Salivary Gland Tumors ◽

Fusion Genes ◽

Clinical Detection

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Recommendation on Advanced Molecular Testing in Hematolymphoid Malignancies in the Veterans Population

Blood ◽

10.1182/blood-2021-154362 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4983-4983

Author(s):

Jadee L Neff ◽

Claudio A. Mosse ◽

Jessica Wang-Rodriguez ◽

Sara Ahmed ◽

Michael Kelley

Keyword(s):

Cancer Care ◽

Clinical Pathways ◽

Hematologic Malignancy ◽

Tumor Board ◽

Molecular Testing ◽

Precision Oncology ◽

Veterans Health ◽

Health Administration ◽

Prognostic Information ◽

Acute Leukemias

Abstract The Veterans Health Administration is the largest integrated provider of cancer services in the nation, with approximately 50,000 new cancer cases diagnosed each year. The goal of the VA's National Oncology Program is to establish a System of Excellence in cancer care with the help of tools, resources, programs, and best practices across the enterprise to ensure every veteran, regardless of location, receives the same high level of cancer care and access to precision diagnostics. This is mediated through a variety of programs, including the National TeleOncology Service and the National Precision Oncology Program which includes standardized clinical pathways for molecular testing, a second opinion service on diagnostic consultations, test result interpretation and treatment recommendations, as well as a molecular oncology tumor board. The VA National Oncology Program and the Pathology and Laboratory Medicine Program offices have collaborated on a recommended guideline for advanced laboratory and molecular testing algorithm in hematologic diagnosis. We aim to offer best practice for all VA providers who must decide the type of ancillary tests at the time of initial clinical presentation in order to gain prognostic information and guide therapy. The recommendations include traditional laboratory tests, such as morphology, flow cytometry, and immunohistochemistry, as well as the use of fluorescent in situ hybridization (FISH), karyotype, polymerase chain reaction (PCR), and next generation sequencing (NGS). An overview of the draft algorithm for acute leukemias and chronic myeloid neoplasms is presented in Table 1; details will be discussed at the annual meeting. Conclusion: The joint effort from VA Oncology and Pathology presents advanced testing algorithms in a variety of hematolymphoid malignancies as a systematic approach to hematopathology diagnosis, classification, as well as offering prognostic and therapeutic information. The recommendations across VA Healthcare would ensure standardized care for all VA patients with hematologic malignancy to benefit from the latest advances in precision medicine. Figure 1 Figure 1. Disclosures Neff: Spring Discovery: Consultancy, Ended employment in the past 24 months; EUSA Pharma: Speakers Bureau; Enzyvant: Consultancy.

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