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

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 32 ◽  
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.

scholarly journals Comparative Analysis of Public Knowledge Bases for Precision Oncology

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Steffen Pallarz ◽  
Manuela Benary ◽  
Mario Lamping ◽  
Damian Rieke ◽  
Johannes Starlinger ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Knowledge Bases ◽  
Tumor Board ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Accurate Information ◽  
Precision Oncology ◽  
Cancer Genes ◽  
Qualitative Comparison ◽  
Data Set

PURPOSE Precision oncology depends on the availability of up-to-date, comprehensive, and accurate information about associations between genetic variants and therapeutic options. Recently, a number of knowledge bases (KBs) have been developed that gather such information on the basis of expert curation of the scientific literature. We performed a quantitative and qualitative comparison of Clinical Interpretations of Variants in Cancer, OncoKB, Cancer Gene Census, Database of Curated Mutations, CGI Biomarkers (the cancer genome interpreter biomarker database), Tumor Alterations Relevant for Genomics-Driven Therapy, and the Precision Medicine Knowledge Base. METHODS We downloaded each KB and restructured their content to describe variants, genes, drugs, and gene-drug associations in a common format. We normalized gene names to Entrez Gene IDs and drug names to ChEMBL and DrugBank IDs. For the analysis of clinically relevant gene-drug associations, we obtained lists of genes affected by genetic alterations and putative drug therapies for 113 patients with cancer whose cases were presented at the Molecular Tumor Board (MTB) of the Charité Comprehensive Cancer Center. RESULTS Our analysis revealed that the KBs are largely overlapping but also that each source harbors a notable amount of unique information. Although some KBs cover more genes, others contain more data about gene-drug associations. Retrospective comparisons with findings of the Charitè MTB at the gene level showed that use of multiple KBs may considerably improve retrieval results. The relative importance of a KB in terms of cancer genes was assessed in more detail by logistic regression, which revealed that all but one source had a notable impact on result quality. We confirmed these findings using a second data set obtained from an independent MTB. CONCLUSION To date, none of the existing publicly available KBs on gene-drug associations in precision oncology fully subsumes the others, but all of them exhibit specific strengths and weaknesses. Consideration of multiple KBs, therefore, is essential to obtain comprehensive results.

Factors influencing treatment of inflammatory breast cancer in the United States.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 118-118
Author(s):  
Heather Y. Lin ◽  
Gildy Babiera ◽  
Isabelle Bedrosian ◽  
Simona Flora Shaitelman ◽  
Henry Mark Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Standard Of Care ◽  
High Volume ◽  
The United States ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Cancer Data ◽  
Number Of Patients ◽  
Facility Level

118 Background: Guidelines for treating inflammatory breast cancer (IBC) using trimodality (chemotherapy, surgery and radiation) therapy (TT) remain largely unchanged since 2000. However, many such patients did not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT utilization. Methods: Using the National Cancer Data Base (NCDB), patients who underwent surgical treatment of locoregional IBC from 2003-2011 were identified. We correlated patient, tumor, and treatment data with TT. An observed to expected (O/E) ratio of number of patients treated with TT was calculated for each hospital by adjusting for PL factors. Hierarchical mixed effects models were used to assess the proportion of variation in the use of TT attributable to PL and FL factors, respectively. Results: Among 5,537 patients who met the study criteria, the use of TT fluctuated annually (67.3%-75.7%) and was less likely for patients who were over 70, had a lower income or had an N0 tumor (all p < 0.05). By insurance type, TT use was lowest among Medicare patients. Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%) were identified as significantly low and high outliers for the use of TT (p < 0.05), respectively. While comprehensive cancer centers represented the majority of high outliers, the TT use by facility type overall was not significantly different demonstrating variability within comprehensive cancer center practice. The percentage of the total variance in the use of TT attributable to facility (11%) was almost triple the variance attributable to the measured PL factors (3.4%). Conclusions: The use of standard of care TT varied widely across facilities with some high volume centers clearly underutilizing TT. To improve clinical outcomes for this rare and aggressive malignancy, it is critical to identify facility level factors impacting the use of TT to ensure the guideline adherence of IBC treatment.

Quality assessment of tumor boards across an academic and community cancer network.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 122-122
Author(s):  
Daniel Aaron Roberts ◽  
Robert Stuver ◽  
Igor Schillevoort ◽  
Jessica A. Zerillo
Keyword(s):  
Quality Assessment ◽  
Response Rate ◽  
Gynecologic Oncology ◽  
The United States ◽  
Tumor Board ◽  
Cancer Center ◽  
Measurement Tool ◽  
Tumor Boards ◽  
Assessment Survey ◽  
Cancer Network

122 Background: Cancer tumor boards (TB), or multidisciplinary team meetings are standard of care in oncology care worldwide. Specific components are described by the American College of Surgeon's Commission on Cancer Program. Most data show consistent improvement in outcomes including a change in diagnostic findings, treatment, and possibly improved survival with TBs. Methods: We adapted a performance assessment tool based on a validated survey implemented in the United Kingdom. An initial survey aimed at assessing tumor board structure and design was sent to 21 TB leaders, and subsequently a tumor board quality assessment survey was sent to 175 participants throughout an academic and community network. The quality assessment survey required participants to identify an answer on a 5-point Likert scale in the categories of "very poor, poor, average, good, and very good". Results: TB leaders representing 16 of 21 (response rate 76%) TBs responded to the structure/design survey. Twelve TBs were from the academic center and included diseases such as Gynecologic Oncology, Cutaneous Oncology, Genitourinary Oncology, and Sarcoma, while four were from community sites. TB leaders indicated that 55% of TBs did not receive CME credit and 60% did not document their recommendations. One hundred eleven TB participants of 175 (response rate 63%) responded to the quality assessment survey. Participants identified the following strengths: 1) all relevant subspecialties present for meetings, 2) respectful teamwork and culture, and 3) operating on an organized agenda. Areas for improvement included: 1) inconsistent tumor board recommendation documentation and 2) post-meeting coordination of care. Results were reviewed with network and cancer center leadership as well as with the Cancer Committee. Conclusions: We assessed our own tumor boards across our cancer network by utilizing an adapted version of a validated TB performance measurement tool for the first time in the United States. Through this assessment we identified key areas for improvement including the need for obtaining CME credit for TB attendance, and developed a policy, process, and template for documenting TB recommendations in an easily accessible centralized location.

Precision oncology for the treatment of salivary gland tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17577-e17577
Author(s):  
Damian Tobias Rieke ◽  
Mario Lamping ◽  
Serge Leyvraz ◽  
Theo Daniel Kim ◽  
Lutz Brinkmann ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Rna Sequencing ◽  
Salivary Gland Tumors ◽  
Tumor Board ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Rna Seq ◽  
Mixed Response ◽  
Antiandrogen Therapy ◽  
Panel Sequencing

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.

scholarly journals Multiobjective Optimization Identifies Cancer-Selective Combination Therapies

2020 ◽  
Author(s):  
Otto I. Pulkkinen ◽  
Prson Gautam ◽  
Ville Mustonen ◽  
Tero Aittokallio
Keyword(s):  
Multiobjective Optimization ◽  
Cost Effective ◽  
Selective Inhibition ◽  
Search Space ◽  
Optimization Method ◽  
Drug Combinations ◽  
Braf V600e ◽  
Patient Specific ◽  
Precision Oncology ◽  
Massive Number

ABSTRACTCombinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments.

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

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.

scholarly journals Multiobjective optimization identifies cancer-selective combination therapies

2020 ◽  
Vol 16 (12) ◽  
pp. e1008538
Author(s):  
Otto I. Pulkkinen ◽  
Prson Gautam ◽  
Ville Mustonen ◽  
Tero Aittokallio
Keyword(s):  
Multiobjective Optimization ◽  
Cost Effective ◽  
Selective Inhibition ◽  
Search Space ◽  
Optimization Method ◽  
Drug Combinations ◽  
Braf V600e ◽  
Patient Specific ◽  
Precision Oncology ◽  
Massive Number

Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments.

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

JAMIA Open ◽  
2019 ◽  
Vol 2 (4) ◽  
pp. 505-515 ◽  
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.

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

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.

scholarly journals Hepatitis C Variability, Patterns of Resistance, and Impact on Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Cristina Simona Strahotin ◽  
Michael Babich
Keyword(s):  
Hepatitis C ◽  
Antiviral Agents ◽  
Cost Effective ◽  
Standard Of Care ◽  
The United States ◽  
Resistance Mechanisms ◽  
Cost Effective Method ◽  
New Treatments ◽  
Cure Rates ◽  
Effective Treatments

Hepatitis C (HCV), a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, is the most common indication for liver transplantation in the United States. Although annual incidence of infection has declined since the 1980s, aging of the currently infected population is expected to result in an increase in HCV burden. HCV is prone to develop resistance to antiviral drugs, and despite considerable efforts to understand the virus for effective treatments, our knowledge remains incomplete. This paper reviews HCV resistance mechanisms, the traditional treatment with and the new standard of care for hepatitis C treatment. Although these new treatments remain PEG-IFN-α- and ribavirin-based, they add one of the newly FDA approved direct antiviral agents, telaprevir or boceprevir. This new “triple therapy” has resulted in greater viral cure rates, although treatment failure remains a possibility. The future may belong to nucleoside/nucleotide analogues, non-nucleoside RNA-dependent RNA polymerase inhibitors, or cyclophilin inhibitors, and the treatment of HCV may ultimately parallel that of HIV. However, research should focus not only on effective treatments, but also on the development of a HCV vaccine, as this may prove to be the most cost-effective method of eradicating this disease.

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