Comparative Analysis of Public Knowledge Bases for Precision Oncology

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.

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Effect of age and ethnicity on the tumor location, nuclear accumulation of p53 and clinical outcome in colorectal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.559 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 559-559

Author(s):

Ravi Kumar Paluri ◽

Michael Behring ◽

James Posey ◽

Upender Manne

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Prognostic Significance ◽

Tumor Location ◽

Genetic Alterations ◽

Proximal Colon ◽

Nuclear Accumulation ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Race Ethnicity

559 Background: The race/ethnicity based research in colorectal cancer (CRC) care continues to remain a high priority in developing personalized medicine, and to improve overall clinical outcomes. The role of p53 abnormalities in prognostication of CRC has been evaluated earlier. The incidence of nuclear accumulation of p53 (p53nac) and its prognostic relevance in African American (AA) and non-Hispanic white patients (pts) have been investigated, and it was suggested that the clinical consequences of p53nac in CRC varies with anatomic location of the tumor and the race of the patient. However, the clinical value of p53nac in relation to age, the tumor location, and race together is not assessed. Thus, we evaluated prognostic significance of p53nac by considering the tumor location, age, race/ethnicity and p53nacin CRCs in AA and white pts. Methods: Formalin fixed paraffin embedded CRC tissues from 242 AAs and 346 whites who underwent surgery were assessed for p53nac by routine immunohistochemistry (IHC). The routine (not antigen retrieval) IHC will identify the majority of genetic alterations ( > 95% missense point mutations) and have significant association with patient survival in CRC. The association between phenotypes, p53nac status, clinicopathologic features, and overall survival were evaluated using the x2 test and Cox regression analyses. Results: Approximately equivalent proportions of distal (52%) and proximal adenocarcinomas (48%) were positive for p53nac in AA pts. In contrast, distal CRC from whites more frequently were positive for p53nac than from the proximal colon (67% vs. 34%, x2 P = 0.006). p53nac was found to be a strong predictor of poor overall survival in young ( < 65 yr) white pts with proximal tumors [hazard ratio (HR) = 2.8, 95% Confidence Intervals (CI):1.2-6.4] but not in AAs (HR = 0.7, 95% CI: 0.41-1.21). Conclusions: The findings of this study suggest that p53nac is a strong prognostic marker for young white pts with proximal colon adenocarcinomas. Our findings are clinically relevant because several small-molecule inhibitors of mutant p53 are under investigation. These studies were supported by a pilot project grant by the UAB Comprehensive Cancer center.

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Development of a patient-oriented navigation model for lung cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18033 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18033-e18033

Author(s):

Christine Holmberg ◽

Kathrin Gödde ◽

Hella Fuegemann ◽

Jacqueline Mueller-Nordhorn ◽

Nina Rieckmann ◽

...

Keyword(s):

Lung Cancer ◽

Data Analysis ◽

Cancer Patients ◽

Secondary Data ◽

Secondary Data Analysis ◽

Tumor Board ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Optimal Care ◽

Lung Cancer Patients

e18033 Background: Patient navigation is seen to support and enable patient-oriented, optimal care both in palliative and in screening settings. However, the evidence remains inconclusive on what patient groups are best targeted by navigation and what may be improved by such a care model. Lung cancer patients are at particular risk for sub-optimal care because they face complex care trajectories due to severe and rapid disease progression and accompanying comorbidity. Methods: To develop a navigation model for lung cancer, we conducted a mixed-methods study to investigate who may be at risk of receiving sub-optimal care in the German health care setting. To capture the patient perspective a longitudinal qualitative component was included with patients (N = 20) assessed at three dtime points. In addition, a secondary data analysis of cancer registry data of a comprehensive cancer center was conducted and a repository of patient support offers gathered. Results of the study components were integrated to develop a patient-oriented navigation model. Results: Secondary data analysis showed that medical care functioned according to tumor board recommendations. Patient data revealed institutional barriers that conflict with individual needs and preferences. A lack of contact persons, information provision as well as bureaucratic difficulties were identified. Patients without a social network seem particularly in need for support. Identification of regional support offers shows that there are resources available to meet some of these needs. However, knowledge on such offers was not common among patients and caregivers. Navigators should provide practical support, give advice on social care issues and refer to existing support offers. Conclusions: Social networks crucial. Patients lack knowledge to use available resources. Navigation needs to be implemented within existing care structures to reach patients.

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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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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 closer look at next generation sequencing (NGS) in breast cancer: A retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13023 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13023-e13023

Author(s):

Bahar Laderian ◽

ANA CRISTINA Sandoval Leon ◽

Loulwa Alsharhan ◽

Dorraya El Ashry ◽

Marc E. Lippman

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Stage Iv ◽

Tumor Board ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Consecutive Series ◽

Subsequent Response ◽

Number Of Patients ◽

Progression Of Disease

e13023 Background: Targeted cancer therapy has been posited to revolutionize treatment paradigms in oncology. There are, a paucity of data regarding the use of NGS in breast cancer (BC). Herein we report our experience with NGS in a consecutive series of BC patients. Methods: Using an IRB approved protocol, we retrospectively identified patients with BC treated at the Sylvester Comprehensive Cancer Center (UMMSOM) who underwent NGS. Data were collected on demographics, tumor characteristics, genomic mutation profiles, and subsequent response to targeted therapy after 3 months. Results: Between January 2013 and April 2016, 101 BC patients underwent NGS. The mean age at diagnosis was 49. Ninety-one percent were stage IV, 6% were stage III, 2% were stage II, and 1% were stage I. Fifty percent had estrogen receptor (ER)+, HER2- tumors, 31% had triple-negative tumors, 13% had HER2+, ER+ tumors, and 6% had HER2+, ER- tumors. Ninety-six percent had at least one mutation, of which 78% had a targetable mutation. Sixteen patients received targeted therapy (TT). The average time between NGS and TT was 5 months ranging 0-22 months, during which seven patients received other systemic therapy. The most common reasons for not receiving TT were no actionable mutations (24%), not meeting criteria for an available clinical trial (14%), stable disease (SD) (13% ), lost to follow up (11%), physician decision (11%). Of the 16 patients who received TT, 7 patients had progression of disease, 3 died before response could be evaluated and presumably had no benefit, 2 discontinued TT due to side effects, 1 had SD, 1 had a partial response, and 2 were too early to be assessed. Conclusions: The majority of BC patients in our series had actionable mutations. However, TT was not offered to a significant number of patients for a multiplicity of reasons and the clinical benefit in those patients treated according to NGS findings was dismal. While NGS is surely a promising technology that should be utilized in combination with molecular tumor board, a host of reasons limit its usefulness at this time and its expense may well not justify its use outside of clinical trials.

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A virtual tumor board-driven synaptic knowledge network.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.8_suppl.89 ◽

2017 ◽

Vol 35 (8_suppl) ◽

pp. 89-89

Author(s):

Laurence J. Heifetz ◽

Ahrin B. Koppel ◽

Elaine Melissa Kaime ◽

Daphne Palmer ◽

Thomas John Semrad ◽

...

Keyword(s):

Clinical Trial ◽

Rural Areas ◽

Cancer Care ◽

Knowledge Network ◽

Tumor Board ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Hospital District ◽

Number Of Patients ◽

Tumor Boards

89 Background: In 2006, Tahoe Forest Hospital District—a 25-bed hospital in Truckee, CA, a mountain resort community one hour from regional and two hours from academic cancer services—designed and implemented an oncology program utilizing effective telecommunications with a committed academic partner, the UC Davis Comprehensive Cancer Center in Sacramento. Methods: The UC Davis Cancer Care Network was established with four remote cancer programs, enabling participation in daily virtual tumor boards, clinical trial enrollment, and quality assurance assistance. (Richard J. Bold, et. al., Virtual tumor boards: community-university collaboration to improve quality of care. Community Oncol 10(11):310-315, November 2013.; Laurence J. Heifetz, MD, et. al., A Model for Rural Oncology. J Oncol Pract, 7:168-171, May 2011.). An increasing number of patients were observed to in-migrate to Truckee from even more remote rural areas in the mountains. In 2013, the now Gene Upshaw Memorial Tahoe Forest Cancer Center developed four remote telemedicine clinics to allow even more physically distant patients the capacity to be followed locally. Results: Since we opened the remote telemedicine clinics, our Sullivan-Luallin patient satisfaction scores have averaged 4.82/5.00 for “overall satisfaction with the practice” and 4.90/5.00 for “recommending your provider to others”; our in-migration rate of patients from outside our primary catchment area increased from 43% to 52%: and clinical trial accrual rate averaged 10%. Conclusions: Reducing cancer health disparities is an ASCO mission. (cover, ASCO Connection, July 2014; Laurence J. Heifetz, MD. Country Docs with City Technology Can Address Rural Cancer Care Disparities. Oncol, 29(9):641-644, September 2015.). We believe this synaptic knowledge network effectively addresses that mission for rural communities. This model can be scaled in many configurations to address the inherent degradation of quality care as a function of physical distance to an academic center that rural doctors and patients deal with on a daily basis. The key is to insist on a cultural shift – Do something smart at lunch every day. Attend a virtual tumor board.

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Otolaryngology in the Time of Corona: Assessing Operative Impact and Risk During the COVID-19 Crisis

Otolaryngology ◽

10.1177/0194599820930214 ◽

2020 ◽

Vol 163 (2) ◽

pp. 307-315 ◽

Cited By ~ 2

Author(s):

Hannah N. Kuhar ◽

Ashley Heilingoetter ◽

Maxwell Bergman ◽

Noah Worobetz ◽

Tendy Chiang ◽

...

Keyword(s):

Best Practice ◽

Elective Surgery ◽

Neck Surgery ◽

Academic Medical Centers ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Policy Changes ◽

Data Set ◽

Medical Centers ◽

Academic Medical

Objective Limited research exists on the coronavirus disease 2019 (COVID-19) pandemic pertaining to otolaryngology–head and neck surgery (OHNS). The present study seeks to understand the response of OHNS workflows in the context of policy changes and to contribute to developing preparatory guidelines for perioperative management in OHNS. Study Design Retrospective cohort study. Setting Pediatric and general adult academic medical centers and a Comprehensive Cancer Center (CCC). Subjects and Methods OHNS cases from March 18 to April 8, 2020—the 3 weeks immediately following the Ohio state-mandated suspension of all elective surgery on March 18, 2020—were compared with a 2019 control data set. Results During this time, OHNS at the general adult and pediatric medical centers and CCC experienced 87.8%, 77.1%, and 32% decreases in surgical procedures as compared with 2019, respectively. Aerosol-generating procedures accounted for 86.8% of general adult cases, 92.4% of pediatric cases, and 62.0% of CCC cases. Preoperative COVID-19 testing occurred in 7.1% of general adult, 9% of pediatric, and 6.9% of CCC cases. The majority of procedures were tiers 3a and 3b per the Centers for Medicare & Medicaid Services. Aerosol-protective personal protective equipment (PPE) was worn in 28.6% of general adult, 90% of pediatric, and 15.5% of CCC cases. Conclusion For OHNS, the majority of essential surgical cases remained high-risk aerosol-generating procedures. Preoperative COVID-19 testing and intraoperative PPE usage were initially inconsistent; systemwide guidelines were developed rapidly but lagged behind recommendations of the OHNS department and its academy. OHNS best practice standards are needed for preoperative COVID-19 status screening and PPE usage as we begin national reopening.

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First Experiences with Alpelisib in Clinical Routine: Case Reports from a German Breast Center

Breast Care ◽

10.1159/000514794 ◽

2021 ◽

Vol 16 (2) ◽

pp. 129-134

Author(s):

Anna Hester ◽

Franziska Henze ◽

Christiane Travi ◽

Nadia Harbeck ◽

Rachel Wuerstlein

Keyword(s):

Side Effects ◽

Case Reports ◽

Growth Factor Receptor ◽

Supportive Therapy ◽

Tumor Board ◽

Control Treatment ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Breast Center ◽

Grade 3

Introduction: The phosphatidylinositol-3-kinase (PI3K) inhibitor alpelisib is the only approved agent for treating PIK3CA-mutated, hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Trials have reported hyperglycemia, diarrhea, and rash as the main grade 3 side effects. Methods: In a managed access program (ClinicalTrials.gov ID: NCT03706573; start: 06/2019), 8 HR+ HER2– ABC patients with a median 4.5 prior therapy lines were treated with alpelisib at the Breast Center of the Ludwig-Maximilian University (LMU) Hospital, Munich, based on the results of a new-generation sequencing (NGS) panel and PIK3CA mutation analysis by the Molecular Tumor Board of the Comprehensive Cancer Center, Munich. Results: Median therapy duration was 3.42 months for patients who discontinued and 3.95 months for those still on alpelisib (4 pts). Five had hyperglycemia (1 with grade 3) with fasting glucose levels of up to 450 mg/dL that required hospitalization and insulin therapy. Two experienced rash (grades 1 and 3) and 2 reported grade 3 diarrhea. Supportive therapy as well as interruption and/or dose reduction were necessary to control treatment-associated side effects. Conclusion: Patient education and a well-trained, interdisciplinary team including diabetologists, from the initiation of alpelisib treatment onwards, are essential to safely treat ABC patients with this new drug and to maintain their quality of life and ensure their survival.

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Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis

Cancers ◽

10.3390/cancers13051151 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1151

Author(s):

Rouven Hoefflin ◽

Adriana Lazarou ◽

Maria Elena Hess ◽

Meike Reiser ◽

Julius Wehrle ◽

...

Keyword(s):

Treatment Adherence ◽

Objective Response ◽

Tumor Board ◽

Treatment Recommendation ◽

Comprehensive Cancer Center ◽

Precision Oncology ◽

Single Center ◽

Clinical Routine ◽

Molecular Tumor Board ◽

Over Time

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.

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Framework for Implementing and Tracking A Molecular Tumor Board at an NCI‐Designated Comprehensive Cancer Center

The Oncologist ◽

10.1002/onco.13936 ◽

2021 ◽

Author(s):

Neha M. Jain ◽

Lauren Schmalz ◽

Christopher Cann ◽

M.B.A. Adara Holland ◽

D.O. Travis Osterman ◽

...

Keyword(s):

Tumor Board ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Molecular Tumor Board

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