Precision Oncology: Who, How, What, When, and When Not?

2017 ◽  
pp. 160-169 ◽  
Author(s):  
Lee Schwartzberg ◽  
Edward S. Kim ◽  
David Liu ◽  
Deborah Schrag
Keyword(s):  
Cost Effective ◽  
Molecular Profiling ◽  
Molecular Testing ◽  
Precision Oncology ◽  
High Quality ◽  
Tissue Samples ◽  
Development Of Resistance ◽  
Target Drug ◽  
Number Of Patients ◽  
Next Generation Sequencing Ngs

Precision oncology, defined as molecular profiling of tumors to identify targetable alterations, is rapidly developing and has entered the mainstream of clinical practice. Genomic testing involves many stakeholders working in a coordinated fashion to deliver high-quality tissue samples to high-quality laboratories, where appropriate next-generation sequencing (NGS) molecular analysis leads to actionable results. Clinicians should be familiar with the types of genomic variants reported by the laboratory and the technology used to determine the results, including limitations of current testing methodologies and reports. Interpretation of genomic results is best undertaken with multidisciplinary input to reduce uncertainty in clinical recommendations relating to a documented variant. Non–small cell lung cancer has emerged as a prototype disease where genomic data from at least several well-documented alterations with approved targeted agents are essential for optimal treatment from diagnosis of advanced disease. Due to the development of resistance to targeted therapies, resampling and retesting of tumors, including using liquid biopsy technology after clinical progression, may be important in making treatment decisions. The value of molecular profiling depends on avoiding both underutilization for well-documented variant target-drug pairs and overutilization of variant-drug therapy without proven benefit. As techniques evolve and become more cost effective, the use of molecular testing may prove to add more specificity and improve outcomes for a larger number of patients.

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 The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4324
Author(s):  
Karin P. S. Langenberg ◽  
Eleonora J. Looze ◽  
Jan J. Molenaar
Keyword(s):  
Precision Medicine ◽  
Pediatric Patients ◽  
Molecular Profiling ◽  
Immune Monitoring ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Childhood Malignancies ◽  
Combination Strategies ◽  
Number Of Patients ◽  
Definition Of

Over the last years, various precision medicine programs have been developed for pediatric patients with high-risk, relapsed, or refractory malignancies, selecting patients for targeted treatment through comprehensive molecular profiling. In this review, we describe characteristics of these initiatives, demonstrating the feasibility and potential of molecular-driven precision medicine. Actionable events are identified in a significant subset of patients, although comparing results is complicated due to the lack of a standardized definition of actionable alterations and the different molecular profiling strategies used. The first biomarker-driven trials for childhood cancer have been initiated, but until now the effect of precision medicine on clinical outcome has only been reported for a small number of patients, demonstrating clinical benefit in some. Future perspectives include the incorporation of novel approaches such as liquid biopsies and immune monitoring as well as innovative collaborative trial design including combination strategies, and the development of agents specifically targeting aberrations in childhood malignancies.

scholarly journals Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1098
Author(s):  
Yifan Wang ◽  
Anna Lakoma ◽  
George Zogopoulos
Keyword(s):  
Real World ◽  
Cancer Susceptibility ◽  
Molecular Profiling ◽  
Ductal Adenocarcinoma ◽  
Precision Oncology ◽  
Sequencing Technologies ◽  
Cancer Susceptibility Genes ◽  
Challenges And Opportunities ◽  
Next Generation Sequencing Ngs ◽  
Insight Into

The advent of next-generation sequencing (NGS) has provided unprecedented insight into the molecular complexity of pancreatic ductal adenocarcinoma (PDAC). This has led to the emergence of biomarker-driven treatment paradigms that challenge empiric treatment approaches. However, the growth of sequencing technologies is outpacing the development of the infrastructure required to implement precision oncology as routine clinical practice. Addressing these logistical barriers is imperative to maximize the clinical impact of molecular profiling initiatives. In this review, we examine the evolution of precision oncology in PDAC, spanning from germline testing for cancer susceptibility genes to multi-omic tumor profiling. Furthermore, we highlight real-world challenges to delivering precision oncology for PDAC, and propose strategies to improve the generation, interpretation, and clinical translation of molecular profiling data.

scholarly journals Molecular-based precision oncology clinical decision making augmented by artificial intelligence

2021 ◽  
Author(s):  
Jia Zeng ◽  
Md Abu Shufean
Keyword(s):  
Artificial Intelligence ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Molecular Data ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Current Application ◽  
Next Generation Sequencing Ngs ◽  
Molecular Sequencing

The rapid growth and decreasing cost of Next-generation sequencing (NGS) technologies have made it possible to conduct routine large panel genomic sequencing in many disease settings, especially in the oncology domain. Furthermore, it is now known that optimal disease management of patients depends on individualized cancer treatment guided by comprehensive molecular testing. However, translating results from molecular sequencing reports into actionable clinical insights remains a challenge to most clinicians. In this review, we discuss about some representative systems that leverage artificial intelligence (AI) to facilitate some processes of clinicians’ decision making based upon molecular data, focusing on their application in precision oncology. Some limitations and pitfalls of the current application of AI in clinical decision making are also discussed.

The Formability and Elongation of Aluminum Alloys AA5083 and AA3003 for Micro-Truss Sandwiches Manufacturing

2020 ◽  
Vol 38 (9A) ◽  
pp. 1396-1405
Author(s):  
Arwa F. Tawfeeq ◽  
Matthew R. Barnett
Keyword(s):  
Aluminum Alloy ◽  
Strain Rate ◽  
Cost Effective ◽  
Tensile Tests ◽  
Truss Structures ◽  
High Quality ◽  
Trade Off ◽  
Clad Layer ◽  
Higher Temperature ◽  
Different Shapes

The development in the manufacturing of micro-truss structures has demonstrated the effectiveness of brazing for assembling these sandwiches, which opens new opportunities for cost-effective and high-quality truss manufacturing. An evolving idea in micro-truss manufacturing is the possibility of forming these structures in different shapes with the aid of elevated temperature. This work investigates the formability and elongation of aluminum alloy sheets typically used for micro-truss manufacturing, namely AA5083 and AA3003. Tensile tests were performed at a temperature in the range of 25-500 ○C and strain rate in the range of 2x10-4 -10-2 s-1. The results showed that the clad layer in AA3003 exhibited an insignificant effect on the formability and elongation of AA3003. The formability of the two alloys was improved significantly with values of m as high as 0.4 and 0.13 for AA5083 and AA3003 at 500 °C. While the elongation of both AA5083 and AA3003 was improved at a higher temperature, the elongation of AA5083 was inversely related to strain rate. It was concluded that the higher the temperature is the better the formability and elongation of the two alloys but at the expense of work hardening. This suggests a trade-off situation between formability and strength. 

Cost Avoidance and Clinical Benefits Derived from a Pharmacy-Managed Anemia Program

2000 ◽  
Vol 35 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Robert A. Quercia ◽  
Ronald Abrahams ◽  
C. Michael White ◽  
John D'Avella ◽  
Mary Campbell
Keyword(s):  
Cost Savings ◽  
Cost Effective ◽  
Hemodialysis Patients ◽  
Cost Avoidance ◽  
Number Of Patients ◽  
Epoetin Alpha ◽  
Clinical Benefits ◽  
Unit Dose ◽  
One Year ◽  
Alpha Therapy

A pharmacy-managed anemia program included distribution and clinical components, with the goal of making epoetin alpha therapy for hemodialysis patients more cost-effective. The Pharmacy Department prepared epoetin alpha doses for patients in unit-dose syringes, utilizing and documenting vial overfill. Pharmacists dosed epoetin alpha and iron (oral and intravenous) per protocol for new and established patients. Baseline data were obtained in 1994, one year prior to implementation of the program, and were re-evaluated in 1995 and 1998. Cost avoidance from utilization of epoetin alpha vial overfill in 1995 and 1998 was $83,560 and $91,148 respectively. In 1995 and 1998, cost avoidance from pharmacy management of anemia was $191,159 and $203,985 respectively. The total cost avoidance from 1995 through 1998 was estimated at $1,018,638. The number of patients with hematocrits under 31% decreased from 32% in 1994 to 21% and 14% in 1995 and 1998 respectively. We conclude that a pharmacy-managed anemia program for hemodialysis patients results in significant cost savings and better achievement of target hematocrits.

scholarly journals 2D-3D integration of hexagonal boron nitride and a high-κ dielectric for ultrafast graphene-based electro-absorption modulators

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hitesh Agarwal ◽  
Bernat Terrés ◽  
Lorenzo Orsini ◽  
Alberto Montanaro ◽  
Vito Sorianello ◽  
...  
Keyword(s):  
Boron Nitride ◽  
Hafnium Oxide ◽  
High Speed ◽  
Hexagonal Boron Nitride ◽  
Temperature Stability ◽  
Cost Effective ◽  
Fold Increase ◽  
Building Blocks ◽  
High Quality ◽  
New Device

AbstractElectro-absorption (EA) waveguide-coupled modulators are essential building blocks for on-chip optical communications. Compared to state-of-the-art silicon (Si) devices, graphene-based EA modulators promise smaller footprints, larger temperature stability, cost-effective integration and high speeds. However, combining high speed and large modulation efficiencies in a single graphene-based device has remained elusive so far. In this work, we overcome this fundamental trade-off by demonstrating the 2D-3D dielectric integration in a high-quality encapsulated graphene device. We integrated hafnium oxide (HfO2) and two-dimensional hexagonal boron nitride (hBN) within the insulating section of a double-layer (DL) graphene EA modulator. This combination of materials allows for a high-quality modulator device with high performances: a ~39 GHz bandwidth (BW) with a three-fold increase in modulation efficiency compared to previously reported high-speed modulators. This 2D-3D dielectric integration paves the way to a plethora of electronic and opto-electronic devices with enhanced performance and stability, while expanding the freedom for new device designs.

scholarly journals Autologous Platelet-Rich Fibrin (PRF) as an Adjunct in the Management of Osteoradionecrosis and Medication-Related Osteonecrosis of Jaws. Case Series in A Single Centre

2021 ◽  
Vol 11 (8) ◽  
pp. 3365
Author(s):  
Benjie Law ◽  
Hui Yuh Soh ◽  
Syed Nabil ◽  
Rama Krsna Rajandram ◽  
Abd Jabar Nazimi ◽  
...  
Keyword(s):  
Case Series ◽  
Cost Effective ◽  
Control Group ◽  
Platelet Rich Fibrin ◽  
Tissue Healing ◽  
Number Of Patients ◽  
Short Period ◽  
Oral And Maxillofacial Region ◽  
Surgical Adjunct ◽  
Autologous Platelet

Osteoradionecrosis (ORN) of the jaws and medication-related osteonecrosis of the jaws (MRONJ) are uncommon but serious diseases affecting the oral and maxillofacial region with clinically similar appearance but distinct pathophysiology. Management of ORN and MRONJ is inherently challenging and the treatment outcomes are unpredictable. The use of autologous platelet concentrates (APCs) to promote hard and soft tissue healing is well described in the literature, and the efficacy of leucocyte and platelet-rich fibrin (L-PRF) has been well documented in a number of clinical studies. The aim of this study was to present our treatment strategy and the outcomes of incorporating L-PRF as a surgical adjunct in management of ORN and MRONJ in our centre. Methods: eight cases of ORN and MRONJ were treated with a combination of sequestrectomy and L-PRF as a surgical adjunct. Results: the overall success was 87.5%. Using L-PRF as an adjunct, we were able to predictably manage ORN and MRONJ without causing significant morbidity. Conclusion: our experience shows that L-PRF may be used as a valuable and cost-effective adjunct to surgical management of ORN and MRONJ. However, due to a limited number of patients, and a short period of review, the true effectiveness of the method is yet to be demonstrated in a longer follow-up study including a greater number of patients, besides the inclusion of a control group.

scholarly journals EPEN-45. NORMALIZING AND FACILITATING GENOMIC TESTING AT DIAGNOSIS IN PEDIATRIC EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Emily Owens Pickle ◽  
Ana Aguilar-Bonilla ◽  
Amy Smith
Keyword(s):  
Current Practice ◽  
Molecular Classification ◽  
Molecular Data ◽  
Molecular Profiling ◽  
Genomic Testing ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Pediatric Ependymoma ◽  
Need Support ◽  
Almost All

Abstract The current consensus is that diagnosis and treatment of ependymoma should be based upon clinical and molecular classification. As we move into this paradigm, it is important all ependymoma cases undergo tumor collection, preservation, and molecular profiling at diagnosis. Our group of 6 sites gathered data on a cohort of 72 ependymoma cases. Sites were asked to report known molecular findings; 60/68 eligible cases (88%) did not include genetic findings. The low number of cases with molecular findings was surprising and since cases were diagnosed from as early as 2004, we asked collaborators to share their current practice in profiling (e.g., how frequently; in what setting were ependymomas sent for testing) to try and better understand current practice at sites. Since the publication of ependymoma molecular data, sites with a neuro-oncology program report sending almost all newly diagnosed ependymomas for molecular testing, whereas current practices at sites without dedicated neuro-oncology were less consistent. Profiling in the setting of relapse was more frequently reported at all centers. The implementation of molecular testing at diagnosis may need support at sites without dedicated neuro-oncology. Lead investigators for upcoming ependymoma clinical trials will need to think carefully about the logistics of profiling at centers where this is not standard practice at diagnosis.

57 Precision neoantigen discovery using novel algorithms and expanded HLA-ligandome datasets

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A62-A62
Author(s):  
Dattatreya Mellacheruvu ◽  
Rachel Pyke ◽  
Charles Abbott ◽  
Nick Phillips ◽  
Sejal Desai ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cell Lines ◽  
Antigen Processing ◽  
Large Scale ◽  
Prediction Models ◽  
K562 Cells ◽  
Machine Learning Algorithms ◽  
Training Data ◽  
High Quality ◽  
Tissue Samples

BackgroundAccurately identified neoantigens can be effective therapeutic agents in both adjuvant and neoadjuvant settings. A key challenge for neoantigen discovery has been the availability of accurate prediction models for MHC peptide presentation. We have shown previously that our proprietary model based on (i) large-scale, in-house mono-allelic data, (ii) custom features that model antigen processing, and (iii) advanced machine learning algorithms has strong performance. We have extended upon our work by systematically integrating large quantities of high-quality, publicly available data, implementing new modelling algorithms, and rigorously testing our models. These extensions lead to substantial improvements in performance and generalizability. Our algorithm, named Systematic HLA Epitope Ranking Pan Algorithm (SHERPA™), is integrated into the ImmunoID NeXT Platform®, our immuno-genomics and transcriptomics platform specifically designed to enable the development of immunotherapies.MethodsIn-house immunopeptidomic data was generated using stably transfected HLA-null K562 cells lines that express a single HLA allele of interest, followed by immunoprecipitation using W6/32 antibody and LC-MS/MS. Public immunopeptidomics data was downloaded from repositories such as MassIVE and processed uniformly using in-house pipelines to generate peptide lists filtered at 1% false discovery rate. Other metrics (features) were either extracted from source data or generated internally by re-processing samples utilizing the ImmunoID NeXT Platform.ResultsWe have generated large-scale and high-quality immunopeptidomics data by using approximately 60 mono-allelic cell lines that unambiguously assign peptides to their presenting alleles to create our primary models. Briefly, our primary ‘binding’ algorithm models MHC-peptide binding using peptide and binding pockets while our primary ‘presentation’ model uses additional features to model antigen processing and presentation. Both primary models have significantly higher precision across all recall values in multiple test data sets, including mono-allelic cell lines and multi-allelic tissue samples. To further improve the performance of our model, we expanded the diversity of our training set using high-quality, publicly available mono-allelic immunopeptidomics data. Furthermore, multi-allelic data was integrated by resolving peptide-to-allele mappings using our primary models. We then trained a new model using the expanded training data and a new composite machine learning architecture. The resulting secondary model further improves performance and generalizability across several tissue samples.ConclusionsImproving technologies for neoantigen discovery is critical for many therapeutic applications, including personalized neoantigen vaccines, and neoantigen-based biomarkers for immunotherapies. Our new and improved algorithm (SHERPA) has significantly higher performance compared to a state-of-the-art public algorithm and furthers this objective.

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