Joanna Roder

Biodesix

INTRODUCTION: The blood-based VeriStrat® proteomic test (VS) predicts patient response to therapy based on the intensities of eight different features in a mass spectrum obtained from MALDI-TOF analysis of human serum/plasma specimens. An interim analysis of the INSIGHT clinical trial (NCT03289780) demonstrated that VS labels, VS Good and VS Poor,...

Additive feature explanations using Shapley values have become popular for providing transparency into the relative importance of each feature to an individual prediction of a machine learning model. While Shapley values provide a unique additive feature attribution in cooperative game theory, the Shapley values that can be generated for even a sin...

Accurate and precise measurement of the relative protein content of blood-based samples using mass spectrometry is challenging due to the large number of circulating proteins and the dynamic range of their abundances. Traditional spectral processing methods often struggle with accurately detecting overlapping peaks that are observed in these sample...

Additive feature explanations using Shapley values have become popular for providing transparency into the relative importance of each feature to an individual prediction of a machine learning model. While Shapley values provide a unique additive feature attribution in cooperative game theory, the Shapley values that can be generated for even a sin...

Background Biomarkers of immune checkpoint inhibitor (ICI) efficacy can be used for patient selection. PD-L1 expression in tumor tissue is used to determine eligibility for combination or monotherapy in 1st line NSCLC. 1, 2 The liquid-biopsy mass spectrometry-based PIR test was developed to capture the role of patient biology on ICI outcomes. ³ The...

Background Modern machine learning (ML) models based on highly multivariate attribute sets (e.g. unbiased -omics data) can be very successful at generating clinically useful predictions, but at the price of less transparency in how individual attributes are used to make those predictions. In short, ML test algorithms tend to be ”black boxes”. Shapl...

Background Immunotherapy has become a key element in the arsenal of treatments for advanced non-small cell lung cancer (NSCLC). The anti-PD-L1 Response Test (ART), based on mass spectrometry of pretreatment serum, captures the effect of host biology on outcomes after atezolizumab (A) therapy. It stratified outcomes on A and was predictive of benefi...

Rationale: Prognostic tools for aiding in the treatment of hospitalized COVID-19 patients could help improve outcome by identifying patients at higher or lower risk of severe disease. The study objective was to develop models to stratify patients by risk of severe outcomes during COVID-19 hospitalization using readily available information at hosp...

Background Machine learning (ML) can be an effective tool to extract information from attribute-rich molecular datasets for the generation of molecular diagnostic tests. However, the way in which the resulting scores or classifications are produced from the input data may not be transparent. Algorithmic explainability or interpretability has become...

Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death. Guidelines recommend obtaining a screening ultrasound with or without alpha-fetoprotein (AFP) every 6 months in at-risk adults. AFP as a screening biomarker is plagued by low sensitivity/specificity, prompting interest in discovering alternatives. Mass spec...

e21135 Background: There is an unmet need for reliable biomarkers predictive of treatment outcome with immunotherapy in patients with non-small cell lung cancer (NSCLC). The aim of our study is to examine, in front-line patients, the potential utility of a proteomic signature, PIR (primary immune response), developed and validated in 2 nd line pati...

Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n?=?176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were...

Rationale Prognostic tools for aiding in the treatment of hospitalized COVID-19 patients could help improve outcome by identifying patients at higher or lower risk of severe disease. Objectives The study objective was to develop models to stratify patients by risk of severe outcomes during COVID-19 hospitalization using readily available informatio...

Introduction Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient’s disease. Novel approaches for comprehensively assessing biologic...

Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method...

Background: Understanding of biological processes associated with irAEs for patients treated with immune checkpoint inhibitors (ICI) is limited. We used serum-based, proteomic scores at baseline and after treatment initiation to explore mechanisms of irAEs for patients with non-small cell lung cancer (NSCLC) treated with ICI. Methods: Under an o...

p> Background: Understanding of biological processes associated with response and resistance to immune checkpoint inhibitors (ICI) with or without chemotherapy is limited. We used serum-based, proteomic scores at baseline and after treatment initiation to explore mechanisms of early resistance for patients with non-small cell lung cancer (NSCLC)...

Purpose: Pretreatment selection of non-small-cell lung cancer (NSCLC) patients who derive clinical benefit from treatment with immune checkpoint inhibitors would fulfill an unmet clinical need by reducing unnecessary toxicities from treatment and result in substantial health care savings. Patients and methods: In a retrospective study, mass spec...

The therapeutic landscape in metastatic melanoma has changed dramatically in the last decade, with the success of immune checkpoint inhibitors resulting in durable responses for a large number of patients. For patients with BRAF mutations, combinations of BRAF and MEK inhibitors demonstrated response rates and benefit comparable to those from immun...

Mass spectral data from multiple samples are suitable for a hypothesis-free development of clinically useful multivariate tests using modern machine learning techniques. However, the transition from discovery to adoption of proteomic tests has proved challenging. Slow adoption of these tests in clinical practice is, in part, related to insufficient...

Background: Early detection is critical to improve outcome in hepatocellular carcinoma (HCC). Despite inadequate sensitivity (SS) and specificity (SP), abdominal ultrasound and alpha-fetoprotein (AFP) are considered methods of choice for HCC surveillance. As less than 30% of patients (pts) are diagnosed early enough for resection or transplantation...

Background: Early detection is critical to improve outcome in hepatocellular carcinoma (HCC). Despite inadequate sensitivity (SS) and specificity (SP), abdominal ultrasound and alpha-fetoprotein (AFP) are considered methods of choice for HCC surveillance. As less than 30% of patients (pts) are diagnosed early enough for resection or transplantation...

Background Modern genomic and proteomic profiling methods produce large amounts of data from tissue and blood-based samples that are of potential utility for improving patient care. However, the design of precision medicine tests for unmet clinical needs from this information in the small cohorts available for test discovery remains a challenging t...

Background Modern molecular profiling techniques are yielding vast amounts of data from patient samples that could be utilized with machine learning methods to provide important biological insights and improvements in patient outcomes. Unsupervised methods have been successfully used to identify molecularly-defined disease subtypes. However, these...

Background Set enrichment methods are commonly used to analyze high-dimensional molecular data and gain biological insight into molecular or clinical phenotypes. One important category of analysis methods employs an enrichment score, which is created from ranked univariate correlations between phenotype and each molecular attribute. Estimates of th...

Background: The VeriStrat test provides accurate predictions of outcomes in all lines of therapy for patients with non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic role of VeriStrat in patients enrolled on the MARQUEE phase III trial of tivantinib plus erlotinib (T+E) versus placebo plus erlotinib (P+E) in previous...

Abstract Background The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility o...

A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pre-treatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multi-peptide vaccine and from patients...

OBJECTIVES VeriStrat® is a blood-based test that utilizes matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry to assign a binary classification of VeriStrat Good or VeriStrat Poor that is associated with treatment outcomes in cancer patients. A number of other studies have shown an association between VeriStrat...

A method was developed that allows the evaluation of complex biological processes from mass spectrometry of human serum samples. Applying gene set enrichment analysis ideas to matched protein expression data from a panel of 1129 proteins and deep MALDI® mass spectral data from a set of 49 human serum samples with lung cancer (n=45) or non-cancer (n...

P15 Novel IL-2/mAb complexes mediate potent anti-tumor immunity which is augmented with anti-PD-1 mAb therapy Mark Rubinstein1, Kristina Andrijauskaite1, Marzena Swiderska-syn1, Kristin Lind2, Agnes Choppin2, Marina K Roell2 1Medical University of South Carolina, Charleston, SC, USA; 2XOMA Corporation, Berkeley, CA, USA Correspondence: Mark Rubin...

Background: VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patien...

Background. The durability of antitumor responses observed in patients treated with antibodies blocking PD-1 supports a central role for these drugs in current melanoma therapy. However, not all patients achieve a durable response, so identification of biomarkers able to aid therapeutic decision making is needed. We have recently reported on a mass...

Introduction The durability of antitumor responses observed in patients treated with antibodies blocking PD-1 has provided a central role for these drugs in melanoma therapeutics. Identifying predictive biomarkers to aid therapeutic decision making is critical for realizing the full potential of these immunotherapies. We report on the development o...

Background: MET, the high-affinity receptor for hepatocyte growth factor, is frequently deregulated in human cancer and is thought to be involved in resistance to EGFR TKIs. Tivantinib is an orally administered MET inhibitor currently under development as a cancer therapy. The Phase 3 MARQUEE trial enrolled 1048 subjects with locally-advanced or me...

Improved screening protocols (SP) for patients at high risk of developing HCC could lead to improved patient outcome and possibly cure if detected early. The current SPs, ultrasound with the possible addition of alphafetoprotein (AFP) measurement, suffer from insufficient sensitivity and specificity, and less than 30% of patients are diagnosed earl...

Allogeneic hematopoietic stem cell transplantation (AHSCT) has been shown to provide longterm disease-free survival for otherwise fatal malignant or nonmalignant hematological disorders. Acute and chronic graft-versus-host disease (aGvHD and cGvHD) are a major complication following AHSCT and are associated with a substantial morbidity and mortalit...

While existing scoring systems provide physicians with methods of assessing prognosis of patients with MDS and help with the choice of appropriate treatment regimens, some patients defined as lower risk still have poor outcomes and tests which can refine current stratifications are of clinical interest. Serum samples, clinical and survival data wer...

Immunotherapies offer the promise of greatly improved outcomes, but often in only a minority of patients. It is of great importance to be able to identify which patients are likely to benefit from new immunotherapy advances. Developing tests to identify patients likely to benefit from immunotherapeutics presents special issues due to the lack of cl...

A mass-spectral method is disclosed for determining whether a breast cancer patient is likely to benefit from administration of a combination treatment in the form of a targeted anti-cancer drug in addition to an endocrine therapy drug. The method obtains a mass spectrum from a blood-based sample from the patient. The spectrum is subject to one or...

Background: We have previously reported that adjuvant treatment with a therapeutic vaccine targeting the mutated Ras oncogene product generated mutation-specific T cell responses associated with a trend toward improved survival in patients with post-operative residual disease (R1 resections) but no improvement in the overall population¹. Initial an...

An established multivariate serum protein test can be used to classify patients according to whether they are likely to have a good or poor outcome after treatment with EGFR tyrosine-kinase inhibitors. We assessed the predictive power of this test in the comparison of erlotinib and chemotherapy in patients with non-small-cell lung cancer. From Feb...

LBA8005 Background: Second-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. Improved PFS in E-treated pts is associated with EGFR sensitizing mutations. However, a test for optimizing treatment in pts with wild-type or unknown EGFR mutation status or squamous histology is of clin...

A method and system for validating machine performance of a mass spectrometer makes use of a machine qualification set of samples. The mass spectrometer operates on the machine qualification set of samples and obtains a set of performance evaluation mass spectra. The performance evaluation spectra are classified with respect to a classification ref...

LBA8005 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.

5575 Background: To address the unmet need for non-invasive tests to predict outcomes in OC we investigated the effect of the serum test, VeriStrat (VS), in independent cohorts of OC patients (pts) who were treated with platinum based chemotherapy following surgery. VS assigns “Good” (VSG) and “Poor” (VSP) classifications and has been shown to be p...

8044 Background: The eLung trial randomized chemotherapy naïve advanced NSCLC patients (pts) to 1 of 3 PD and concurrent CET followed by CET maintenance until progression, stratified by non-squamous (NSQ) and squamous (SQ) histology. Primary outcome results were reported (ESMO, Schwartzberg 2012). Pre-treatment tumor tissue and serum samples were p...

Purpose: In a multicenter randomized phase II trial of gemcitabine (arm A), erlotinib (arm B), and gemcitabine and erlotinib (arm C), similar progression-free survival (PFS) and overall survival (OS) were observed in all arms. We performed an exploratory, blinded, retrospective analysis of plasma or serum samples collected as part of the trial to...

A method and system for validating machine performance of a mass spectrometer makes use of a machine qualification set of samples. The mass spectrometer operates on the machine qualification set of samples and obtains a set of performance evaluation mass spectra. The performance evaluation spectra are classified with respect to a classification ref...

A method and system for predicting in advance of treatment whether a cancer patient is likely, or not likely, to obtain benefit from administration of a yeast-based immune response generating therapy, which may be yeast-based immunotherapy for mutated Ras-based cancer, alone or in combination with another anti-cancer therapy. The method uses mass s...

BACKGROUND: VeriStrat(®) is a serum proteomic test used to determine whether patients with advanced non-small cell lung cancer (NSCLC) who have already received chemotherapy are likely to have good or poor outcomes from treatment with gefitinib or erlotinib. The main objective of our retrospective study was to evaluate the role of VS as a marker of...

Background: The serum proteomic test VeriStrat has been shown to be able to classify advanced non-small cell lung cancer (NSCLC) patients for overall survival (OS) after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, VeriStrat was evaluated as a pre-treatment stratification tool in patients...