Patient-Centered Engagement and Symptom/Toxicity Monitoring in the New Era of Tumor Next-Generation Sequencing and Immunotherapy: The OncoTool and OncoPRO Platforms

Patients with advanced cancer (stages III-IV) have unique treatment needs.¹ Disease progression and metastasis are common consequences of the failure of standard cancer treatment regimens, and many patients with advanced disease subsequently seek additional treatment options. With the increasing use of tumor next-generation sequencing (NGS) to identify tumor characteristic–matched treatment options, patients with cancer now have more opportunities to enroll in tumor NGS–aligned clinical trials or receive immune checkpoint inhibitor therapies, which are now considered first-line therapy for select patients. Using tumor NGS to guide cancer treatments could lead to improved outcomes for individual patients and reduce the treatment burden because treatment recommendations are tailored to patient characteristics on an individual basis. This assertion is currently being tested via large-scale clinical trials (eg, the National Cancer Institute Molecular Analysis for Therapy Choice [MATCH] trial).²

Despite the potential benefits of tumor NGS testing, it is not without risks and complications. First, tumor NGS testing has the potential to reveal an increased risk for hereditary cancers.³ Second, the results of tumor NGS testing do not always convey definitive treatment recommendations because the majority of patients who undergo tumor NGS testing will not initiate tumor NGS–aligned treatment.⁴ Third, adequate patient health literacy and numeracy are essential for understanding the complexities of tumor NGS testing (eg, germline testing vs somatic testing).^5,6 Low health literacy and/or numeracy can lead to confusion and suboptimal patient-provider communication. Therefore, there is a distinct need for patient-centered educational resources to enhance patients’ understanding of this complex approach to cancer care.^5,6 Finally, treatments for advanced cancer (both established and experimental) can be highly toxic and, in some cases, life-threatening, as in the case of patients enrolling in clinical trials or initiating immune checkpoint inhibitor treatments and newer molecularly targeted therapies.^7–9 Similarly, the drive to evaluate the safety and efficacy of novel regimens in clinical trials presents an added burden to patients and providers regarding the monitoring and prompt reporting of adverse events. Patients may, therefore, benefit from education about potential treatment toxicities and ongoing monitoring so that they can recognize and report toxicities early. Providers need tools to routinely and remotely monitor patient-reported toxicities that might occur between clinic visits and to integrate patient-reported toxicities and symptoms into clinical care for prompt intervention.

To address these unmet needs, our team has developed OncoTool and OncoPRO, 2 web-based, patient-centered platforms designed to 1) provide patient-centered education about the goals of advanced cancer care, tumor NGS testing, advanced cancer treatments (eg, immunotherapies), clinical trials, and treatment-associated toxicities; 2) conduct remote and routine monitoring of patient-reported outcomes (PROs), including symptoms and toxicities; 3) link PRO action-able data and toxicities with clinical care via patients’ electronic health records (EHRs); and 4) and facilitate patient-provider communication and prompt management of severe symptoms and toxicities.

Patient Engagement in Advanced Cancer Care

OncoTool is a patient-centered, web-based educational resource tailored at the group level for people with advanced cancer(Figs. 1 and 2). OncoTool aims to foster more accurate expectations about the potential benefits of tumor NGS testing. Through the OncoTool platform, patients are provided with easy-to-comprehend descriptions of potential treatment options (eg, chemotherapy, radiation therapy, and immunotherapy) and associated toxicities as well as evidence-based strategies for managing symptoms and toxicities and improving stress management (eg, coping skills) and health-related quality of life Furthermore, because many patients with advanced cancer explore clinical trial opportunities, OncoTool includes detailed information about clinical trials in general, including what they represent, the phases and goals of clinical trials, and the pros and cons of participating in a clinical trial, to assist with decision-making self-efficacy. Finally, because patients with advanced cancer may face numerous treatment decisions, we include an interactive decision-making questionnaire to help patients to explore different decision-making styles (eg, patient-based, physician-based, or shared), and we provide suggestions for ways to communicate a patient’s preferred decision-making style to providers (Fig. 3). The content of OncoTool was chosen on the basis of a combination of theory (eg, a biopsychosocial model,¹⁰ theories of stress and coping,^11,12 and models of chronic care and self-management¹³) and qualitative interviews with key stakeholders (eg, oncologists, nurses, and genetic counselors) and patients. The content is adaptable, such that researchers or providers can adjust the educational content to meet the specific needs of a study or treatment regimen (eg, immunotherapy or tumor NGS testing) or disease (eg, breast cancer). Patient usage and click-level data are captured through the OncoTool platform so that researchers can assess patterns of use.

Figure 1.

Home screen of the OncoTool platform (https://oncotool.brightoutcome.com/#/home).

Figure 2.

Static content on the OncoTool platform (https://oncotool.brightoutcome.com/#/home).

Figure 3.

Interactive decision-making style questionnaire on the OncoTool platform (https://oncotool.brightoutcome.com/#/home).

Symptom and Toxicity Monitoring

OncoTool is fully integrated into OncoPRO, which provides capabilities for remote, routine, and tailored assessments of PROs (Fig. 4). The OncoPRO platform is programmed to send reminders to patients when it is time to complete an assessment, and upon completion, patients are provided with immediate feedback on their reported symptoms and toxicities. This feedback is linked with clinical care via alerts that are generated for patients who report symptoms and/or toxicities exceeding predetermined clinical thresholds. Alerts are communicated to patients’ providers in real time through the EHR in-basket system, so that providers are kept apprised of individual patients’ toxicities on a regular basis (eg, daily or weekly) and can take early action to address and ideally reverse toxicities. EHR in-basket messages include a read receipt, which allows researchers to track if and when a provider opens an alert message. If a message is not opened, researchers can resend the message or contact the provider via other methods (eg, telephone). In ongoing trials of the OncoTool and OncoPRO platforms, the system of linking symptom/toxicity assessments with patients’ EHRs is being managed externally, with research staff manually sending EPIC in-basket messages to providers as appropriate. Notably, the OncoTool and OncoPRO platforms are capable of being integrated into EHRs (eg, EPIC), and this provides opportunities for streamlining the EHR-integration procedures in the future. Finally, the OncoPRO and OncoTool platforms each contain an administrator and provider–facing dashboard that allows researchers and providers to track patients’ symptoms and toxicities remotely (Fig. 5).

Figure 4.

Flow of information during remote monitoring of PROs via the OncoTool and OncoPRO platforms and integration of PRO data into EHRs and clinical care. EHR indicates electronic health record; PRO, patient-reported outcome.

Figure 5.

Provider-facing dashboard on the OncoTool platform showing reports of patient-reported symptoms (https://oncotool.brightoutcome.com/#/home).

In our current trials using OncoTool and OncoPRO, we have programmed the platforms to accommodate select measures from the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests¹⁴ and the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).¹⁵ PROMIS computer adaptive tests allow for brief and accurate computerized administration of calibrated PROMIS item banks. With item-response theory, item administration is tailored to individuals on the basis of responses to previous items. This results in a minimal number of items administered (median, 5 items per domain) with excellent measurement reliability. PRO-CTCAE is a library of 124 items assessing 78 symptomatic adverse events from a patient’s perspective(eg, fatigue and nausea) that collectively form 14 symptom clusters that can be experienced in oncology clinical trials (eg, gastrointestinal, respiratory, neurological, and pain). PRO-CTCAE is designed to alert providers to potential concerns related to the frequency, intensity, or interference of a symptom/ toxicity, each assessed with a single item. Similar to past research¹⁶ and in an effort to reduce the burden of repeated assessments and optimize symptom and toxicity management, we identified a core set of 15 items to be administered to patients, regardless of disease site and treatment regimen, as guided by key stakeholders (including oncologists) and information derived from the literature. We then built upon these core items and tailored the assessment battery to individual patients. Several oncologists collaboratively created an algorithm to identify which additional PRO-CTCAE items should be administered on the basis of a patient’s disease site (eg, breast or prostate), treatment regimen (eg, chemotherapy or immunotherapy), and the expected toxicities associated with those parameters. The algorithm resulted in 15 core PRO-CTCAE items and a range of additional items that can be added to the core PRO-CTCAE according to the disease site and type of treatment (eg, chemotherapy or immunotherapy).

The measures and algorithms within the OncoTool and OncoPRO platforms allow researchers to make comparisons across diseases and treatments and can be adapted to meet the particular needs of a study or patient population, such as patients undergoing advanced treatment with immune checkpoint inhibitors or oral anticancer medications (eg, tyrosine kinase inhibitors and endocrine therapies).

Ongoing/Upcoming Trials to Establish Feasibility

OncoTool and OncoPRO are currently being tested across several studies and treatment conditions. To date, we have initiated 4 trials incorporating the OncoTool and OncoPRO platforms: 1 trial including patients with advanced cancers who are undergoing tumor NGS testing and 3 other trials in which we will adapt the platform for patients initiating treatment with immune checkpoint inhibitors and tyrosine kinase inhibitors and for patients with breast cancer. From these ongoing trials, we have learned that it is of paramount importance to engage key stakeholders, including providers, from the initiation of research activities to ensure that appropriate and relevant patient education content is being provided and that platforms such as OncoTool and OncoPRO are seamlessly integrated into the established clinic flow. The introduction of a new feature or protocol within EHRs may affect clinic flow, and researchers can be mindful to minimize disruptions to the clinic workflow. Early provider investment and engagement can facilitate this balance. In addition, the benefits of using the OncoTool and OncoPRO platforms may ultimately reduce the burden on the health care system. For example, early toxicity monitoring and intervention could lead to fewer emergency department visits and/or hospitalizations, although this has not yet been tested. Findings from qualitative interviews with key stakeholders and results of ongoing trials with OncoTool and OncoPRO are forthcoming and will inform the potential reach and scalability of these platforms for oncology patients.

Author Bios

Betina Yanez, PhD

Betina Yanez is an assistant professor in the Northwestern University Feinberg School of Medicine Department of Medical Social Sciences and is a member of the Robert H. Lurie Comprehensive Cancer Center. She is codirector of the Biopsychosocial Mechanisms and Health Outcomes Program in the Department of Medical Social Sciences. Her work bridges behavioral medicine, health equity, and precision medicine to research improvements in the patient-centered and clinical outcomes of individuals diagnosed with cancer.

Laura C. Bouchard, PhD

Laura C. Bouchard is a postdoctoral fellow in the National Cancer Institute–funded T32 Behavioral and Psychosocial Research Training Program in Cancer Prevention and Control in the Department of Medical Social Sciences at the Northwestern University Feinberg School of Medicine. Her research focuses on the development and testing of behavioral interventions to improve quality of life for diverse patients with cancer.

David Cella, PhD

David Cella is the Ralph Seal Paffenbarger Professor and chairman of the Department of Medical Social Sciences at the Northwestern University Feinberg School of Medicine and is the associate director of cancer prevention and control at the Robert H. Lurie Comprehensive Cancer Center. Dr. Cella has received several grants and contracts to study questions regarding quality-of-life measurement in clinical trials, the efficacy of psychosocial interventions in oncology, and medical outcomes research. A theme of his work has been ensuring that the voice of the patient is reflected in clinical care and research.

Jeffrey A. Sosman, MD

Jeffrey A. Sosman is a professor of medicine in the Division of Hematology and Oncology at the Northwestern University Feinberg School of Medicine and is coleader of the Translational Research in Solid Tumors Program and director of the Melanoma Program at the Robert H. Lurie Comprehensive Cancer Center. He also serves as the director for faculty development at the Robert H. Lurie Comprehensive Cancer Center. Dr. Sosman is a melanoma expert and active clinical investigator well recognized in the field of immune-based therapy for solid tumors, including melanoma.

Sheetal M. Kircher, MD

Sheetal M. Kircher is an assistant professor of medicine in the Division of Hematology and Oncology at the Northwestern University Feinberg School of Medicine and is the medical director of the Cancer Survivorship Institute at the Robert H. Lurie Comprehensive Cancer Center. Dr. Kircher specializes in gastrointestinal malignancies, and her research interests are related to health care delivery throughout the cancer continuum.

Nisha A. Mohindra, MD

Nisha A Mohindra is an assistant professor of medicine in the Division of Hematology and Oncology at the Northwestern University Feinberg School of Medicine and is the director of operations for the Multidisciplinary Thoracic Oncology Clinic of the Robert H. Lurie Comprehensive Cancer Center. She specializes in thoracic malignancies, and her research interests are related to novel therapeutics for lung cancer and the management of immune-related toxicity.

Massimo Cristofanilli, MD

Massimo Cristofanilli is a professor of medicine in the Division of Hematology and Oncology at the Northwestern University Feinberg School of Medicine and is the associate director for translational research at the Robert H. Lurie Comprehensive Cancer Center. He is also the associate director for precision medicine and is the director of the Northwestern OncoSET (Sequence, Evaluate, Treat) Program. Dr. Cristofanilli is a breast cancer expert, and his research focuses on advancing a patient-centered, biology-driven model of cancer care that combines sophisticated tissue- and blood-based molecular diagnostic technologies and innovative treatments.

Frank J. Penedo, PhD

Frank J. Penedo the Sylvester Professor of Psychology and Medicine at the University of Miami. He serves as the associate director of cancer survivorship and translational behavioral sciences and as the director of the Cancer Survivorship Program at the Sylvester Comprehensive Cancer Center. Dr. Penedo’s research focuses on evaluating the role of psychosocial, sociocultural, and biobehavioral processes in adjustment, health-related quality of life, and health outcomes in chronic disease populations with a major emphasis on cancer control and survivorship.