Introduction

Despite recent dramatic advances and achievements, the need for new paradigm shifts in oncology which lead to better survival benefits and morbidity reduction is both strong and growing [1]. Comprehensive genomic profiling (CGP) and related tailored therapies, known as precision oncology, may provide cancer patients with such eagerly awaited new opportunities [2]. Moreover, CGP databases will benefit future clinical trials which target rare genomic alterations by providing data on distribution and allowing access to clinical trials. Two types of comprehensive genomic profiling are generally recognized, somatic and germline genomic sequencing. CGP testing can be used to identify different types of genomic variants, including significant variants that are actionable/druggable or variants of uncertain significance.

Japanese national health care system provides the population with universal health coverage. Enrollment in the system is mandatory for all Japanese and foreign residents. All tests—including CGP testing—are first examined for approval by The Pharmaceuticals and Medical Devices Agency (PMDA) and Japanese Ministry of Health, Labor, and Welfare (MHLW). The government then decides whether to provide insurance reimbursement. With reimbursement for CGP testing now approved, Japanese citizens have high expectations for this testing, despite the fact that actionable/druggable variants are only identified in 12.2% of samples [3].

Currently, there are no guidelines for healthcare professionals on how they should explain and communicate the details of CGP testing and its results to patients; how should the patient be involved regarding the decision to undergo CGP testing; or how should we deal with uncertainty in such a complex area [4]. While guidelines are being debated, little is known about the knowledge of cancer patients and their family members have about CGP, or how they feel toward it. Moreover, little is known about their values and preferences for subsequent treatment, their anxiety experiences after receiving CGP test results, or the psychological impact that these outcomes will have [5]. A very few studies have examined the responses of cancer patients recommended and underwent CGP testing with results demonstrating that patients are complaining of too much information and are misunderstanding that leads to unrealistic expectations [6–8]. Patient hopes that CGP testing would be effective was heightened with the promise of brand new genomically matched therapies only then to be challenged by no identified actionable/druggable variants, or by limitation of access to relevant genomically matched trials [6].

To our knowledge, no studies of patients undergoing CGP testing have reported longitudinal patient reported outcome data. The availability of such data would aid the understanding of patient uncertainty in the genomic testing process and the long-term psychosocial impact on patients. To remedy this, the Q-CAT (QOL for Cancer Genomics and Advanced Therapeutics among Patients and Their Family Members) study is being conducted as a psycho-social/ethical study with longitudinal data collection; at the time of consent of CGP testing (T0), at receipt of the result of CGP testing (T1), three months after receipt of the result of CGP testing (T2), six months after receipt of the result of CGP testing (T3). By following the patient longitudinally, we could evaluate both immediate and gradual reality in psychosocial influence of CGP testing toward patients and their family members.

Objective

The aims of this study are to identify the prevalence of psychological distress, quality of life (QOL), and satisfaction with CGP testing among patients and their family members by gathering electronic patient-reported outcomes (ePROs), and qualitative data.

Methods

Variable

The patient-reported measures to be collected are summarized in Fig 1.

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Fig 1. Schedule table of Q-CAT.

https://doi.org/10.1371/journal.pone.0283968.g001

Depression.

The nine items of PHQ-9 will be used to measure depression. Higher PHQ-9 scores indicate greater possibility of major depression (a PHQ-9 score ≥10, the cut off score, had a sensitivity of 88% and a specificity of 88% for major depression) [9].

Anxiety.

The seven items of General Anxiety Disorder-7 (GAD-7) will be used to measure anxiety. Higher scores indicate greater possibility of generalized anxiety disorder (a GAD-7 score ≥10 had a sensitivity of 89% and specificity of 82% for generalized anxiety disorder) [10].

QOL.

The 30 items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module Core 30 (EORTC QLQ−C30) will be used to measure QOL. Higher scores indicate a better level of global QOL scale and functional scales [11]. For symptom-oriented scales, higher scores indicate more severe symptoms.

Qualitative interviews.

All participants with a PHQ-9 score above cut-off, and a small convenience-selected subset of participants will be invited at baseline and at each follow-up time-point to participate in structured interviews based on SCID-IV [12].

Knowledge.

A 10-item study original questions will be used to assess knowledge on CGP testing; such as the purpose of CGP testing, availability of genomically matched therapeutic options, limitation of CGP testing, likely frequency of informative results, methodology of CGP testing. Scores will be summed from 0 to 10, with high scores indicating greater knowledge.

Satisfaction with oncologist.

The five items of the Patient Satisfaction Questionnaire (PSQ) will be used to measure satisfaction. Lower scores indicate higher satisfaction [13].

Quality of communication.

The 11 items on the quality of communication in the Health Information National Trends Survey (HINTS) will be used to measure quality of communication. High scores indicate greater communication [14].

Symptoms.

The nine items of the Edmonton Symptom Assessment System (ESAS) will be used to measure symptoms. High scores indicate greater morbidity [15].

Demographic data.

Age, gender, marital status, occupation and education level will be collected by patient report at baseline.

Disease details.

Data available from the patient’s electronic health record at the National Cancer Center Hospital, including primary site of the cancer, detailed TNM staging, cancer family history, Eastern Cooperative Oncology Group (ECOG) performance status, treatment and co-morbidities, will be collected at baseline. The results of CGP testing will be collected later, including gene alterations, whether they are actionable, whether they are druggable, whether the patients actually receive genomically matched therapy.

Social support.

The seven items of The Multidimensional Scale of Perceived Social Support (MSPSS) will be used to measure quality of communication. High scores indicate greater social support [16].

Data source and procedure

Patients will provide consent for the study to the Q-CAT staff at the same time they give consent to the CGP or within one week thereafter. Subjects will be asked to fill out an ePRO survey application software or hard copy at baseline (T0), 1 to 4 weeks after receiving the results of CGP testing (T1; approximately 2–3 months post baseline), 3 months (T2) after T1, and 6 months (T3) after T1. These timelines were chosen to understand the both short- and long-term impact of the test results: short-term impact was defined at the timing of treatment decision was made, and longer-term impact was defined at the timing of undergoing or close to completion of the genomically matched therapeutics, if they are taken. Additionally at each time point, selected patients will be interviewed used the Structured Clinical Interview for DSM-V-RV (SCID), which is a semi-structured interview for making the major DSM-5 diagnoses such as mood disorders, neurotic, stress-related and somatoform disorders, and behavioral syndromes associated with physiological disturbances and physical factors [17–19]. Patients to be interviewed include all patients with a Patient Health Questionnaire (PHQ-9) total score of > 10 and approximately 20–40 participants who score <10 as a convenience sample. The 4 week and lifetime prevalence rates of comorbid psychiatric disorders will be determined easier by this scale (Fig 2).

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Fig 2. Patient flow diagram.

https://doi.org/10.1371/journal.pone.0283968.g002

Discussion

This study focuses on QOL among those who undergo CGP testing, using ePROs.

CGP testing has the potential to embody “precision oncology”, and in turn lead to genome-related, tailored therapeutics in accordance with the genomic alteration of individual cancer patients. The true benefits of precision oncology will only be achieved if patients benefit from matched therapies through genomic alterations identified by CGP testing. Presently, however, despite dramatic growth in the expectations of both patients and family members, only a small portion of patients who undergo CGP testing—approximately 10%—obtain such benefit. To better understand and eventually bridge this gap between perception and reality, we have planned this study to give consideration to the feelings of patients and their families.

There is also the uncertain possibility that the germline variant will be discovered, which has subsequent implications for testing the blood relatives of patients. And so, physicians who ordered and obtained consent for CGP testing often face the challenge of communicating the uncertainty both to ensure informed consent for testing, and to diminish their unrealistic expectations.

Among cancer patients who have actually undergone CGP testing, very little is known about the psychological impact of CGP testing, their knowledge of and attitudes toward CGP testing, their preferences and values for subsequent treatment, and their experience of uncertainty after receiving the test results. Patients’ hopes to get benefit from CGP testing will be further enhanced by the realization of genomically matched therapies but challenged by no identified actionable/druggable variants or by limited access to genomically matched trials.

To our knowledge, no previous studies of patients underwent CGP testing have reported longitudinal patient reported outcome data which would allow an understanding of the experience of patient uncertainty across the CGP testing process and the long-term psychosocial impact on the patients. The Q-CAT study constitutes a psycho-social/ethical study to gather ePROs and qualitative data.

Study limitation includes an institutional bias, as this research is performed in a single institute; however, our institute is one of the largest high volume cancer centers in Japan with higher rates of genomically matched therapy options. Moreover, patients and/or family members may be lost to follow up (patient death, not coming to appointments, etc) given this research is collecting longitudinal ePROs data, thus results may be incomplete. Even though we didn’t limit cancer types, there might be a possibility of having selection bias of patients who have higher risk cancer, thus needing GCP data. These patients may have more underlying depression and anxiety than someone who has a lower risk cancer. This would speak to the generalizability of the collected data for all patients who have cancer no matter their risk. In order to approach this issue, analysis by cancer types might be helpful to understand the backgrounds. Some elements may become confounding factors that affect the mood during the interviews, such as symptoms and other life events during the clinical course.

This will be the first study in Japan to longitudinally collect QOL data via ePRO on the experience of cancer patients and their family members with CGP. The results obtained will be analyzed according to participant background and will be used in ongoing ethical discussions, including how to effectively obtain informed consent for genomic profiling, how to explain genomic results, and how to manage patient expectations.

The findings of Q-CAT study are essential to ensuring that as CGP testing gradually integrates into a part of routine medical care, ethical considerations are taken into account, and the needs of patients and their family members are adequately supported during and after receipt of results.

Given the scarcity of longitudinal QOL data obtained via ePRO, the results of our research might become important educational tools for medical staff in providing the results of CGP testing to cancer patients and their family members. Further, the results will surely form the fundamental basis of psychological support tools for cancer patients undergoing CGP testing.

Supporting information

Acknowledgments

The authors are grateful to our Q-CAT colleagues for the precise and sophisticated dedication they provide every day, especially Midori Shimaoka, Ayako Sato, Risa Ohtoshi, Ikumi Tanaka, Tomo Fujiwara and Yuko Okamura. Also, we wish to express our strongest gratitude to Tsuyoshi Kawamura for creating the wonderful questionnaire application for utilizing ePRO for Q-CAT on the iPad. Q-CAT could not be realized without the commitment of the doctors, nurses, and all medical members of the National Cancer Center Hospital Tokyo, Japan; and foremost and by far, of the patients and their families themselves.