Original Research

Overcoming barriers to clinical trial enrollment in patients with bone and soft tissue sarcoma: a paradigm for an increasingly heterogeneous cancer population

The Sarcoma Journal. 2019 December;3(4):8-20

Ari Rosenberg, MD

Sheetal Kircher, MD

Elizabeth A. Hahn, MA

Karl Bilimoria, MD, MS

Jeffrey D. Wayne, MD

Alfred Rademaker, PhD

Al Benson III, MD

John Hayes, MD

Terrance Peabody, MD

Samer Attar, MD

Mark Agulnik, MD

Abstract

Background: Clinical trials remain a cornerstone in the development of new cancer therapies. Patients diagnosed with bone and soft tissue sarcoma typically have comparatively low rates of trial participation, which may contribute to lack of progress. This cross-sectional survey study was designed to characterize patient attitudes, knowledge, perceived ability (ie, self-efficacy), receptivity, and willingness to participate in trials. As well, we explored perceptions related to tumor molecular profiling (TMP).

Methods: Patients with sarcoma who were evaluated at Northwestern Medicine (NM) between 2012 and 2017 were identified through the Enterprise Data Warehouse (NMEDW). A link to an online self-administered survey was emailed to patients. Data were analyzed using Spearman correlations and the Mann-Whitney test.

Results: Surveys were e-mailed to 750 patients, of which 20 emails bounced back and 309 were opened; 283 patients completed at least a portion of the survey and this population was used in this analysis (37.7% of total and 91.6% of opened). Of the responding patients, median age was 56 years, 59.4% were female, and 26.8% reported metastatic disease. Greater knowledge of trials correlated with increased positive attitudes toward trial participation (r=0.5; P<0.001) and positive attitudes correlated with greater trial perceived ability (r=0.4; P<0.02). Patients with metastatic disease had more positive attitudes compared with patients with non-metastatic disease (P=0.03). Trial enrollment was associated with greater knowledge (P=0.002) and positive attitudes (P=0.001). Among patients who reported knowledge of TMP (n=46), 65% credit TMP with a >50% chance of isolating a targetable result. Of patients who had TMP performed (n=18), important considerations included wanting to live as long as possible and helping future cancer patients, but not wanting to be part of research.

Conclusions: Increasing awareness, knowledge, and attitudes towards trials among patients with sarcoma may lead to increased trial enrollment and greater progress in cancer treatment. Patient-focused interventions and research-site optimization are critical to maximizing accrual rates and biomarker-driven therapeutics. Lessons from a sarcoma patient population can be used to optimize trial enrollment in an era of increasingly heterogeneous cancer populations.

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References

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Introduction

The development of new cancer therapies relies on the successful development and completion of clinical trials. While clinical trials have led to significant improvements in cancer treatment, the success is dependent upon patient enrollment and participation. Unfortunately, fewer than 5% of adult patients enroll in trials.^1-3This represents a significant barrier to the development and approval of new cancer treatments. Reasons for low accrual into trials are multifactorial, but include structural barriers (eg, clinic access), clinical barriers (eg, eligibility criteria), and physician and patient attitudes towards trial enrollment.^4,5One study at the University of California Davis Cancer Center reported 49% of patients declined participation despite meeting eligibility criteria,^3,6suggesting that psychosocial barriers such as knowledge of trials and attitudes towards clinical research are a major impediment to accrual.^7-9

Bone and soft tissue sarcoma represent a heterogeneous group of tumors of mesenchymal origin that are an important cause of morbidity and mortality. Local disease is often treated with a multidisciplinary approach including surgery, radiation, and systemic therapy. Metastatic disease is predominantly treated palliatively with systemic therapy.¹⁰ Given its rarity and heterogeneity, trial accrual is of particular importance in sarcoma and often requires multiple sites to enroll adequate numbers of patients. While sarcoma represents <1% of adult malignancies overall, it constitutes ~15% of malignancies in the adolescent and young adult (AYA) population (15- 39 years old).^11,12 Sarcoma represents a patient population in which low trial accrual has been correlated with lack of progress in cancer-related outcomes in both the adult and AYA populations.¹³ The reasons for low accrual rates among patients with sarcoma are poorly understood.

Sarcomas represent a molecularly and biologically heterogeneous group of malignancies with over 100 different subtypes.¹² As a result, there has been significant interest in performing molecular profiling, or genetic sequencing, to identify “targetable” mutations. Targetable mutations refer to a specific genetic change identified within the tumor molecular profile for which there is a specific drug that may demonstrate activity against a particular tumor. Given the widespread utilization of this technology in sarcoma, identifying and understanding patient perceptions with regard to molecular profiling is critically important in this disease.¹⁴

In this study, we use a cross-sectional design to describe patient perceptions of trial enrollment among patients with bone and soft tissue sarcoma through validated measures, including attitudes towards clinical trials, knowledge of clinical trials, and perceived ability (ie, self-efficacy) to carry out actions involved in making an informed decision about clinical trial participation, receptivity to learning more about clinical trials, and willingness to participate in clinical trials.6 In addition, we describe this patient cohort’s perceptions of molecular profiling, as current and future trials are increasingly driven by molecular or other biomarkers.

Methods

This was a cross-sectional electronic survey study of patients with bone and soft tissue sarcoma treated at Northwestern Medicine (NM) over a 5-year period. NM Enterprise Data Warehouse (NMEDW) is a single, comprehensive, and integrated repository of all clinical and research data sources within NM. The study was approved by the Northwestern University Institutional Review Board.

Survey

The investigators designed a self-administered, online survey, which was built using Research Electronic Data Capture (REDCap). The survey consisted of three sections that were answered using skip logic—a custom path through the survey that varied based on patients’ answers: (1) Patient demographic information and trial perceptions (answered by all patients); (2) Thoughts about molecular profiling (answered by patients who answered “yes” to the question, “Have you heard about molecular profiling of tumors?”); and (3) Considerations to undergo molecular profiling (answered by patients who answered “yes” to the question, “Have you undergone profiling of your cancer?”).