Patient-Reported Outcomes: Engaging Your Core!

The PRO Core team was assembled to help expedite the development of PRO sub-studies within both NCORP and NCTN trials in SWOG and to develop a uniform framework for design of these sub-studies and analysis of the data collected. The PRO Core strongly supports investigators looking to incorporate PROs and quality-of-life measures into their studies.

The team includes, among others, members of our symptom management and survivorship committee (including co-chairs Lynn Henry, MD, PhD, and Michael Fisch, MD), statisticians and data coordinators from our Statistical and Data Management Center (SDMC), and our group-co-chair-elect Dawn Hershman, MD, MS, along with staff from our SDMC and Network Operations Center.

The core’s work at the SDMC is directed by Joseph Unger, PhD, an expert in PRO study design and analysis, and is coordinated by Salene M.W. Jones, PhD, a psychometrician and expert in PRO implementation. Both are based at the Fred Hutch Cancer Center. 

In providing scientific oversight of PRO design, the team adheres to several basic principles, including relying on validated PRO instruments, assessing PRO feasibility in light of the trial’s main objectives, ensuring the burden on both patients and sites is minimized, and taking steps to avoid bias in assessing PRO data. The core’s guiding design and analysis principles were published in 2019.

To maximize participation in PRO sub-studies, the team advises that PRO eligibility criteria be limited, requiring only that the patient be eligible for the clinical study and be able to answer the PRO questions in one of the validated languages.

Since 2019, the PRO Core has overseen 38 PRO sub-studies embedded within SWOG treatment trials. The team also provides guidance on the design and implementation of PROs for cancer control and prevention studies, for which PRO and quality-of-life instruments are commonly used as primary endpoints.

Numerous SWOG papers and abstracts over these five years have reported on PRO results. Notably, members of the core team also oversee secondary analyses of PRO data from SWOG trials, and this work has produced several important recent publications on predicting risk based on patient-reported symptoms and quality-of-life measures.  

Here are just a few of the PRO-derived findings SWOG has published over the last few years: 

• patients with high-risk resected melanoma treated with adjuvant pembrolizumab had improved quality of life compared to those treated with ipilimumab or high-dose interferon (JAMA Oncology 2023)
• a risk model using baseline PROs identified Lung-MAP patients with advanced cancer at high risk of poor survival outcomes (JNCI 2023)
• baseline fatigue was associated with poorer overall survival in patients with advanced cancer (JCO Oncology Practice 2021)
• better health-related quality of life was associated with better overall survival in patients with advanced cancer (JCO Oncology Practice 2022)
• patients with higher levels of early patient-reported symptoms during aromatase inhibitor (AI) therapy were at greater risk of discontinuing that therapy (JNCI 2021)
• patients with AI-associated musculoskeletal symptoms (AIMSS) who reported less pain and better functional status were more likely to experience meaningful pain reduction in trials of interventions for AIMSS (Cancer Research 2021)
• cancer-related cognitive impairment was greater with chemo-endocrine therapy than with endocrine therapy alone (Cancer Research 2023)
• patient-reported fatigue was also greater with chemo-endocrine therapy than with endocrine therapy alone (Cancer Research 2023)
• patients with more fatigue at baseline were more likely to experience severe adverse events during treatment (Journal of Clinical Oncology 2024)

For investigators looking for guidance from the PRO Core on a trial proposal, the key message is engage early – before statistical and triage reviews. Look to the Study Chair Workbench page on the SWOG Protocol Development Process. It has a section on patient-reported outcomes that includes a SWOG PRO standard operating procedures document – absolutely required reading if your proposal will include PROs or quality-of-life objectives.

In addition to helping assess the instruments you’ll be using to gather PROs, the core team will work with you to get the needed permissions for using those instruments, an essential step that must be completed before the first PRO is collected.

A reminder for early-career investigators looking to become involved in SWOG – PROs are key elements in many of our clinical trials. Approaching a committee chair or a member of the PRO Core team to express interest in serving as co-chair of a PRO sub-study attached to a treatment trial can lead to an important position on a study that will make you, and your skills and interests, better known to committee leaders.

This post just skims (in a voluminous way) the surface of what SWOG’s PRO Core team does, and what they have contributed to and accomplished over the core’s first five years. I fully expect its next five years will be even more impressive.

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Trial of the Week

S1931: Phase III Trial of Immunotherapy-Based Combination Therapy with or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

Also known as the PROBE trial, S1931 aims to answer the question of whether patients with metastatic renal cell carcinoma who are receiving immunotherapy should – or should not – have cytoreductive nephrectomy.

Patients get 10 – 12 weeks of an immune-based combination therapy (three options are specified in the protocol). If their cancer responds or does not progress in that time, they may be randomized to either continued immunotherapy or cytoreductive surgery followed by continued immunotherapy.

Because the question of whether the primary tumor should be removed can be a challenging one to present clearly to patients, we’ve recorded a video introduction to the S1931 trial that can help them better understand the issues, and why it’s important that we are looking to this trial to get definitive answers. 

Drs. Hyung Kim and Ulka Vaishampayan are S1931 study chairs, and Dr. Abhishek Tripathi is ECOG-ACRIN study champion.

Activated in late 2020, the trial has enrolled 157 patients to date, on its way to a target accrual of 364. Of the more than 400 sites that have opened the study, the top-accruing site (by a good margin!) is the University of Michigan Comprehensive Cancer Center. 

Learn more at the SWOG S1931 page or the CTSU S1931 page!