Although the ASCO (American Society for Clinical Oncology) will be a virtual meeting this year, The Life Raft Group continues to be at the forefront in collaborating in efforts to improve treatment for cancer patients. This year, two important abstracts will be presented online that illustrate these efforts.

The first is a collaborative effort that was inspired by the work of the Pediatric & SDH-Deficient GIST Consortium, an offshoot of the LRG’s work with the Biden Cancer Initiative.

Diagnostic algorithm for gastrointestinal stromal tumor (GIST) using patient registry data impacts pathology guidelines.
Sara Rothschild, Jerry Call, Christopher L. Corless, Anthony Gill, Markku Miettinen, Brian Rubin; The Life Raft Group, Wayne, NJ; OHSU Knight Cancer Institute, Portland, OR; Royal North Shore Hospital/University of Sydney, St Leonards, Australia; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Cleveland Clinic, Cleveland, OH

The Life Raft Group (LRG) identified that succinate dehydrogenase (SDH) deficient GISTs are under-recognized. In the LRG Registry only 30% of KIT/PDGFRA wildtype patients had received the advanced mutational testing (or SDHB staining) required to identify this unique subtype of GIST with a different natural history and response to treatment, and very strong familial associations. We proposed that two changes would significantly increase the diagnosis of SDH-deficient GIST patients: 1. SDHB staining for all GIST patients with a stomach primary tumor at initial biopsy, 2. Initial pathology report should contain strong recommendations for specific mutational testing.

The LRG collaborated with key medical opinion leaders on a diagnostic algorithm that illustrated the need for wider use of targeted diagnostic procedures and submitted the algorithm to the College of American Pathologists (CAP) GIST editorial board.

Because SDH-deficient GISTs require germline genetic analysis and, if mutation related, subsequent surveillance for paragangliomas/pheochromocytomas, and cascade genetic testing for family members, it is necessary to screen all gastric GISTs for loss of SDH by immunohistochemistry. This is best accomplished by immunohistochemical staining for SDHB, which is lost in all genetic subtypes of SDH-deficient GISTs. If SDHB is absent, additional staining for SDHA may be performed, as this protein is selectively lost in SDHA-mutant GISTs and this may help focus genetic analysis. All patients with SDH-deficient GIST should be referred to a genetic counselor. The CAP incorporated both SDHB and SDHA testing paradigms into the updated GIST protocols which were published in August 2019.

We believe this will result in significantly better diagnosis and treatment for SDH-deficient GIST patients. We encourage other groups that advise on guidelines to develop similar recommendations. This is a great example of a patient advocacy group utilizing real world evidence derived from a patient registry to influence protocols for treatments that affect GIST patients on a large scale.

The second, is a by-product of the LRG’s participation in a Working Group designed to determine consistent terminology around bio marker or mutational testing. The goal is to communicate to patients and the larger community in plain, patient friendly and consistent language.

On March 2019, Denisse Montoya, Director of GIST Patient Registry, attended to a pan-tumor roundtable meeting along with a group of 20 patient advocacy groups, three professional societies and 18 pharmaceutical and diagnosis companies. Following from this meeting, working groups participated in many meetings where different goals for consistent terminology were established by each group. Additionally, a survey and framework analysis were conducted across different cancer groups.

Consistent Testing Terminology Working Group
Using Consistent Terms in Precision Medicine to Eliminate Patient Confusion

Biomarker testing has advanced precision medicine in cancer. However, not all eligible patients benefit from biomarker-driven therapies due to suboptimal testing rates. A working group of 20 patient advocacy groups representing solid/hematologic malignancies, three professional societies, and 18 pharmaceutical and diagnostics companies identified patient confusion from inconsistent testing terms as a possible contributing factor to biomarker testing underutilization. The group aimed to address patients’ confusion by identifying and adopting consistent, plain language terms for biomarker and germline genetic testing that are applicable across cancer types.

Following a stakeholder roundtable discussion on barriers to precision medicine, working group members participated in interviews on their goals for consistent testing terminology for their constituents. We then conducted a framework analysis covering five themes: available testing by cancer type; purpose of test; biospecimen source; terms used in patient education; and preferred plain language term. Working group members were surveyed on preferences for germline testing terminology and also deployed a preliminary patient survey to their constituents to gain insight on preferences for germline testing terms.

Interviews, framework analysis, and surveys revealed notable differences across cancer communities. We identified at least 33 different terms related to biomarker, genetic and genomic testing being used in patient education and clinical care among the different cancer communities and stakeholders. Terminology was complicated by the variety of testing modalities and gene mutations tested for across cancers. Following multiple discussions, working group members agreed on two umbrella terms to distinguish between somatic and germline testing with additional context for specific cancer communities. “Biomarker testing” was selected as the somatic testing term. “Genetic testing for an inherited mutation” and “genetic testing for inherited cancer risk” were selected as preferred germline testing terms.

Our findings highlight the disparate testing terminology landscape and the need for consistent terms to reduce patient confusion, improve communication, facilitate shared decision- making and assure concordance in policy development.

Review abstract here.

View all the ASCO abstracts on GIST HERE

LRG Staff
Author: LRG Staff