Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience

Abstract

PURPOSE Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.

The challenge of the Molecular Tumor Board empowerment in clinical oncology practice: A Position Paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIC-SIF-SIGU-SIRM Italian Scientific Societies

“…In fact, if clinical validity can receive internal validation, for example in the context of a clinical study under an innovative design, clinical utility validation should include clinical benefit and be cost-effectiveness. The published experiences of advanced cancer patients treated according to the MTB recommendation demonstrate that adherence to MTB leads improved outcomes compared to the patients treated according to the physician's choice (Kato et al, 2020;Green et al, 2021). Particularly, a critical result of the MTB implementation is the increased enrollment in clinical trials.…”

An Overview of Comprehensive Genomic Profiling Technologies to Inform Cancer Care

“…25 Turnaround times between sample collection to results are also likely to be shorter with liquid biopsies. 7,28,29 Analysis of ctDNA can have additional functional uses, such as monitoring cancer progression, therapeutic response (e.g., resistance development), and possibly detecting early indications of recurrence through subsequent testing or longitudinal analysis. 7,30 However, because liquid biopsies do not directly target the primary tumour, they generally have reduced sensitivity compared with tissues samples, and, in some circumstances (e.g., certain cancer types, early-stage tumours, or patient-related factors), there may be limited ctDNA shed by tumours, which makes detection challenging.…”

“…31 Evidence from primary studies and systematic reviews also indicated that although liquid-based tests can detect actionable mutations, tissue-based tests generally have higher sensitivity and detection capability. 26,29,[52][53][54][55] Tissue-based tests provide higher quality genetic signals if the tumour can be accessed appropriately.…”

“…56,57 However, liquid-based CGP may be able to detect a higher rate of resistance mutations or signs of clonal hematopoiesis (mutations in stem cells that may or may not be linked to the tumour) among different cancers. 29,48,58 In 1 study of 1,288 people, liquid biopsy-based CGP led to a 65% increase in detecting driver mutations among people with NSCLC who were also tested with tissue-based assays. 59 CGP may be better at detecting global mutation changes, such as tumour mutation burden, and characterizing tumour heterogeneity, which may not be possible with tissue-based assays that sample a fixed site of a tumour.…”

“…For example, 1 study reported that CGP technologies may help recruitment for biomarker-based clinical trials for a variety of cancers. 29 CGP technologies could also support care of people with cancers of unknown primary origin because they could improve diagnosis and inform targeted therapy. 64 Overall, further research is needed to assess different CGP assays and whether they are associated with improved clinical outcomes and/ or other non-clinical benefits compared with single-biomarker assays.…”