A year ago, most people outside of the science and healthcare community were unfamiliar with the concept of next-generation sequencing (NGS). Fast-forward to today, and you cannot read the news without hearing concerns about new SARS-CoV-2 variants spreading across the globe, and the increased need for viral genome sequencing to better identify and track emerging virus mutations.
While sequencing has only recently become headline news, the approach has been used for years to enable fundamental biomedical discoveries and has seen the progressive transition to clinical testing settings. In oncology, for example, targeted NGS has been instrumental in helping the healthcare community deliver on the promise of precision medicine by enabling clinicians to access precise data about a tumor’s genetic makeup and match patients with targeted treatments to improve outcomes. What began as a revolutionary research tool in large academic medical centers a decade ago has emerged as an important platform for clinicians to accelerate the most effective treatment of their patients.
In 2020, the U.S. Food and Drug Administration (FDA) approved 20 new personalized drugs and biologics.1
For patients who are candidates for targeted therapies, these therapies are often more efficacious and also less toxic than existing front-line therapies, such as chemotherapy or radiation. As more targeted therapies become available, demand for multi-biomarker testing to match patients with these treatments is growing – creating a case for more hospitals to offer NGS assays to their patients.
Five years ago, NGS for clinical assessment was typically performed in academic medical centers with a deep understanding of the technical aspects of sequencing and knowledge of what to do with the vast amounts of information. However, technological advancements have now enabled targeted genomic sequencing with faster turnaround times, reduced tumor specimen requirements and increased ease of use, requiring less training and hands on time. As a result, an insourced sequencing model is becoming a very attractive proposition for many hospitals, including community-based hospitals where the majority of cancer patients are diagnosed and treated. In other words, bringing testing closer to the patient.
Faster results
Faster turnaround times are critical to identify patients who may be eligible for targeted, potentially more effective, therapies, particularly for late-stage patients who do not have time to spare. In lung cancer, as one example, patients usually do not demonstrate symptoms until their disease has progressed. Their cancer often goes undiagnosed until stage IV.2 The five-year survival rate for advanced lung cancer is less than 25 percent,3 but a recent drop in lung cancer deaths indicates that new treatments, such as immune checkpoint inhibitors and targeted therapies, are improving patient outcomes.4 For patients to benefit from these treatments, comprehensive molecular test results are needed – quickly. In one survey, 76 percent of oncologists responded that improvement in turnaround times would lead to improved patient care.5
While insourced NGS is becoming more tenable, many hospitals continue to rely on single-gene testing. Not only does sequential single-biomarker testing fail to offer a comprehensive view of the molecular profile of a patient’s tumor, due to the difficulty of obtaining large amounts of a tumor sample through biopsy, there is often insufficient cancer tissue to generate more than two or three test results.
As the utility of NGS for clinical assessment has become clearer, clinicians have sought ways to get these tests done. However, to get a comprehensive view of a tumor’s molecular profile, clinicians have had to send a patient’s tumor sample out to a centralized reference lab for NGS testing, a process that can take 10 days or more. In addition, there may be higher failure rates due to compromised material during shipment or lack of sufficient material.6 For many cancer patients, waiting for this amount of time to even begin treatment is simply not an option. In the absence of the information needed to match a patient’s tumor profile with a targeted therapy, a patient may have already been started on a conventional treatment, such as chemotherapy or radiation, in an attempt to take quick action.
Today, however, it is possible for a pathology lab at an accredited community hospital to perform NGS and generate test results in one to two days. Some community hospitals are already putting this new technology into action. As one example, William Osler Health System (Osler) in Ontario, Canada, recently began insourcing comprehensive genomic sequencing with a fully automated solution. Previously, the hospital’s care teams would wait up to two months to receive actionable results from outsourced molecular profiling. Then, Osler brought biomarker testing in-house and was able to rapidly accelerate turnaround times, with test results available 94 percent of the time in a patient’s first consult, compared to just 17 percent of the time when they were outsourcing testing. Now, by adopting an automated NGS solution, with just one test, Osler clinicians can access a more comprehensive view of a patient’s tumor with the same rapid turnaround times.
Enhanced efficiency
Research has shown that therapy selection by NGS is also economical. A 2018 University Hospitals Cleveland Medical Center study on late-stage non-small cell lung cancer patients demonstrated how in-house NGS enabled clinicians to identify a broader set of actionable drug targets 50 percent faster than the time recommended by National Comprehensive Cancer Network (NCCN) guidelines – at no additional cost to the hospital.7
Previously, NGS was only economical for high throughput applications, but the availability of more accessible, automated solutions means NGS can now be run cost-efficiently with lower sample volumes. In addition, new, fully automated systems can be run by one lab technician, rather than a team of highly trained technicians or researchers, allowing labs to adopt this capability with existing staff and minimal training. The automation of NGS also minimizes hands-on time to reduce the risk of human error while accelerating time-to-results.
Improved patient outcomes
In-house testing means patients can benefit from the stronger collaboration that naturally occurs between pathologists and oncologists. Molecular tumor boards are becoming more common, in which oncologists, molecular pathologists, and staff meet to formulate the best treatment options for each patient. The board provides a forum in which oncologists can ask questions about a patient’s particular gene mutation to gain information that will impact prognosis or the selection of therapy. Similarly, the pathologist becomes part of the patient’s care team, rather than just the issuer of a written report, and facilitates translation of the NGS results to inform clinical treatment.
The future of NGS in community hospital settings
Over the last several years, an increasing number of community hospitals have embraced the role that NGS can have on informing patient care. Unfortunately, the coronavirus pandemic has forced many hospitals and patients to cancel or postpone oncology visits and tests. In the interim, some oncology labs have leveraged their expertise in molecular testing to join global SARS-CoV-2 surveillance efforts, especially as new strains have fueled a call for increased sequencing to understand these variants, including whether they are more transmissible, increase disease risk or demonstrate vaccine escape.
In addition to creating new capabilities for oncology labs with existing NGS programs, the pandemic has also accelerated adoption of NGS in labs that have not previously been exposed to this technology. While increased SARS-CoV-2 sequencing will remain important even as vaccination rates increase, wider prevalence of community-based access to NGS will open the doors for increased use of this technology for applications beyond COVID-19 research. Some labs that have adopted NGS technology for SARS-CoV-2 research are also speaking with local health systems about sequencing cancer patient samples, for example.
Ultimately, the pandemic has raised the profile of NGS and accelerated adoption by more labs that can immediately find utility sequencing SARS-CoV-2 samples and later apply this same technology to oncology and other disease areas, increasing the accessibility of precision medicine throughout more communities. The goal is to ensure all patients have access to comprehensive test results that can guide more effective, targeted therapy selection and improve health outcomes. The democratization of NGS is a huge step forward in making this possible.
References
- Personalized medicine at FDA: the scope & significance of progress in 2020. Personalized Medicine Coalition 2020: 7-8.
- What is stage IV lung cancer? Cancer Treatment Centers of America. 2020. https://www.cancercenter.com/cancer-types/lung-cancer/stages/stage-iv-lung-cancer. Accessed March 31, 2021.
- Your chances of surviving lung cancer. WebMD. 2019. https://www.webmd.com/lung-cancer/guide/lung-cancer-survival-rates. Accessed March 31, 2021.
- Sharpless N. Lung cancer deaths are declining faster than new cases. Advances in treatment are making the difference. August 13, 2020. STAT. https://www.statnews.com/2020/08/13/lung-cancer-deaths-declining-faster-than-new-cases-due-to-advances-in-treatment/. Accessed March 31, 2021.
- Menezes J; Joy V; Vora A. What can we learn from oncologists? A survey of molecular testing patterns. Poster presented at: AMP 2018 Annual Meeting; November 1-3, 2018; San Antonio, TX.
- Heeke S et al. Comparison of tumor mutational burden using the Ion Oncomine TML and FoundationOne assays with routine clinical FFPE tissue samples to predict durable clinical benefit in lung cancer and melanoma patients – a multivariate analysis integrating PD-L1 and CD8+ evaluation. Paper presented at: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA.
- Sadri N; Miller T; Yang M; Dowlati A; Friedman J; Bajor D; Chang R; Willis J. Clinical utility of reflect testing using focused next generation sequencing for management of patients with advanced lung adenocarcinoma. JCO. 2018; 36(15), e24199-e24199. doi: 10.1200/JCO.2018.36.15_suppl.e24199.
