Natasha Clinton, MSN, APRN, AOCNP, BCMAS

Precision Medicine (PM) is “an approach to disease prevention and treatment that seeks to maximize effectiveness by considering individual variability in genes, environment, and lifestyle,” according to the Precision Medicine Initiative (PMI).

 After former President Obama announced the PMI in his State of the Union address on January 20, 2015—“to bring us closer to curing diseases like cancer and diabetes and to give all of us access to the personalized information we need to keep ourselves and our families healthier”—the National Health Institute and other global agencies commenced a group under the PMI called the PMI Cohort Program.

The goal of PM is to advance medical and scientific discoveries to offer more tailored, precise, and accurate health interventions to maximize the health benefits for patients.

 Essential components of PM include the integration of information from several different sources, including genetic and genomic profiles, imaging data, records from wearable health-tracking devices and lifestyle choices, germline data, and pharmacogenomics. The access and application of these data and associated bioinformatics, using computing power and technological expertise to translate PM into personalized health care, are key.

For community practices, using PM will be greatly beneficial to patients and the practice. To maximize these benefits, PM needs to be integrated into the fabric of the community setting. All professionals in a practice will have to be involved in the development of a PM system, including physicians, pharmacists, lab personnel, nurses, and the patients. Although there have been obstacles to implementing diagnostic and screening tests, these can be overcome and will provide more options for patients with cancer.

Next-generation sequencing (NGS), which is rapidly replacing Sanger sequencing, has matured enough as a technology and found its place both in clinical practice and research. In addition, whole exome sequencing (WES) and/or whole genome sequencing (WGS) are becoming part of daily operation for oncologists and hematologists for exploring clinical trials and drug development for malignancies. The cost efficiency of NGS has improved significantly due to technological, scientific, and operational advances. The cost of deciphering the entire human genome has dropped from $10,000 in 2011 to approximately $1000 in 2021.

 Other drivers of PM include more accurate sequencing, a growing number of targeted therapies, and the recognition of biodiversity in the human genome— especially in oncology and rheumatic illnesses.

Even in monetary aspects, the global market for PM is growing rapidly. Market research estimated the 2016 global market at $44 billion in revenue, and this revenue is forecast to more than triple to $140 billion by 2026.

The rapid strides in sequencing techniques, bioinformatics, and PM have not been matched with efforts of implementation in day-to-day practice. Factors like integration into practice guidelines, lack of consensus and standardization between different stakeholders regarding minimum number of mutational analysis, germline studies, platforms for testing, and payer coverage threaten realization of PM.

In addition to factors mentioned above, the biggest challenge for success in PM adoption is lack of diversity in the knowledge of genomics and bioinformatics in research and studies. Minority communities often face discrimination in health care and receive poor medical treatment.

 Outreach to these communities, especially in the research field, has also been characterized by a long history of exploitation, abuse, and marginalization.

 Although hesitancy from ethnic minorities is frequently cited as an excuse for the lack of representative data in PM and clinical trials, real-life observation is somewhat different, with researchers observing that willingness to participate did not differ significantly between ethno-racial groups.

 They also argued that underrepresentation of minority populations is more likely due to the research design of the study or limited accessibility.

Results from genome-wide association studies (GWAS) representing 1.7 million samples conducted in 2009 showed that 96% of participants were of European ancestry. Seven years later, the same GWAS analysis revealed that despite the colossal 35 million samples collected, 81% of participants were still of European ancestry. Clearly, racial and ethnic diversity of the samples still had a long way to go.10 The successful implementation of PM requires the clinical integration of the following (FIGURE 1):

Molecular testing of patients for actionable mutations

Interpretation of molecular profiling results and identification of matched therapies

Identification of patients for clinical trials

The creation of a longitudinal journey to understand pharmacogenomics

Equitable access to genomic and genetic as well as treatment data

With so many testing options, including NGS, WES, WGS, and whole transcriptome sequencing, healthcare providers now face a complex decision: whether to outsource this testing to centralized laboratories, implement it in their own labs, or create a hybrid model bringing part of the testing in house and using tertiary labs with full bioinformatics and sophisticated testing for thousands of genes for support. With the advent of NGS panels, genomic profiling has become leaner, cheaper, and more user friendly. Everything is quicker in house, with much less chance of losing important material or information. One of the best arguments for in-house genomic profiling is the control it affords over the preanalytical parameters, tissue specimen selection, and sample quality.

For many community oncologists, the latter option to create a collaborative model may enhance the uptake of appropriate molecular testing and address an unmet need, as most of the underserved, marginalized population is served by small- to medium-sized community cancer clinics. We must focus on doing those routine tests quickly, cost effectively, and as locally as possible in collaboration with tertiary labs that have additional testing capabilities and bioinformatics.

Additionally, centralized testing in a collaborative model is another very valuable option. When an FDA-approved treatment option is not available based on local minipanel testing results, additional testing with a much larger panel may provide options for clinical trials for new drug development. This testing may also identify germline mutations, such as BRCA1/2 or other homologous repair defects, and identify other family members at risk. This would allow others to implement appropriate clinical interventions to monitor their risk for disease. A bioinformatics platform will enhance assimilation of genomic, pharmacogenomics, and germline data to create a longitudinal journey and ultimately bring health care equity, address disparities, and enhance new drug developments. Benefits of insourcing NGS include the following (FIGURE 2):

In summary, even though the field of PM is still evolving and changing, driver mutation and biomarker-guided therapies have already improved treatment options for thousands of patients with cancer and thousands more are eligible for clinical trials. Because of limitations in access to overall testing, limited uptake of testing—at the most, 25% in non–small cell lung cancer in Caucasians and 14% in ethnic minorities—and skewed data disproportionately representative of Caucasians, the success of PM is not likely to be accomplished unless we explore different ways to approach testing. These include:

Making widespread testing accessible locally;

Improving access to testing for minorities;

Performing additional testing at tertiary centers when an actionable mutation is not identified; and

Adding germline testing (if NGS panel only includes somatic testing)

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5. Global precision medicine market to reach $141.70 billion by 2026, reports BIS Research. BIS Research. News release. December 15, 2017. Accessed April 18, 2021. https://prn.to/3sYEwF6 

6. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung cancer mutation consortium experience. 

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Articles

The goal of precision medicine is to advance medical and scientific discoveries to offer more tailored, precise, and accurate health interventions to maximize the health benefits for patients.

The Role of In-Office Next Generation Sequencing to Advance Precision Medicine in Community Oncology

The crisis of coronavirus disease 2019, also known as COVID-19, presents a set of unprecedented circumstances to the health care community. The disease has a particular impact on patients with cancer and their oncology care teams who are trying to maintain the right balance between the use of immunosuppressive treatment and risk of cancer progression. Wenhua Liang, PhD, and colleagues analyzed the risk for severe COVID-19 in patients with cancer.1 They reported that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. They emphasized that patients with malignancy had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer to prioritize treatment versus risk of death and adverse outcomes. Patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (3 of 4 patients [75%]) of clinically severe events than did those not undergoing chemotherapy or surgery, observed by logistic regression (odds ratio, 5.34; 95% CI, 1.80-16.18; 

 = .0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. 

The authors of this study have proposed 3 major strategies for treating patients with cancer in the COVID-19 crisis. The first approach is an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with COVID-19, especially in older individuals or those with other comorbidities.

Oncologists and institutions caring for these patients face the continued challenges of administering treatment while simultaneously reducing the risk of complications in the event they end up contracting COVID-19. Stopping chemotherapy may be an option for patients in complete remission on maintenance therapy. In those patients, we may be able to switch chemotherapy from intravenous to oral therapies. This change would decrease the frequency of clinic visits. A chemotherapy break may be an option when feasible. Delays or modifying adjuvant treatment may be balanced with the risk of recurrence. The prophylactic growth factors and antibiotics in high-risk chemotherapy regimens is of paramount importance. When the absolute benefit of adjuvant chemotherapy may be quite small, and if non-immunosuppressive options are available (eg, hormonal therapy in estrogen receptorpositive early-stage breast cancer), risk of COVID-19 infection may be considered as an additional factor in weighing the patient’s available treatment options.

Providers caring for patients with cancer undergoing cytotoxic chemotherapy need to consider changing their treatment plan when feasible to reduce the risk of life-threatening complications as well as reducing the frequency of their clinic visits. Targeted therapies are approved for a number of aggressive cancers from non–small cell lung cancer, stage IV melanoma, to acute myeloid and lymphoid leukemia. These therapeutic options offer an opportunity to consider treatment of patients with the likelihood of a better response while at the same time increasing dose density and intensity without raising the toxicity profile.

Precision medicine–guided targeted therapies as well as immunotherapy may have a special role in identifying patients who may need cancer treatment. Most targeted agents are orally administered. The toxicity and adverse event profiles of many orally administered targeted therapies is significantly different from chemotherapy. A much higher complication rate from cytotoxic chemotherapy places patients with cancer at a much higher risk of complications from COVID-19 infection. Rigorous biomarker testing and appropriate therapeutic choice should be considered in this patient population, especially in the face of a global pandemic.

Assessing Cancer by Treatment Priority Determination: Top, Intermediate, and Low Priority

Instead of an arbitrary approach, a system to determine the priority for consultation and treatment of patients with cancer may provide a consistent approach for all patients and providers (

 It is also important to avoid, as much as possible, having different levels of care. We recommend following an “assessment for patients with cancer and treatment priority determination” that would assist cancer clinics and decision makers in the management of these patients. Given the dynamic situation, it is likely that this will vary from day to day, and daily accommodation reassessment may be required. The patient priority assessment and classification would allow flexibility determined by the local circumstances and available resources. The local or regional circumstances and the availability of resources may influence a cancer clinic’s ability to follow the criteria.

This virus was previously referred to as novel betacoronavirus severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2).

 What started in early December 2019 with 3 patients diagnosed with unexplained pneumonia in the Wuhan province of China has led to a global pandemic. At the time this article was written, more than 3 million cases have been reported and 207,973 deaths across Europe, the Americas, Western Pacific, Eastern Mediterranean, Southeast Asia, and Africa are attributed to the disease.

 The United States alone has 1,005,147 cases and 57,505 deaths.

In March 2020, the World Health Organization declared COVID-19, caused by SARS-CoV-2, a public health emergency of international magnitude and a global pandemic.

 According to the World Health Organization, the definition of pandemic is a worldwide spread of a new disease for which most people do not have immunity.

A sudden surge in the cases of COVID-19 due to the pandemic, along with efforts to contain it, has led to multiple challenges that no country has experienced in the last several decades. The global pandemic from COVID-19 poses a unique set of challenges not only for patients with cancer who need their treatment, but also for caregivers, oncologists, and the overall care team. It is recognized that there is a need to treat patients with cancer during a pandemic, due to their immunocompromised state from the nature of their disease or type of treatment they are receiving. Further, it is of paramount importance that the oncology care team develop and evolve a systemic approach that prioritizes patients, disease, and types of treatment. So far, the efforts of organizations and individual oncologists are being rapidly outpaced by the increasing number of patients with COVID-19. It is likely that this will be a dynamic situation that will vary each day.

Deaths from COVID-19 have been caused by multiple organ dysfunction. This observation might be attributable to the widespread distribution of angiotensin-converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.

 Patients with cancer are more susceptible to infection than individuals without cancer because of their malignancy and anticancer treatments, such as chemotherapy.

 These patients might be at increased risk of COVID-19 and have a poorer prognosis. 

Rapid growth in the number of patients with COVID-19 symptoms has led to capacity pressures to the health care system on a local, regional, and national level. Cancer clinics and hospital inpatient and outpatient areas have started experiencing capacity challenges. Patients with cancer are faced with difficult decisions and anxieties related to the risks of treatment versus exposure and increased risk of contracting COVID-19. It is expected that the COVID-19 global pandemic will hit in 1 or more waves. At the peak of the COVID-19 wave, a significant portion of hospital or clinic staff will be ill or unavailable to work (eg, due to school closures, family obligations, fear, disease, illness, etc.

COVID-19 has left an indelible mark on the history of the world. Although the death toll world wide approaches 140,000, it is only through humanity’s collective ingenuity and compassion to care for one another will we weather this pandemic. We are making daily progress and we applaud all health care workers who find themselves on the frontlines against this disease.

1. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21(3):335-337. doi:10.1016/S1470-2045(20)30096-6 

2. Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium [published online ahead of print, 2020 Apr 24]. Breast Cancer Res Treat. 2020;1-11. doi:10.1007/s10549-020-05644-z 

3. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S01406736(20)30211-7. 

4. Coronavirus disease (COVID-19) pandemic. Coronavirus disease (COVID-19) outbreak situation. World Health Organization website. Updated March 31, 2020. Accessed March 31, 2020. bit.ly/2QZvZlg. 

5. Coronavirus Disease 2019 (COVID-19). Cases in U.S. Centers for Disease Control and Prevention website. Updated March 31, 2020. Accessed March 31, 2020. https://bit.ly/2vKBtc6. 

6. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. World Health Organization website. Published March 11, 2020. Accessed March 31, 2020. https://bit.ly/3al0yJE. 

7. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. doi: 10.1038/s41586-020-2012-7 

8. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-637. doi: 10.1002/path.1570 

9. Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol. 2009;10(6):589-597. doi: 10.1016/S1470-2045(09)70069-5

"We recommend  following an assessment for patients with cancer and treatment priority determination that would assist in the management of these patients."

Natasha Clinton, MSN, APRN, AOCNP, BCMAS | Authors

Articles

The Role of In-Office Next Generation Sequencing to Advance Precision Medicine in Community Oncology

COVID-19 Presents an Opportunity for Precision Medicine to Play Expanded Role in Care