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Seminars in Oncology Nursing, Vol 30, No 2 (May), 2014: pp 130-136
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE ALLISON A. VORDERSTRASSE, MARILYN J. HAMMER, AND JENNIFER R. DUNGAN OBJECTIVES: Identify and discuss the nursing implications of personalized and precision oncology care.
DATA SOURCES: PubMed, CINAHL. CONCLUSION: The implications in personalized and precision cancer nursing care include interpretation and clinical use of novel and personalized information including genetic testing; patient advocacy and support throughout testing, anticipation of results and treatment; ongoing chronic monitoring; and support for patient decision-making. Attention must also be given to the family and ethical implications of a personalized approach to care.
IMPLICATIONS FOR NURSING PRACTICE: Nurses face increasing challenges and opportunities in communication, support, and advocacy for patients given the availability of advanced testing, care and treatment in personalized and precision medicine. Nursing education and continuing education, clinical decision support, and health systems changes will be necessary to provide personalized multidisciplinary care to patients, in which nurses play a key role.
KEY WORDS: Personalized medicine, nursing, genomics, oncology
NCOLOGY care has shifted toward personalized and targeted approaches with the scientific and technologic advances of the past decade.1-7 Many personalized and precision advances are focused on ‘omics’-based platforms to calculate risks,
O
contribute to diagnosis, classify tumor types, identify likely response to treatments, and predict recurrence, metastasis, remission, morbidity, and mortality.7-9 Precision treatment based on individual tumor genetic markers is currently a reality in cancer care and the landscape of clinical
Allison A. Vorderstrasse, DNSc, APRN: Assistant Professor, Duke University School of Nursing, Durham, NC. Marilyn J. Hammer, PhD, DC, RN: Assistant Professor, New York University College of Nursing, New York, NY. Jennifer R. Dungan, PhD, RN: Assistant Professor, Duke University School of Nursing, Durham, NC.
Address correspondence to Allison A. Vorderstrasse, DNSc, APRN, DUMC 3322, 307 Trent Drive, Durham, NC 27712. e-mail: [email protected] Ó 2014 Elsevier Inc. All rights reserved. 0749-2081/3002-$36.00/0. http://dx.doi.org/10.1016/j.soncn.2014.03.007
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE
practice continues to evolve with new scientific advances. The implementation of personalized and precision medicine requires major health systems changes, including the incorporation of information technology to handle the data and introduce support tools for clinical use of the information.10 However, it also brings important implications for nursing to the forefront as nurses must have adequate preparation and knowledge of the ongoing evidence to care for patients using personalized strategies. As patient advocates, educators, and providers of direct care, nurses will be on the front lines of implementation of state of the science care. A major driver for the need to discuss implications related to personalized and precision medicine are the rapid advancements in genome science and technology, particularly over the last decade, and ongoing discoveries.6-9,11-13 Layered on to those advancements are health care systems and policy initiatives such as the ‘patient centered medical home’ (ie, comprehensive coordination of patient-centered care)14 and patient-centered care that have also influenced aspects of the implementation of personalized approaches to health care. Specific to oncology, there is an ever-increasing complexity to and utilization of genetic (somatic and germline) testing in clinical care. Nurses in oncology have witnessed increased utility of genomic analysis for individualized tumor analysis and the evolution of targeted drugs for blocking more specific biochemical pathways.5-7,11,12,15 Congruent with this, the fields of pharmacogenetics and pharmacogenomics target individualized drug metabolism and gene therapy for exacting patient responses.16 These aspects of scientific research have really allowed for ‘precision’ care to be implemented. However, these advancements are also changing the scope of nursing care and practice as nurses address patient implications of personalized and precision medicine.17 Given the amount and types of data that will be collected in electronic health records with personalized medicine strategies, there is also a great need for evidence-based means of synthesizing biomarker, clinical and patient-reported data, and a standardized means of utilizing and communicating the information to providers and patients. For example, in oncology, family history or genetic testing algorithms may trigger results with treatment or screening recommendations to providers and patients. Or, results of pathology and tumor genetic
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markers may direct providers and patients to appropriate or targeted treatment or even clinical trials based on this information. Patients need education and information as to what this type of testing entails; the results they should anticipate receiving; and how it may potentially help them and their providers decide on treatment steps. With the increasing amounts and types of ‘omics’ profiles and additional clinical data, nurses will also be looking at ways to optimize the use of personal patient data of multiple types in patient care.18 Nurses need to be at the forefront of patient care with a multidisciplinary team to truly deliver personalized and precision care. In terms of risk testing for patients and their families, advances aimed at personalized and precision care provide patients with earlier and increased information about cancer risk. Nurses need to be prepared to assist patients in interpreting the results of clinical genetic testing, as well as commercially available consumer-based testing, and/or referring to genetic specialists as needed. It is likely that these activities will be in concert with a genetic counselor; however, nurses are anticipated to fill the increasing gap in services related to genetic counseling that are consistent with the scope of nursing practice.17,19 Nurses need to assess other clinical risk factors; discuss and clarify patient values and priorities; provide information to enhance decision making around screenings or risk-reducing treatments; and provide support for family notification and testing as indicated.20 When nurses anticipate these needs and coordinate efforts with other members of the health care team, the likelihood of patients benefiting from personalized and precision care increases.
PATIENT ASSESSMENT AND MANAGEMENT The first step in providing personalized care is to assess the patient’s current understanding of their risk or disease status, as well as their personal health concerns or priorities. As demonstrated in one study regarding patient attitudes about personalized medicine in cancer care, most patients were not aware of or able to define ‘personalized medicine.’21 However, many identified the relevant benefits of approaches such as somatic testing and were willing to undergo targeted somatic and germline testing. Nurses play a key role in personalized medicine as they interact with and provide information and anticipatory guidance to patients before undergoing genetic or
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other testing. Nurses at all levels will need to be prepared to explain and discuss the implications of genetic testing and other risk testing with patients in an informed manner. An understanding of and ability to explain the tests, their validity and the meaning of results that will be obtained are necessary to provide patient-centered and personalized care. Without anticipatory guidance, patients may experience increased anxiety or stress related to the waiting for genetic and other test results. If sequencing or other germline mutations are being analyzed, the larger picture may include the ethical, legal, and social implications of this information, as well as unanticipated or incidental findings.22 Nurses should be ready to help patients understand these tests and again, what they can expect the tests to tell them and what the tests do not indicate. Helping patients decide what they would like to know or receive in their results is a key discussion to have. For example, after an initial diagnosis of melanoma, patients may then face a ‘waiting game’ to anticipate genomic or other pathology test results that will guide the next stage of their care. During this period, they may also have further questions or anxiety about the potential results. Maintaining active follow-up with patients and addressing information needs will be an important role for nurses in this phase of care. Such an experience can be viewed through an unusual case of a skin disorder genetically linked to a history of melanoma in a 54-year-old man.23 In this case study, Mota-Burgos and colleagues explain that the patient presented with dome-shaped papules around his face, biopsied and diagnosed as fibrofolliculomas along with the finding of a few acrochordons. He also presented with lipomas of the extremities and, upon comprehensive evaluation, was found to have several adenomatous polyps in his colon. This combination of skin tumors is diagnosed as Birt-Hogg-Dube syndrome. Unlike most patient presentations of this disorder, however, this patient also had a history of stage IIIB melanoma. Genetic testing revealed an unusual mutation linked with the more common mutation found in Birt-Hogg-Dube syndrome. The patient’s daughter also had the facial tumors, but declined having them biopsied. She was genetically tested, however, and was found to have the same rare mutation.23 From this level of information, it may be hypothesized that this mutation is a potential risk for melanoma and that the daughter may be at risk. This situation brings up several issues
and concerns. At this point, the rare mutation is only hypothesized to be linked with melanoma. However, because the daughter also has the facial tumors that appear to be similar to her father’s, should she be aggressively screened and monitored for melanoma? Should emphasis be placed on more strongly encouraging her to undergo the facial biopsies? And what about other family members not discussed in this case study? When genomic and other test results are received, nurses will often be present with other members of the health care team and will need to actively ensure that patients have a good understanding of the results and their meaning. In the case of results that guide cancer treatment, algorithms and clinical decision support tools may provide the oncologist, nurse, and patient with clear and personalized recommendations for treatment options or prognosis. In this case scenario, because of the rarity of the newly discovered mutation, clear algorithms are not available and clinical decisions are unable to be based on strong evidence. Providing the level of information that the patient can handle and as much information as possible while facilitating unbiased support are essential practices for the nurse in such a situation. Because of the patient focus on their current life-threatening illness, for some patients titrating the information and results to meet their needs over time is very important.24 In terms of more extensive genetic testing, such as with genome or exome sequencing, patients may learn of incidental findings relevant to their health and/or that of their family members that require intensive genetic counseling, if the patient and/or family members even agree to receive the results.21,25 Such a situation can be quite overwhelming. The daughter of the patient with melanoma, in our example, declined having a biopsy. Although she agreed to the specific genetic test, she may have declined undergoing full genome sequencing, had that been suggested. Further, her willingness to receive such results may be met with resistance. Some patients and families may express concerns regarding ethical, legal, and social issues with genetic or genomic testing. Overall, helping patients process and handle the family dynamics around familial obligations, desires to notify and educate family members, and extending any screening and testing are important. With initiatives that focus on care coordination (ie, medical homes),14 nurses may need to assist
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE
patients with coordination of care between specialists (ie, oncologists) and primary care providers. This may entail communication with patients to ensure an accurate understanding of their disease status and plan of care, as well as coordinated records sharing or communication with other health care providers. Improved survival rates mean that chronic cancer care is now very common, even in some patients with metastasis of their cancer. Active and ongoing psychological and informational support and monitoring by nurses during the testing, decision-making, and chronic surveillance periods are critical to patients’ coping and psychological well-being.26 With the rapid scientific advances in treatment guided by genetic mutations, there may not always be well-defined treatment guidance based on test results but clinical trials for targeted therapies may be ongoing. Nurses can be instrumental in helping patients find trial information for their type of cancer and test results using such sites as the National Institutes of Health.27 In some health care systems, the referral to relevant clinical trials is built into the electronic health records based on test results or diagnoses.
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IMPLICATIONS FOR NURSING EDUCATION Health care aimed at personalized and precision medicine—especially with the use of ‘omics’-based technologies—requires nursing and other health care staff to be knowledgeable and competent in their understanding, synthesis, and application of these advances in science. There are many current genomics education initiatives targeted toward nurses and other health care professionals. For example, the G2C2 (Genetics/Genomics Competency Center) developed by the National Human Genome Research Institute (NHRGI)28 contains learning and assessment tools for health professionals to improve and determine their genetic literacy. The Oncology Nursing Society also offers an online course specific to oncology care and genomics which could be helpful to nurses in this specialty area.17 Educational resources are also available on the International Society of Nurses in Genetics (ISONG) website (http://www. isong.org/ISONG_educational_resources.php). It can be difficult to access clinically relevant, up-to-date evidence that has been synthesized regarding genetic or molecular testing and personalized care. There are some recommendations
TABLE 1. Examples of Independent Molecular Testing Laboratories34-36 Company 34
Caris Life Sciences FoundationOne35
Oncotype DX36
Life Technologies37
Ambry Genetics38
Services
URL
Tumor genetic profiling and blood-based cancer diagnostics Genomic profiling of tumor tissue to help physicians make treatment decisions for patients with cancer by identifying the molecular growth drivers of their cancers and helping oncologists match them with relevant targeted therapeutic options Offers assays for: A. Breast cancer to help predict the benefit of chemotherapy and likelihood of cancer recurrence. B. Colon cancer to help quantify recurrence risk in stage II and stage III colon cancer and enable an individualized approach to treatment planning. C. Prostate cancer to provide a more precise and accurate assessment of risk based on individual tumor biology, enabling physicians and their patients to make treatment decisions Clinical tests: PervenioÔ Lung RS test to improve risk stratification of patients with early-stage, non-squamous NSCLC at high risk of mortality after tumor resection Provides assays and panels for multiple cancers, particularly hereditary cancers
http://www.carislifesciences.com http://www.foundationone.com
http://www.oncotypedx.com
http://www.lifelabdx.com
https://www.ambrygen.com/tests
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available in situations where the evidence has been independently evaluated by unbiased groups of experts such as the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group. An example is the EGAPP recommendations for testing of tumor tissue for mutations in EGFR pathway downstream effector genes (specifically KRAS mutations) in patients with metastatic colorectal cancer, which may be utilized to guide clinical decisions regarding anti-EGFR therapy due to the associations with treatment response.29 While there are ongoing efforts to establish such resources, nurses should be well-prepared to evaluate the science of genomics and oncology in the literature. Basic genetic and genomics educational resources30 are helpful to give nurses the required prerequisite knowledge to apply to consideration of various tests. To inform and assist in patient decision-making, knowledge about the clinical validity and utility of testing is essential.31 Nurses should be able to review and synthesize available literature or decision support information regarding the validity (clinical sensitivity and specificity) of the testing in the context of the disease or condition (prevalence, penetrance, expressivity), but also understand that health care decisions may be made in light of lessthan-perfect clinical validity and utility. Burgeoning advances in clinical decision support technology are aimed at helping to integrate clinical validity and utility factors within decision algorithms to assist nurses and health care professionals to access this information within the clinical workflow.32,33 Nurses in the community may need to advocate for patients to seek second opinions or pursue molecular testing options. There are a number of independent, CLIA-certified laboratories that provide molecular testing outside of the traditional hospital pathology department (see Table 1).34-38 Due to continuing advancements in the technologies and resulting changes in tests and panels offered by labs, nurses may wish to access comprehensive lists of genetic testing companies that can be found using the genetests.org website. The physician can create an account, arrange for tissue to be sent to the laboratory, and receive results in 1 to 2 weeks. The cost of testing for standard of care use is generally covered by insurance. Cancer clinical trials provide molecular analysis as part of the trial for indications not yet considered standard of care and patients can be assisted to find clinical trial options through www.ClinicalTrials.gov.39
TABLE 2. Summary of Nursing Implications of Personalized and Precision Oncology Care Patient Assessment and Management Pre-diagnosis Assess clinical risk factors Screening as appropriate (family history, clinical risk factor testing, environmental risks) Explain genetic risk testing (implications, results, validity, familial implications) Diagnostics Discuss genetic testing for relevant mutations associated with clinical presentation Discuss tumor testing for identification of somatic mutations Treatment/Prognosis Identify patients for whom any ‘omics or genetic testing platforms are appropriate for guidance in treatment considerations or prognostication Discuss recommended therapies based on tumor type and mutation identification Use clinical decision support tools to integrate personalized approaches and patient data (biomarker, patient-reported data, clinical data) into patient treatment plan discussions Ongoing Monitoring and Management Support patient in determining and following through on family implications for genetic test results Psychosocial support for patient throughout chronic phase of oncology care Implications for Nursing Education Understanding of and ability to explain genetic and genomic tests, their validity and the meaning of results that will be obtained Navigation of the ethical, legal and social issues involved in genetic and genomic testing Awareness of referral base for genetic counseling, clinical trials, or specialty care
IMPLICATIONS FOR PATIENT EDUCATION In line with nursing education, patient education will be necessary for full implementation of personalized and precision oncology care (see Table 2). While some patient education and discussion of personalized implications for patients will be a part of the nurse-patient interactions and communication, there are resources for patients to learn independently. For example, the National Institutes of Health/National Human
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE
Genome Research Institute40 and National Cancer Institute41 have online informational resources for patients regarding genetic and genomic testing, and pharmacogenomics in oncology.
CONCLUSION As a member of the health care team, nurses must be prepared to move ahead with the advances in personalized and precision medicine
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and to facilitate their use in clinical practice. This will require nursing education, patient education, health systems changes, and the engagement of a multidisciplinary team in oncology care. The improved and personalized care provided to patients should lead to continued improvements in patient outcomes, as long as nurses and other health care professionals keep the focus on the personalized needs and priorities of each patient.
REFERENCES 1. Chan BA, Coward JI. Chemotherapy advances in smallcell lung cancer. J Thorac Dis 2013;5(Suppl 5):S565-S578. 2. Cho JY. Molecular diagnosis for personalized target therapy in gastric cancer. J Gastric Cancer 2013;13:129-135. 3. Dobashi Y, Goto A, Endo T, Ooi A. Genetic aberrations as the targets of oncology research: involvement of paraffinembedded tissues. Histol Histopath 2014;29:191-205. 4. Fay M, Poole CM, Pratt G. Recent advances in radiotherapy for thoracic tumours. J Thorac Dis 2013;5(Suppl 5):S551-S555. 5. Hsu C, Po Ching L, Morita S, Hu FC, Cheng AL. Perspectives on the design of clinical trials combining transarterial chemoembolization and molecular targeted therapy. Liver Cancer 2012;1:168-176. 6. Wigle DA. Biologic approaches to drug selection and targeted therapy: hype or clinical reality? Thorac Surg Clin 2013;23:421-428. 7. Kalia M. Personalized oncology: recent advances and future challenges. Metabolism 2013;62(Suppl 1):S11-S14. 8. Dancey J. Genomics, personalized medicine and cancer practice. Clin Biochem 2012;45:379-381. 9. Tremblay J, Hamet P. Role of genomics on the path to personalized medicine. Metabolism 2013;62(Suppl 1):S2-S5. 10. Abrahams E, Ginsburg GS, Silver M. The personalized medicine coalition: goals and strategies. Am J Pharmacogenomics 2005;5:345-355. 11. Heller F. Genetics/genomics and drug effects. Acta Clinica Belgica 2013;68:77-80. 12. Ulahannan D, Kovac MB, Mulholland PJ, Cazier JB, Tomlinson I. Technical and implementation issues in using next-generation sequencing of cancers in clinical practice. Br J Cancer 2013;109:827-835. 13. Youn H, Chung JK. Reporter gene imaging. Am J Roentgenology 2013;201:W206-W214. 14. Patient-Centered Primary Care Collaborative. Defining the medical home - a patient-centered philosophy that drives primary care excellence. Available at: http://www.pcpcc.org/ about/medical-home. Accessed December 4, 2013. 15. Dancey JE, Bedard PL, Onetto N, Hudson TJ. The genetic basis for cancer treatment decisions. Cell 2012;148:409-420. 16. Cascorbi I, Bruhn O, Werk AN. Challenges in pharmacogenetics. Eur J Clin Pharmacol 2013;69(Suppl 1):17-23. 17. Oncology Nursing Society (ONS). The role of the oncology nurse in cancer genetic counseling. Available at: http://www.ons.org/CourseDetail.aspx?course_id¼98. Accessed December 6, 2013.
18. Chen R, Mias GI, Li-Pook-Than J, Lam HY, Chen R, Miriami, et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 2012;148:1293-1307. 19. Kirk M, Calzone K, Arimori N, Tonkin E. Genetics-genomics competencies and nursing regulation. J Nurs Scholarsh 2011;43:107-116. 20. Stacey D, DeGrasse C, Johnston L. Addressing the support needs of women at high risk for breast cancer: evidence-based care by advanced practice nurses. Oncol Nurs Forum 2002;29:E77-E84. 21. Gray SW, Hicks-Courant K, Lathan CS, Garraway L, Park ER, Weeks JC. Attitudes of patients with cancer about personalized medicine and somatic genetic testing. J Oncol Pract 2012;8:329-335. 22. Crawford G, Foulds N, Fenwick A, Hallowell N, Lucassen A. Genetic medicine and incidental findings: it is more complicated than deciding whether to disclose or not. Gen Med 2013;15:896-899. 23. Mota-Burgos A, Acosta EH, Marquez FV, Mendiola M, Herrera-Ceballos E. Birt-Hogg-Dube syndrome in a patient with melanoma and a novel mutation in the FCLN gene. Int J Dermatol 2013;52:323-326. 24. Dizon DS, Politi MC, Back AL. The power of words. Am Sco Clin Oncol Educ Book 2013: pp 442-446. 25. Johansen Taber KA, Dickinson BD, Wilson M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern Med 2014;174:275-280. 26. Bredart A, Kop JL, Depauw A, et al. Short-term psychological impact of the BRCA1/2 test result in women with breast cancer according to their perceived probability of genetic predisposition to cancer. Br J Cancer 2013;108: 1012-1020. 27. National Cancer Instititute Center for Clinical Research. Available at: https://bethesdatrials.cancer.gov/. Accessed December 9, 2013. 28. NHGRI. Natinal Institutes of Health/National Human Genome Research Institute. 2013. Available at: http://www. genome.gov/. Accessed December 4, 2013. 29. Recommendations from the EGAPP Working Group. Can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med 2013;15: 517-527. 30. Eggert J. The biology of cancer: what do oncology nurses really need to know. Semin Oncol Nurs 2011;27:3-12.
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31. Center for Disease Control and Prevention (CDC). Genetic testing: ACCE model system for collecting, analyzing and disseminating information on genetic tests. 2010. Available at: http://www.cdc.gov/genomics/gtesting/ACCE/FBR/index. htm. Accessed December 9, 2013. 32. Aronson SJ, Clark EH, Babb LJ, Baxter S, Farwell LM, Funke BH, et al. The GeneInsight Suite: a platform to support laboratory and provider use of DNA-based genetic testing. Human Mutat 2011;32:532-536. 33. Madhavan S, Gusev Y, Harris M, Tanenbaum DM, Gauba R, Bhuvaneshwar K, et al. G-DOC: a systems medicine platform for personalized oncology. Neoplasia 2011;13:771-783. 34. Caris Life Sciences. Available at: http://www. carislifesciences.com. Accessed February 12, 2014.
35. FoundationOne. Available at: http://www.foundationone. com. Accessed February 12, 2014. 36. Oncotype DX. Avaiable at: http://oncotypedx.com. Accessed February 12, 2014. 37. Life Technologies. Available at: http://www.lifelabdx. com. Accessed April 4, 2014. 38. Ambry Genetics. Available at: https://www.ambrygen. com/tests. Accessed April 4, 2014. 39. ClinicalTrials.gov. Available at: www.ClinicalTrials.gov. Accessed February 12, 2014. 40. NHGRI. For You: Patients. Available at: http://www. genome.gov/Patients/. Accessed December 6, 2013. 41. National Cancer Institute (NCI). Cancer topics. Available at: http://www.cancer.gov/cancertopics. Accessed December 9, 2013.
Seminars in Oncology Nursing, Vol 30, No 2 (May), 2014: pp 130-136
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE ALLISON A. VORDERSTRASSE, MARILYN J. HAMMER, AND JENNIFER R. DUNGAN OBJECTIVES: Identify and discuss the nursing implications of personalized and precision oncology care.
DATA SOURCES: PubMed, CINAHL. CONCLUSION: The implications in personalized and precision cancer nursing care include interpretation and clinical use of novel and personalized information including genetic testing; patient advocacy and support throughout testing, anticipation of results and treatment; ongoing chronic monitoring; and support for patient decision-making. Attention must also be given to the family and ethical implications of a personalized approach to care.
IMPLICATIONS FOR NURSING PRACTICE: Nurses face increasing challenges and opportunities in communication, support, and advocacy for patients given the availability of advanced testing, care and treatment in personalized and precision medicine. Nursing education and continuing education, clinical decision support, and health systems changes will be necessary to provide personalized multidisciplinary care to patients, in which nurses play a key role.
KEY WORDS: Personalized medicine, nursing, genomics, oncology
NCOLOGY care has shifted toward personalized and targeted approaches with the scientific and technologic advances of the past decade.1-7 Many personalized and precision advances are focused on ‘omics’-based platforms to calculate risks,
O
contribute to diagnosis, classify tumor types, identify likely response to treatments, and predict recurrence, metastasis, remission, morbidity, and mortality.7-9 Precision treatment based on individual tumor genetic markers is currently a reality in cancer care and the landscape of clinical
Allison A. Vorderstrasse, DNSc, APRN: Assistant Professor, Duke University School of Nursing, Durham, NC. Marilyn J. Hammer, PhD, DC, RN: Assistant Professor, New York University College of Nursing, New York, NY. Jennifer R. Dungan, PhD, RN: Assistant Professor, Duke University School of Nursing, Durham, NC.
Address correspondence to Allison A. Vorderstrasse, DNSc, APRN, DUMC 3322, 307 Trent Drive, Durham, NC 27712. e-mail: [email protected] Ó 2014 Elsevier Inc. All rights reserved. 0749-2081/3002-$36.00/0. http://dx.doi.org/10.1016/j.soncn.2014.03.007
NURSING IMPLICATIONS OF PERSONALIZED AND PRECISION MEDICINE
practice continues to evolve with new scientific advances. The implementation of personalized and precision medicine requires major health systems changes, including the incorporation of information technology to handle the data and introduce support tools for clinical use of the information.10 However, it also brings important implications for nursing to the forefront as nurses must have adequate preparation and knowledge of the ongoing evidence to care for patients using personalized strategies. As patient advocates, educators, and providers of direct care, nurses will be on the front lines of implementation of state of the science care. A major driver for the need to discuss implications related to personalized and precision medicine are the rapid advancements in genome science and technology, particularly over the last decade, and ongoing discoveries.6-9,11-13 Layered on to those advancements are health care systems and policy initiatives such as the ‘patient centered medical home’ (ie, comprehensive coordination of patient-centered care)14 and patient-centered care that have also influenced aspects of the implementation of personalized approaches to health care. Specific to oncology, there is an ever-increasing complexity to and utilization of genetic (somatic and germline) testing in clinical care. Nurses in oncology have witnessed increased utility of genomic analysis for individualized tumor analysis and the evolution of targeted drugs for blocking more specific biochemical pathways.5-7,11,12,15 Congruent with this, the fields of pharmacogenetics and pharmacogenomics target individualized drug metabolism and gene therapy for exacting patient responses.16 These aspects of scientific research have really allowed for ‘precision’ care to be implemented. However, these advancements are also changing the scope of nursing care and practice as nurses address patient implications of personalized and precision medicine.17 Given the amount and types of data that will be collected in electronic health records with personalized medicine strategies, there is also a great need for evidence-based means of synthesizing biomarker, clinical and patient-reported data, and a standardized means of utilizing and communicating the information to providers and patients. For example, in oncology, family history or genetic testing algorithms may trigger results with treatment or screening recommendations to providers and patients. Or, results of pathology and tumor genetic
131
markers may direct providers and patients to appropriate or targeted treatment or even clinical trials based on this information. Patients need education and information as to what this type of testing entails; the results they should anticipate receiving; and how it may potentially help them and their providers decide on treatment steps. With the increasing amounts and types of ‘omics’ profiles and additional clinical data, nurses will also be looking at ways to optimize the use of personal patient data of multiple types in patient care.18 Nurses need to be at the forefront of patient care with a multidisciplinary team to truly deliver personalized and precision care. In terms of risk testing for patients and their families, advances aimed at personalized and precision care provide patients with earlier and increased information about cancer risk. Nurses need to be prepared to assist patients in interpreting the results of clinical genetic testing, as well as commercially available consumer-based testing, and/or referring to genetic specialists as needed. It is likely that these activities will be in concert with a genetic counselor; however, nurses are anticipated to fill the increasing gap in services related to genetic counseling that are consistent with the scope of nursing practice.17,19 Nurses need to assess other clinical risk factors; discuss and clarify patient values and priorities; provide information to enhance decision making around screenings or risk-reducing treatments; and provide support for family notification and testing as indicated.20 When nurses anticipate these needs and coordinate efforts with other members of the health care team, the likelihood of patients benefiting from personalized and precision care increases.
PATIENT ASSESSMENT AND MANAGEMENT The first step in providing personalized care is to assess the patient’s current understanding of their risk or disease status, as well as their personal health concerns or priorities. As demonstrated in one study regarding patient attitudes about personalized medicine in cancer care, most patients were not aware of or able to define ‘personalized medicine.’21 However, many identified the relevant benefits of approaches such as somatic testing and were willing to undergo targeted somatic and germline testing. Nurses play a key role in personalized medicine as they interact with and provide information and anticipatory guidance to patients before undergoing genetic or
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other testing. Nurses at all levels will need to be prepared to explain and discuss the implications of genetic testing and other risk testing with patients in an informed manner. An understanding of and ability to explain the tests, their validity and the meaning of results that will be obtained are necessary to provide patient-centered and personalized care. Without anticipatory guidance, patients may experience increased anxiety or stress related to the waiting for genetic and other test results. If sequencing or other germline mutations are being analyzed, the larger picture may include the ethical, legal, and social implications of this information, as well as unanticipated or incidental findings.22 Nurses should be ready to help patients understand these tests and again, what they can expect the tests to tell them and what the tests do not indicate. Helping patients decide what they would like to know or receive in their results is a key discussion to have. For example, after an initial diagnosis of melanoma, patients may then face a ‘waiting game’ to anticipate genomic or other pathology test results that will guide the next stage of their care. During this period, they may also have further questions or anxiety about the potential results. Maintaining active follow-up with patients and addressing information needs will be an important role for nurses in this phase of care. Such an experience can be viewed through an unusual case of a skin disorder genetically linked to a history of melanoma in a 54-year-old man.23 In this case study, Mota-Burgos and colleagues explain that the patient presented with dome-shaped papules around his face, biopsied and diagnosed as fibrofolliculomas along with the finding of a few acrochordons. He also presented with lipomas of the extremities and, upon comprehensive evaluation, was found to have several adenomatous polyps in his colon. This combination of skin tumors is diagnosed as Birt-Hogg-Dube syndrome. Unlike most patient presentations of this disorder, however, this patient also had a history of stage IIIB melanoma. Genetic testing revealed an unusual mutation linked with the more common mutation found in Birt-Hogg-Dube syndrome. The patient’s daughter also had the facial tumors, but declined having them biopsied. She was genetically tested, however, and was found to have the same rare mutation.23 From this level of information, it may be hypothesized that this mutation is a potential risk for melanoma and that the daughter may be at risk. This situation brings up several issues
and concerns. At this point, the rare mutation is only hypothesized to be linked with melanoma. However, because the daughter also has the facial tumors that appear to be similar to her father’s, should she be aggressively screened and monitored for melanoma? Should emphasis be placed on more strongly encouraging her to undergo the facial biopsies? And what about other family members not discussed in this case study? When genomic and other test results are received, nurses will often be present with other members of the health care team and will need to actively ensure that patients have a good understanding of the results and their meaning. In the case of results that guide cancer treatment, algorithms and clinical decision support tools may provide the oncologist, nurse, and patient with clear and personalized recommendations for treatment options or prognosis. In this case scenario, because of the rarity of the newly discovered mutation, clear algorithms are not available and clinical decisions are unable to be based on strong evidence. Providing the level of information that the patient can handle and as much information as possible while facilitating unbiased support are essential practices for the nurse in such a situation. Because of the patient focus on their current life-threatening illness, for some patients titrating the information and results to meet their needs over time is very important.24 In terms of more extensive genetic testing, such as with genome or exome sequencing, patients may learn of incidental findings relevant to their health and/or that of their family members that require intensive genetic counseling, if the patient and/or family members even agree to receive the results.21,25 Such a situation can be quite overwhelming. The daughter of the patient with melanoma, in our example, declined having a biopsy. Although she agreed to the specific genetic test, she may have declined undergoing full genome sequencing, had that been suggested. Further, her willingness to receive such results may be met with resistance. Some patients and families may express concerns regarding ethical, legal, and social issues with genetic or genomic testing. Overall, helping patients process and handle the family dynamics around familial obligations, desires to notify and educate family members, and extending any screening and testing are important. With initiatives that focus on care coordination (ie, medical homes),14 nurses may need to assist
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patients with coordination of care between specialists (ie, oncologists) and primary care providers. This may entail communication with patients to ensure an accurate understanding of their disease status and plan of care, as well as coordinated records sharing or communication with other health care providers. Improved survival rates mean that chronic cancer care is now very common, even in some patients with metastasis of their cancer. Active and ongoing psychological and informational support and monitoring by nurses during the testing, decision-making, and chronic surveillance periods are critical to patients’ coping and psychological well-being.26 With the rapid scientific advances in treatment guided by genetic mutations, there may not always be well-defined treatment guidance based on test results but clinical trials for targeted therapies may be ongoing. Nurses can be instrumental in helping patients find trial information for their type of cancer and test results using such sites as the National Institutes of Health.27 In some health care systems, the referral to relevant clinical trials is built into the electronic health records based on test results or diagnoses.
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IMPLICATIONS FOR NURSING EDUCATION Health care aimed at personalized and precision medicine—especially with the use of ‘omics’-based technologies—requires nursing and other health care staff to be knowledgeable and competent in their understanding, synthesis, and application of these advances in science. There are many current genomics education initiatives targeted toward nurses and other health care professionals. For example, the G2C2 (Genetics/Genomics Competency Center) developed by the National Human Genome Research Institute (NHRGI)28 contains learning and assessment tools for health professionals to improve and determine their genetic literacy. The Oncology Nursing Society also offers an online course specific to oncology care and genomics which could be helpful to nurses in this specialty area.17 Educational resources are also available on the International Society of Nurses in Genetics (ISONG) website (http://www. isong.org/ISONG_educational_resources.php). It can be difficult to access clinically relevant, up-to-date evidence that has been synthesized regarding genetic or molecular testing and personalized care. There are some recommendations
TABLE 1. Examples of Independent Molecular Testing Laboratories34-36 Company 34
Caris Life Sciences FoundationOne35
Oncotype DX36
Life Technologies37
Ambry Genetics38
Services
URL
Tumor genetic profiling and blood-based cancer diagnostics Genomic profiling of tumor tissue to help physicians make treatment decisions for patients with cancer by identifying the molecular growth drivers of their cancers and helping oncologists match them with relevant targeted therapeutic options Offers assays for: A. Breast cancer to help predict the benefit of chemotherapy and likelihood of cancer recurrence. B. Colon cancer to help quantify recurrence risk in stage II and stage III colon cancer and enable an individualized approach to treatment planning. C. Prostate cancer to provide a more precise and accurate assessment of risk based on individual tumor biology, enabling physicians and their patients to make treatment decisions Clinical tests: PervenioÔ Lung RS test to improve risk stratification of patients with early-stage, non-squamous NSCLC at high risk of mortality after tumor resection Provides assays and panels for multiple cancers, particularly hereditary cancers
http://www.carislifesciences.com http://www.foundationone.com
http://www.oncotypedx.com
http://www.lifelabdx.com
https://www.ambrygen.com/tests
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available in situations where the evidence has been independently evaluated by unbiased groups of experts such as the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group. An example is the EGAPP recommendations for testing of tumor tissue for mutations in EGFR pathway downstream effector genes (specifically KRAS mutations) in patients with metastatic colorectal cancer, which may be utilized to guide clinical decisions regarding anti-EGFR therapy due to the associations with treatment response.29 While there are ongoing efforts to establish such resources, nurses should be well-prepared to evaluate the science of genomics and oncology in the literature. Basic genetic and genomics educational resources30 are helpful to give nurses the required prerequisite knowledge to apply to consideration of various tests. To inform and assist in patient decision-making, knowledge about the clinical validity and utility of testing is essential.31 Nurses should be able to review and synthesize available literature or decision support information regarding the validity (clinical sensitivity and specificity) of the testing in the context of the disease or condition (prevalence, penetrance, expressivity), but also understand that health care decisions may be made in light of lessthan-perfect clinical validity and utility. Burgeoning advances in clinical decision support technology are aimed at helping to integrate clinical validity and utility factors within decision algorithms to assist nurses and health care professionals to access this information within the clinical workflow.32,33 Nurses in the community may need to advocate for patients to seek second opinions or pursue molecular testing options. There are a number of independent, CLIA-certified laboratories that provide molecular testing outside of the traditional hospital pathology department (see Table 1).34-38 Due to continuing advancements in the technologies and resulting changes in tests and panels offered by labs, nurses may wish to access comprehensive lists of genetic testing companies that can be found using the genetests.org website. The physician can create an account, arrange for tissue to be sent to the laboratory, and receive results in 1 to 2 weeks. The cost of testing for standard of care use is generally covered by insurance. Cancer clinical trials provide molecular analysis as part of the trial for indications not yet considered standard of care and patients can be assisted to find clinical trial options through www.ClinicalTrials.gov.39
TABLE 2. Summary of Nursing Implications of Personalized and Precision Oncology Care Patient Assessment and Management Pre-diagnosis Assess clinical risk factors Screening as appropriate (family history, clinical risk factor testing, environmental risks) Explain genetic risk testing (implications, results, validity, familial implications) Diagnostics Discuss genetic testing for relevant mutations associated with clinical presentation Discuss tumor testing for identification of somatic mutations Treatment/Prognosis Identify patients for whom any ‘omics or genetic testing platforms are appropriate for guidance in treatment considerations or prognostication Discuss recommended therapies based on tumor type and mutation identification Use clinical decision support tools to integrate personalized approaches and patient data (biomarker, patient-reported data, clinical data) into patient treatment plan discussions Ongoing Monitoring and Management Support patient in determining and following through on family implications for genetic test results Psychosocial support for patient throughout chronic phase of oncology care Implications for Nursing Education Understanding of and ability to explain genetic and genomic tests, their validity and the meaning of results that will be obtained Navigation of the ethical, legal and social issues involved in genetic and genomic testing Awareness of referral base for genetic counseling, clinical trials, or specialty care
IMPLICATIONS FOR PATIENT EDUCATION In line with nursing education, patient education will be necessary for full implementation of personalized and precision oncology care (see Table 2). While some patient education and discussion of personalized implications for patients will be a part of the nurse-patient interactions and communication, there are resources for patients to learn independently. For example, the National Institutes of Health/National Human
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Genome Research Institute40 and National Cancer Institute41 have online informational resources for patients regarding genetic and genomic testing, and pharmacogenomics in oncology.
CONCLUSION As a member of the health care team, nurses must be prepared to move ahead with the advances in personalized and precision medicine
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and to facilitate their use in clinical practice. This will require nursing education, patient education, health systems changes, and the engagement of a multidisciplinary team in oncology care. The improved and personalized care provided to patients should lead to continued improvements in patient outcomes, as long as nurses and other health care professionals keep the focus on the personalized needs and priorities of each patient.
REFERENCES 1. Chan BA, Coward JI. Chemotherapy advances in smallcell lung cancer. J Thorac Dis 2013;5(Suppl 5):S565-S578. 2. Cho JY. Molecular diagnosis for personalized target therapy in gastric cancer. J Gastric Cancer 2013;13:129-135. 3. Dobashi Y, Goto A, Endo T, Ooi A. Genetic aberrations as the targets of oncology research: involvement of paraffinembedded tissues. Histol Histopath 2014;29:191-205. 4. Fay M, Poole CM, Pratt G. Recent advances in radiotherapy for thoracic tumours. J Thorac Dis 2013;5(Suppl 5):S551-S555. 5. Hsu C, Po Ching L, Morita S, Hu FC, Cheng AL. Perspectives on the design of clinical trials combining transarterial chemoembolization and molecular targeted therapy. Liver Cancer 2012;1:168-176. 6. Wigle DA. Biologic approaches to drug selection and targeted therapy: hype or clinical reality? Thorac Surg Clin 2013;23:421-428. 7. Kalia M. Personalized oncology: recent advances and future challenges. Metabolism 2013;62(Suppl 1):S11-S14. 8. Dancey J. Genomics, personalized medicine and cancer practice. Clin Biochem 2012;45:379-381. 9. Tremblay J, Hamet P. Role of genomics on the path to personalized medicine. Metabolism 2013;62(Suppl 1):S2-S5. 10. Abrahams E, Ginsburg GS, Silver M. The personalized medicine coalition: goals and strategies. Am J Pharmacogenomics 2005;5:345-355. 11. Heller F. Genetics/genomics and drug effects. Acta Clinica Belgica 2013;68:77-80. 12. Ulahannan D, Kovac MB, Mulholland PJ, Cazier JB, Tomlinson I. Technical and implementation issues in using next-generation sequencing of cancers in clinical practice. Br J Cancer 2013;109:827-835. 13. Youn H, Chung JK. Reporter gene imaging. Am J Roentgenology 2013;201:W206-W214. 14. Patient-Centered Primary Care Collaborative. Defining the medical home - a patient-centered philosophy that drives primary care excellence. Available at: http://www.pcpcc.org/ about/medical-home. Accessed December 4, 2013. 15. Dancey JE, Bedard PL, Onetto N, Hudson TJ. The genetic basis for cancer treatment decisions. Cell 2012;148:409-420. 16. Cascorbi I, Bruhn O, Werk AN. Challenges in pharmacogenetics. Eur J Clin Pharmacol 2013;69(Suppl 1):17-23. 17. Oncology Nursing Society (ONS). The role of the oncology nurse in cancer genetic counseling. Available at: http://www.ons.org/CourseDetail.aspx?course_id¼98. Accessed December 6, 2013.
18. Chen R, Mias GI, Li-Pook-Than J, Lam HY, Chen R, Miriami, et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 2012;148:1293-1307. 19. Kirk M, Calzone K, Arimori N, Tonkin E. Genetics-genomics competencies and nursing regulation. J Nurs Scholarsh 2011;43:107-116. 20. Stacey D, DeGrasse C, Johnston L. Addressing the support needs of women at high risk for breast cancer: evidence-based care by advanced practice nurses. Oncol Nurs Forum 2002;29:E77-E84. 21. Gray SW, Hicks-Courant K, Lathan CS, Garraway L, Park ER, Weeks JC. Attitudes of patients with cancer about personalized medicine and somatic genetic testing. J Oncol Pract 2012;8:329-335. 22. Crawford G, Foulds N, Fenwick A, Hallowell N, Lucassen A. Genetic medicine and incidental findings: it is more complicated than deciding whether to disclose or not. Gen Med 2013;15:896-899. 23. Mota-Burgos A, Acosta EH, Marquez FV, Mendiola M, Herrera-Ceballos E. Birt-Hogg-Dube syndrome in a patient with melanoma and a novel mutation in the FCLN gene. Int J Dermatol 2013;52:323-326. 24. Dizon DS, Politi MC, Back AL. The power of words. Am Sco Clin Oncol Educ Book 2013: pp 442-446. 25. Johansen Taber KA, Dickinson BD, Wilson M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern Med 2014;174:275-280. 26. Bredart A, Kop JL, Depauw A, et al. Short-term psychological impact of the BRCA1/2 test result in women with breast cancer according to their perceived probability of genetic predisposition to cancer. Br J Cancer 2013;108: 1012-1020. 27. National Cancer Instititute Center for Clinical Research. Available at: https://bethesdatrials.cancer.gov/. Accessed December 9, 2013. 28. NHGRI. Natinal Institutes of Health/National Human Genome Research Institute. 2013. Available at: http://www. genome.gov/. Accessed December 4, 2013. 29. Recommendations from the EGAPP Working Group. Can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med 2013;15: 517-527. 30. Eggert J. The biology of cancer: what do oncology nurses really need to know. Semin Oncol Nurs 2011;27:3-12.
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31. Center for Disease Control and Prevention (CDC). Genetic testing: ACCE model system for collecting, analyzing and disseminating information on genetic tests. 2010. Available at: http://www.cdc.gov/genomics/gtesting/ACCE/FBR/index. htm. Accessed December 9, 2013. 32. Aronson SJ, Clark EH, Babb LJ, Baxter S, Farwell LM, Funke BH, et al. The GeneInsight Suite: a platform to support laboratory and provider use of DNA-based genetic testing. Human Mutat 2011;32:532-536. 33. Madhavan S, Gusev Y, Harris M, Tanenbaum DM, Gauba R, Bhuvaneshwar K, et al. G-DOC: a systems medicine platform for personalized oncology. Neoplasia 2011;13:771-783. 34. Caris Life Sciences. Available at: http://www. carislifesciences.com. Accessed February 12, 2014.
35. FoundationOne. Available at: http://www.foundationone. com. Accessed February 12, 2014. 36. Oncotype DX. Avaiable at: http://oncotypedx.com. Accessed February 12, 2014. 37. Life Technologies. Available at: http://www.lifelabdx. com. Accessed April 4, 2014. 38. Ambry Genetics. Available at: https://www.ambrygen. com/tests. Accessed April 4, 2014. 39. ClinicalTrials.gov. Available at: www.ClinicalTrials.gov. Accessed February 12, 2014. 40. NHGRI. For You: Patients. Available at: http://www. genome.gov/Patients/. Accessed December 6, 2013. 41. National Cancer Institute (NCI). Cancer topics. Available at: http://www.cancer.gov/cancertopics. Accessed December 9, 2013.
