Newly standardized grading criteria will help to regulate the management of CAR T-cell therapy­–related toxicities, like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require early and persistent management. As more CAR T-cell therapy drug becomes FDA approved, the utilization of this grading system may become more vital, said David G. Maloney, MD, PhD, in a virtual presentation given during the 2021 Pan Pacific Lymphoma Conference.

“Real-world evidence suggests that we have improved toxicity management from the original clinical trials, probably because of early treatment and patient selection. Fortunately, most of these toxicities resolve, but product selection is associated with different rates of toxicity. It is important to consider this,” said Maloney, a professor in the Clinical Research Division and the Leonard and Norma Klorfine Endowed Chair for Clinical Research at Fred Hutchinson Cancer Research Center, medical director of Cellular Immunotherapy at Seattle Cancer Care Alliance, and a professor of medicine in the Division of Oncology at the University of Washington School of Medicine.

Currently, FDA approvals for CAR T-cell therapies exist in aggressive non-Hodgkin lymphoma (NHL) with tisagenlecleucel (Kymriah), axicabtagene ciloleucel (axi-cel; Yescarta), and lisocabtagene maraleucel (liso-cel; Breyanzi), mantle cell lymphoma with brexucabtagene autoleucel (Tecartus), follicular lymphoma with axi-cel, pediatric or adolescent/young adult acute lymphoblastic leukemia with tisagenlecleucel, and multiple myeloma with idecabtagene vicleucel (ide-cel; Abecma).

“Each of these products is associated with a somewhat unique toxicity profile and they have their own REMS [Risk Evaluation and Mitigation Strategy] programs with the FDA, which makes the management of these toxicities somewhat challenging,” Maloney said.

Regarding the CD19-directed CAR T-cell therapies approved for use in aggressive NHL, treatment-related toxicities consist of CD19-independent events, such as chemotherapy-related toxicities, infection, anaphylaxis, recombinant lentivirus, and transformation, and CD19-dependent events, such as CRS, ICANS, B-cell depletion/infection, and tumor lysis syndrome.

Although fever is the defining characteristic of CRS, other associated complications can include hypotension, capillary leak, coagulopathy, marrow dysfunction, multiorgan failure, hypoxia, and hemophagocytic lymphohistiocytosis–like syndrome. ICANS can comprise headache, speech disturbances, delirium, seizures, focal deficits, and cerebral edema.

“There is an overlap between CRS and neurologic toxicity. Patients with really low-grade CRS often don’t have neurotoxicity, whereas patients with very severe CRS can often have very severe neurologic toxicity,” Maloney said.

Although tisagenlecleucel, axi-cel, and liso-cel are relatively similar products, differences in co-stimulatory domains elicit some differences regarding the onset and speed of CRS and ICANS, Maloney explained. However, no randomized trials comparing the therapies have been conducted and the pivotal trials utilized different grading systems for toxicity.

To standardize grading, the American Society for Transplantation and Cellular Therapy (ASTCT) set forth consensus grading criteria for CRS and ICANS.2

Both CRS and ICANS are graded 1 through 4 and overall grade is determined by the worst parameter. Regarding CRS, all grades feature a fever of 38 degrees Celsius or higher. Grade 1 CRS is fever only, with grade 2 through 4 featuring increasing severity of hypotension and/or hypoxia.

“The CRS grade is largely determined by the supportive strategies that are necessary to treat and support the patients,” said Maloney.

ICANS grading is determined by Immune Effector Cell-Associated Encephalopathy (ICE) score, Cornell Assessment of Pediatric Delirium score, depressed level of consciousness, seizure, motor findings, and elevated intracranial pressure/cerebral edema.

Both grading systems indicate that resolution of CRS or ICANS occurs when signs attributing to grading are no longer apparent.

Notably, CRS and ICANS are almost always reversible, but ICANS typically presents later than CRS, Maloney explained. Additionally, CAR T-cell counts in the blood tend to follow a crescendo-decrescendo pattern.

As such, increased proliferation of CAR T cells through factors, such as tumor burden, antigen escape, more concentrated infusion of CAR T cells, and the addition of fludarabine to cyclophosphamide-based lymphodepleting chemotherapy, is associated with a greater pre-treatment risk of severe CRS and ICANS. Additionally, severe CRS can lead to CAR T-cell expansion.

“CAR T-cell proliferation and peak count are associated with both response and toxicity,” Maloney said. “Earlier intervention is often considered in patients with high pre-treatment risk and in frail patients with pre-existing comorbidities.”

Earlier intervention should also be considered for patients with high post-infusion risk, including those with early or rapid progression of clinical toxicity, because they are at risk of more severe CRS and ICANS.

As the field develops a greater understanding of CAR T-cell therapy, management strategies for CRS and ICANS are improving, although they still vary widely between institutional practices, Maloney said.

“The goal of treatment of CRS and ICANS is to control these severe acute toxicities and prevent persistent toxicities while waiting for resolution of CRS or ICANS, and to avoid impairment of anti-tumor activity,” Maloney said.

Ultimately, general management strategies for CRS and ICANS include admittance to an intensive care unit for any-grade toxicity, investigation/exclusion of other etiologies, monitoring of vitals, ICE score, daily labs, and imaging if indicated, use of supportive care, and integration of immune modulation therapies if needed.

Supportive care measures include cooling, acetaminophen, antibiotics, granulocyte colony–stimulating factor, transfusions, fluids, oxygen, seizure prophylaxis, vasopressors, airway protection, and ventilation. Immune modulation options that interrupt the cytokine cascade include tocilizumab (Actemra), which is FDA approved to treat CAR T-cell therapy­–induced severe or life-threatening CRS, as well as siltuximab (Sylvant) and anakinra (Kineret). Corticosteroids are also utilized for immune modulation.

“CRS is not the only cause of fever, and ICANS [is] not the only cause of encephalopathy in these patients. Always consider the differential diagnosis to avoid a disaster,” Maloney noted.

Additional considerations, such as risk before and after infusion, stability of CRS components, age, variations in clinical trial designs, differences in CAR T-cell constructs, and variations in institutional practices can influence one’s interpretation of the CRS management guidelines, Maloney added.

Prolonged cytopenias and hypogammaglobulinemia are also frequently seen with CAR T-cell therapy, Maloney said.

Prolonged cytopenia that last more than 30 days post-infusion is observed in more than 30% of patients across approved CAR T-cell therapies. Notably, cytopenias are more frequent and more severe in patients with high-grade CRS, and treatment options include transfusion support, autoimmune processes, and transplant in rare cases.

Hypogammaglobulinemia is an on-target toxicity that arises from the ongoing elimination of CD19 B cells so long as functional CAR T cells are present. Patients with low immunoglobulin G (IgG) at presentation are more likely to develop hypogammaglobulinemia, but a minority of patients with normal IgG at infusion will require ongoing intravenous immune globulin support, which is suggested for patients with IgG less than 400 mg/dL.

Notably, patients who receive CAR T-cell therapy require ongoing follow-up for second malignancies and potential genetic risks from therapy, concluded Maloney.

Maloney D. Management of CAR-T toxicities. Presented at: 2021 Pan Pacific Lymphoma Conference; August 9-13, 2021; Big Island, HI. https://bit.ly/3ABmu04.

Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. 

 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758

Articles

Newly standardized grading criteria will help to regulate the management of CAR T-cell therapy¬–related toxicities, like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

New Toxicity Grading Criteria Help Standardize Management of CAR T-Cell Therapy-Related AEs 

 The noninvasive immunochemical fecal occult blood test (iFOBT) is highly effective at screening for colon cancer, according to a recent study published in the Canadian Medical Association Journal (CMAJ). The test examines the stool for hidden blood, which could come from anywhere in the gastrointestinal (GI) tract, and possibly indicates a colon tumor or precancerous growths known as polyps. The iFOBT is considered to have a greater sensitivity than the standard FOBT. If GI bleeding is detected, a follow-up colonoscopy is used to search for the origin of the blood.

	In the iFOBT study in CMAJ, researchers from Taiwan recruited nearly 2800 individuals to undergo iFOBT, blood tests, colonoscopy, and an upper GI tract endoscopy. The iFOBT correctly detected almost 90% of colorectal cancers, adenomas and significant lower GI lesions. The study also demonstrated that the iFOBT was ineffective at detecting upper GI tract diseases, such as esophageal or gastric cancers.

	John Theurer Cancer Center, Hackensack, NJ

	Colorectal cancer is the third most common cancer and the second leading cause of cancer deaths in the United States. An effective way to reduce mortality from colorectal cancer is to screen for it and its precursor, the adenoma. Unfortunately, in the United States, colorectal cancer screening is underused. Various factors contribute to this underuse, including patient factors such as lack of awareness regarding screening, lack of insurance coverage, and fear of undergoing colonoscopy.

	Colonoscopy still remains the gold standard and is recommended for individuals aged ≥50 years, assuming no increased risk factors. Patients with increased risk factors for colon cancer (eg, family history, history of inflammatory bowel disease, history of colonic polyps, and/or inherited genetic abnormality) require screening earlier than age 50 with colonoscopy. Colonoscopy not only detects colon cancers, but can remove precancerous polyps as well.

	Studies have shown that patient preferences for colorectal cancer screening tests vary, and many patients prefer the fecal occult blood test (FOBT) over more invasive tests (ie, sigmoidoscopy and colonoscopy). Given this information, the lower cost of FOBT compared with other screening methods, and the results of this study, it would seem prudent to utilize FOBT for those patients who are either unwilling or unable to undergo colonoscopy as screening. Any positive test result would then require colonoscopy, and patients might be more willing to undergo colonoscopy upon receiving a positive FOBT. Of course, FOBT will not detect adenomas (precancerous polyps); however, a new DNA stool test is being studied that could improve the detection of cancers and precancerous polyps.

	Therefore, FOBT may help increase colorectal cancer screening due to its non-invasiveness and low cost compared to alternative methods. Increased screening will lead to earlier detection, which would help reduce the number of colorectal cancer deaths. Any means of achieving that goal should be employed.

	Chiang TH, Lee YC, Tu CH, et al. Performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract [published online ahead of print August 2, 2011]. 

The iFOBT test examines the stool for hidden blood, which could come from anywhere in the GI tract, and possibly indicates a colon tumor or precancerous growths known as polyps.

Noninvasive Stool Test Effectively Detects Colon Cancer

	More than 30,000 oncologists from around the world gathered in Chicago, Illinois, from June 3-7 for the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO). With its “Patients, Pathways, Progress” theme, the conference showcased the latest clinical advances in oncology research. 

 has sifted through the thousands of abstracts presented at ASCO and identified studies to highlight for you. Our abstract selection process focused on research with the potential to change practice, important studies that failed to meet expectations, and topics particularly relevant to oncology nurses. Here is our special ASCO coverage, including personal perspectives from oncology nurses.

	Side Effects Not Prohibitive to Using Exemestane for Breast Cancer Prevention

	Lisa Schulmeister, RN, MN, APRN-BC, OCN®

	In media reports and interviews, oncologists have expressed excitement about the MAP.3 trial’s findings, and note that exemestane may be an alternative to tamoxifen or bilateral prophylactic mastectomy in reducing breast cancer risk in high-risk postmenopausal women.

	In the trial, side effects that were increased with exemestane use included hot flashes, fatigue, insomnia, gastrointestinal effects, and arthritis. However, the absolute differences in side-effect occurrence between the 2 arms were small, with the exception of hot flashes. Forty percent of the exemestane cohort reported hot flashes versus 32% of the placebo arm.

	The study arms showed no difference in cardiovascular events, clinical skeletal fractures, osteoporosis, and other malignancies. Additionally, exemestane has fewer side effects compared with other agents used to prevent breast cancer, such as tamoxifen.

	One notable limitation of the MAP.3 study was that the median follow-up duration was only 3 years.

Exemestane Is a New Option for Prevention of Breast Cancer in Postmenopausal Women

	Bay Regional Medical Center, Bay City, MI

	Hot flashes affect quality of life in those who have experienced menopause and its aftereffects, as well as those who are undergoing therapy for breast cancer. Flaxseed was seen as a possible relief for hot flashes in a phase III randomized trial at the Mayo Clinic, whose disappointing results were discussed at ASCO by its principal investigator, Sandhya Pruthi, MD, PhD.

	In a pilot study, flaxseed did show an association with decreased number and intensity of hot flashes. However, when compared to a placebo in the phase III trial, the differences were not significant.

	Flaxseed can still be looked at as a healthy component in foods, lending its omega-3 essential fatty acids, its lignans with estrogen and antioxidant qualities, and fiber, both soluble and insoluble.

Flaxseed Ineffective in Controlling Hot Flashes

	Ipilimumab is very unlike chemotherapy in regard to what nurses usually deal with in the infusion room. The drug stimulates the patient’s immune system to go after the cancer, which can also affect other organs. So you can see things as [simple] as a rash when the drug affects the skin cells, or more severe symptoms, such as colitis, which at first people think of as just diarrhea, but it can turn into a very serious, life-threatening situation. Ipilimumab can have similar harmful effects on the liver, as well as the thyroid, adrenal, and pituitary glands.

	Because it is the immune system causing the side effects, it is not just a matter of a drug clearing out of a patient’s system…so nurses have to intervene right away. We developed a patient checklist to monitor patients that goes over things such as number of daily bowel movements, skin integrity, fatigue levels, and more. The goal is to prevent patients receiving ipilimumab from reaching a grade 3 toxicity. There are a lot of times when patients get severe enough grade 3 reactions that we can’t give them any more ipilimumab. With early intervention, however, we can manage the side effects and safely continue the treatment.

Two Studies Herald New Era in Melanoma Therapy

	Genetic Research Is Changing Clinical Practice in Lung Cancer Treatment

	Assistant Director, Senior Medical Liaison

	Although genetic research has made great advances in many other cancer types, the genetic/genomic understanding of lung cancer remains somewhat limited. This appears to be changing, as genetic research results presented at ASCO promise to have a significant impact not only at a level of discovery, but also on the potential to reduce the annual prevalence of lung cancer, as well as have a positive impact on patient quality of life, survivorship, and our society’s economy.

	Preliminary results from the Lung Cancer Mutation Consortium (LCMC) reported at ASCO support pivotal practice changes in lung cancer involving the identification of gene mutations and planning treatment.

	As advancements in targeting cancer behaviors continue, so do the complexities of patient care. These complexities offer the oncology nursing profession complex challenges and unique opportunities. Among the challenges are potential barriers to patient understanding (culture, religion, knowledge, and level of literacy and language) and patient access to timely and appropriate care. Opportunities include expanding professional knowledge, education of peers and patients, nursing research, and advocacy at the patient, physician, payer, and government (local and federal) levels.

	Additional items for oncology nurses to understand as genetic testing changes clinical practice in lung cancer treatment are:

		The genomic mechanism of action aspects of lung cancer and how to interpret medical science language for patient understanding

		The complexities of access to genetic testing and advocating for this important scientific measure

		The importance of a standardized approach for specimen collection processes to ensure efficiencies in testing and reporting

		Important clinical trials and current treatment regimens available to be prepared to answer patient questions

Genetic Testing Delivers Personalized Lung Cancer Therapy

	Otolaryngology Clinical Nurse Specialist

	The Ohio State University Medical Center, Columbus

	With deaths in 2011 resulting from ovarian cancer estimated at more than 15,000, researchers have been working diligently to provide improved outcomes. In the phase III OCEANS trial, not only was there a progression-free survival (PFS) benefit of >4 months in the bevacizumab arm, but those women also had significant tumor shrinkage and a more durable response. In addition, complete response (CR) was seen in 8% more of the women with the addition of bevacizumab.

	The response was not without difficulty. Although both groups had some adverse events, the bevacizumab group had a higher rate of serious adverse events, including 8% higher rates of grade 3-5 adverse events. These more serious events were typical of known adverse events with bevacizumab, namely hypertension, proteinuria, and bleeding/thrombotic events. However, one of the most harmful side effects of bevacizumab, gastrointestinal perforation, was not seen at all in the women receiving bevacizumab in this trial.

	Given the improved PFS, CR, and duration of response with OCEANS, the bevacizumab combination should be considered as a viable option for women with recurrent platinum-sensitive ovarian cancer. Oncology nurses should be aware of the risks associated with bevacizumab therapy and be diligent in their assessments and education regarding adverse events. Preventative measures for bleeding/thrombosis should be initiated with treatment and education regarding symptoms and precautions for bleeding/thrombosis, hypertension, and proteinuria are imperative for better patient outcomes.

Bevacizumab Added to Chemotherapy Provides Meaningful Benefit in Recurrent Ovarian Cancer

Personal perspectives from oncology nurses of abstracts presented at ASCO on research with the potential to change practice, important studies that failed to meet expectations, and topics particularly relevant to oncology nurses.

ASCO 2011: What Nurses Need to Know

	Cancer and Careers is the only program of its kind, dedicated to empowering and educating people with cancer to thrive in their workplace by providing expert advice, interactive tools, and educational events. Through a comprehensive website, free publications, career coaching, and a series of support groups and educational seminars for employees with cancer and their healthcare providers and coworkers, Cancer and Careers strives to eliminate fear and uncertainty for working people with cancer.

	Cancer and Careers offers a variety of tools and resources for those working during or after cancer treatment. 

 is filled with articles, downloadable tools, charts, and checklists covering everything from telling your boss, to scheduling treatments, to knowing your legal rights. The website (available in English and Spanish) now features expanded content for lower income workers, including where to get pro-bono legal advice and financial assistance, as well as what to do if you do not have insurance.

	Two of the most popular areas of the website are the 

. The Diary is an interactive tool for people to share their personal experiences of working through cancer. The Coaching Center is a one-of-a-kind resource that offers survivors free access to professional coaches who address individual questions on how to manage their careers during and after treatment, as well as articles on universal professional development issues that affect employees with cancer.

	Another great (and free!) resource Cancer and Careers offers is a 

, including the newly updated 3rd edition of the 

Most Important Resources for Working People with Cancer

Survival Guide to Working With Cancer as a Chronic Illness

, which feature indispensable advice on nutrition, fitness, and beauty. All publications are available in English and Spanish.

	For those who prefer in-person events, Cancer and Careers also offers nationally-held 

, addressing the unique challenges of cancer in the workplace. The series offers people with cancer guidance on some of the biggest issues faced when trying to balance both treatment and work. The Oncology Nursing Society and Association of Oncology Social Work—accredited 

 addresses the complexities people face as they try to balance their cancer treatment and recovery with employment. The New York City conference features experts discussing legal issues, health insurance, and career counseling. The event is intended for patients, survivors, healthcare professionals, and caregivers. To register, go to 

 for people with cancer dealing with issues across the work continuum. This teleconference series provides unprecedented access to expert guidance and referrals. To register, go to 

	This underserved community of younger patients and survivors aged 18-40 years has its own set of unique challenges to tackle, including the issue of working through treatment early in a career. Cancer and Careers offers Job Search Tools, including an Interview Cheat Sheet, Networking Tracker, Case Studies, and Sample Resumes. Cancer and Careers also presents at conferences for this audience, including the 

. At these events, Cancer and Careers provides vital information on the issues of working through treatment for young professionals with cancer. 

Educational Series for Healthcare Professionals

, which provides oncology nurses, social workers, patient navigators, and other support providers with concise, targeted information on combining work and cancer treatment so that they can effectively inform their patients. This semi-annual, accredited program includes a multi-part seminar series that is accessible via webinars or teleconferences, and archived on the Cancer and Careers website for replay anytime. There is also a dedicated website area for healthcare professionals on advising patients who are combining work and treatment. The section includes articles, access to archived presentations, and a downloadable community seminar kit that enables healthcare professionals to host their own educational events.

Cancer and Careers is the only program of its kind, dedicated to empowering and educating people with cancer to thrive in their workplace.

Advocacy Spotlight: Cancer and Careers

Oral oncolytic treatment offers benefits to both patients with cancer and oncology nurses. The self-administered medications empower patients with a level of control over their cancer treatment experience. Patients can conveniently administer oral therapies at home, reducing their time spent traveling to and receiving treatment at infusion centers. The reduction in clinical visits also frees oncology nurses to address their other clinical responsibilities.

	Along with these advantages, oral oncolytics present several challenges. With increased patient responsibility and reduced clinical oversight, treatment adherence and side-effect management become major concerns. The high costs of the medications also introduce reimbursement issues.

	Patient nonadherence and symptom mismanagement can lead to disease progression, unnecessary treatment changes, and increased toxicities. This creates an additional burden for clinicians with increased appointments and hospital admissions.

	With the continued escalation in oral oncolytic use (oral agents represent approximately 25% of the overall oncology research pipeline), oncology nurses must be prepared to facilitate proper use of the treatments. At the ONS 36th Annual Congress, OncLive Nursing discussed oral oncolytics with Susan Moore, RN, MSN, ANP, AOCN.

	Susan Moore, RN, MSN, ANP, AOCN, led a clinical practice session on adherence to oral oncolytics at the ONS Congress.

What are the advantages of oral oncolytic treatment compared with infusion therapy?

Well, for the patient, one of the advantages is that they can take this medicine at home, so they don’t have to schedule an infusion appointment to come in and be treated; they don’t have to [deal with] the…delays in traffic or delays [at] the clinic. They can take their medicine at home. So for some patients, taking oral agents gives them an increased sense of control—a sense that they’re somewhat in charge of their treatment. Now they’re not making decisions about the doses, we hope, and they’re following our instructions on how to take it. But it gives them…a little bit better control than having to be dependent on coming into the infusion center.

	Please discuss some of the available evidence of patient nonadherence to oral oncolytic therapy.

	The majority of the evidence at this point comes from women with early-stage breast cancer, who have been given, for example, a 5-year regimen of tamoxifen or an aromatase inhibitor that they take after they finish their surgery and any adjuvant chemotherapy that they had to have. And what we’re finding is that women tend to fall off of their therapy, sometimes as early as 2 or 3 years after starting, and so the incidence of nonadherence increases as the woman goes along in that 1-to-5-year range.

	View clips from the exclusive interview with Susan Moore on 

	And the second is easily—very easily&mdash;measured, and that’s in patients who are taking imatinib, or Gleevec, for chronic myelogenous leukemia, or CML. And [for] those patients, it’s relatively easy now to measure their BCR-ABL and see what their level is, and that will more or less tell us if the patient is being adherent with their therapy or not.

	So those are some areas where we do have definitive evidence. A lot of the rest of it is anecdotal, that people will say, “Well, my patient says she takes her medicine 90 percent of the time,” but we don’t really have good clinical studies at this point.

	"For some patients, taking oral agents gives them an increased sense of control—a sense that they’re somewhat in charge of their treatment."

	What are some indicators that a patient may have adherence issues with oral oncolytic treatment?

	Patients who tended not to follow instructions during the time of their adjuvant therapy [and] missed appointments. [Also, patients who] have a poor refill rate with their retail pharmacy— and those records are easy to get. If you’re the prescriber, you can call the pharmacy or get online with the pharmacy and find out if patients are refilling their prescriptions on time. So somebody who fails to do those things, or doesn’t call the clinic to tell the nurse or the physician that they’re having a particular side effect&mdash;they wait until it’s out of control, or they don’t report it until a visit 2 months later&mdash;that’s somebody that I would really want to think twice about putting on a chemotherapy where the side effects or the failure to adhere to the treatment could create some toxicities and problems.

	A sample of FDA-approved oral oncolytics 

		ALL indicates acute lymphoblastic leukemia; CML, chronic myelogenous leukemia; EGFR, epidermal growth factor receptor; GIST, gastrointestinal stromal tumors; NSCLC, non—small cell lung cancer; RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor.

	What are some of the effects of patient nonadherence?

	Some of the effects can be non-efficacy, [or] a lowered efficacy. All of the data that we give a patient saying that we believe, let’s say, in early-stage breast cancer that if you complete this regimen of therapy that you have a 98 percent cure rate, well, that’s not based on the patient stopping the medicine after 2 years, or taking it for 6 months, and stopping for 3 months and [then] starting again. It’s based on taking the medicine every day or as it’s ordered for the length of time that it’s ordered. So one of the things that can happen is that we have decreased efficacy.

	The second can be if the patient doesn’t take the medicine the way they’re supposed to, we could have increased toxicities. So if someone takes more medicine than they’re supposed to, or they’re afraid to stop taking it when we ask them to hold it for a day or 2 because of a side effect, they can end up in the hospital or can end up with toxicities that are so severe that we actually have to stop the medication because of the toxicity, not because it’s stopped working.

	What can oncology nurses do to facilitate patient adherence to oral oncolytic treatment?

	Educate, educate, educate. That’s the key, and that’s what nurses are good at. We learned how to educate patients from our very first days in nursing school, and it’s something that we refine over the years. So we don’t want to use a script. We want to use a very individualized approach, tailored to that patient, and hopefully have another family member or a good friend there, because they may hear things a little bit differently than the patient does because of the patient’s anxiety. So that helps us to have a second person in the home or nearby that can help. But basically good patient education, and not just once, but educating the patient every time you have an encounter with them while they’re on this medicine, whether it’s in the clinic [or] over the phone. It takes 2 seconds to ask, “How is it going? Have you missed any medication? If you did miss them, why? And let me help you figure out how to get back on track.” So it’s a quick thing to do. It’s just something we have to do continually.

	5 oral oncolytics in late-stage clinical development 

		ALK, anaplastic lymphoma kinase; RCC, renal cell carcinoma; NSCLC, non—small cell lung cancer; PFS progression free survival; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2.

	What steps are involved with adapting a practice for use of oral oncolytic treatments?

	Probably the thing that’s the most difficult is for the physician to release the nurse for time for patient education. In most situations, it’s not a billable event and the physician sees this, especially in a small practice, as this is a nurse who’s spending an hour doing something for which I can’t bill, and she could be instead in the clinic giving an IV infusion, where I could bill for the medication and the nursing time to administer it. So that’s the first hurdle that most, especially small practices, have to get over.

	The second is if there is the money in the budget to hire a full-time clinical nurse specialist or nurse practitioner, some type of an advanced-practice nurse, within the practice. This really helps to make sure that education stays on key.

	And the other is to help the nurses to be able to do research on adherence, either themselves or to utilize research that’s out there to try to improve their education techniques. In the end, the message I always give to the physician is that the better your nurse is [at educating] the patient, the fewer hospital visits the patient will have, and the fewer phone calls you’ll have to make to try to resolve side effects or try to resolve problems of nonadherence. So it sort of pays you back if you let the nurse do his or her job.

Oral oncolytic treatment, a self-administered medication, empowers patients with a level of control over their cancer treatment experience.

Spotlight on Oral Oncolytics

Carlton Brown, PhD, RN, has been a member of ONS for 18 years and is in the second year of his 2-year term as president. He is also an assistant professor in the University of Delaware’s School of Nursing.

	Brown formerly served in the US Army, most recently as a clinical nurse educator at Walter Reed Army Medical Center (WRAMC) in Washington, DC. He also worked as a clinical head nurse and clinical nurse specialist at WRAMC.

	His most recent research includes “The Effect of an Oral Care Protocol on Oral Mucositis in Patients With Head and Neck Cancer Treated With Radiotherapy” and “The Lived Experience of Oral Mucositis in Head and Neck Cancer Patients Treated With Radiation.”

	At the ONS 36th Annual Congress, Brown spoke with OncLive Nursing about a variety of topics concerning the current and future state of oncology nursing.

 How will healthcare reform affect oncology nurses?

We know that there are probably 30 to 35 million Americans who right now are uninsured, and in 2014, when every person will have healthcare insurance, that’s obviously going to create a burden on nursing, on all of the healthcare providers. And so…it’s really frustrating when people say that we’re not really having a nursing shortage right now, because it’s kind of in disguise because of the economy, but healthcare reform is going to add more patients to the workload system.

	The good news is that there is a lot within healthcare reform to encourage nurses to get a more advanced degree, so maybe to go to become a nurse practitioner or clinical nurse specialist. There are loans for that. There are repayment plans for people who already have an education…There’s going to be scholarships. I think for any individual, now is a great opportunity to either become a nurse because of healthcare reform and the opportunities written into the law, but also it will be important for those who are currently practicing nursing to become more advanced in their practice.

	Will you discuss oncology nurses’ use of social media applications?

	Social media is something that I’m very proud that oncology nurses [are] doing. Of course, we have Facebook, Twitter, and LinkedIn, and we have done a really good job with [those]. I think it’s a good way to connect all nurses together, but in particular…those nurses that may be in less populated areas…I was asked at [the] opening ceremony yesterday to do a tweet that would connect all of the nurses who were following ONS, pulling them all in.

	[Also] the [ONS] Board just recently decided to add [technology as] a new pillar to our strategic plan…because I think that we really need to be thinking about what are the new things beyond social media. What are we going to be needing in 5 years and 10 years from now, trying to stay very pertinent to our members, and social media has been a good example of a way to reach out to our members.

	We started to discuss this topic earlier, but let’s explore it a little further. Is there a shortage in oncology nursing, and, if so, what strategies is ONS employing to address the issue?

	Well, I’d say that right now…the shortage not only in oncology nursing, but also in nursing [overall], is kind of in disguise. The economy has been very diffi cult, and so, in the past you may have had 3 or 4 wards or units that stayed at 50 or 60 percent capacity of patients, and you had nurses working on all of those. And I think that there are some hospitals that have closed a couple of wards and went to 100 percent capacity, and have kind of put those nurses out of jobs. And so I know that on both the east coast and the west coast, there are nurses who are having diffi culty finding jobs. However, in the middle of the country…there’re plenty of jobs for nurses. So the way it looks right now, it looks like we are in disguise of the nursing shortage.

	However, once the economy recovers, many of these nurses who may have wanted to retire in the last 5 years are going to retire. So we are going to be in a shortage of nursing, and, as I’ve already mentioned, we have 30-plus million more Americans that are going to be needing healthcare, and I think that we’re going to be in a world of hurt in 10 years. The problem, one of the major problems, because I’m a faculty member at a school of nursing, is that we have a faculty shortage. I mean we’re turning—when I say we, [I mean] here in the United States&mdash;we are turning nursing students away every year because we don’t have enough faculty to teach those students, and that’s because the pay for a faculty member is very sad. It’s very low. So I’ve been a nurse for 20 years and have a PhD in nursing. Any nurse who graduates can go to work in an emergency room on a nightshift and make more in her fi rst 6 months as a nurse than I’m making as a faculty member. And that’s kind of how it is with society anyway. We don’t pay teachers well…If you think about a high school teacher, it’s not something that you’re going to get rich at.

	So, yes, we have a nursing shortage. It’s going to get worse, and it’s going to be quite a problem, and [addressing the] faculty shortage is one of the solutions.

	[The Oncology Nursing Society is] working with schools of nursing to try to help attract nursing students to oncology nursing. We’re trying to fi nd ways to attract nurses that might be practicing in other areas to oncology nursing. It is on our mind. We are working with the American Nursing Association, as far as faculty issues are concerned. So it is in our foresight and we are working on it, but I think it’s going to be quite a problem. Probably 5 or 10 years from now, we’re really going to feel the effect of the nursing shortage.

	Carlton Brown, PhD, RN, addresses attendees at the ONS 36th Annual Congress.

	Beyond attracting faculty, are there other issues with oncology nursing education that need to be addressed?

	Lately we’ve been talking about [the fact that] there are 3 million nurses in the United States, and many of them don’t consider themselves oncology nurses, per se, but we know that many of them on a daily basis come into contact with an oncology patient— maybe in a home health arena, maybe in hospice palliative care, maybe in some kind of technology center [with a] mammogram. And so at the Oncology Nursing Society, we’ve been thinking about how can we better prepare those nurses who do not consider themselves oncology nurses? How do we get the content out to those nurses, so that they continue to provide quality cancer care to patients? And so if anything, that’s really the area where we will be doing work in the next 5 years, creating a portal online where information about oncology nursing is positioned, so that [a nurse] doesn’t necessarily need to be a member of ONS to get this access. It’s going to be free access. So that’s one of the areas that we’re working on.

	Please discuss the textbook you edited, A Guide to Oncology Symptom Management, and its focus on evidence-based practice?

	Thank you for mentioning my…textbook. It covers 20 symptoms, such as hair loss, nausea, constipation, and depression, and it is [written] from an evidencebased practice approach. In other words, we have sifted through all of the research to say, “What is the best way to treat a particular symptom?”

	And so…my textbook…presents all of the options out there, and then works through the evidence to say, “What is the best evidence practice for each of those symptoms?”

	There’s a second textbook [A Patient’s Guide to Cancer Symptom Management] out now that just came out 2 months ago, and we took [the fi rst] textbook and…wrote [another] textbook…at the fi fthand sixth-grade level for patients. So now a patient can sit down and read it and say [for example] “I have nausea. Let me read up on what that means.”

	View clips from the exclusive interview with Carlton Brown on 

	Oral oncolytics and genetic testing will be major factors in oncology going forward. What is ONS doing to prepare oncology nurses for this future?

	Oral medications [are] a big area. [Treatment is now] very focused…In the old days, let’s say you had a lung cancer. There was a standard group of chemotherapies that every lung cancer patient… received. And now we’ve been able to genetically look at that cancer and say, “What’s specifi c about it?” and then give some of these oral chemotherapy agents. Genetic testing is another big area. Now that the human genome has been mapped, we will eventually be able to look at genes and say, “You’re at risk for pancreatic cancer,” long before you’re diagnosed.

	So we talk a lot about adherence [to] oral medication, because [maybe] you’re somebody that’s never had to take a medication in your life, and now you’ve got to take this medication 4 times a day at a particular time. So we’re looking at ways…to help patients to remember to take it…We are doing research around adherence.

	And then we have our own genetics program. ONS has published a couple of genetics textbooks. Genetics really [will] be the wave of the future, as I said, because of the [mapping of the] human genome…We can even now see who is [at a] higher risk for nausea. We can see who…is [at a] higher risk for hair loss. So we have not even begun to tap cancer care from the genome approach.

	[And going back to] healthcare reform. In the old days you [had] to be worried about genetic testing. Let’s say that you do genetic testing and you’re at risk for colon cancer, and that information falls into the hands of the…insurance company, and they just say, “Okay, here’s somebody that’s at risk for colon cancer. Let’s cancel their insurance because that way we don’t have to pay for their care.” And that’s always been the big fear. Well, as of 2014, [with] healthcare reform, it’s illegal to cancel a person’s insurance either by a preexisting condition, if you’ve had cancer before, or if you’re diagnosed with cancer in the future. So that will open it up so that people will be more likely to have genetic testing, and then allow it to be used for their future care, almost like a preventative focus.

	"It takes the right person to do it, but [being an oncology nurse] is a great job, and I think there are going to be incredible economic opportunities."

	What would you say to an undergraduate nurse to convince him or her to become an oncology nurse?

	People think that oncology nursing is sad, but to me, it’s a great job. I think that a nurse is meant to work in a particular area. For instance, I’m not a pediatrics person. I can’t work with children. I just would want to sit down and cry with them, if they’re in pain or something like that. It takes the right person to do it, but [being an oncology nurse] is a great job, and I think there are going to be incredible economic opportunities.

	You know, the one thing I’ve not mentioned is there’s also a shortage of medical oncologists, and so that’s going to [create openings] for more advanced practice nurses literally taking care of more and more patients.

	So it’s not a sad job, but everybody can’t do it. Patients are experiencing…one of the worst times in their life, and it’s an honor to be there and to help and improve that, and for many of those patients, it means cancer survival. You know, we’ve got 12 million cancer survivors right now. Cancer is no longer…a death sentence…

	So I…encourage nursing students to go and work on an oncology ward for a couple of weeks to see if [they] like it. Maybe it isn’t for [them], but, as you can see, with [ONS having] 37,000 members, there [are] a lot of nurses that actually do like it, and it’s a great job.

Recently there have been several retrospectives on the War on Cancer. Are we winning the War?

	I guess that depends on what day you ask me and what patient I’m taking care of at the time. We certainly are winning the War on Cancer…[There are] 12 million cancer survivors. We are really making inroads; the incidences of cancers are down. Are we where we want to be? I mean we can’t really rest until no other patient is diagnosed with cancer. Will that happen in my lifetime? I’m not sure, but as long as we are having people who are smoking, people who are not doing proper preventative situations, we are going to continue to see cancer.

	But, there are several cancers that we have really stopped…[the] number of incidences, so I think that we’re winning. Some days it feels like we’re not winning, that we take a step back, but I think it’s one of those [things where we] take 2 steps forward and [then] take a step back…If you’re diagnosed with cancer now, as opposed to 20 years ago, your opportunities for long-term survival are so much better. And…the other question [is] how do you defi ne winning? [For example] is it quality of life for patients? So I think that we’re winning, [but] we still have a lot of work to do.

	What take-home message(s) do you have for nursing attending the ONS Congress?

	Get active in your local legislation. We have new laws for healthcare reform that will protect patients with cancer, and it’s going to be the nurse’s responsibility to educate them about what those new changes are. I would tell them to get involved with legislation, understand these new laws, and get that information out to patients, so patients can understand that an insurance company does not have a right to cancel [their] insurance because [they’re] diagnosed with cancer. So…get involved, learn about healthcare reform legislation, and start sharing that [information] with patients.

Carlton Brown, PhD, RN, has been a member of ONS for 18 years and is in the second year of his 2-year term as president.

Interview Series: Carlton Brown, PhD, RN ONS President

 Nurse scientist Donna Berry, PhD, RN, received the 2011 ONS Distinguished Researcher Award, which recognizes a nurse researcher whose work has enhanced the science and practice of oncology nursing. Berry is the director of the Phyllis F. Cantor Center for Research in Nursing and Patient Care Services at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston, Massachusetts. Berry discussed several of her research topics with 

, including patient adherence to oral oncolytic therapy, symptom management, patient quality of life, and patient decision making in cancer treatment.

: What are some of the challenges oncology nurses face when patients take oral oncolytics?

 Nurses have to prepare [patients] to give themselves chemotherapy, or give themselves their anti-tumor therapy, whereas traditionally, the nurse was right with the patient, giving an IV chemotherapy or an IM, intramuscular injection. But now the patients are going to do this at home…and…without adequate understanding, the patients may not take the medication as prescribed and they can get in big trouble. Their blood counts could go down. They could get really sick—have gastrointestinal side effects. So patient education becomes critical for these drugs, and nurses don’t always have that kind of time scheduled into their visit.

	So one of the ways that we’ve started to address that, not just at Dana-Farber, but at other cancer centers as well, is to provide a very systematic way of preparing people to take oral oncolytics, and that begins with the prescription, when the patient makes a decision…with their cancer specialist, to take the oncolytic and to receive the prescription. Then we teach them about the side effects, but we know very well they’re not hearing everything we’re saying.

	So we’ve designed and tested 2 different projects, one led by our nurse practitioner, Robin Sommers, and I’ve mentored her to do this on the project, to teach the patients as we get the prescription and follow up with a 72-hour phone call that takes them through a series of questions to teach and inquire at the same time—teach and inquire about everything that’s happening. “Where do you keep your medication? How often are you taking it? Have you experienced anything new since you’ve been taking that pill?” And that way, at 72 hours after [the patient begins treatment], we get some really good information, and it is the critical time that we can tweak what might not be quite right.

	We [also] ask the patients to keep track at home, using a diary of how often they’re taking [the medication], and they do really well using the diary. When we pilot tested it in the first 30 [patients], 27 of them did a really great job of keeping track of things with their diary. What we did notice is that many of them didn’t know what to do about their side effects, so we have continuing work to do and we’re following up on that.

	Then we have another project…in the gastrointestinal treatment center…We have another project with our patients with lung cancer taking erlotinib [Tarceva], which is one of our oral oncolytics. And we’re doing a very similar process, only this time it’s the feasibility of can this [adherence intervention] actually happen without, say, a research nurse involved?

	It’s not a study. It’s actually what’s going on in real practice. Do the nurses have time to go over this? Do they make the phone calls? Is it possible? Is it practical? We’re taking the evidence that these follow-up phone calls and these written instructions work, and we’re testing whether it’s practical in a busy cancer clinic.

	So that’s how we’ve gone about it. We’re not using any high technology or anything fancy yet. We’re simply looking at it practically to do this systematic teaching, systematic follow up with this questionand-answer inquiry and asking patients to track it. And it looks good. It looks really good so far.

	Dana-Farber Cancer Institute, Boston, Massachusetts

	What is the current and future status of evidence-based practice in oncology nursing?

	That’s a really excellent question because the future is where we’re going very rapidly. We have a practice in oncology that has traditionally stood shoulder to shoulder with our physician colleagues. And during the last few decades, our physician colleagues have developed monumental treatments for cancer that have changed the cure rates. And we have been right there, alongside the physicians, as they’re treating these tumors, working on that with them.

	Now, as our nursing science and our nursing interventions have evolved, it’s time for us to be right beside each other, nurse scientist and clinical nurses, and bring those interventions that nurse scientists have developed into the practice, and that’s where we’re poised, right at [this] time, to do that.

	The future is going to be eliminating the science and practice gap. I say, “Scrap the gap.” Don’t put a bridge over it because if you bridge it, it stays there. You have to scrap it, fi ll it in. We have to have clinical nurse scientists doing research in our clinical settings on a daily basis. We have to have clinical [nurses] that know [what’s] happening on a daily basis. And then we have to have the nurse scientist engaged in helping practitioners build it into practice.

	That doesn’t mean that we need huge clinical trials that cost $1.4 million, like we do for the original research studies. We need feasibility studies, like I told you about with the oral oncolytics. We need application studies, evaluation studies. But in order for that to happen, the people who know how to do [these studies] have to be involved…Nurse scientists like myself have to be involved, and we’ve got to fi nd a way to do that… The future is to bring it together.

	How does the Symptom Management Excellence Initiative facilitate the implementation of an evidence-based standardized approach to cancer symptom control?

	Well, the Symptom Management Excellence Initiative is possible because the Cantor Foundation, and Mr. Richard Cantor, who’s the president of that, he truly believes that nurses need to have resources to raise the bar on their practice to a level that they’re using evidence every day, that the best evidence for interventions is at their fingertips. And so he has sponsored us to do the Symptom Management Excellence Initiative.

	What we do is…bring together data from patients, from nurses, from physicians, and when I say data I mean, “What are the most pressing symptoms that we need to deal with? What do our patients tell us that bothers them the most? What do they have more commonly? What are the symptoms that aren’t being regulated by The Joint Commission [in the same way that] pain is [regulated]?…Where can we make the most improvement?” That’s what our Symptom Management Excellence, SME, Initiative is all about.

	View clips from the exclusive interview with Donna Berry on 

	We started with fatigue. It was the most common [symptom], one of the most important to manage, and had evidence, strong evidence that an activity-based intervention could make a difference in mitigating or reducing fatigue. So with our patients that hit a moderate level of fatigue, we’re going to be implementing a home-based walking program with them. We’re going to give them the opportunity, using our electronic monitoring system, to track their steps [using] a pedometer, their fatigue levels, [and] how many minutes they spend walking. We’ll start them out with 10 [minutes] and move them up to 30 minutes each day for at least 5 days a week, and help them graph that electronically over time or on paper.

	And hopefully, we’re doing this without research staff. This is all clinical staff. It’s nurse practitioners. It’s physicians. It’s nurses who are already working in the clinic, direct-care nurses, not researchers. Can we do it? Can we make this happen? If we can’t, [with] where we are at Dana-Farber right now, I think it’ll be a long time before we can do it, because we’re doing it very systematically and really keeping track of how well it works.

	How does the Electronic Self-Report Assessment for Cancer (ESRA-C) system facilitate communication between oncology nurses and patients to improve management of patients’ quality-of-life concerns?

	So the ESRA-C, the Self-Report Assessment for Cancer… [provides] a series of questions about symptoms, side effects, and quality-of-life concerns…and then of those things [it asks] what are the most important… to deal with today. The program [then] automatically creates a color-graphic summary. It’s 2 pages. Within 60 seconds, the nurse or the physician specialist looks at it, says, “Those are the 4 problems my patient [is] having.” And it’s a 60-second glance. It’s not a 10-to- 15-minute interview of yes-no questions, you know, the 20-question, “How’s that, how’s this, how are you doing?” It is a 60-second glance. [A] big red bar tells you where to start with the patient because that’s where they’re having the most trouble.

	So what we found in our research is that if you provide that summary to a clinician, that the symptoms and quality-of-life issues are discussed more often than when that’s not available. That’s really, really important, but that’s just the first step. That just means [the issues are] talked about. So in the next phase of our study, not only are we providing the summary so that symptoms and quality-of-life issues get talked about, we’re [also] coaching the patients to [describe] specific [details] about the symptoms. “It started 2 days ago. It’s worse than when I saw you last. On a scale of 0 to 10, it’s about a 7.”

	We [then] give them tips on how to handle these symptoms at home with reputable sources, and we help them understand [that] they’re not alone. They’re not the only person that’s experienced this. We give them real-time data on what percent of our patients have experienced that symptom either before or after treatment. So they get that message, “You’re not alone. There’s something to be done about it. Here’s what you tell your clinical team and [here are] self-care tips on what you can do.” At the end of the day, we hope…these patients will experience lower symptom distress.

 Berry is studying the feasibility and efficacy of an oncology nurse— led verbal and written patient educational program designed to facilitate patient adherence to oral oncolytic therapy. The intervention includes a follow-up phone call within 72 hours after treatment begins and patient diaries for self-monitoring treatment progress and symptoms.

Symptom Management Excellence (SME) Initiative

 The program combines patient-reported data, multidisciplinary input, and evidence-based practice to implement standardized approaches to cancer symptom management.

Electronic Self Report Assessment-Cancer (ESRA-C)

 A computerized patient self-reporting program involving a touch-screen survey that assesses symptoms and quality-of-life issues. The system generates a report that helps clinicians better address patient needs.

Nurse scientist Donna Berry, PhD, RN, received the 2011 ONS Distinguished Researcher Award, which recognizes a nurse researcher whose work has enhanced the science and practice of oncology nursing.

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