At the recent National Comprehensive Cancer Network (NCCN) 19th Annual Conference, experts discussed this year’s updates to the NCCN Clinical Practice Guidelines in Oncology. The meeting also included reviews of NCCN Task Force reports on issues in supportive care. We asked eleven NCCN panel members to select the most significant updates and insights presented at the conference.

“The most significant changes are the addition of two newly approved agents for chronic lymphocytic leukemia, obinutuzumab and ibrutinib. That’s quite a lot in a single year. These drugs have the potential to make major changes in how we treat patients, particularly as we have more important non-chemotherapy options. Additionally, the brand-new guidelines for several rare lymphomas are important educational tools. Because they are for rarer diseases, they will hopefully provide useful guidance for clinicians who infrequently encounter these illnesses.”

				Obinutuzumab (Gazyva) plus chlorambucil was added as an option for previously untreated patients with chronic lymphocytic leukemia (CLL). The combination therapy is an option for those patients without an 11q or 17p deletion who are frail with significant comorbidities, and both older and younger patients either with or without comorbidities. The combination is also an option for CLL patients with either an 11q or 17p deletion.

				Ibrutinib (Imbruvica) was added as a treatment option for CLL patients with or without an 11q or 17p deletion who have received at least one prior therapy.

				For patients with diffuse large B-cell lymphoma, recommended follow-up imaging posttreatment was changed from CT scans every “6 months to 2 years” to “only as clinically needed.”

				PET-CT scan should now be considered to evaluate at presentation and following initial response to therapy in follicular lymphoma.

				Rituximab (Rituxan) plus low-dose CHOP chemotherapy (R-mini-CHOP) was added under a separate heading for patients with comorbidities aged ≥80 years with aggressive B-cell lymphoma.

				Two additional guidelines for two rare lymphomas added:				

						Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders

						T-cell Large Granular Lymphocyte Leukemia

						“These guidelines are largely educational to define these diseases and help clinicians accurately recognize and distinguish these disorders from other types of lymphomas or even benign, reactive processes. There are also some basic therapy recommendations. Because there is little data on these disorders, these recommendations are largely based on expert experience and retrospective studies.”

		Waldenström’s Macroglobulinemia, Multiple Myeloma

		Dana-Farber/Brigham and Women’s Cancer Center

“The updates for Waldenström’s incorporate major progress in our ability to identify a common mutation that helps determine proper treatment. As for multiple myeloma, none of the updates will radically change clinical practice, but we did add a new footnote that may indicate major changes to come. A small study has shown benefit to treating smoldering multiple myeloma rather than observing it. Further studies—which could make such treatment a standard of care&mdash;are starting up and we’re urging doctors to enroll eligible patients.”

				Ibrutinib (Imbruvica) now appears as a non—stem cell toxic, salvage therapy option.

				MYD88 L265P AS-PCR testing of bone marrow has proven itself useful in working up certain patients.

				The intent of therapy should be based on palliation of symptoms and not necessarily levels of IgM, unless the patient is exhibiting evidence of symptomatic hyperviscosity.

				Bortezomib (Velcade) plus prednisone now appears, under category 2B, as an option for maintenance therapy.

				Bortezomib plus thalidomide (Thalomid) now appears, under category 2B, as an option for maintenance therapy.

				Recent studies on smoldering myeloma show that patients with certain characteristics including IgG levels >3 g/dL, IgA >2 g/dL, urinary Bence Jones protein >1 g/24 hours, or abnormal free light chain ratios, have an increased risk of progression to active myeloma.

				There is a growing consensus that the classical definition of smoldering myeloma using certain tests such as plain x-rays is outdated. Efforts to modify these criteria and reclassify some patients previously classified as “asymptomatic” to having “active disease” are under way.

				Retrospective studies suggest a 2- to 3-year minimum length of remission before caregivers consider a second autologous stem cell transplant for salvage therapy (category 2B).

		Robert H. Lurie Comprehensive Cancer Center of Northwestern University

“Substantial findings in two research areas have produced widespread changes in the recent guidelines. First, trials of pertuzumab demonstrated value in a number of situations. Second, research showed that axillary lymph node dissection, while still indicated in some situations, provides no survival benefit in others.”

				A pertuzumab (Perjeta)—containing regimen may be administered preoperatively to patients with ≥T2 or ≥N1, HER2+, early-stage breast cancer.

				Patients who qualify for a neoadjuvant pertuzumab-containing regimen but do not receive it can be considered for pertuzumab after surgery on the same schedule and dosage as presurgical regimens.

				Paclitaxel + trastuzumab (Herceptin) was added to the list of therapies for patients with low-risk, stage l, HER2+ disease, particularly those not eligible for other standard adjuvant regimens due to comorbidities.

				Clinically negative axillary lymph node(s) should have axillary ultrasound; suspicious nodes should be sampled by FNA or core biopsy and clipped with image-detectable marker.

				Clinically positive axillary lymph node(s) should be sampled by FNA or core biopsy and clipped with image-detectable marker.

				Positive clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy.

				Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided because of cardiac toxicity risks.

				For patients who have particularly favorable tumors, patients whose adjuvant systemic therapy is unlikely to be affected, the elderly, or patients with serious comorbid conditions, the performance of axillary lymph node dissection may be considered optional—except where definitive data supports it.

				In patients with HER2+ and axillary node—positive breast cancer, trastuzumab should be incorporated into adjuvant therapy (category 1).

				Trastuzumab should also be considered for patients with HER2+, node-negative tumors ≥1 cm (category 1).

				Trastuzumab should optimally be given concurrently with paclitaxel as part of the AC followed by paclitaxel regimen, and should be given for 1-year total duration.

“In this year’s NCCN prostate cancer guideline update, three definitions and clarifications have been added that more accurately assess risk and will allow patients and physicians to make better treatment decisions. Still, more data are necessary on active surveillance monitoring strategies to provide clarity on this issue. The Early Detection Panel, led by Peter Carroll, MD, and our Treatment Panel have re-emphasized strongly our interdependence and the need for patients and physicians to consider carefully the recommendations of the two guidelines to minimize the risks posed by overdetection and overtreatment of lowrisk prostate cancer. Additionally, the panel tried to place the new FDA-approved therapies for men with advanced prostate cancer in the approximate order in which they should be considered in the pre- and postchemotherapy settings. The guidelines may assist with proper choice and sequence of treatments in advanced disease, which has become more challenging due to the FDA approval of five new agents since 2010.”

Articles

Conference Highlights

At the recent National Comprehensive Cancer Network (NCCN) 19th Annual Conference, experts discussed this year's updates to the NCCN Clinical Practice Guidelines in Oncology. The meeting also included reviews of NCCN Task Force reports on issues in supportive care. We asked eleven NCCN panel members to select the most significant updates and insights presented at the conference.

2014 NCCN Guideline Updates: Experts Highlight New Recommendations for Clinical Practice

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

Oncology Nursing Consultant, Adjunct Assistant Professor of Nursing

		Louisiana State Health Sciences Center in New Orleans, Louisiana

In 2012, the National Cancer Institute (NCI) convened a working group to explore the overdiagnosis of cancer, which often leads to the overtreatment of cancer. The group recognized that public awareness of early detection and improved cancer screening have increased the likelihood of identifying cancers that do not become clinically apparent and are not life threatening.

Policies that prevent or reduce the chance of overdiagnosis and overtreatment are needed, and the NCI group proposed that the term “cancer” be redefined and, in some cases, eliminated. For instance, ductal carcinoma in situ, which clinicians now recognize is not cancer, should be renamed to exclude the word carcinoma. The group also suggested that many lesions detected during breast, prostate, thyroid, lung, and other cancer screenings should not be called cancer and instead be reclassified as IDLE conditions or “indolent lesions of epithelial origin.”

The NCI group recommended that fewer unnecessary screenings be performed and that patients should only be diagnosed with cancer when lesions/tumors are lethal and require immediate treatment. Also needed are better methods to recognize and monitor indolent and non-aggressive lesions/tumors.

Historically, clinicians recommended—and patients demanded&mdash;aggressive treatment of all types of cancer.

We now know that some types of cancer, when left alone, will never grow, spread, or harm the patient. The question then becomes, who should be watched and who should be treated? Much of the research in this area has focused on the treatment of prostate cancer and breast cancer.

The 2013 Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) randomized 695 men who had early prostate cancer to either treatment with surgery or watchful waiting with no initial treatment (N Engl J Med. 2014; 370(10):932-942). In the surgery group, 63 deaths were due to prostate cancer, and in the watchful waiting group, 99 of the deaths were due to prostate cancer. The researchers noted that surgery reduces the risk of dying from prostate cancer by 44%, but as they looked closer at different groups, what emerged was that this does not apply to all patients. Surgery improved outcomes for men diagnosed at a younger age or with intermediate-risk disease. Thus, patients must individually assess the risks of surgery and weigh the possible benefits, and consider factors such as age, comorbidities, and overall quality of life.

Study findings presented at the 2013 San Antonio Breast Cancer Symposium (SABCS) similarly noted that certain groups of women with breast cancer may be able to safely forgo treatment or receive less treatment (Abstract S2-02). A study conducted in Mumbai, India, randomized 350 women with large breast cancers that had shrunk after initial chemotherapy to receive no further treatment and half to receive surgery (mastectomy or lumpectomy and node dissection). After 2 years, 40% of both groups were alive, which suggests that chemotherapy alone is enough.

In another study presented at SABCS, 1326 women 65 years or older with early-stage, hormone-positive breast cancers were randomized to receive radiation therapy or not receive radiation therapy. After 5 years, 96% of both groups were alive, and most of the deaths that occurred did not occur from breast cancer (Abstract S2-01).

Only 1% of women given radiation therapy had cancer recur in the treated breast versus 4% of those who did not receive radiation therapy. The researchers concluded that for every 100 women treated with radiation, one will have a recurrence anyway, four will have a recurrence prevented, and 95 will have received unnecessary treatment.

We are entering an era of “less is more” treatment, and treatment decisions are increasingly being individualized to the patient and not the type of cancer or stage of disease. Patients are becoming more sophisticated consumers as well, thanks in part to the massive amount of information that is publicly available.

Patients now are better informed about the success of lesser treatment or no treatment of certain cancers and conditions. Increasingly, patients want to know what is the best treatment—not the most aggressive treatment&mdash;and want to know what is best for them as an individual.

Nurse's Notes

In 2012, the National Cancer Institute (NCI) convened a working group to explore the overdiagnosis of cancer, which often leads to the overtreatment of cancer. 

Rethinking Cancer Diagnosis and Treatment

		Jessica Coviello, DNP, APRN, ANP-BC, and Raymond R. Russell, MD, PhD

The cardio-oncology program at Smilow Cancer Hospital at Yale-New Haven is a combined inpatient and outpatient consultative service that addresses the cardiovascular complications of cancer and its treatment. This innovative program is one of the few in the United States dedicated to addressing the cardiovascular side effects of cancer therapy and maximizing cardiovascular outcomes for cancer survivors.

Working together as a team in the care of the cancer patient, the goal of the program is to minimize cardiotoxicity during cancer treatment and cardiovascular risks during cancer survival.

The program was launched in 2011 in response to emerging data that indicate that newly developed drugs for cancer treatment are having unanticipated side effects. Drugs such as Herceptin, an effective drug in the treatment of breast cancer, can have cardiotoxic side effects that are just beginning to be understood and researched. Similarly, some of the new, targeted chemotherapeutic agents can affect heart and vascular function or the electrical conduction system of the heart. Led by cardiologists with expertise in cardiac imaging, the cardio-oncology team members work closely with Smilow oncologists to ensure patients can continue essential cancer treatment while maximizing the protection of their hearts. In addition, the program has a holistic, preventive approach that focuses on wellness in survivorship.

A comprehensive cardiovascular assessment prior to starting chemotherapy is not currently part of the standard cancer treatment in cancer centers, but protocols at Smilow include this important assessment.

The American Heart Association (AHA) recommends that cardiovascular screening tests begin at age 20. Although many patients have had some part of the assessment done in the past, it is rare that a recent, complete assessment has been performed.

This is an essential part of care at Smilow and provides the baseline information to insure cardiovascular health with close monitoring.

The extent of cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, prior chest radiotherapy, and the presence of cardiovascular risk factors or history of heart disease prior to treatment.

Known risk factors for cardiotoxicity from certain chemotherapeutic agents include age over 65 years, preexisting heart disease, as well as exposure to multiple cardiotoxic agents or radiation therapy. Other cardiovascular risk factors that warrant treatment include hypertension, dyslipidemia, diabetes, and obesity.

Additional risk factor stratification involves a thorough history and fasting laboratory tests that include a standard lipid profile as well as glucose, serum insulin, and lipoprotein-a. A baseline 3D echocardiogram to measure left ventricular function is done and repeated every 3 to 6 months during treatment depending upon the chemotherapy protocol.

			Provide care for patients with cardiovascular risk factors or coexisting heart disease who now have to undergo cancer treatment.

			Establish care for patients with heart failure following traditional treatments associated with cardiac dysfunction, including anthracyclines, radiation, and newer agents.

			Study the potential cardiovascular complications of cancer and cancer therapy and establish treatment strategies for these complications.

			Provide presurgical and prechemotherapeutic cardiovascular risk assessment.

The calculation that is commonly used to describe the function of the left ventricle is called the ejection fraction. The left ventricular ejection fraction (LVEF) is stated as a percentage and represents blood being pumped out of the heart with each beat.

A normal heart pumps a little more than half of the heart’s blood volume with each beat. Normal LVEF ranges from 55% to 70%. An LVEF of 55, for example, means that 55% of the total amount of blood in the left ventricle is pumped out with each heartbeat. The LVEF may be lower when the heart muscle has become damaged due to a heart attack, heart muscle disease (cardiomyopathy), or other causes such as cardiotoxivcity. An EF of less than 40% may confirm a diagnosis of heart failure. Someone with diastolic failure can have a normal EF but show other signs that their heart is tired, such as left ventricular hypertrophy. If the ejection fraction is abnormal before chemotherapy or drops 15% during treatment, the cardio-oncology team prescribes medicine to normalize the heart function and protect it from further changes. A beta blocker or ACE inhibitor might be added. These drugs have been shown to have cardiac benefit in clinical trials in Europe.

A heart-healthy diet and daily walking are recommended to patients; 30 minutes of daily walking or other forms of aerobic activity are encouraged. Patients who exercise through their treatment report feeling healthier and stronger as they complete therapy. The cardio-oncology team will continue to monitor patients throughout treatment and yearly for the first 5 years following cancer therapy. The team includes two cardiologists with expertise in cardiac imaging and an advanced practice nurse who work closely with Smilow oncologists to ensure that patients can continue essential cancer treatment while maximizing the protection of their hearts.

The cardio-oncology and oncology teams work closely to develop diagnostic and therapeutic plans aimed at providing the greatest protection to the heart while supporting optimum cancer therapy for the patient (

			1. Curigliano G, Cardinale D, Suter T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012;23(suppl 7):vii155-vii166.

Partner Perspectives

The cardio-oncology program at Smilow Cancer Hospital at Yale-New Haven is a combined inpatient and outpatient consultative service that addresses the cardiovascular complications of cancer and its treatment. 

Continuing Essential Cancer Treatment While Maximizing Protection of the Heart

Nobody Is Listening: Stories of Inflammatory Breast Cancer

 chronicles the accounts of women affected by inflammatory breast cancer, the most aggressive type of breast cancer. The book is coauthored by Massimo Cristofanilli, MD, director of Jefferson Breast Care Center, and patient advocate Patti Bradfield, founder of the Inflammatory Breast Cancer Foundation. 

 sat down with Cristofanilli to discuss the book and his efforts to raise awareness about this deadly disease.

What is inflammatory breast cancer? What makes this disease so deadly?

Inflammatory breast cancer (IBC) is quite different from any other type of breast cancer because instead of presenting with a lump that can be detected by mammogram, it usually is seen in a matter of a few weeks with redness and swelling. IBC represents between 3% and 5% of all breast cancers, but statistics are not very accurate and epidemiologic studies have been made difficult by the clinical definition of IBC. This is a much higher-mortality disease, usually between 40% and 50% survival with a high risk of recurrence in the chest wall and lymph nodes in the first 2 to 3 years.

Within 18 months, most of these patients are lost to the disease. IBC is an aggressive disease that typically affects a younger population (aged 50-52 years) compared with standard breast cancer (aged 57-60 years). The most aggressive phenotypes are represented more frequently in IBC than in regular breast cancer.

How do the experiences of a patient with IBC differ from those with other types of breast cancer?

Typically, a patient wakes up one morning and they have a swollen breast and feel that it may be an infection. A patient will then go to their primary physician or OB/GYN and usually receive antibiotics. Obviously, antibiotics do not help a patient because this is not an infection: it is cancer. It takes a number of weeks before a patient actually receives imaging, ultrasound, mammogram, MRI, and biopsy. During this process, or following it, a physician will realize that the tumor is already advanced. In these cases, a patient will need to go and look for appropriate care—potentially a surgeon to perform a core biopsy or skin biopsy, followed by a medical oncologist for preoperative or neoadjuvant chemotherapy. There is no chance to do surgery upfront for this patient, and all patients will receive a mastectomy, with no opportunity for an immediate reconstruction or more conservative surgery.

All patients also will receive radiation therapy that is more comprehensive and usually larger than typical radiation therapy for a more localized form of breast cancer.

The treatment of IBC is more complex and usually prolonged, with a number of possible complications from more aggressive treatments.

These patients always live with the fear that this tumor has advanced past optimum treatment and can come back. If the tumor does not completely disappear following neoadjuvant chemotherapy, there is a very high chance that the tumor will come back in the skin, lymph nodes, and distant sites. A patient with IBC lives with a constant fear of disease of which little is known, compared with standard breast cancers.

Who is the intended audience for your book, Nobody Is Listening: Stories of Inflammatory Breast Cancer?

The intended audience is all women who have had IBC and never had a chance to tell their story, as well as women who are not aware of this disease. Most of the breast cancer that we talk about is a breast cancer with a lump with a great chance to be detected by mammogram. We hear about how important mammogram screening is, but now we know that there is a different type of breast cancer that can be very aggressive and kill women rapidly. There remains a need to understand the real impact of IBC. When I started my effort to raise awareness of IBC, several patients told me that they went to the Susan G. Komen Race for the Cure several years ago, and no one knew about IBC.

If the professionals, the ones who deal with breast cancer every day, are not talking about IBC, I think we have a problem. We hope that even physicians, general practitioners, and healthcare providers would realize the impact of this type of disease in our society.

Was there a particular event or patient that inspired the writing of this book?

Patti Bradfield decided to take on this project for her daughter, whose life was lost to IBC.

There is plenty of explanation in the book about how her daughter’s IBC diagnosis completely changed her life. Once Patti and I met, it became clear that we had the same mission.

My commitment was to progressing the treatment of IBC, but at the same time, I agreed with Patti that we needed to do more for education and awareness.

What kind of impact do you hope this book has?

I think the hope is to start a serious conversation about what we should do about educating women, primary care physicians, and nurse practitioners. These women deserve the best chance possible when this disease presents itself. One day, if we have enough resources, we can find out what causes this disease and how to prevent it. That’s a dream, but I think it is something that we need to hang on to.

What is the most important takeaway on this subject for the oncology practitioner?

Listen to your patients. If they come to you with something that is totally unusual, you have to consider the worst and try to help in a much quicker way. I have seen patients referred, given an antibiotic, then sent to the imaging center for a mammogram, and eventually sent for a biopsy. This sometimes takes weeks, if not months. This is a disease that is very aggressive: be aware of it, be aggressive in trying to look for help and information. It can be a very deadly situation for these young women.

Feature Story

Nobody Is Listening: Stories of Inflammatory Breast Cancer chronicles the accounts of women affected by inflammatory breast cancer, the most aggressive type of breast cancer.

Raising Awareness of Inflammatory Breast Cancer

	Director, Pain Management and Palliative Care

	Englewood Hospital and Medical Center Englewood, New Jersey

	Director for Life Planning Palliative Medicine Services Baptist Memorial Health Care Memphis, Tennessee

	Professor, Department of Neurology Albany Medical College Director, Comprehensive Pain Program Albany Medical Center Albany, New York

	Professor of Anesthesiology Associate Vice Chair of Chronic Pain Division Director, Pain Medicine Division Penn State Hershey Pain Management Hershey, Pennsylvania

	Medical Oncologist Western Connecticut Medical Group Danbury, Connecticut

Breakthrough pain is a common and disabling reality for patients with advanced cancer. Its root causes vary, and experts agree that this type of pain is often inadequately managed. Treatments are available, yet a greater awareness and understanding of these formulations is needed in the oncology setting. An expert group of pain specialists, together with an oncology nurse and medical oncologist, assembled recently to share insights on therapies to manage breakthrough pain, offering perspectives on diagnosis, assessment, individualized treatment approaches, and patient monitoring.

For the full discussion from this Peer Exchange panel, moderated by Jeffrey A. Gudin, MD, 

Approximately 70% of patients with advanced cancer will indicate pain as their primary complaint, noted Vitaly Gordin, MD. Patients with cancer may experience several types of pain, including sudden-onset pain, chronic pain, and breakthrough pain. In many situations, these patients may experience persistent pain that lasts more than 12 hours per day, which can be controlled with various medications.

However, breakthrough pain, defined by the National Cancer Institute as “intense increases in pain that occur with rapid onset even when pain-control medication is being used,” can result in severe, transient pain flares. “Breakthrough cancer pain comes in very short spurts, and normally doesn’t have a good target to hit,” explained Marc Rappaport, DO.

“It varies from patient to patient,” added Jeri Ashley, RN. “Sometimes it begins and then it progressively gets worse until it’s managed. Other times it spikes and goes back down before the patient even reaches for the medicine bottle.” Breakthrough pain occurs in cancer patients not only with active disease, but also those in remission—for example, patients experiencing postchemotherapeutic effects such as neuropathy, or postsurgical pain, which are the most common pain-related issues in patients receiving curative therapy, according to Rappaport. “There still are breakthrough cancer pain issues that they have to deal with long-term.” As an example, he cited a 40-year-old patient with chronic postmastectomy pain, although her therapy was curative.

Because pain is so heterogeneous, noted Gudin, “the best management of an individual’s pain—including breakthrough pain in cancer&mdash; requires a thorough assessment to individualize treatment strategies.”

Among the diagnostic tools available are the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology— Adult Cancer Pain, the Brief Pain Inventory (BPI) developed by Charles Cleeland, MD, for rapid assessment of the severity and impact of pain in cancer patients, and the MD Anderson Symptom Inventory (MDASI).

Numeric rating scales can be employed to assess the severity of breakthrough pain for patients with cancer, noted Gudin; however, in addition to numerical tools, daily activities and medical history should also be considered, such as whether the patient is at the end of the dose or has undertaken new activities, explained Charles E. Argoff, MD. Including these questions in the assessment will provide an accurate measure of the events leading to the breakthrough pain. For example, "Is this breakthrough pain occurring at the end of a person's dose, when they're about to take their next drug?"Argoff continued. "Is the pain spiking idiosyncratically, idiopathically for no apparent reason, which is, of course, less predictable, or is the pain spiking because they're now more active than ever before, being positive, and they're gardening?"

“We need to be very diligent in collecting the history, doing the physical exam, and ordering proper diagnostic studies,” stressed Gordin. He also reiterated that “every new onset of pain should be assumed to be a recurrence of cancer unless proven otherwise.”

Panel members concurred that matching therapies to the particular needs of the patient with cancer is essential in developing treatment plans that will improve the patient’s quality of life.

“The nurse, of all the healthcare team members, probably has more time with the patient than any other, and the opportunities are great for what can be accomplished,” said Ashley. And here, she stressed, building a rapport early on with the patient is critical. She outlined a number of key elements in these patient consultations. For example, “What do they fear? What are their concerns about their pain, their condition, and their opioids (if that is what they are taking)?”

“Listening is a skill that we all need to do better,” Ashley continued, “so that we meet patients where they are; therefore, when they mention a specific pain, we’re able to address it more accurately, based on that assessment.”

Ashley noted that the oncology nurse is often the first to hear from a patient whether or not a pain medication is working. “The nurse giving adequate reports about pain management—both at assessment and reassessment&mdash;is critical to informing the physician.”

The reassessment piece is an essential component of effective pain management, continued Ashley. “I cannot stress that enough,” and this must include evaluating every patient for the risk of misuse or addiction. Gudin concurred: “Cancer patients aren’t spared from abuse, addiction, diversion, and misuse issues.”

“How do we get the oncologists more engaged and educated in the use of rapid-onset opioids,” asked Rappaport, in stressing the importance of including treatments in the rapid-onset class as part of the oncology team’s armamentarium.

In this class are transmucosal immediaterelease fentanyl (TIRF) formulations. Gudin explained that fentanyl agents cross through the blood—brain barrier rapidly, and that there are a number of delivery systems available, though practitioners may not be aware of them.

The original formulation was oral transmucosal fentanyl citrate, said Ashley, which is a rapid-acting lozenge on a stick which patients roll inside their buccal mucosa until pain relief is achieved. This method has yielded good responses in many patients, she added, though in long-term users, there can be detrimental dental effects from the sugar coating.

Newer tablet formulations, including a sublingual tablet, have comparable efficacy within the class, said Gudin. For the cancer population that Rappaport treats, “The sublingual tablet is very useful. I use it initially with some of the esophageal, gastric, and head and neck cancer patients, because the absorption in this area is relatively untouched by the mucositis from the radiation.” An intranasal spray formulation is also available.

Gordin noted that while he does not have experience with the sprays, “It’s a very quick onset, very powerful, one of the most powerful opioid analgesics available. The patient has to wait for a response before delivering the next spray." Physicians need to be very knowledgeable in educating the patient, he stressed.

Argoff underscored the importance of clinician knowledge. “You cannot prescribe these medications without taking a short course and passing it.” TIRF products are only available through an FDA Risk Evaluation and Mitigation Strategy (REMS) program (www.tirfremsaccess.com).

“Each step along the way, there’s mandatory education for everyone involved—the clinicians, the patients, the pharmacist&mdash;to promote safe use,” said Gudin. The experts agreed that there is a learning curve with these agents, but as practitioners become more familiar with them and make use of the TIRF-REMS access program, they are likely to become more comfortable prescribing them.

Whatever the preferred delivery route, the clinician must spend time with the patient to go over their titration schedule, “starting low” and then titrating progressively until the appropriate dose is reached, explained Rappaport.

Gudin advises practitioners to pick one or two of the products, and “become fluent with the label, with the package insert, know how to dose them, starting low, and how to titrate them.” “These medications are very potent,” added Gordin, noting that many patients with cancer are elderly and/or are already quite debilitated by the disease itself. Among the concerns in this population, especially, is excessive sedation with respiratory suppression, and as with any opioid, constipation. There is also a risk of a patient falling if started on too high a dose. “These are the most common concerns on the top of my list when I assess a patient and determine the dose.”

Ashley reminded clinicians of safety issues regarding storage. “We talk with patients a lot about lockboxes and keeping the medicines away from children, not driving while using these agents at least until the patient has been cleared by the physician for driving,” she continued, as well as reminding patients to make sure any pets do not ingest them.

Selecting an agent, said Rappaport, is very dependent upon each patient’s specific needs and other side effects. “You just have to keep an open mind as to which one.”

There are also rapid onset anti-inflammatory medications, noted Argoff, with studies pointing to a synergistic effect when a nonsteroidal and an opioid are used in combination. “A patient might actually get even better relief if we advise them to combine (the rapid-onset opioid) with another approach. We have to be creative with the tools we have.”

“Finding the proper agent or combination of agents is very important,” agreed Gordin. “The most powerful agents are opioids, and the majority of these patients, when they come seeking help for pain, they have very severe pain, and we should not deprive them of such a powerful tool as opioid analgesics.”

“Improved quality of life for the patient is what it really comes down to,” concluded Rappaport. “It’s invaluable once you get your feet wet and see how you do make an impact in a patient’s quality of life.”

Cover Story

Breakthrough pain is a common and disabling reality for patients with advanced cancer. Its root causes vary, and experts agree that this type of pain is often inadequately managed. 

Managing Breakthrough Pain Calls for Individualized Treatment Strategies

 Careful adherence to safety guidelines for administering chemotherapy is not only critical in the inpatient setting but also in ambulatory facilities and increasingly in the home with a growing number of oral agents in use now and in the oncology drug pipeline.

The Oncology Nursing Society (ONS) recently published an update of its chemotherapy and biotherapy practice guidelines,

 which recognizes these developments and also includes specific advice to assist patients in managing chemotherapy in the home setting, covering such issues as safe storage, disposal, what to do in the event of a spill, and how to protect family members from exposure.

At the recent ONS Congress, Stephanie Lee, BSN, RN, ONC, and Sarah Mendez, MA, RN, AOCNS, both from the New York University Langone Medical Center (NYULMC), presented their research on the development of standardized instructions for educating nurses about managing patients receiving oral chemotherapy.

The protocol they developed included delivering brief, inservice training to other units at NYULMC, focusing on patient medication verification, consent, treatment planning, as well as emphasizing the need to involve two nurses in this process. Nurses were also educated on the proper use of personal protective equipment when handling oral chemotherapy, the correct disposal of medication packaging, and body waste.

“Many nurses are not familiar with the safety precautions and protocols regarding oral chemotherapy, often consulting the nurses on the hematology/oncology unit for assistance,” the researchers explained.

“Providing this type of education throughout the hospital helped nurses become familiar and confident when caring for patients receiving oral chemotherapy,” they continued. “Overall, it improved quality of care and safety to both patients and nurses.

“Luckily, we do have guidelines from ONS, as well as OSHA and other places, which are all in sync,” said Colleen O’Leary, RN, MSN, AOCNS, during a recent interview. She is a clinical nurse specialist at the Ohio State University Comprehensive Cancer Center James Cancer Hospital and Solove Research Institute in Columbus.

O’Leary, who also coordinates Nursing Evidence-Based Practice at her institution, stressed the need to engage nurses experienced in administering chemotherapy. “You don’t want to have a brand new person doing that, and you have to have that independent double check,” so that there is more than one person looking at it and checking, for example if the dose and body surface area calculation is correct.

She stressed that these guidelines apply in both the inpatient and the ambulatory setting. Sometimes, she added, processes have not been as rigorous in ambulatory areas, but now there is a growing understanding that these precautions must be applied and guidelines adhered to across the board.

“Obviously, we do not want to do anything to harm our patients,” O’Leary said, “putting them at risk for extravasation or wrong doses, but we need to protect ourselves, too, from exposures. Nobody wants to have a mistake in the medication, especially with chemotherapy. Vigilance really is the key.”

		Polovich M, Olsen M, LeFebvre K, eds. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 4th ed. Pittsburgh, PA: 

		Mayer DK. Safe management of chemotherapy in the home. 

		Lee S, Mendez S. Educating Nurses on safe administration and management of oral chemotherapy. 

Careful adherence to safety guidelines for administering chemotherapy is not only critical in the inpatient setting but also in ambulatory facilities and increasingly in the home with a growing number of oral agents in use now and in the oncology drug pipeline.

Chemotherapy Safety Precautions Essential Across Practice Settings and in the Home

	Betsy Guimond is an Assistant Clinical Professor of Nursing and the Doctor of Nursing Practice Coordinator at Duquesne University School of Nursing, Pittsburgh, Pennsylvania.

Persistent infection with specific subtypes of human papillomavirus (HPV) has been definitively linked to progression to cervical cancer. The identification of the link between HPV and cancer has led to the development of a vaccine to prevent infection from the most prevalent cancer-causing subtypes (16 and 18) in the United States. Although vaccination against HPV is recommended for males and females because of the protection afforded against nongender— specific HPV-related cancer and disease, uptake and completion has been underwhelming—about 36% for teenage girls and 13% for boys.

The decision to refuse or delay vaccination has been linked to concerns about the safety profile for the HPV vaccine.

 Some researchers have pointed to the Vaccine Adverse Events Reporting System (VAERS) data as evidence of substantial risk associated with vaccination,

 but evidence does not exist that the deaths listed in the VAERS data are attributable to the vaccine. Arguments against vaccination also do not consider its benefits in reducing significant morbidity related to cervical biopsies, nor does it consider reduction in other HPV-related diseases.

Anaphylaxis is always an issue with vaccine, which is best dealt with by careful observation after vaccination. Syncope too, is a very real risk in vaccination, particularly for adolescents, but the risk is no greater for HPV vaccination than for other vaccines.

 Because nuanced questions around clinical trials fit easily into the anti-vaccine narrative and are often used out of context as arguments against dissemination of vaccine, healthcare providers must be able to address these concerns when they are posed by concerned parents or patients.

Reduction in vaccine-preventable HPV strains has been demonstrated in several large studies. When compared with prevaccine era data in the United States,

 a 56% decrease was reported in the prevalence of vaccine-preventable HPV among 14- to 19-year-olds. Data from countries where school-based programs are in effect show similar trends. In Australia, substantially lower rates of cervical abnormalities have been attributed to the quadrivalent HPV vaccine.

		Applying the 4-Cs Framework in a Discussion of HPV Vaccine

			Commit to staying up-to-date with the vaccine news by subscribing to CDC email or Twitter feeds to receive the latest information regarding HPV vaccination safety.

			Convey understanding that the potential for risk exists for one lot of the vaccine.

			Communicate the evidence that the risk is limited to a single lot and review the lot number of the vaccine that you are giving with the individual to allay their concern. Or, if vaccination has occurred, reassure patients and parents that the reaction is limited to redness and swelling at the site of vaccination.

			Collaborate about risks and concerns. Acknowledge that there are risks for all vaccines and address each concern in a respectful way. Provide anticipatory guidance that allows the parent or young adult to schedule an appointment for vaccination after you have presented the safety profile and long-term benefits of vaccination.

It can be difficult for many healthcare providers and parents to address the advantages of a vaccine that prevents sexually transmitted disease, and this challenge in communication may contribute to some of the confusion regarding how to recommend HPV vaccination in preteen children. An insidious belief persists that vaccination is tacit approval for sexual behavior, despite the lack of evidence that sexual behaviors are influenced by vaccination status.

 Further, the effectiveness of the vaccine is greater among children who are following the regular immunization schedule rather than the catch-up schedule for adolescents or young adults.

I developed the 4 Cs framework to facilitate difficult discussions when confronting misinformation about health-related topics. This framework may prove helpful when discussing the safety and efficacy of HPV vaccination.

 To communicate evidence-based practice, nurses should: commit to staying up-to-date with evidence; convey understanding about concerns; communicate the evidence/ answer questions; and collaborate with parents and young adults to acknowledge risks and concerns surrounding vaccination. For example, in December 2013, the CDC reported that one lot of Gardasil vaccine was being voluntarily recalled because of the potential for approximately 10 vials to contain glass particles.

 Although the risk of injury was very low, the potential for misrepresentation was high, making it an ideal opportunity to demonstrate the 4 Cs framework (Box).

The framework encourages the nurse to be knowledgeable about the evolving science supporting the safely of HPV vaccination and to seek common ground related to risk reduction for individuals who are at risk for HPV-related cancers.

		Stokely S. Update on HPV vaccination coverage in the US: Advisory Committee on Immunization Practices. http://www.cdc.gov/vaccines/ acip/meetings/downloads/slides-oct-2013/02-HPV-Stokley.pdf. Accessed April 15, 2014.

		Dorell C, Yankey D, Jeyarajah J, et al. Delay and refusal of human papillomavirus vaccine for girls, national immunization survey-teen, 2010. 

		Tomljenovic L, Shaw CA. Who profits from uncritical acceptance of biased estimates of vaccine efficacy and safety? 

		Briones R, Nan X, Madden K, Waks L. When vaccines go viral: an analysis of HPV vaccine coverage on YouTube.

		Markowitz LE, Hariri S, Lin C, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. 

		Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. 

		Macartney KK, Chiu C, Georgousakis M, Brotherton JM. Safety of human papillomavirus vaccines: a review. 

		Guimond ME. Confronting confirmation bias about breast cancer screening with the four Cs. 

		Centers for Disease Control and Prevention. Voluntary recall of one Lot of Gardasil HPV Vaccine. December 20, 2013. http://www.cdc.gov/ media/releases/2013/s1220-gardasil-vaccine.html. Accessed April 15, 2014.

Persistent infection with specific subtypes of human papillomavirus (HPV) has been definitively linked to progression to cervical cancer.