Oncology Nurse Advisor March/April 2015

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ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015

March/April 2015

www.OncologyNurseAdvisor.com A F O R U M F O R P H YS I C I A N A S S I S TA N T S

STEM CELL TRANSPLANTATION ■ Earn 1.0 contact hours

FREE CONTINUING EDUCATION INSIDE! Aspergillus infection in HSCT recipients, PAGE 18

ONCOLOGY NURSING

Screening for psychosocial distress in the inpatient setting

SIDE-EFFECT MANAGEMENT

Sexual dysfunction in a breast cancer survivor

COMMUNICATION CHALLENGES

The constancy of vulnerability

REFLECTIONS

Patient expectations for post cancer treatment surveillance

VOLUME 6, NUMBER 2

THE TOTAL PATIENT

Audiotherapy provides effective pain relief for pediatric patients

Best practices: Managing fungal infections in the immunosuppressed host Aspergillus fumigatus, a common fungus that can cause allergic disorder, respiratory infection, and invasive disease in humans.


PUBLISHING STAFF Editor Joyce Pagán editor.ona@haymarketmedia.com Senior digital content editor Rick Maffei Oncology writer Jason Hoffman, PharmD, RPh Contributing writer Bette Weinstein Kaplan Group art director, Haymarket Medical Jennifer Dvoretz Assistant art director Livvie Zurlini Production director Kathleen Millea Grinder Production manager Krassi Varbanov krassi.varbanov@haymarketmedia.com Circulation manager Paul Silver

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Oncology Nurse Advisor (ISSN 2154-350X), March/April 2015, Volume 6, Number 2. P ­ ublished 6 times annually by Haymarket Media Inc, 114 West 26th Street, 4th Floor, New York, NY 10001. Oncology Nurse Advisor is available for single copy purchases at the following rates. Price per copy: USA $20; Foreign $30. To order call (800) 558-1703. For advertising sales, call (646) 638-6000 (M-F, 9am-5pm, ET). Postmaster: Send changes of address to Oncology Nurse Advisor, P.O. Box 316, Congers, NY 10920. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher.

EDITORIAL BOARD Ann J. Brady, MSN, RN-BC Huntington Cancer Center Pasadena, California Jia Conway, DNP, FNP-BC, AOCNP, NP-C Cancer Care Associates of York York, Pennsylvania Marianne Davies, DNP, ACNP, AOCNP Smilow Cancer Center @ Yale New Haven New Haven, Connecticut Frank dela Rama, RN, MS, AOCNS Palo Alto Medical Foundation Palo Alto, California Donald R. Fleming, MD Cancer Care Center, Davis Memorial Hospital Elkins, West Virginia Susanne Menon, NP, OCN Center for Gynecologic Oncology Massachusetts General Hospital Cancer Center Boston, Massachusetts Leah A. Scaramuzzo, MSN, RN-BC, AOCN Billings Clinic, Inpatient Cancer Care Billings, Montana Lisa A. Thompson, PharmD, BCOP Kaiser Permanente Colorado Rosemarie A. Tucci, RN, MSN, AOCN Lankenau Hospital Wynnewood, Pennsylvania

6 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


CONTENTS 10

IN THE NEWS • Update: Disposal of unused medications • Epigenetic therapy boosts efficacy of chemotherapy in some lung cancers • Children of melanoma survivors need better sun protection … and more

14

ONCOLOGY NURSE ADVISOR FORUM • Assessing patency of an implanted port • Maximum tolerated doses of gemcitabine … and more

17

NAVIGATOR NOTES The art of assisting with cancer care decisions

10

30

March/April 2015

Frank dela Rama, RN, MS, AOCNS

18

CONTINUING EDUCATION How to manage Aspergillus infection in HSCT recipients Connie C. Chettle, MS, MPH, RN

37 25

FEATURES Screening for psychosocial distress: A review Tyler Cole, BSN, RN

28

Sexual dysfunction in a breast cancer survivor: A case study Ashleigh Long, PhD; Marcela del Carmen, MD, MPH; Don S. Dizon, MD

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HPV-positive oropharyngeal cancer has cure potential Bette Weinstein Kaplan

39 FIND US ON

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JOIN OUR COMMUNITY Submit a question to an oncology nurse advisor

CONTENTS

March/April 2015

Have a question? Our panel of oncology clinicians is available to answer your questions. Submit questions to editor.ona@HaymarketMedia.com. Answer the ONA poll question

33

STAT CONSULT Olaparib (Lynparza)

35

RADIATION & YOUR PATIENT Identifying biomarkers for radiation pneumonitis Bryant Furlow

37

COMMUNICATION CHALLENGES The constancy of vulnerability Ann J. Brady, MSN, RN-BC

39

ISSUES IN CANCER SURVIVORSHIP The unmet needs of cancer survivors: Quantifying the long-term effects of cancer Bette Weinstein Kaplan

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THE TOTAL PATIENT Postoperative audiotherapy provides effective pain relief for pediatric patients Bette Weinstein Kaplan

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FROM CANCERCARE Psychosocial challenges of pregnancy-associated breast cancer Allison Nilsen, MSW, LCSW

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REFLECTIONS Post cancer treatment surveillance Donald R. Fleming, MD

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ASK A PHARMACIST Ideal hydration infusion rate; sequence with gemcitabine Lisa A. Thompson, PharmD, BCOP

8 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com

ONA asks… Answer our poll question and compare your opinions with those of your colleagues on key nursing issues at OncologyNurseAdvisor.com Subscribe to ONA newsletters Stay current with daily news reports and special series from key oncology conferences on our Web site, sign up for our e-newsletters at OncologyNurseAdvisor.com/subscribe. Earn CE credits Each issue offers one new CE activity co-provided by the Nurse Practitioner Healthcare Foundation. Activities are active for 2 years. Socialize electronically Keep up with the oncology field through our social media. We’re on Twitter and Facebook. Now, we’re on Pinterest, too. Follow us!


The Pharmacology Courses You Need Available now on myCME! Developed by NPACE, one of the nation’s leading providers of nurse practitioner continuing nursing education, these courses will help you meet your state and national certification pharmacology credit requirements in one convenient web-based location. • Satisfy the new ANCC pharmacotherapeutic requirement • Clinically relevant topics, latest updates, clinical pearls, and tools you can implement immediately • Created by NPs, for NPs

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IN THE NEWS Update: Disposal of unused medications You may be used to the Drug Enforcement Agency (DEA) holding Drug Take-Back events in April and September.

California breast density law slow to have an impact Ten months after California legislators enacted a controversial law mandating that radiologists notify women if they have dense breast tissue, researchers have found that half of primary care physicians are still unfamiliar with the law and many Breast density laws do not feel comfortable answering still controversial breast density-related questions from patients. The findings suggest that if the law is going to have any significant impact on patient care, primary care providers need more education about breast density and secondary imaging options.

“Overall, the impact of the breast density legislation probably is not significant if primary care physicians are not educated or aware of it,” said lead author Kathleen Khong, MD, a University of California Davis radiologist and staff physician. “We should put some emphasis on educating primary care physicians so that when they get questions from patients, they can be comfortable in addressing the issues.” The California law requires notifying patients whose breast density is defined as heterogeneously dense or extremely dense that dense breasts make it harder to read mammograms. The researchers point out that breast density has long been a required part of any radiologic report following mammography, but unless a patient asks to see the report, the information is shared only with the patient’s providers. Led by patient advocates, the legislation is intended

10 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com

PHOTOS: © THINKSTOCK

Because the Controlled Substances Act did not permit hospitals, pharmacies, and other institutions to accept unused controlled substances, these events were created to provide patients with a means to dispose of these medications. Since the first event in 2010, more than 2,100 tons of prescription medications have been collected, preventing these from diversion or entering the water supply due to improper disposal. The Secure and Responsible Drug Disposal Act of 2010 authorized the DEA to develop regulations for the transfer of unused controlled substances and other prescription drugs to authorized collectors. These regulations, finalized in September 2014, allow certain DEA registrants (eg, pharmacies, hospitals/clinics with an on-site pharmacy, narcotic treatment programs) to become authorized collectors with the DEA. These authorized collectors may utilize an on-site collection receptacle or operate via a mail-back program. Some communities may still choose to hold a local drug take-back event; however, the DEA will no longer be sponsoring these nationally. Patients can locate an authorized collector in their community by calling the DEA’s Office of Diversion Control’s Registration Call Center at 1-800-882-9539, or by visiting https://www.deadiversion.usdoj.gov/pubdispsearch/spring/ main?execution=e1s1. An important note is that not all drug take-back programs will accept chemotherapy drugs or syringes, so patients should check with each program prior to transferring these substances to an authorized collector. For more information about these programs, visit http://www.deadiversion.usdoj.gov/drug_disposal/fact_sheets/ disposal_public.pdf.


Read more at https://bit.ly/1MNCxcU.

Epigenetic therapy boosts efficacy of chemotherapy in some lung cancers

institutions in the ECOG-ACRIN Cancer Research Group. ECOG-ACRIN investigators examined two different experimental treatment options in this work. In step one, patients were treated with PROSTVAC-V/ TRICOM and PROSTVAC-F/TRICOM. This virus is modified to produce a PSA protein that helps focus the body’s immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell’s ability to destroy its target (TRICOM). The second part of the study included the addition of hormone therapy to the PROSTVAC-VF/ TRICOM combination. In this step, 20 of the 27 eligible patients experienced a complete response at 7 months.

An existing drug may help some patients with non-small cell lung cancer (NSCLC) whose tumors have become resistant to chemotherapy. The findings, in human cancer cells and in mice, suggest a window of vulnerability in this disease. NSCLC Response in NSCLC is a highly genetically complex cancer subtypes improved with many different subtypes, each bearing different mutations. In two common subtypes that do not respond to standard chemotherapy, tumors with BRG1 or EGFR mutations, the researchers increased the effectiveness of etoposide by adding an epigenetic therapy already in clinical testing. Conversely, when the same epigenetic therapy (inhibition of the enzyme EZH2) was added to certain tumors without BRG1 and EGFR mutations, the tumors become more resistant to chemotherapy. Together, the findings advance the idea of individualized, precision medicine in cancer, incorporating epigenetic therapy guided by tumor genetic testing.

Vitamin D can protect some people with colorectal cancer by perking up the immune system’s vigilance against tumor cells. This new research represents the first time a link between vitamin D and the immune response to cancer has been shown in a large Sunshine vitamin human population. The finding adds prevents cancer to a growing body of research showing that vitamin D, which is known as the sunshine vitamin because it is produced in response to sunlight exposure, plays a key role in cancer prevention.

Read more at https://bit.ly/1xjuWiF.

Read more at https://bit.ly/1FFCP3B.

Study examines vaccine therapy for prostate cancer progression

New imaging technique improves detection of IBC in dense breast tissue

A vaccine therapy that stimulates the body’s own immune defenses can be given safely and earlier in the course of prostate cancer progression, according to researchers in a multi-institutional cooperative group. Their study aims to increase treatment options for patients with prostate cancer who experience early relapse. As part of a phase II clinical trial, adult patients with advanced prostate cancer whose cancer is resistant to hormone therapy and had either surgery or radiation were recruited from member

A new breast imaging technique nearly quadruples detection rates of invasive breast cancer (IBC) in women with dense breast tissue, according to the results of a major study. Approximately half of all women at screening age have dense breast tissue, according to Deborah Rhodes, MD, a Mayo Clinic Breast Clinic physician in Rochester, Minnesota, and the senior author of this study. Molecular Breast Imaging (MBI) is a supplemental imaging technology designed to find tumors that would

Read more at https://bit.ly/1CxHZgV.

Vitamin D boosts immune system to protect against colorectal cancer

www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 11

PHOTOS: © THINKSTOCK

to increase awareness of dense breasts and encourage patients to discuss the clinical issues with their doctors. According to published research, 28 states have passed, rejected, or considered dense-breast notification legislation since 2009.


IN THE NEWS otherwise be obscured by surrounding dense breast tissue on a mammogram. Tumors and dense breast tissue can both appear white on a mammogram, making tumors indistinguishable from background tissue in women with dense breasts. MBI increased the detection rate of invasive breast cancers by more than 360% when used in addition to regular screening mammography, according to the study. Read more at https://bit.ly/1MRpkxF.

experience possible cancer symptoms decide whether or not to seek medical help. They sent out a health survey that was completed by more than 1,700 people, ages 50 years and older, from three London PCP practices. The survey specifically did not mention cancer, but incorporated a list of 17 symptoms including 10 cancer alarm warning signs, such as persistent cough or hoarseness, unexplained lump, persistent change in bowel or bladder habits, and a sore that does not heal. Read more at https://bit.ly/18LHcNt.

SBRT plus chemotherapy improves survival in stage 4 lung cancer A clinical trial that combined stereotactic body radiation therapy (SBRT) with a specific chemotherapy regimen more than doubled survival rates for certain patients with stage 4 lung cancer. The combination of erlotinib with SBRT improved overall survival time to 20 months compared with historic 6- to 9-month survival times among patients treated with erlotinib only. The combination improved progression free survival from the historical 2 to 4 months to 14.7 months for similarly selected patients with lung cancer. This phase II clinical trial involved 24 patients with stage 4 non-small cell lung cancer (NSCLC) whose cancer continued to spread during their initial therapy. Such patients typically have poor survival rates, and SBRT is not typically used to treat these patients. Read more at https://bit.ly/1x54WHp.

PHOTOS: © THINKSTOCK

Patients’ dismissal of trivial symptoms could delay cancer diagnosis People who dismiss their symptoms as trivial or worry about wasting the doctor’s time may decide against going to their primary care physician (PCP) with red-flag cancer warning symptoms. Others might decide not to get possible cancer symptoms Red-flag symptoms checked out because they fear a canmay be ignored cer diagnosis; they adopt a stiff upper lip; they lack confidence in the health care system; or they think their problem is due to aging. Researchers with Cancer Research UK in London and Hull in the United Kingdom looked at how people who

Children of melanoma survivors need better sun protection A groundbreaking new study has discovered that children of melanoma survivors are not adhering optimally to sun protection recommendations. This is concerning as sunburns are a major risk factor for melanoma, and children of survivors are at increased Sunscreen alone is risk for developing the disease as not enough adults. University of California Los Angeles (UCLA) researchers used the California Cancer Registry to identify and survey 300 melanoma survivors with children ages 17 years and younger over a 3-year period. The study targeted both Latino melanoma survivors and non-Latino white melanoma survivors. In the observational study, the team asked parents about their attitudes towards melanoma prevention, how at risk for melanoma they believed their child to be, and their current use of sun protection strategies for their child. They found that many parents relied on sunscreen to protect their child against sun exposure, and fewer parents reported that their child wore a hat or sunglasses or attempted to seek shade when exposed to the sun. Read more at https://bit.ly/1BTxumr.

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ONCOLOGY NURSE ADVISOR FORUM Our Consultants Ann J. Brady, MSN, RN-BC, symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California.

Jia R. Conway, DNP, CRNP, FNP-C, AOCNP, oncology nurse practitioner at Cancer Care Associates of York in York, Pennsylvania. Abimbola Farinde, PharmD, MS, BCPP, CGP, LCDC, PM/ PRC, FASCP, FACA, FNAP, Rsci, ARSPharmS, clinical pharmacist specialist, Clear Lake Regional Medical Center, Webster, Texas Donald R. Fleming, MD, hematologist/oncologist, Cancer Care Center, Davis Memorial Hospital, Elkins, West Virginia. Kerstin L. Lappen, RN, MS, ACNS, ACHPN, clinical nurse specialist, palliative care consult service, Abbott Northwestern Hospital, Allina Health System, Minneapolis, Minnesota. K. Lynne Quinn, RN, MSN, CRNP, AOCNP, director of oncology, Bryn Mawr Hospital and Bryn Mawr Health Center, Bryn Mawr, Pennsylvania.

Lisa A. Thompson, PharmD, BCOP, clinical pharmacy ­specialist in oncology, Kaiser Permanente, Colorado

Rosemarie A. Tucci, RN, MSN, AOCN, manager for oncology research & data services, Lankenau Hospital, Wynnewood, Pennsylvania

QUESTIONS & ANSWERS ASSESSING PATENCY OF AN IMPLANTED PORT A patient has no blood return from their implanted port and is scheduled to receive a doxorubicin-containing regimen. The nurse administers CathFlo per the package insert, and a second dose is needed. Neither dose results in a blood return. The nurse calls the prescriber, who consults with Interventional Radiology (IR) to evaluate the implanted port for placement and orders a port flow study. The catheter tip is correctly placed, but a fibrin tail extends off the end of the catheter. The IR physician says the port is okay to use. For how long is it okay to use the port for chemotherapy? When should the port be replaced? The nurse elects to place a peripheral IV and administers the doxorubicin dose with no problems. How should this issue be dealt with next cycle? —Name withheld on request Fibrin overgrowth on the internal catheter is not exceptionally unusual. What must first be determined is whether it is actually a fibrin sheath or a tail (also known as a flap). A sheath, which looks like a sock covering part of the catheter including the tip, creates issues in infusing, as often solutions will infuse but may also travel back along the catheter creating issues of irritability and/or necrosis. The tail acts like a one-way valve, allowing infusion without complications or difficulty but prevents withdrawal of blood or other fluids to determine patency. Either way, a 2-mg infusion of CathFlo (low-dose altepase) is the choice for dealing with this issue. Assuming that the thrombolytic was administered by the insert directions (30 minute installation) twice, the other option is to allow the CathFlo to remain in the catheter overnight. This has been used successfully and without complications. Since today’s chemotherapy was then administered via a peripheral line, the issue is definitely what to do next cycle. If an overnight installation still fails to open the catheter to withdrawal of fluids, the surgeon should be notified for the possibility of having to replace the device before more chemotherapy is administered. —Rosemarie A. Tucci, RN, MSN, AOCN

MAXIMUM TOLERATED DOSES OF GEMCITABINE How much more toxicity and myelosuppression has been associated with gemcitabine (Gemzar) when it is infused over periods longer than 30 minutes? —Name withheld on request The maximum tolerated gemcitabine doses were 65 mg/m2 when the drug was infused over 30 minutes and 150 mg/m2 when the drug was injected over 5 minutes, in clinical trials. The limiting toxicities reported in these clinical trials included thrombocytopenia, flulike symptoms, and loss of strength and energy; therefore, adhering

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14 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


The Pharmacology Courses You Need Available now on myCME! Developed by NPACE, one of the nation’s leading providers of nurse practitioner continuing nursing education, these courses will help you meet your state and national certification pharmacology credit requirements in one convenient web-based location. • Satisfy the new ANCC pharmacotherapeutic requirement • Clinically relevant topics, latest updates, clinical pearls, and tools you can implement immediately • Created by NPs, for NPs

Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. ®

Nurse Practitioner Associates

for Continuing Education

Take a closer look at myCME, the fastest growing online resource for CE pharmacology credits.

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ONCOLOGY NURSE ADVISOR FORUM Fibrin overgrowth on the internal catheter is not exceptionally unusual. What must first be determined is whether it is actually a fibrin sheath or a tail (also known as a flap). to the recommended duration for administration is important due to the potential for increased toxicity. —Abimbola Farinde, PharmD, MS, BCPP, CGP, LCDC, PM/PRC, FASCP, FACA, FNAP, Rsci, ARSPharmS

FINDING A QUALIFIED ACUPUNCTURE PRACTITIONER Many patients seek acupuncture to help manage their chemotherapy-induced nausea and vomiting (CINV) and pain. How can nurses help patients fi nd a qualified practitioner who understands the needs of oncology patients? —Name withheld on request The National Cancer Institute recommends patients seek treatment from a qualified acupuncture practitioner who uses a new set of disposable (single-use) needles for each patient. AcuFinder.com is an online acupuncture referral service. The search page lists several criteria for refining your search, such as location, style of acupuncture, and technique. Its Area of Expertise menu includes “Oncology Support.” Search results include contact information, profile of the practitioner, link to practitioner’s web site, and directions. Acupuncturists may be licensed (L.Ac.) or certified, and patients should understand the difference when considering a practitioner. Although requirements to be a licensed acupuncturist in the United States are regulated by individual state law, general requirements include completion of an accredited acupuncture and Oriental medicine program that includes didactic instruction and clinical hours (a master’s level program) at a nationally recognized college of acupuncture, pass the National Certifi cation Commission for Acupuncture and Oriental Medicine (NCCAOM) exam, and complete continuing education courses to maintain their license.

Certified acupuncturists may be chiropractors and physicians who completed additional training. They are required to complete a certificate program, which can be completed in home study. They are not required to pass the NCCAOM certifi cation exam, nor are they required to complete continuing education to maintain their certifi cation. Lastly, patients should ask their health insurance provider whether their plan covers complementary and alternative medicines. Most insurance plans do not at this time; however, portions of the Affordable Care Act (ACA) may lead to changes in some states. —The Editors

HAIR DYE USE DURING CHEMOTHERAPY Is it safe to use hair dyes concurrently with chemotherapy? I always heard it was contraindicated, but I have not read any research on the subject. —Connie Flood, RN, OCN Whether hair dyes might raise cancer risk is not yet clear, and most studies to date have not found a significant link. Currently, no specific medical advice is suggested for current use of hair dye or for those who previously used hair dye, so the decision to initiate or to continue hair dye use involves an in-depth discussion of the risks versus benefit between the patient and the provider before a final decision can be made. —Abimbola Farinde, PharmD, MS, BCPP, CGP, LCDC, PM/PRC, FASCP, FACA, FNAP, Rsci, ARSPharmS

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NAVIGATOR NOTES

© THINKSTOCK

A

s oncology nurse navigators, we often are faced with helping patients and families make tough decisions about cancer treatment. In my own practice with prostate cancer, there can be several, seemingly equal, effective treatment options, with no true standout. Given our expertise and experience with patients, we are in a prime position to help with decision-making—not to give true medical advice, but to help patients and families arrive at a wellthought out decision. Shared Decision Making (SDM) is defined as a collaborative process that allows patients and their providers to make health care decisions together, taking into account the best scientific evidence available, as well as the patient’s values and preferences. SDM honors both the provider’s expert knowledge and the patient’s right to be fully informed of all care options and the potential harms and benefits. Using examples of decision making outside of health care can be a great way to shine a new light on using SDM in our practice. Poker—a science or an art? Successful poker players need to excel both in the rational (mathematical probabilities, odds), as well as the irrational or emotional (trying to gauge the mood and emotion of the other players, or even acting deliberately to affect how the others play and react). A premier poker player—and former physicist!—even says, “As a physicist, it can be hard admitting that you just can’t reason your way to the winning hand. But that’s the reality of poker. You can’t construct a perfect model of it. It’s based on a seemingly infinite amount of information. In that sense, poker is a lot like real life. “The best poker players don’t pretend that poker can be solved. They know the game is ultimately a mystery.”

The art of assisting with cancer care decisions Frank dela Rama, RN, MS, AOCNS

The mystery of prostate cancer

Prostate cancer treatment decisionmaking is also very much a mystery. Men are overwhelmed with a seemingly infinite amount of information. The stakes are high here, much higher than in poker, dealing with life itself. I have had the privilege of helping many men through this decision-making process, including highly intelligent engineers, scientists, and physicians. When they try to approach the decision from a purely rational perspective, it can become a very frustrating, drawn-out process, drowning in a sea of statistics,

with no easy percentages, such as 0% or 100%, anywhere to be found. We have to bring emotions into this thought process, not only to help the process along, but also to ensure the men are satisfied with their decision, given all the information currently on hand. Emotions here fall into a few categories. • The what ifs Of all the possible side effects, “Which ones could I live with? Which ones would ruin my life?” • Gut level feelings “I just got along better with that doctor vs. the other …” “My brother did great with that treatment, so I think I’ll go that route.” • How decisions affect my loved ones “I’m debating between active surveillance and surgery, but I think my wife would be too worried day to day if I decided just to watch and wait versus take it out.” Even more than poker, cancer is still a mystery. Dealing with cancer is both a science and an art, from both the patient’s and health care provider’s perspectives. Decisions are rarely 100% based on statistics and rationality alone. Decisions purely based upon emotion can be impulsive and sometimes foolish. As oncology nurse navigators, we can take on the role of a shared-decision making coach, advocating for patients as a nonvested third party with their best interests in mind. All I know is that the men who carefully—but not compulsively— considered all aspects of their prostate cancer treatment seem to be the most satisfied and comfortable with their decision, even years out, no matter what the outcome. ■ Frank dela Rama is a clinical nurse specialist, oncology/genomics, and prostate cancer navigator at Palo Alto Medical Foundation in Palo Alto, California.

www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 17


CONTINUING EDUCATION Disclosure of Conflicts of Interest Medical Education Resources ensures balance, independence, objectivity, and scientific rigor in all our educational programs. In accordance with this policy, MER identifies conflicts of interest with its instructors, content managers, and other individuals who are in a position to control the content of an activity. Conflicts are resolved by MER to ensure that all scientific research referred to, reported, or used in a continuing education activity conforms to the generally accepted standards of experimental design, data collection, and analysis. MER is committed to providing its learners with high-quality activities that promote improvements or quality in health care and not the business interest of a commercial interest. The faculty reported the following financial relationships with commercial interests whose products or services may be mentioned in this activity: Name of faculty

Reported Financial Relationship

Connie C. Chettle, MS, MPH, RN

No financial relationships to disclose

The content managers reported the following financial relationships with commercial interests whose products or services may be mentioned in this activity: Name of Content Manager

Reported Financial Relationship

Joyce Pagán

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Planners and Manager from MER

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Disclaimer The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Medical Education Resources or Haymarket Medical. The authors have disclosed if there is any discussion of published and/or investigational uses of agents that are not indicated by the FDA in their presentations. The opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of Medical Education Resources or Haymarket Medical. Before prescribing any medicine, primary references and full prescribing information should be consulted. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

EDUCATIONAL OBJECTIVES After participating in this activity, clinicians should be better able to • Describe the major risk factors for invasive aspergillosis • Explain prophylaxis and treatments for Aspergillus infection • List preventive measures that can reduce the risk for aspergillosis

STATEMENT OF NEED/PROGRAM OVERVIEW Patients undergoing hematopoietic stem cell transplantation (HSCT) are more susceptible to invasive fungal infections because their therapy includes immunosuppression. Aspergillosis is the most common fungal infection and the most common cause of infectious death among HSCT recipients. Successful treatment depends on early diagnosis; however, diagnosis can be difficult. This activity discusses the host and environment risk factors that contribute to invasive aspergillosis, as well as diagnostic tests and treatment options for managing the treatment of these patients. FACULTY Connie C. Chettle, MS, MPH, RN Epidemiologist St. George, Utah LEARNING GOAL/PURPOSE To better understand how cancer immunotherapies use the body’s natural defenses to identify and kill cancer cells. NURSING CREDIT Medical Education Resources is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This CE activity provides 1 contact hour of continuing nursing education, of which 0.20 is pharmacology. Medical Education Resources is a provider of continuing nursing education by the California Board of Registered Nursing, Provider #CEP 12299, for 1 contact hour. METHOD OF PARTICIPATION There are no fees for participating in and receiving credit for this activity. During the period February 2015 through February 2016, participants must 1) read the learning objectives and faculty disclosures, 2) study the educational activity, 3) complete the posttest by selecting the best answer to each question on the posttest, 4) complete the evaluation form, and 5) continue to next section to claim credits and view your certificate. A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better. Statements of credit are available at the conclusion of the activity. MEDIA

Journal article and Web site (myCME.com; OncologyNurseAdvisor.com) Co-provided by Medical Education Resources and Haymarket Media Inc.

18 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


TARGET AUDIENCE

PROGRAM INFORMATION

• This activity has been designed to meet the educational needs of registered nurses and nurse practitioners involved in the management of patients with cancer.

• Estimated time to complete this activity: 1 hour • Release date: February 2015 • Expiration date: February 2016

How to manage Aspergillus infection in HSCT recipients This review discusses common risk factors, treatment options, and preventive measures for aspergillosis in hematopoietic stem cell transplantation recipients. CONNIE C. CHETTLE, MS, MPH, RN

© EYE OF SCIENCE / SCIENCE SOURCE

A

49-year-old female presented to the hospital with a 3-week history of severe headache, nasal stuffiness, facial pain, and numbness at the left side of her nose and under her left eye. The area around her left eye was swollen and the skin under the eye and along the side of her nose was slightly darkened and discolored. The patient stated she was having difficulty moving her left eye. Her past medical history included an allogeneic stem cell transplant for leukemia, corticosteroids for chronic graft-versus-host disease (GVHD), and cytomegalovirus infection. Nasal endoscopy revealed blackish crusting and extensive necrotic tissue in the nasal cavity. Computed tomography (CT) showed evidence of sinus wall erosion and extension of infection to the orbital area. The patient refused treatment that would have included extensive surgical resection. She died 3 weeks after admission. Aspergillosis is the most common invasive fungal infection in patients undergoing

Inhaled Aspergillus fumigatus spores can lead to respiratory aspergillosis. The fungus may occasionally invade tissue spreading from the lungs to the brain, kidneys, liver, and skin.

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CONTINUING EDUCATION | Aspergillus infection in HSCT recipients hematopoietic stem cell transplantation (HSCT) and the main cause of infectious death. In allogeneic HSCT recipients, the incidence of Aspergillus infection is estimated to be 5% to 10% and mortality from invasive aspergillosis ranges from 80% to 100%.1,2 THE ORGANISM Aspergillus infections are caused by a ubiquitous, filamentous fungal saprophyte widely found in both outdoor environments—air, water, soil, decomposing organic debris—and indoor environments—ventilation systems, dust, etc. In nature, Aspergillus forms a dense mass of branching thread-like hyphae (mycelium). It reproduces by generating enormous numbers of small spores called conidia. These small spores are 2 to 3 microns in size and extend out on long chains from a mycelial mass that easily detaches to become airborne. The spores/conidia are well-adapted for air dispersal. Their small size and hydrophobicity allow them to remain airborne for long periods of time.3 When they eventually settle out, they contaminate all surfaces in contact with the air (indoor or outdoor) and with any air movement, they become airborne over and over again.3 People become exposed to Aspergillus

Invasive aspergillosis usually involves the lungs or paranasal sinuses but can involve virtually any organ in the immunosuppressed host. when these airborne spores are inhaled and settle into the nose, paranasal sinuses, or the lungs. The average immunocompetent human inhales hundreds of Aspergillus conidia each day without detrimental consequences. The conidia that access terminal airways are cleared by alveolar macrophages capable of ingesting and killing the conidia. In addition, macrophages secrete cytokines and chemokines to recruit a secondary defense.1 Conidia that escape the macrophage killing and germinate into the more invasive hyphae (branching, threadlike filaments) are destroyed by infiltrating neutrophils.4 In immunocompromised hosts, however, macrophage function is sufficiently disabled to allow conidial germination and the formation of hyphal forms that can invade the lung tissues and pulmonary vasculature and disseminate through the blood stream. The hyphal invasion of blood vessels with vascular thrombosis and tissue infarction is a central feature of invasive aspergillosis (IA). The resulting

tissue necrosis limits the penetration of immune cells to the infection site. Aspergillus fumigatus is the most common cause of invasive aspergillosis, accounting for approximately 90% of cases, although other Aspergillus species—Aspergillus flavus, Aspergillus niger, and Aspergillus terreus—have also been isolated from patients with invasive disease.5 HOST RISK FACTORS Certain host factors place HSCT recipients at increased risk of Aspergillus infection. These include (1) type of transplant (autologous vs allogeneic, peripheral blood vs bone marrow); (2) graft-versus-host disease (acute grades 3-4 or chronic extensive GVHD); (3) prolonged corticosteroid use (mean minimum dose of 0.3 mg/kg/d of prednisolone or equivalent for more than 3 weeks); (4) neutropenia (neutrophil count less than 500/mm3 for more than 10 days); and (5) recurrent cytomegalovirus (CMV) infection requiring ganciclovir therapy. CMV, a herpes virus, is associated with an increased risk for invasive fungal infections and serious disease. After a primary infection, CMV remains latent in the human body for life and can reactivate. The risk for recurrence (reactivation) is especially high in seropositive immunocompromised patients. To prevent CMV recurrence, prophylactic therapy with ganciclovir/valganciclovir is often used during the period from engraftment to 100 days after transplantation. The use of ganciclovir increases the risk for invasive aspergillosis, with a hazard ratio of 13.5. This is even higher than the hazard risk for corticosteroids, graft versus host disease, or neutropenia.2 In addition to these risk factors, the baseline medical status of the HSCT recipient (underlying medical condition, previous immune status, prior medications, prior latent infections, etc.), can also lead to an increased risk of infection.1,2,6 Traditionally, patients who received bone marrow stem cells were at highest risk for Aspergillus infection during their prolonged periods of neutropenia. However, with the current use of peripheral stem cells for transplantation, Aspergillus infections occur predominantly in nonneutropenic patients, late after engraftment during intensive therapy with corticosteroids for chronic GVHD.7 The patients at highest risk for Aspergillus infections are allogeneic HSCT recipients because of the longer time needed for engraftment (prolonged neutropenia) and the increased risk of graft versus host disease. Note: autologous transplant recipients have a shorter period of pre-engraftment neutropenia and do not develop graft versus host disease; therefore, these patients have less risk for infection.6 Among allogeneic HSCT recipients, the two periods of greatest risk for invasive aspergillosis are the pre-engraftment

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period (Phase I), which is up to 20 to 40 days posttransplantation, and the late post engraftment period (Phase III), which is more than 100 days after transplantation and continues until the HSCT recipients stops all immunosuppressive medication for GVHD.1,6 In the pre-engraftment period, the onset of aspergillosis is usually due to neutropenia and the breakdown of barrier defenses, whereas the later and more common onset of aspergillosis is due to development of GVHD and the need for chronic corticosteroid therapy. In the pre-engraftment period, fungal infections have been reported as high as 10% to 20% with risk increasing after 5 to 7 days of continuous neutropenia. Candida and Aspergillus account for more than 80% of these fungal episodes.6 In the postengraftment period, the risk of aspergillosis increases due to intensive immunosuppressive therapy using corticosteroids for chronic GVHD. Corticosteroids impair the killing of conidia and hyphae by macrophages and neutrophils. Corticosteroids also increase the linear growth rate of Aspergillus by as much as 40% and cell synthesis by greater than 150%.8 Cytomegalovirus and the drug (ganciclovir) used to treat the virus are also associated with increased risk for invasive aspergillosis.2 CLINICAL MANIFESTATIONS Invasive aspergillosis usually involves the lungs or paranasal sinuses but can involve virtually any organ in the immunosuppressed host. Infection most commonly occurs when airborne conidia are inhaled into the sinuses or lungs. Most Aspergillus conidia, because of their small size, are able to penetrate deep into the lungs. As a result, the lungs are the site of 80% to 90% of invasive Aspergillus infections. Symptoms are usually nonspecific and subtle, which makes early diagnosis difficult. Patients with invasive pulmonary aspergillosis (IPA) may present with fever unresponsive to antibiotics (although fever may not be present in patients receiving corticosteroids), dry nonproductive cough, and dyspnea. They may also have pleuritic chest pain caused by pulmonary vascular invasion by the fungi. This can lead to cavitation and/or hemoptysis. Erosion into the wall of a large central blood vessel can cause a massive pulmonary hemorrhage.5,9 Rhinocerebral aspergillosis occurs in 10% to 20% of patients with IA. With immunocompromised persons, inhaled Aspergillus conidia can settle in the nasal turbinates, germinate, and invade the sinuses. From the sinuses, the hyphae can then rapidly extend into the palate causing necrosis and perforation into the oral cavity or the nasal septum. Extension into the eye can result in proptosis, cranial nerve palsies, and loss of vision; extension into the brain can lead to a variety of central nervous system symptoms depending on

TABLE 1. Criteria for probable invasive fungal disease11 Host factors • Recent history of neutropenia (<500 neutrophils/mm3 for more than 10 days, related to the onset of fungal disease) • Receipt of an allogeneic stem cell transplant • Prolonged use of corticosteroids at a mean minimum dose of 0.3 mg/ kg/d of prednisone equivalent for more than 3 weeks • Treatment with other recognized T cell immunosuppressants such as cyclosporine, TNF-α blockers, specific monoclonal antibodies, or nuceloside analogues during the past 90 days Clinical criteria • Lower respiratory tract fungal disease The presence of one of the following signs on CT ▪ Dense, well-circumscribed lesions with or without a halo sign ▪ Air-crescent sign ▪ Cavity • Sinonasal infection Imaging showing sinusitis plus at least 1 of the following signs ▪ Acute localized pain (including pain radiating to the eye) ▪ Nasal ulcer with black eschar ▪ E xtension from the paranasal sinus across bony barriers, including into the orbit • CNS infection One of the following signs ▪ Focal lesions on imaging ▪ Meningeal enhancement on MRI or CT

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Mycological criteria • Direct test (cytology, direct microscopy, or culture) Mold in sputum, bronchoalveolar lavage fluid, bronchial brush, or sinus aspirate samples, indicated by one of the following ▪ Presence of fungal elements indicating a mold ▪ Recovery by culture of a mold (eg, Aspergillus) • Indirect tests (detection of antigen or cell-wall constituents) Aspergillus ▪G alactomannan antigen detected in plasma, serum, bronchoalveolar lavage fluid, or CSF ▪ β-D-glucan detected in serum

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the location of the advancing infection. Aspergillus sinusitis is associated with a high mortality rate with the disease being very aggressive. Symptoms include headache, nasal congestion, loss of smell, black nasal/eye discharge, and pain in the face and around the eye.5,10 Cerebral aspergillosis, the most lethal form of invasive disease, occurs in 10% to 20% of patients with IA and nearly always causes death. The fungus disseminates to the brain either through direct extension from the paranasal sinuses or via hematogenous dissemination from a pulmonary infection. Symptoms include focal seizures, changes in mental status, hemiparesis, cranial nerve palsies, and hemorrhagic infarcts caused by vascular invasion.2,5 Continues on page 22

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CONTINUING EDUCATION | Aspergillus infection in HSCT recipients DIAGNOSIS Early diagnosis of aspergillosis is difficult, and a definitive diagnosis is often not possible in clinical practice ( Table 1). Blood cultures have limited value for detecting IA because they are often not positive, even in disseminated disease, and the presence of Aspergillus in the respiratory tract or urine can simply reflect colonization or contaminants. Serologic tests that identify components of the Aspergillus cell wall such as the Aspergillus serum galactomannan antigen test and the β-D-glucan serum assay are helpful. Unfortunately, these tests are not always reliable. They have low sensitivity in patients receiving antifungal prophylaxis—which includes virtually all HSCT recipients and patients with hematologic malignancies; medications such as β-lactam antibiotics (piperacillin/tazobactam and amoxicillin-clavulanate) can be associated with false-positive results due to the presence of galactomannan in the antibiotic formulations; and corticosteroid-induced immunosuppression also decreases the reliability of the tests. In addition, the galactomannan test is not specific for Aspergillus infection. It cannot determine whether the infection is caused by Aspergillus, Zygomycetes, or any of several other non-Aspergillus mold infections.2,7 A CT scan is usually the first significant diagnostic test when invasive pulmonary aspergillosis is suspected. The presence of multiple nodules and the halo sign, which appears as an area of low attenuation due to alveolar hemorrhage surrounding the nodular lesion, is strongly suggestive of Aspergillus infection in a neutropenic HSCT patient. The appearance of the halo sign is transient. It appears usually in the first week of infection and may not be seen later in the course of disease in non-neutropenic patients.10 In addition, other fungi and bacteria (eg, Zygomycetes, Pseudomonas aeruginosa) can produce a similar finding. An air crescent sign, caused by contraction of infarcted tissues, appears late in the course of infection and is highly specific for angio-invasive molds. For patients with paranasal or CNS TABLE 2. Major sources of Aspergillus conidia3,9 Host factors • Building renovations, excavations, and construction work • Ventilation systems • Dust (eg, infrequently cleaned areas of houses, basements, and attics) • Fresh and dried flowers and the soil of ornamental plants • Foods, including tea, fruits, spices (particularly pepper) • Tobacco and marijuana smoke (release large quantities of conidia) • Gardening (eg, grass cutting, digging, potting plants, raking leaves) • Household cleaning (eg, vacuuming, dusting) • Water storage tanks • Bedding and pillows • Computer fans

symptoms, CT scans of the paranasal sinuses and/or brain should be considered and endoscopic sinonasal examinations with biopsies should be performed.2 The gold standard for proven Aspergillus infection is detection of hyphae in tissue taken from the site of disease plus isolation of the organism in culture.11 TREATMENT FOR INVASIVE ASPERGILLOSIS Successful treatment depends on early diagnosis of aspergillosis, and more importantly, on decreasing the host immune defects such as neutropenia and/or high-dose corticosteroid therapy. Voriconazole and amphotericin B deoxycholate (d-AMB) are the only drugs approved in the United States for primary treatment of invasive aspergillosis. Voriconazole has the best clinical activity against Aspergillus and is considered the gold standard for treatment of aspergillosis. It has milder side effects (visual disturbances, liver function test abnormalities, and skin reactions) and is better tolerated than amphotericin B.7 Liposomal amphotericin B can be used as a second-line agent for patients who cannot tolerate voriconazole and in cases where Aspergillus is resistant to voriconazole (resistance to voriconazole was 17% in 2007). For salvage therapy, the lipid formulation of amphotericin B, caspofungin, micafungin, posaconazole, and itraconazole are suggested.2 As exposure cannot be entirely eliminated, prophylaxis with antifungal agents may be needed. Posaconazole is recommended as an antifungal prophylactic for HSCT recipients, especially those with GVHD who are at high risk for invasive aspergillosis.10 PREVENTING ASPERGILLOSIS With the continuing increase in the number of HSCT recipients, the prevention of invasive aspergillosis has become a major issue in managing patients posttransplant. Aspergillus is ubiquitous in the environment and given the uncertainty of the incubation period for infection, determining whether aspergillosis was acquired inside or outside the hospital is often difficult. A clear understanding of where Aspergillus conidia can be found in both the hospital and home environments is needed to protect high-risk patients from exposures. Table 2 lists the major sources of Aspergillus conidia to consider. Although some degree of Aspergillus exposure in hospitals is unavoidable, any increase in airborne conidia raises the risk of infection for HSCT patients. To lessen their exposure, HSCT patients should be placed in a protected environment during hospitalization. Patient rooms should have the following features: • Ventilation to provide 12 air exchanges/h or more.

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• HEPA filters with 99.97% efficiency for removing particles 0.3 microns or greater in diameter from incoming air. • Directed airflow (ie, air intake occurs at one side of the room and air exhaust occurs at the opposite side of the room). • Positive air pressure relative to the corridor, toilets, anterooms, and other hospital areas. • Well-sealed rooms to prevent infiltration of air from outside the room that could allow entry of conidia. • Self-closing doors to maintain constant pressure differentials. • Routine daily cleaning with special attention to dust control (ie, damp dusting of exhaust vents, window sills, and all horizontal surfaces).

Clinical symptoms are nonspecific and diagnostic tests are insensitive. Therefore, preventive measures are of major importance. • Floor surfaces should be smooth and nonporous. No carpeting in patient rooms or hallways. Patients should not be exposed to vacuuming that can cause aerosolization of fungal conidia. Vacuums should be equipped with HEPA filters. • No upholstered furniture in rooms. • Potted plants, dried or fresh flowers, and fruits should not be allowed in patient rooms and other hospital areas of patient exposure.9,12 • Patients should wear N-95 respirators when they leave their protected environment for treatment or diagnostic tests in other areas of the hospital. In addition to air, hospital water and plumbing systems should be considered as a potential source of Aspergillus infection. Aspergillus is commonly found in hospital water distribution systems where it forms biofilms on the inner surfaces of water tanks and pipes. Aerosolization of waterborne Aspergillus conidia from these systems can increase conidial air counts in patient rooms despite the widespread implementation of air precautions. The highest counts are

usually concentrated in patient bathrooms where aerosolization from showers, running faucet water, and flushing toilets occurs. Note that chlorination has no effect on Aspergillus. In order to help prevent Aspergillus infections from aerosolized water, minimizing patient exposure is recommended. High-risk patients should avoid showering and exposure to faucet water, and f lushing toilets. Commercially bottled sterile or boiled water should be provided for drinking and brushing teeth instead of tap water. To avoid the aerosolization associated with showering, sponges and bed baths might be considered.9 As an added protection, certain foods should be avoided during the high-risk periods of neutropenia/GVHD. This is because Aspergillus is frequently found on food. For example, in a food contamination survey, Aspergillus was cultured from 100% of black pepper and tea bag samples; 12% to 66% of fruits, with apricots and other fruits with downy skins registering the heaviest contamination; and 20% of freeze-dried soups.13 Smoking tobacco and/or marijuana has also been shown to release large quantities of Aspergillus conidia.3 CONCLUSION Invasive aspergillosis is a devastating complication after hematopoietic cell transplantation. The high mortality associated with this infection presents a challenge for health care professionals. Clinical symptoms are nonspecific and diagnostic tests are insensitive, making diagnosis difficult. Therefore, preventive measures are of major importance in the care of all HSCT recipients. ■ Connie Chettle is an epidemiologist living in St. George, Utah. REFERENCES 1. Chai LY, Vonk AG, Kulberg BJ, Netea MG. Immune response to Aspergillus fumigatus in compromised hosts: from bedside to bench. Future Microbiol. 2011;6(1):73-83. http://www.medscape.com/viewarticle/ 734798. Accessed February 11, 2015. 2. Kriengkauykiat J, Ito JI, Dadwal SS. Epidemiology and treatment approaches in management of invasive fungal infections. Clin Epidemiol. 2011:3;175-191. 3. O’Gorman CM. Airborne Aspergillus fumigatus conidia: a risk factor for aspergillosis. Fungal Biol Rev. 2011;25(3):151-157. 4. Sherif R, Segal BH. Pulmonary aspergillosis: clinical presentation, diag-

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nostic tests, management and complications. Curr Opin Pulm Med. 2010;16(3):242-250. 5. Barnes PD, Marr KA. Aspergillosis: spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am. 2006;20(3):545-561. References continue on page 24

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CONTINUING EDUCATION | Aspergillus infection in HSCT recipients 6. Chawla R, Davies HD. Infections after bone marrow transplantation. Medscape Web site. http://emedicine.medscape.com/article/1013470overview#a1. Updated June 27, 2013. Accessed February 11, 2015. 7. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156-174. 8. Boucher HW, Patterson TF. Aspergillosis. In: Hospenthal DR, Rinaldi MG,

Diseases Mycosis Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813-1821. 12. Tomblyn M, Chiller T, Einsele H, et al; Center for International Blood and Marrow Transplant Research; National Marrow Donor program; European Blood and Marrow Transplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow

eds. Diagnosis and Treatment of Human Mycoses. Totowa, NJ: Humana

Transplant Group; Infectious Diseases Society of America; Association

Press; 2008:chap 9.

of Medical Microbiology and Infectious Disease Canada; Centers for

9. Warris A, Verweij PE. Clinical implications of environmental sources for Aspergillus. Med Mycol. 2005;43 suppl 1:S59-S65. 10. Walsh FJ, Anaissie EJ, Denning DW, et al; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327-360.

Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. 13. Bouakline A, Lacroix C, Roux N, et al. Fungal contamination of food in hematology units. J Clin Microbiol. 2000;38(11):4272-4273.

11. De Pauw B, Walsh TJ, Donnelly JP, et al; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections

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FEATURE | Psychosocial screening

Screening for psychosocial distress: A review Distress screening at pivotal points in care helps nurses identify which patients need additional support as they cope with their disease and treatments. TYLER COLE, BSN, RN

A

© THINKSTOCK

cancer diagnosis is often accompanied with many unanswered questions and concerns, leading to one of the most underestimated effects of cancer: psychosocial distress. In addition to personal and financial concerns, side effects of the disease and treatments can exacerbate the symptoms of distress. Distress is defined as “a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment.”1 The term was adopted in the health care setting as an alternative to terms such as depression, and its use is proven to increase effective communication with patients.1 It encompasses the full spectrum of psychological and social factors and carries less of a social stigma, making it easier for patient self-identification. In addition, the increase in options for detection and treatment of cancer has led to an increase in the number of long-term side effects that often impact a patient’s quality of life. Nurses have the opportunity to play a key role in assessing psychosocial distress in oncology patients with the use of existing screening tools at pivotal points in the patient’s treatment. This paper analyzes the research on screening for psychosocial distress and concludes with nursing implications for practice and calls for further research. ROUTINE SCREENING The Institute of Medicine (IOM) released an expert opinion on providing quality integrated

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FEATURE | Psychosocial screening care for the patient with cancer, focusing on psychosocial needs, and recommended that all oncology patients be provided with adequate care that meets the standards for whole body, psychosocial health care.2 When assessing a patient’s psychosocial health, routine screening for symptoms of distress is critical. Because distress can occur at any point within the patient’s care continuum, screening at both the inpatient and outpatient levels is important. Distress screening in the outpatient and

Future nursing-led research should focus on refining the screening process within the inpatient setting. clinic setting has become more widely adopted over the past few years, but many facilities still lack inpatient screening. A study focusing on inpatient oncology screening discovered high levels of psychosocial and physical distress in two-thirds of the 80 patients who participated.3 The American College of Surgeons (ACOS) Commission on Cancer (CoC) requires all cancer centers to implement routine screening for psychosocial distress as of January 2015; however, this recommendation does not delineate between inpatient and outpatient services and the definition of routine is unclear.3 In the inpatient setting, identification and treatment of co-morbid psychosocial conditions may be limited due to inadequate screening, either by the physician team or frontline nursing staff. There are several reasons why distress may go unrecognized within the health care setting. Patients with symptoms of distress often have difficulty verbalizing their concerns to their caregivers, especially in today’s fast paced health care setting.4 Furthermore, many clinicians assume that distress is a normal part of the cancer diagnosis, but do not assess for specific needs or probe for problems.4 If psychosocial needs are to be addressed in the inpatient setting, identifying patient needs and initiating appropriate interventions in a timely manner is critical. These interventions include coordination of referrals that aid in providing the patient with quality holistic care based on screening results.2 NCCN DISTRESS THERMOMETER ACOS recommends the use of a distress-screening tool that assesses a multitude of psychosocial symptoms. A standardized screening tool should be used at routine intervals to improve the consistency of care and the overall outcome for the

patient.5 By utilizing a standardized screening tool, health care providers can perform effective and timely screenings, thereby identifying at-risk patients. Even though several instruments exist for identifying psychosocial distress, the National Comprehensive Cancer Network Distress Thermometer (NCCN DT) has become one of the most widely used and verified screening tools specifically for oncology patients.1 The NCCN DT is a self-administered tool with a 0-10 thermometer scale and a 34-point problem list to help identify the areas and severity of distress patients experienced during the previous week with a sensitivity of 0.77 and specificity of 0.68.6 Buchmann demonstrated its effectiveness in his evaluation of psychosocial distress in patients with head and neck cancer.7 He concluded that utilizing this tool was helpful in identifying patients with high levels of psychosocial distress and successfully providing interventions for those patients. In another study, the NCCN DT was used to demonstrate that patients’ distress increased throughout their treatment time, and higher numbers of referrals for supportive services led to increased patient satisfaction scores.8 CLINICAL IMPLICATIONS AND RECOMMENDATIONS ACOS, NCCN, the Oncology Nursing Society (ONS), and IOM each released statements highlighting the significant role that psychosocial health plays in an oncology patient’s course of care.1,2,5 NCCN urges health care workers to assess for distress at appropriate intervals, as indicated throughout their treatment and disease process.1,5 If screening is only performed one time in a patient’s course of care, a change in level of distress may go unrecognized and subsequently untreated.5 Therefore, psychosocial distress screening should be performed with each visit in the outpatient setting, especially prior to chemotherapy or radiation therapy. In the inpatient setting the same screening tool can be used at key points, such as on admission to a unit, prior to surgery, post surgery, prior to chemotherapy, prior to bone marrow transplant, and at the time of discharge. When a patient is found to have psychosocial distress, the nurse should refer the patient to supportive services to more fully assess how the patient is coping and recommend additional interventions as part of the overall treatment plan.5 Many interventions and referrals are available for the patient experiencing distress including chaplain services, outpatient psycho-oncology referrals, financial services, psychiatry, social workers, and psychiatric liaison nurses. The goal of psychosocial distress screening is to identify those in need of intervention and to utilize best resources possible for those interventions. If other providers fail to

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screen and treat patients with high levels of distress it may decrease their quality of life, jeopardize their outcomes, and increase health care costs.9

2. Clark PG, Rochon E, Brethwaite D, Edmiston KK. Screening for psychological and physical distress in a cancer inpatient treatment setting: a pilot study. Psychooncology. 2011;20(6):664-668. doi:10.1002/pon.1908.

CONCLUSION Implementing a nurse-driven, standardized distress screening tool in the inpatient setting will help ensure that patients receive cohesive and consistent care in both the inpatient and outpatient settings while aspiring to improve quality of life and treatment outcomes for oncology patients. Nurses must become the leaders in developing and defining effective screening protocols for distress in order to provide patients with high quality, individualized care that addresses their emotional, physical, psychological, and spiritual needs throughout their journey of care. Future nursing-led research should focus on refining the screening process within the inpatient setting, creating practical referral systems, developing screenings for distress specifically within the pediatric and geriatric population, and coordinating care between inpatient and outpatient visits. ■

3. Hegel MT, Moore CP, Collins ED, et al. Distress, psychiatric syndromes, and impairment of function in women with newly diagnosed breast cancer. Cancer. 2006;107(12):2924-2931. http://onlinelibrary.wiley.com/ doi/10.1002/cncr.22335/abstract. Accessed March 25, 2015. 4. Adler NE, Page AEK, eds; Committee on Psychosocial Services to Cancer Patients/Families in a Community Setting; Board on Health Care Services. Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. Washington, DC: The National Academies Press; 2008. http:// www.nap.edu/openbook.php?record_id=11993&page=23. Accessed March 25, 2015. 5. Johnson RL, Gold MA, Wyche KF. Distress in women with gynecologic cancer. Psychooncology. 2010;19(6):665-668. 6. Buchmann L, Conlee J, Hunt J, et al. Psychosocial distress is prevalent in head and neck cancer patients. Laryngoscope. 2013;123(6):1424-1429. doi:10.1002/lary.23886. 7. Fulcher CD, Gosselin-Acomb TK. Distress assessment: practice change through guideline implementation. Clin J Oncol Nurs. 2007;11(6):817-821.

Tyler Cole works on a surgical oncology floor at the Medical University of South Carolina, in Charleston, South Carolina; he is also a Doctorate of Nursing Practice student at the Medical University of South Carolina College of Nursing.

doi:10.1188/07.CJON.817-821. 8. Pirl WF, Braun IM, Deshields TL, et al. Implementing screening for distress: the joint position statement from the American Psychosocial Oncology Society, Association of Oncology Social Work and Oncology Nursing Society. https://apos-society.org/docs/APOS.AOSW.ONS.

REFERENCES

StmtDistressScreening.16July13.pdf. Published July 16, 2013. Accessed

1. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Distress management. (2014). National Comprehensive

March 25, 2015. 9. Zabora J, BrintzenhofeSzoc K, Curbow B, et al. The prevalence

Cancer Network. http://www.nccn.org/professionals/physician_gls/pdf/

of psychological distress by cancer site. Psychooncology.

distress.pdf. Accessed March 25, 2015.

2001;10(1):19-28.

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FEATURE | Benign sexual headache

Sexual dysfunction in a breast cancer survivor: A case study This case study examines a case of sex-related headaches in a breast cancer survivor after treatment for ductal carcinoma in situ (DCIS). ASHLEIGH LONG, PhD; MARCELA DEL CARMEN, MD, MPH; DON S. DIZON, MD

T

© THINKSTOCK

he Oncology Sexual Health Clinic at the Massachusetts General Hospital in Boston was established in late 2012 and aims to provide resources for patients who experience changes related to sexuality, sexual relationships, and intimacy after a diagnosis and/or treatment for cancer—an area that has proven to be a great need and interest within the oncology community. A LIVESTRONG survey in 2010, which included more than 3,000 cancer survivors, reported that more than 60% of respondents had sexual function and satisfaction issues after cancer, making it the third most frequently reported physical concern in this group of patients.1 While sexual health concerns are common among the general population, we must constantly keep an open mind to concerns related to sexual health in cancer survivors, because as illustrated in this case study, not all concerns are related to their prior treatment for cancer. CASE Joan* is a 65-year-old woman with a remote history of ductal carcinoma in situ (DCIS) who was referred to the Oncology Sexual Health Clinic for evaluation of sexual dysfunction. She stated that she experiences severe headaches during sex and that they occur near climax. The headaches occur regardless of whether she *Names and case details were changed to protect patient privacy.

28 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


achieved climax alone or with a partner, and the headaches do not occur at any other time. Ultimately, the headaches were severe enough that she had abstained from sexual activity for the past 6 years. She described the headaches as “crushing,” located in her frontal and temporal regions with radiation down both sides of her face. There were no associated symptoms, and, specifically, she denied tingling or numbness, seizures, or loss of consciousness. Of note, the headaches had not changed in character or occurred with any other physical activities. As she was no longer sexually active, she was not currently experiencing the headaches, however, she longed for sexual relations and a new partner—something that she had not been able to maintain because of the headaches. Prior to the onset of symptoms Joan reported a very fulfilling sexual life, without issues of attraction, pain, or orgasm. She denied any conscious precipitating event, including prior histories of physical or emotional abuse, sexual trauma, or other life-altering circumstances. Her family history was notable for a brother who sustained and succumbed to a subarachnoid hemorrhage 10 years previously. She had sought medical help when the headaches first started, and underwent radiologic imaging with brain MRI. This was reportedly negative without evidence of prior ischemic events or aneurysms. In terms of her cancer history, she had been diagnosed with right breast ductal carcinoma in situ 8 years prior, for which she was treated with mastectomy, at which time she also underwent a contralateral prophylactic mastectomy with immediate reconstructions. She was on no medications and her social history was otherwise unrevealing. On examination she was wellappearing. Her cranial nerve examination and a gross neurologic examination were normal. Based on Joan’s presentation and description of her pain symptoms, what is the most likely diagnosis? a. Complicated migraine b. Situational anxiety disorder c. Metastatic brain cancer d. Benign sexual headache e. Subarachnoid bleed DISCUSSION The most likely diagnosis would be benign sexual headache. For patients with a history of DCIS, a common consideration is the use of endocrine therapy for secondary prevention. The most commonly administered agent

is tamoxifen,1 though accumulating data suggest that for postmenopausal women, aromatase inhibitors may also be effective.2 However, endocrine therapies are also associated with sexual dysfunction in breast cancer survivors, with the most common symptoms being related to vulvovaginal side effects, which commonly includes pain related to penetrative intercourse (dyspareunia). However, Joan was not taking either of these medications to explain her symptoms. In addition, she did not appear to have any concerns of her

Following the exclusion of more ominous conditions, patients with benign sexual headache have a favorable prognosis. body image, which could lead to issues with intimacy or attraction. Indeed, she appeared quite comfortable in her own skin, and presented with a desire to be with a partner. Given that she had a prior evaluation to rule out an anatomic etiology, the long-standing nature of her symptoms, and the specific events that incited her headaches, her likely diagnosis is benign sexual headache (BSH; also referred to as coital cephalagia, primary sexual headache). BSH is a clinically recognized headache disorder that occurs exclusively during, or immediately after, sexual activity. It is a rare condition with a reported incidence of 0.25% to 1.0% in the general population.3 The diagnosis is one of exclusion and more serious etiologies must be ruled out, including subarachnoid hemorrhage, cerebral infarction, or reversible vascular phenomenon.4-6 Further classification of BSH can be made relative to the timing of symptom onset during sexual intercourse (eg, pre-orgasmic, or type 1; orgasmic, or type 2; or following orgasm, type 3).6 The etiology of BSH remains unclear, likely due to the rarity of the condition. Although the presence of another primary headache syndrome appears to be a risk factor for BSH,7 it was not present in this patient. Following the exclusion of more ominous conditions, patients with BSH have a favorable prognosis. Treatments are available, and despite the lack of high-quality data, they appear to be effective. For patients with frequent and regularly occurring headaches associated with sex, Continues on page 44

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FEATURE | HPV-related oropharyngeal cancer

HPV-positive oropharyngeal cancer has cure potential A prospective study found that patients with human papillomavirus-related disease had better treatment response than HPV-negative patients. BETTE WEINSTEIN KAPLAN

© DAVID MACK / SCIENCE SOURCE

T

Human papillomavirus virions surrounding a wart. Attached to the capsid (green) are numerous surface proteins (blue spikes).

he time may have come to talk about a cure for some cases of metastatic oropharyngeal cancer caused by human papillomavirus (HPV). This is a remarkable development, given the disease’s history of fatality. Sophie Huang, MRT(T), assistant professor in the Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, presented the details of a recent study at the International Conference on Innovative Approaches in Head and Neck Oncology in Nice, France, in her presentation “Cure” Is a Realistic Goal in HPV-Related Oropharyngeal Cancer With Oligometastasis. Huang and her group defined cure for their study as surviving 2 years or longer without evidence of disease. They note 10% of HPV-positive patients were cured, and are alive and disease-free for 2.0 to 7.7 years following treatment of their limited metastatic disease.1 The etiology of oropharyngeal cancer has changed. The disease used to affect older people who were predominantly smokers and alcohol users; however, it is now more likely due to HPV infection and afflicts a somewhat younger population. If identified and treated early, positive results can be achieved for these patients. For this prospective study, Huang and her colleagues at the Princess Margaret Cancer Centre identified 142 patients with distant metastases (DM) in 1,238 consecutive patients with oropharyngeal cancer treated with definitive radiotherapy from 2000 to 2011. Of this group, 88 patients had cancer related to HPV, and 54 patients who were negative

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FEATURE | HPV-related oropharyngeal cancer for HPV had cancer that was related to smoking. The researchers were searching for answers to how the metastases formed and how they affected the course of the disease, including survival.1 They found that, although rates of DM were similar between HPV-related and smoking-related oropharyngeal cancers, there were differences in terms of time to manifestation, characteristics, and natural course after treatment.

Oropharyngeal cancer is now more likely due to HPV infection and afflicts a younger population. PACE OF MANIFESTATION The time frame for detecting DM differed significantly between the groups. DM occurred in the HPV-negative patients quickly (94% within 2 years following initial radiation treatment), whereas DM occurred in 24% of HPV-positive patients beyond a 2-year time frame, with metastases detected the farthest, at 7.9 years. Huang said, “This observation indicates that HPV-related OPC patients who are disease-free for 2 years after initial treatment are not out of the woods. An important point of exploration is a longer surveillance period with appropriate detection methods to help identify DM earlier before widely disseminating, and to design optimal treatment for those with limited metastatic diseases. The hope is that this might cure HPV-positive patients with distant metastasis.”1 CHARACTERISTICS The researchers reported two types of DM in HPV-positive patients. The types were identified by radiologic and histologic confi rmation. • Disseminating (to more than three organs), often with explosive manner defined as more than 10 lesions in one organ within a 3-month period following detection of DM. • Oligometastasis defi ned as five or fewer indolent (slow growing) lesions in one organ.

FIND US ON

Forty-seven patients in the HPV-positive group had DM in two or more organs, while there were 11 such cases in the HPV-negative group. Although 26 HPV-positive patients had explosive DM, none of the HPV-negative patients did. In both the HPV-positive and -negative patients, metastasis spread most often to the lung (78% vs 89%, respectively), although metastases can also be found in other unusual sites, such as the brain and intra-abdominal organs.1 TREATMENT RESPONSE Twice as many HPV-positive patients with DM were treated than were HPV-negative patients, and this was one factor that led to the better survival of HPV-positive patients. For example, 40 HPV-positive patients received radiation therapy versus eight patients who were HPV-negative. Sixteen HPV-positive patients underwent surgery versus four HPV-negative patients who did not, and 19 HPV-positive patients received chemotherapy while only six in the HPVnegative group did. The HPV-positive patients who received intensive treatments experienced longer disease-free periods compared with the HPV-negative patients who received less aggressive treatment. Their disease progressed more slowly and their treatments came later, often too late. Huang also said that HPV-positive cancer is more sensitive to chemotherapy and radiotherapy. Another factor was the age of the patients. HPV-positive patients are often younger, with an average age at diagnosis of 55 years compared with 65 years for the HPV-negative patients, and they have fewer other health problems, such as smoking-related illnesses. These important factors enable HPV-positive patients to receive more intensive treatments. The Toronto group hopes their results will encourage physicians to treat cases of HPV-positive oropharyngeal cancer earlier and more aggressively.1 ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCES 1. Huang S, Waldron J, O’Sullivan B, et al. “Cure” is a realistic goal in HPVrelated oropharyngeal cancer with oligometastasis. Paper presented at: 5th International Conference on Innovative Approaches in Head and Neck Oncology (ICHNO); February 12-14, 2015; Nice, France.

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STAT CONSULT Olaparib (Lynparza) Drug type

• PARP inhibitor Indications

• Indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy

Mechanisms of action

Dose adjustments

• Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3 • PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair • Olaparib has been shown to inhibit growth of select tumor cell lines and decrease tumor growth both as monotherapy or following platinum-based chemotherapy • Olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death

• To manage adverse reactions, consider dose interruption of treatment or dose reduction • Recommended dose reduction is to 200 mg twice daily • If further final dose reduction is needed, reduce to 100 mg twice daily • If concomitant use of strong CYP3A4 inhibitor cannot be avoided, reduce olaparib dose to 150 mg twice daily • If concomitant use of moderate CYP3A4 inhibitor cannot be avoided, reduce olaparib dose to 200 mg twice daily

Dosage and administration

• Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3 • PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair • Olaparib has been shown to inhibit growth of select tumor cell lines and decrease tumor growth both as monotherapy or following platinum-based chemotherapy • Olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death

Specific populations

• Pregnancy ——Pregnancy Category D ——May cause fetal harm when administered to a pregnant woman • Nursing mothers ——Not established ——Decision should be made whether to discontinue nursing or to discontinue the drug • Pediatric ——Not established • Geriatric ——Adverse events of CTCAE ≥3 were more frequent in patients ages 65 years and older than in those younger than 65 years • Renal impairment ——No dose adjustment to the starting dose is required in patients with CrCL 50-80 mL/min, but patients

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STAT CONSULT should be monitored closely for toxicity; no data in patients with CrCL <50 mL/min or on dialysis • Hepatic impairment ——Not established Cautions

• Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) ——MDS/AML occurred in patients exposed to olaparib, and some cases were fatal ——Monitor patients for hematologic toxicity at baseline and monthly thereafter ——Discontinue if MDS/AML is confirmed • Pneumonitis ——Pneumonitis occurred in patients exposed to olaparib, and some cases were fatal ——Interrupt treatment if pneumonitis is suspected ——Discontinue if pneumonitis is confirmed • Embryo-Fetal Toxicity ——Olaparib can cause fetal harm ——Advise females of reproductive potential of the risk to a fetus and to avoid pregnancy Adverse effects

• Most common adverse effects (>20%) ——Abdominal pain/discomfort, anemia, arthralgia/musculoskeletal pain, asthenia, back pain, cough, decreased appetite, dermatitis/rash, diarrhea, dysgeusia, dyspepsia, fatigue, headache, myalgia, nasopharyngitis/pharyngitis/upper respiratory infection, nausea, vomiting • Most common laboratory abnormalities (>25%) ——Creatinine elevation ——Mean corpuscular volume elevation ——Decrease in hemoglobin ——Decrease in lymphocytes ——Decrease in absolute neutrophil count ——Decrease in platelets Drug interactions

• CYP3A4 inhibitors ——Avoid concomitant use of strong (eg, clarithromycin, ketoconazole, voriconazole) and moderate CYP3A4 inhibitors (eg, aprepitant, ciprofloxacin, fluconazole, verapamil) ——If the inhibitor cannot be avoided, reduce Lynparza dose • CYP3A4 inducers ——Avoid concomitant use of strong (eg, phenytoin, rifampin, carbamazepine) and moderate CYP3A4 inducers (eg, bosentan, nafcillin)

——If a moderate CYP3A4 inducer cannot be avoided, be aware of a potential for decreased efficacy of Lynparza • Anticancer agents ——Comcomitant use may potentiate and prolong myelosuppressive toxicity What to tell your patient

• Olaparib is a prescription medicine used to treat women with advanced ovarian cancer who ——Received previous treatment with three or more prior chemotherapy medicines or a combination of chemotherapy medicines for their cancer, and ——Have a certain type of abnormal inherited BRCA gene • Olaparib may cause serious side effects that can lead to death, including MDS/AML and/or pneumonitis • Tell your health care provider if you experience weakness, weight loss, frequent infections, fever, bruising/bleeding more easily, shortness of breath, or blood in urine or stool • Tell your health care provider if you have new or worsening lung problems • Tell your health care provider about all the medicines you take • Before you take olaparib, tell your health care provider if you ——Have lung or breathing problems ——Have liver problems ——Have kidney problems ——Are pregnant or plan to become pregnant ——Are breastfeeding or plan to breastfeed • Avoid grapefruit, grapefruit juice, and Seville oranges during treatment with olaparib • Take olaparib twice daily exactly as instructed by your health care provider ——If you miss a dose, take your next dose at your usual schedule time • Tell your health care provider if you experience nausea or vomiting ——Medicine can be prescribed to help you manage these symptoms. ——The most common side effects of olaparib are ——Changes in kidney function blood test results; changes in the way food tastes; cough; diarrhea; headache; indigestion or heartburn; nausea or vomiting; loss of appetite; pain in the joints, muscles, and back; pain or discomfort in the stomach area; rash; sore throat or runny nose; tiredness or weakness; upper respiratory infection Prepared by Jason Hoffman, PharmD, RPh.

34 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


© YALE ROSEN / CUSTOM MEDICAL STOCK PHOTO

RADIATION & YOUR PATIENT

Lung is consolidated and pale due to acute radiation pneumonitis

Identifying biomarkers for radiation pneumonitis Bryant Furlow Concurrent erlotinib and radiotherapy has been associated with increased risk of radiation pneumonitis among patients with lung cancer. Radiation pneumonitis (even without concurrent erlotinib) is radiation dose-related, but the molecular-pathway underpinnings of this toxicity remain unclear and the search for molecular biomarkers is nascent. However, recent reports suggest that pretreatment interstitial lung disease is a key risk factor for radiation pneumonitis and that prognostic imaging and blood biomarker tests might well allow for risk stratification of cancer patients who are being considered for thoracic radiotherapy.

R

adiation pneumonitis is a com mon, dose-lim iting— and sometimes life-threatening—complication of external-beam

radiotherapy of the chest and thorax. Also known as radiation-induced lung disease, it is associated with increased vascular permeability and edema and inflammation of the lungs’ alveoli. Rates of symptomatic radiation pneumonitis are as high as 28% among patients treated for lung cancer with stereotactic body radiotherapy (SBRT); symptoms can include cough, chest pain or discomfort, and dyspnea.1 Grade 3 radiation pneumonitis is rare (3% to 4% of cases), but it can profoundly impact patients’ quality of life and is potentially life-threatening.1-3 Recent reports suggest that concurrent erlotinib and thoracic radiotherapy is associated with increased risk of radiation pneumonitis, and that radiation dosimetric variables (V5, V10, V15, V20, and V30) might be predictive of this side effect.4 The genomic and molecular pathways leading to an increased risk of radiation pneumonitis in this and other radiotherapy patient populations are not yet well understood, although a model that has gained favor in recent years is that radiation triggers local infl ammatory pathways. However, even though higher radiation doses do appear to increase risk—even among patients who are not receiving erlotinib—specific, strongly predictive candidate dosimetric variables have not yet been validated.1 However, interstitial lung disease before radiotherapy begins appears to be an important risk factor for severe symptomatic radiation pneumonitis.5 Recent reports suggest that pretreatment computed tomography (CT) or positron emission tomography (PET) imaging and serum biomarkers of interstitial pneumonitis allow risk stratification for patients with lung cancer who are being considered for

SBRT.1,6,7 For example, on CT images, interstitial pneumonitis shadow has been associated with increased risk of severe radiation pneumonitis, particularly when accompanied by high serum levels of surfactant protein D and Krebs von den Lungen-6 (KL6).1 Researchers at the University of Tokyo Hospital in Japan report that lung cancer patients with these risk factors are not considered candidates for SBRT at their hospital, and that the hospital’s rate of severe radiation pneumonitis has declined sharply since that policy was adopted in 2006.1 Consistent with an inflammatorypathway hypothesis, postradiotherapy white blood cell counts appear to be a diagnostic and possibly a predictive biomarker of radiation pneumonitis.8 Other candidate biomarkers to predict or detect radiation pneumonitis in patients undergoing radiotherapy include LIN28B gene variants (which are involved in stem cell self-renewal),

The ACE inhibitor captopril helped mitigate resulting radiation dermatitis. transforming growth factor-beta-1 (TGF-β1, a cytokine involved in cancer and lung fibrosis), circulating endothelial progenitor cells, and antip16 (tumor-suppressor protein) autoantibodies.9-11 Like the white blood cell count fi nding, an association of TGF-β1, which influences production of proinflammatory cytokines, might support the infl ammation model of radiation pneumonitis.8 However, it is important to note that all of these

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RADIATION & YOUR PATIENT candidate biomarkers have been only preliminarily identified and await replication and validation. New prevention and prophylactic measures might also be on the horizon, which might someday allow even patients deemed to be at-risk for radiation pneumonitis to benefit from radiotherapy. For example, a recent study of lab animals suggests that radiation to the skin a few hours after whole-thorax irradiation might reduce morbidity associated with radiation pneumonitis, and that the angiotensinconverting enzyme (ACE) inhibitor captopril helped mitigate resulting radiation dermatitis.12 However, these preclinical study results are preliminary at best, and it is far too early to draw meaningful clinical lessons from such research. ■

2. Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer.

8. Tang C, Gomez DR, Wang H, et al.

JAMA. 2010;303(11):1070-1076. doi:10.1001/

Association between white blood cell count

jama.2010.261.

following radiation therapy with radiation

3. Nishio T, Kunieda E, Shirato H, et al. Dosimetric verification in participating institutions in stereotactic body radiotherapy trial for stage I non-small cell lung cancer: Japan clinical

pneumonitis in non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2014;88(2):319-325. doi:10.1016/j.ijrobp.2013.10.030. 9. Wen J, Liu H, Wang Q, et al. Genetic variants

oncology group trial (JCOG0403). Phys Med

of the LIN28B gene predict severe radiation

Biol. 2006;51(2):5409-5417.

pneumonitis in patients with non-small cell

4. Zhuang H, Hou H, Yuan Z, et al. Preliminary analysis of the risk factors for radiation pneumonitis in patients with non-small-cell lung cancer treated with concurrent erlotinib

lung cancer treated with definitive radiation therapy. Eur J Cancer. 2014;50(10):1706-1716. doi:10.1016/j.ejca.2014.03.008. 10. Liu Y, Xia T, Zhang W, et al. Variations of

and thoracic radiotherapy. Onco Targets Ther.

circulating endothelial progenitor cells and

2014;7:807-813. doi:10.2147/OTT.S62707.

transforming growth factor-beta-1(TGF-β1)

5. Ueki N, Matsuo Y, Togashi Y, et al. Impact

during thoracic radiotherapy are predictive

of pretreatment interstitial lung disease on

for radiation pneumnonitis. Radiat Oncol.

radiation pneumonitis and survival after

2013;8:189. www.ro-journal.com/content/

stereotactic body radiation therapy for lung cancer. J Thorac Oncol. 2015;10(1):116-125.

Bryant Furlow is a medical journalist based in Albuquerque, New Mexico.

therapy. Phys Med Biol. 2014;59(18):5387-5398. doi:10.1088/0031-9155/59/18/5387.

6. Castillo R, Pham N, Ansari S, et al. Pre-

8/1/189. Accessed March 3, 2015. 11. Wang W, Wei J, Zhong W. Autoantibodies against p16 protein-derived peptides predict

radiotherapy FDG PET predicts radiation

radiation pneumonitis in patients with non-

pneumonitis in lung cancer. Radiat Oncol.

small cell lung cancer treated with definitive

REFERENCES

2014;9:74. www.ro-journal.com/content/

radiation therapy. Int J Radiat Oncol Biol Phys.

1. Yamashita H, Takahashi W, Haga A,

9/1/74. Accessed March 3, 2015.

2014;90(5 suppl):S69-S70.

Nakagawa K. Radiation pneumonitis after

7. Cunliffe AR, Armato SG 3rd, Straus C, et al.

12. Gao F, Fish BL, Szabo A, et al. Enhanced survival

stereotactic radiation therapy for lung

Lung texture in serial thoracic CT scans:

from radiation pneumonitis by combined irra-

cancer. World J Radiol. 2014;6(9):708-715.

correlation with radiologist-defined sever-

diation to the skin. Int J Radiat Biol. 2014;90(9):753-

doi:10.4329/wjr.v6.i9.708.

ity of acute changes following radiation

761. doi:10.3109/09553002.2014.922722.

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COMMUNICATION CHALLENGES

The constancy of vulnerability Ann J. Brady, MSN, RN-BC

© SHUTTERSTOCK / VITALEZ

who completed their treatment before her. Excited and planning a party was certainly in character for her, yet I worried that by thinking and saying everything would magically go back to normal and be fine that she was setting herself up for a big let-down. But I did not want to rush to correct her idea. She had been a real trooper, and the last thing I wanted was to take that away from her. So I listened to her plans for her celebratory party without interrupting. She had two more cycles of chemo, enough time to discuss what was next. On that day, she needed to look forward without limits.

The sense of vulnerability at each point of transition can be overwhelming but especially as [patients] complete treatment.

W

hat do you say when a patient makes a statement about their treatment that you don’t agree with? We know what is coming next for our patients. How much do we tell them ahead of time and when?

CASE Susie pointed to the bag of chemo infusing next to her. “Only two more cycles.” She clapped her hands together. “I’m throwing a huge party after this! You have to come and celebrate with me.” She pumped her fist into the air like an Olympic champion. “I can’t wait to get back to normal.” I smiled at her enthusiasm. From the first time I met her she impressed me with how positive and upbeat she was. She embraced every part of her treatment, shaving her head before her hair fell out, cheering on the other patients even when she herself felt lousy, asking when they were going to finish their chemo and bringing a funny card to those

DISCUSSION Most of the time when we, the health care team, discuss the end of treatment with patients, we talk of a new normal as a way of embracing change and to emphasize the importance of re-establishing a sense of normalcy. The NCCN guidelines on Distress Management indicate there are times in cancer care that are considered points of transition. It is at these points of transition that vulnerability increases. Many of the transition points are obvious: diagnosis, surgery, start of chemo, before a scan. But surprisingly, one of the critical points of transition is at the completion of treatment. Up until that point the focus is on treatment. On action. On staying hopeful. On fighting and killing the cancer rather than on what is next. The idea of what comes after the completion of treatment is frightening. In an article about the pervasive anxiety of those living in New York post 9/11, the late historian and Pulitzer Prize-winning journalist David Halberstam, a New Yorker

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COMMUNICATION CHALLENGES

There are many ways to face the transitions of cancer treatment. There is no correct way to handle it.

himself, called that anxiety the constancy of vulnerability.1 As our patients stand outside of the medical oncology office having been told their treatment is complete, they are faced with a fundamental question. Where do I go from here? Where they were prior to diagnosis is no longer available to them. The sense of vulnerability at each point of transition can be overwhelming but especially as they complete treatment. The word complete is itself a misnomer. Complete implies there is nothing else necessary to be done. It seems a likely place to celebrate. When our patients finish treatment we cut them loose. A follow-up appointment is made, and then the patient is essentially shown the door. We know that as they step forward into the world after cancer that there are challenges ahead. Finding that new normal requires a bit of work. How do we help our patients traverse this transition when we are no longer seeing them? The NCCN definition of distress is an experience of normal feelings of vulnerability. It is important to normalize distress at all points of transition. It is important to acknowledge its existence and to educate our patients as they approach each point of transition. Just as I held Susie’s hand before she heard the results from her latest scan, she needed hand holding as she stepped away from us. The next time I saw Susie I started the conversation by asking about her party

JOIN THE CONVERSATION • Do you routinely discuss points of transitions with your patients? • How comfortable are you at discussing the end of treatment with your patients?

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Go to OncologyNurseAdvisor.com/challengestransitions to talk with your colleagues about strategies for effectively counseling patients as they transition through the various stages of cancer care.

plans. ”We are going to have pizza and ice cream and chocolate. All the things I love but haven’t been able to eat.” She made a gagging face. Though she rarely complained about nausea, we had worked hard to manage it. I knew well the foods she had been forced to avoid. I asked her, “What do you think you will do after the party?” She laughed for a moment as if it were an absurd thing to ask, then understood my question was more existential than a simple inquiry about what came after planning for her party. “I’ll get back to my life.” I pushed a bit against her rosy picture, not to upset her, but to open the window a bit. “What do you think will be different?” This time her laugh was nervous. “I can’t go there,” she said. We didn’t have to discuss where going there was when we both knew that finishing treatment did not mean cancer was no longer part of her life. “Yes. I can imagine it is very difficult.” Now it was me who paused before continuing. “I don’t want to go there either. But I want to let you know that this next part has some of its own challenges.” “Nothing could be as bad as chemo.” “I’m sure that is so. What I want is to help you prepare for what is next.” We discussed how she might feel after her end-of-chemo party. She said that before her diagnosis when she planned large parties, afterwards she missed the activity and planning that went into it. From there she made the connection. Once she finished her treatment it wasn’t that she would miss getting chemo, but what would be missing was the sense of purpose she had from fighting the cancer. There is a certain security that comes from waging the battle. How would she continue when the battle was done? Was it ever done? What did she fight when the elements of her fight were changed and missing? We have strategies for managing symptoms. First and foremost is acknowledging that they exist. To manage the transition and the feelings of vulnerability, we talked Continues on page 46

38 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com


ISSUES IN CANCER SURVIVORSHIP

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The unmet needs of cancer survivors: Quantifying the long-term effects of cancer Bette Weinstein Kaplan

T

here are now more people surviving cancer than ever, and the expectation is that 10 years from now more than 19 million people will have put the disease behind them.1 However, many of those survivors continue to have physical and psychological difficulties years after their battles with the disease are over. Just what problems are these people coping with? Mary Ann Burg, PhD, LCSW, of the University of Central Florida, in Orlando, and her colleagues launched a study to get some answers. They based their research on the American Cancer Society’s 2010 ACS Survey of Cancer Survivors II (SCS-II). That survey queried 9,105 cancer survivors about their unmet needs related to their cancer occurrence. It was a national crosssectional survey of survivors selected at random from population-based cancer registries in 14 states. Criteria for inclusion in the SCS-II survey were age 18 years or older and a diagnosis of a local, regional, or distant cancer based on SEER summary staging. Participants had to have had a diagnosis of breast, prostate, colorectal, skin, melanoma, bladder, or uterine cancer 2, 5, or 10 years before the sampling.

AN OPEN-ENDED QUESTION Burg’s team examined a subset of the SCS-II’s respondents who answered the

open-ended question: Please tell us about any needs you have now as a cancer survivor that are not being met to your satisfaction. The significance of an openended question is that, although it allows respondents to answer in depth, those answers are rarely analyzed because they are responded to less frequently than fixed-format questions, and are more difficult to quantify and code. The researchers chose only those cancer survivors who actually had needs, excluding those who responded as satisfied, unsure, or who did not provide a response. After eliminating those surveys, 1,514 survivors’ surveys remained: 524 men and 990 women, ranging in age from 24 years to 97 years. The most frequent cancer among these respondents was breast cancer, then prostate, colorectal, bladder, uterine, and skin cancers. Recent survivors answered the open-ended question more than any other group. Men who had had prostate cancer, as well as people older than 65 years, responded that they currently had physical needs and personal control themes. Physical needs were described as needs and issues experienced in or affecting the body, including pain, symptoms, sexual dysfunction, and care of body (such as diet, exercise, and rest). The researchers defined personal control needs as needs related to a person’s

ability to maintain autonomy in terms of the physical self (sexual function, evacuation, and ambulation) and the social self (disclosure about cancer and the ability to make plans and socialize). It also included wishes to return to “normal” and finding a “new normal.”

Survivors cited a need for more cancer-relation information. Women reported financial needs or system-of-care needs. The latter were related to the health care system, including constraints and flaws that affected early detection, diagnosis, treatment, follow-up care, continuity of care, and inadequate response from health care providers. Women also reported having resource needs related to availability and access to supplies, equipment, therapies, and medications—including alternative and complementary—and transportation services. They also discussed their emotional and mental health issues, their need for social support, and diff iculty communicating. Communication Continues on page 42

www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 39


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THE TOTAL PATIENT

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Postoperative audiotherapy provides effective pain relief for pediatric patients Bette Weinstein Kaplan

C

ontrolling pain following major surger y in ped iatric patients can be difficult. A lthough opioid ana lgesics are effective, they may cause respiratory problems in young patients. As a result, physicians are conservative in prescribing opioids for children; therefore, postoperative pain control in this patient population is often less than ideal. The conundrum is the subject of research recently undertaken by a father and daughter team.1 Santhanam Suresh, MD, is professor of anesthesiology and pediatrics at Northwestern Un iver sit y Feinberg School of Medicine, in Chicago, Illinois. He is also chair of pediatric anesthesiology at Ann & Robert H. Lurie Children’s Hospital of Chicago. His daughter, Sunitha Suresh, designed the project when she was a student in biomedical engineering minoring in music cognition at Northwestern’s McCormick School of Engineering and Applied Science. She will graduate from Johns Hopkins Medical School this year. MUSIC, STORIES, OR SILENCE The team evaluated the analgesic effects of listening to music and audiobooks in children who had recently undergone major surgery. They recruited 60 children ranging in age from 9 years to 14 years for

their randomized prospective study. Fifty-four subjects were included in the study, all of whom were scheduled to undergo major surgical procedures, including orthopedic, neurosurgical, urologic, or general surgeries. The researchers divided the young patients into three groups. Two groups listened to 30 minutes of music or stories through noise-canceling headphones in a therapy session, while the third group, the control group, simply heard silence. The team was hoping to reduce the children’s pain burden with two audio treatments within a 48-hour postoperative period. Prior to the surgery the researchers gave the patients in the music group playlists that included pop, country, rock, and classical genres from which to make their selections. If the children were in the audiobook group, they chose from a list of short audiobooks and stories, including The Hobbit, Alice in Wonderland, and The Complete Tales of Peter Rabbit. Selections were made before the operative procedures so that the patients could choose what they wanted to listen to before they felt the effects of anesthesia. Two audio treatment sessions took place within 48 hours after surgery. The team used the Faces Pain ScaleRevised FPS-R to evaluate each patient’s pain twice, first before an audio treatment and then again 30

minutes after the treatment. 2 They calculated the difference between post and pretreatment pain scores as the main therapeutic effect for this study. CAN MUSIC REPLACE MEDICATION?

The authors wrote that the most important finding of their study was how effectively the music or audiobooks reduced the children’s pain. They believe that the audiotherapy worked by distracting the brain and allowing it to focus on something other than pain. Using regression

Allowing patients to choose their music increased its effectiveness. analysis, they demonstrated that the children in the audio therapy group reported a 1-point reduction on the 10-point pain scale after an hour of audio therapy treatment compared with those in control group. No difference was seen in the children’s pain scores regardless of how high the scores were at the beginning of the audio therapy session. Continues on page 42

www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 41


THE TOTAL PATIENT The audio treatments still worked to reduce their pain. Furthermore, allowing the patients to choose their own music increased the effectiveness of the therapy. The patients were distracted by the music they wanted to hear, or the stories that they found interesting. The music and audiobook groups achieved the same degree of pain relief. In contrast, patients in the control group did not experience any effects from listening to silence.

authors noted that administering IV drugs for pain reduction is difficult, and often impossible, in ambulatory patients or after the patients are dis-

Patients are able to continue audio treatment at home after discharge.

PORTABLE PAIN CONTROL

and they call for further research including measurements of anxiety as well as analgesia. ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCES 1. Suresh S, De Oliveira GS Jr, Suresh S. The effect of audio therapy to treat postoperative pain in children undergoing major surgery: a randomized controlled trial [published online ahead of print January 3, 2015]. Pediatr Surg Int. 2015.

An intriguing aspect of this investigation was the fi nding that the patients are able to continue audio treatment at home after their discharge. The

charged and at home. The researchers suggest that audio therapy should be made available to minimize pain in children undergoing major surgery,

2. Hicks CL, von Baeyer CL, Spafford PA, et al.

Issues in Cancer Survivorship

as emotional and mental health problems. Although Black and Hispanic survivors brought up fi nancial problems most frequently, 20% of all respondents said the cost of treatment was still an issue long after they were fi nished with it. All patient groups were concerned about recurrence, and all of the survivors cited a need for more cancerrelated information and education. The authors noted that knowing how a patient’s experience of unmet needs potentially affects physical and psychological outcomes is important information, especially for oncologists,

rehabilitation specialists, and primary care providers who care for cancer survivors. ■

Continued from page 39

needs were related to discourse (talking) and information exchange (explaining) about cancer and the cancer experience with others (eg, their doctor and family/friends/employers) and among medical providers. COMMONALITIES IN RESPONSES

The researchers wrote that older survivors had more current needs regarding physical or personal control problems. Younger survivors discussed fi nancial difficulties, as well

The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001;93(2):173-183.

Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCE 1. Burg MA, Adorno G, Lopez ED, et al. Current unmet needs of cancer survivors: Analysis of open-ended responses to the American Cancer Society Study of Cancer Survivors II [published online ahead of print January 12, 2015]. CANCER. 2015;121(4):623-630. doi:10.1002/cncr.28951.

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omen who receive a breast cancer diagnosis while pregnant are faced with a myriad of emotions and challenging treatment decisions. A time that normally signifies joy and anticipation for a woman and her family is now mingled with uncertainty and fear. Pregnancyassociated breast cancer (PABC) is becoming more common as more women are waiting to bear children. It is important for women to have complete and accurate information about the treatment options available to them while pregnant. Nurses are uniquely positioned to help patients with PABC navigate complex health care decisions and choose what makes the most sense for them and their families. Nurses can assist patients in communicating fully with the health care team during the course of cancer treatment, obstetric care, and beyond, so care is a transparent and collaborative process. Patients can be encouraged to engage their support network and access all available resources. There are certain psychosocial challenges that nurses should keep in mind when treating patients with PABC. Normal breast changes caused by fluctuating pregnancy hormone levels may mask breast cancer symptoms, rendering the cancer difficult to detect. Screening may be delayed, leading to diagnosis at a later stage and fewer effective treatment options. Women should be counseled about the safety of screening and treatment during pregnancy. Often, it is imperative to begin cancer treatment quickly, when

Psychosocial challenges of pregnancyassociated breast cancer Allison Nilsen, MSW, LCSW

the fetus is not to term and delivery is not yet possible. Treatment for PABC is designed to ensure that the mother has the best possible outcome, with the fetus’ safety also a priority. However, at times these two interests may conflict. In my clinical experience, patients invariably have concerns about this balance and need support along the way. Most likely they are just getting used to the experience of pregnancy and impending motherhood, only to be thrust into

the world of cancer. They may worry about whether they should terminate the pregnancy, what (if any) lasting impact screening and treatment will have on their growing fetus, what to expect in terms of side effects, and about their ability to be there for their child over the long term. I always encourage my clients to have an open, honest conversation with their health care team about their concerns. They can start by writing down a list of their top five most pressing questions that they need to have addressed. This will help the patient’s health care team identify any barriers to treatment in order to create the best possible plan for mother and child. Breast cancer diagnosed at a young age is especially disruptive. Women in their 20s through early 40s are progressing in their careers, building their own families, and juggling various life demands. They may be the family’s primary breadwinner, or the main caretaker for children or parents. The diagnosis impacts the whole person and the entire social system. Nurses and other health care providers will find it helpful to assess the patient’s individual needs and possible obstacles to treatment adherence, along with their available supports. Are grandparents living locally able to offer childcare for young children in the home? Can a woman’s partner or friends help drive her to and from treatment? Does she belong to a church, synagogue, or mosque that may be able to provide meals or other assistance? Is the woman’s workplace understanding and flexible? You can assist the patient

ASCO recommends that medical providers discuss fertility with patients as early as possible­—preferably, before treatment begins. www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 43


FROM in drawing on her available strengths and supports as she moves through the phases of treatment. Premenopausal women are at risk of infertility after PABC treatment. Chemotherapy can lead to early menopause, and tamoxifen is contraindicated during pregnancy. Therefore, the American Society of Clinical Oncolog y (ASCO) recommends that medical providers discuss fertility with patients as early as possible— preferably, before treatment begins. One of the most common refrains that I hear in my work with younger women with cancer is that if they had been fully informed in a timely way about all the methods available to them, they may have made a different choice. The emotional impact of fertility loss is lasting and significant. All women who are within reproductive age should be counseled regarding fertility, even if they are unsure whether they want to have children in the future. Nurses and doctors can help jump-start these conversations.

Benign sexual headache Continued from page 29

indomethacin (25 mg/day to 50 mg/ day) or propranolol (40 mg/day to 200 mg/day) taken before intercourse may be of use, though more frequent administration may be indicated as prevention.6 ■ Ashleigh Long is a student at the University of Kentucky College of Medicine, Lexington. Marcela del Carmen is a gynecologic oncologist at the Massachusetts General Hospital Cancer Center’s Gillette Center for Gynecologic Oncology and the Department of Obstetrics & Gynecology in Boston, Massachusetts. Don Dizon is specialist in

A fertility counselor can further assess what fertility-preserving options are available to these women.1 Women with PABC are often younger and therefore more likely to carry BRCA mutations. Women who have not undergone genetic testing should be referred to a genetic counselor as soon as possible. Extra vigilance is especially critical in this population, as BRCA mutations render women more susceptible to aggressive subtypes such as triple negative breast cancer.2 Finally, nurses can reassure women and families coping with PABC that they are not alone. Many support resources are available. CancerCare’s professional oncology social workers provide free one-on-one counseling, support groups, and educational materials to patients and caregivers coping with cancer (www.cancercare. org, 800-813-HOPE [4673]). People impacted by PABC may benefit from having a safe space to openly discuss fears, concerns, and hopes with a professional trained in cancer-related

gynecologic oncologist at the Gillette Center for Gynecologic Oncology and director, Oncology Sexual Health Clinic, Massachusetts General Hospital Cancer Center.

distress. An organization geared specifically toward women diagnosed with cancer while pregnant is Hope for Two: The Pregnant with Cancer Network (www.hopefortwo.org, 800-743-4471). Hope for Two offers information, a network of peer support for pregnant women with cancer, and the FDA-recognized Cancer and Pregnancy Registry, which tracks pregnancy outcomes. ■ Allison Nilsen is Women’s Cancers Program Director at CancerCare. REFERENCES 1. Warshaw R. Infertility risk high after breast cancer treatment. Living Beyond Breast Cancer Web site. http://www.lbbc.org/ Understanding-Breast-Cancer/BreastCancer-News/Infertility-Risk-High-AfterBreast-Cancer-Treatment/(language)/ eng-US. Accessed February 20, 2015. 2. Risk factors to cover with your doctor. Triple Negative Breast Cancer Foundation Web site. http://www.tnbcfoundation.org/riskfactors. htm. Accessed February 20, 2015.

International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808. 5. Valença MM, Valença LP, Bordini CA, et al. Cerebral vasospasm and headache during

REFERENCES

sexual intercourse and masturbatory

1. Eng-Wong J, Costantino JP, Swain SM. The

orgasms. Headache. 2004;44(3):244-248.

impact of systemic therapy following ductal

6. Frese A, Rahmann A, Gregor N, et al.

carcinoma in situ. J Natl Cancer Inst Monogr.

Headache associated with sexual activity:

2010;2010(41):200-203.

prognosis and treatment options.

2. Olin JL, St Pierre M. Aromatase inhibitors in breast cancer prevention. Ann Pharmacother. 2014;48(12):1605-1610.

Cephalalgia. 2007;27(11):1265-1270. 7. Ostergaard JR, Kraft M. Benign coital headache. Cephalalgia. 1992;12(6):353-355.

3. Rasmussen BK, Olesen J. Symptomatic and nonsymptomatic headaches in a general population. Neurology. 1992;42(6):1225-1231. 4. Headache Classification Committee of the International Headache Society (IHS). The

44 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com

This article is reproduced with permission from Haymarket Media. © 2015 CancerTherapyAdvisor.com. All rights reserved.


REFLECTIONS

© DNA ILLUSTRATIONS / SCIENCE SOURCE

F

or decades, the med ica l community has known that a variety of cancers produce proteins that circulate in the blood and can be quantified to determine the response of a cancer to a specific treatment. These proteins are commonly referred to as tumor markers. Identifying these tumor markers can be especially helpful in cases where the cancer may be difficult to measure in regard to treatment response, such as breast cancer in a patient who presents with isolated bone metastasis. Unfortunately, many patients—and physicians—overestimate the benefit of detecting tumor markers. There is no question that the advent of biomarker detection in malignancies has helped physicians monitor various treatment modalities. As a result, patients often insist on having these markers checked routinely, even when not on therapy. Physicians, too, encourage the practice. In fact, a recent study found that almost half of US oncologists order tumor markers indiscriminately, despite evidence that it does not save or lengthen the life of a patient, in most cases. Frequent measuring of t u mor markers seems to promote a sense of security among patients in that they feel if the markers have not increased, their cancer is under control. Some patients keep log books of their tumor markers that have been obtained over the years, and while they feel comfortable when the tumor marker is stable or reducing, even if it increases within normal ranges, they may panic

Post cancer treatment surveillance Donald R. Fleming, MD

Serum biomarker CA-125 expressed by metastatic ovarian cancer

unnecessarily. Physicians often refer patients to me for consultation due to an elevated screening CEA or CA-199 in an asymptomatic patient. Many times imaging studies, which are very difficult to get insurance carrier approval for based on this information, turn out to be normal. Nevertheless, much anxiety is produced in both the patient and the referring physician. The bottom line is that we have yet to demonstrate that measuring these tumor markers in a patient with no

clinical evidence of active cancer is necessary, and the knowledge obtained from doing so has yet to result in a better outcome for most patients. Recently a high level, randomized, phase III study determined that in ovarian cancer, regardless of whether a patient suspected the cancer had returned based on symptoms versus an elevated level of the tumor marker CA-125 in an otherwise asymptomatic situation, survival was not affected by what triggered reinstituting therapy. Despite these f indings in patients with ovarian cancer, some NCCN recommendations suggest obtaining specific tumor markers ahead of any evidence or symptoms of disease progression. CEA levels for colorectal cancers and alpha fetal protein and beta HCG levels for testicular cancer are examples of this practice, as the belief is that these are useful due to issues related to potential salvage therapeutics.1 Problems with any test used to detect an illness start with issues such as sensitivity, specificity, and both positive and negative predictive values. Sensitivity means that when a condition exists the test has the ability to detect it, and therefore lacks false negative results. Specificity is when a disease is not present and the test has the ability to not show positivity, in other words avoid false positives. The statistical measurements known as positive and negative predictive values can be a little more complicated. Whereas sensitivity and specificity are not determined based on having a particular population in mind,

We have yet to demonstrate that measuring these tumor markers in a patient with no clinical evidence of active cancer is necessary. www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 45


REFLECTIONS predictive value measurements are population-based. A positive predictive value is when a test result demonstrates a certain finding, such as presence of a disease among a defined population and it really exists. Negative predictive value is the opposite. For example, a test used to diagnose coronary artery disease, such as a stress test, would have a higher positive predictive value in the elderly than in an elementary school population, simply because the likelihood of cardiac disease is so much higher among elderly people. In regard to using tumor markers,

these issues play a major role in demonstrating their lack of effectiveness. One of the most feared cancers is pancreatic cancer due to its extremely low cure rate. The best commercially available assay, the CA-19-9, has sensitivity and specificity rates as low as 41% and 33%, respectively, meaning the test can erroneously respectively miss and indicate pancreatic cancer more than it can lead to a correct diagnosis.2,3 In addition to serum tumor markers, patients often wonder why a physician might not order a plethora of followup scans so they can be deemed cancer-free. It is important to explain

Communication Challenges Continued from page 38

about what strategies she could employ. She thought returning to yoga would help, and we talked about finding a studio with classes for those on the mend. I saw Susie when she came for her follow-up appointment. Her enthusiasm was intact but a little restrained. “You know, I’m glad

to patients that a billion cancer cells have to collect in one particular spot to be detected, even on a highly sensitive detection scan such as a CT. Millions of cells could be anywhere and go undetected. A recent randomized trial evaluated lymphoma outcomes when the patient was followed up with regularly scheduled imaging studies versus obtaining similar radiographs only when patients had symptoms of recurrent cancer. Just as in the case of ovarian cancer and the CA-125, the outcome was the same. Too often physicians are judged more by their use of high tech scans than by their astute clinical skills. Too often the request for a PET/CT is the result of advice from a conversation over the fence with a patient’s neighbor than with their oncologist. More recently the choice has been taken out of the hands of the physician and the patient, as insurance companies and the like have refused payment based on this very issue. Patients expect their oncologist to battle their case, but the fact is we often lack the ammunition.4 This is not to say that in the future, with more research, very specif ic proteins to very specif ic tumors may result in early detection, but

that accomplishment has not been attained in today’s oncology practice. Despite these arguments, and often after giving my long-time devoted patient this extensive explanation about tumor markers, they look at me, and say, “That’s all fine. Are you going to order my tumor markers now?” My jaw drops, and I order the tumor markers. ■

you warned me that there can be a let-down after I finished chemo.” She agreed that f inding her new normal was a process. There are many ways to face the transitions of cancer treatment. Some do it as Susie did, with humor and spirit. There is no correct way to handle it. We premedicate for chemo, we tell our patients what they might expect in physical side effects. In the same way, we need to be sure our patients know

what happens when their treatment is finished. ■

46 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2015 • www.OncologyNurseAdvisor.com

Donald Fleming is an oncologist / hematologist at the Cancer Care Center, Davis Medical Center, Elkins, West Virginia. REFERENCES 1. Rustin GJ. Follow-up with CA125 after primary therapy of advanced ovarian cancer has major implications for treatment outcome and trial performances and should not be routinely performed. Ann Oncol. 2011;22(suppl8):viii45-viii48. 2. Bünger S, Laubert T, Roblick UJ, Habermann JK. Serum biomarkers for improved diagnostic of pancreatic cancer: a current overview. J Cancer Res Clin Oncol. 2011;137(3):375-389 3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225-249. 4. Thompson CA, Ghesquieres H, Maurer MJ, et al. Utility of routine post-therapy surveillance imaging in diffuse large B-cell lymphoma. J Clin Oncol. 2014;32(31):3506-3512.

Ann Brady is the symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California REFERENCES 1. Getlin J. Five years after: Anxiety lingers in New York. Los Angeles Times. September 10, 2006. http://articles.latimes.com/2006/sep/10/nation/ na-newyork10. Accessed March 19, 2015.


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ASK A PHARMACIST effective for patients without complicating comorbidities, therefore patient- and product-specific restrictions such as those mentioned should be considered when evaluating the rate of these infusions.

© THINKSTOCK

When giving gemcitabine (Gemzar) and cisplatin (Platinol), is it better to give gemcitabine first to reduce myelosuppression with every indication or only certain ones and if so which ones? —Annette Baker, ADN

Ideal hydration infusion rate; sequence with gemcitabine Oncology patients undergoing chemotherapy treatments find it difficult to maintain adequate hydration and experience increased fatigue, weakness, and dizziness. In an outpatient cancer infusion center providing intravenous (IV) hydration, is a longer infusion time better for the patient? For example, would it be better to infuse 1 liter of normal saline over 1, 2, or 3 hours (without congestive heart failure [CHF])? —Name withheld on request

The optimal rate of infusion for IV hydration depends on the presence of comorbidities (eg, CHF), the presence of any electrolytes (eg, potassium, magnesium) that may be added to the hydration solution, and institutional policies. There is no clinical literature indicating that rates slower than 1 L/hour is more

Multiple factors affect the sequence of chemotherapy agents, such as the pharmacokinetic properties of the medication (eg, does it undergo extensive metabolism or is the agent extensively protein bound). The effectiveness of drugs with cell cycle-specific mechanisms of action (ie, is the drug only active against cells at a specific point in their growth and division) may be heavily influenced by the sequence of administration, as the order of administration may reduce or increase each drug’s cytotoxicity. Other studies have demonstrated that the sequence of administration may influence the adverse effects patients experience with a regimen. One wellknown example of this is administration of cisplatin and paclitaxel (Taxol); when cisplatin is given before paclitaxel, patients experience increased neutropenia. This effect is reduced when paclitaxel is administered first. In some instances, sequencing data for

one agent is applied to all agents in that class (eg, the data with cisplatin and paclitaxel is extrapolated to carboplatin and paclitaxel regimens). Optimal sequencing of many chemotherapy regimens is determined using preclinical models (eg, cancer cell lines in research labs), rather than studying the effects of different sequences of administration in humans. If there is data comparing the effects of chemotherapy sequencing in human subjects, the results are typically from smaller dose-finding trials. The recommendation to administer gemcitabine prior to cisplatin is based on results of phase 1 studies in adults with solid tumors, which indicated that this administration schedule may increase the generation of platinum-DNA adducts (potentially increasing efficacy) and reduce neutropenia. Thus, this is the sequence that was used for subsequent studies of gemcitabine/cisplatin regimens. Because of the interactions and effects discussed, it is critical that chemotherapy medications are administered in the correct sequence. Chemotherapy orders should reflect the intended sequence of administration for agents in the prescribed regimen. If there is a question regarding sequence for a regimen for treatment of a specific cancer, consult your pharmacist to clarify the appropriate order. In many cases, this can be clarified by referring to the pivotal clinical trial of the regimen in the applicable disease state. ■

Lisa A. Thompson, PharmD, BCOP Clinical Pharmacy Specialist in Oncology Kaiser Permanente, Colorado

www.OncologyNurseAdvisor.com • MARCH/APRIL 2015 • ONCOLOGY NURSE ADVISOR 47


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