ONA May/June 2018 by Haymarket Media

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May/June 2018

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

CHEMOTHERAPY ADMINISTRATION

FEATURE

HER2-Positive Breast Cancer: A Review of What We Know

NAVIGATOR NOTES

HusbandWife Congruence of Coping Perception

ASK THE EXPERTS

Aligning Symptoms With Effective Treatment for Myelofibrosis

COMMUNICATION CHALLENGES

Too Much Information: She Heard Enough and Shut Down

RADIATION & YOUR PATIENT

Evolving Role of Radiation Therapy in the Treatment of Mesothelioma

ISSUES IN CANCER SURVIVORSHIP

Testicular Cancer Treatment May Increase Risk for Heart Disease in Survivors

0 CLABSIs for 367 Days: How We Took On Central Line Infections and Won A new nursing protocol led to a dramatic change in patient outcomes.

PUBLISHING STAFF Editor Joyce Pagán editor.ona@haymarketmedia.com Senior digital content editor Rick Maffei Oncology writer James Nam, PharmD Contributing writer Bette Weinstein Kaplan Group art director, Haymarket Medical Jennifer Dvoretz Graphic designer Vivian Chang Production editor Kim Daigneau Production director Louise Morrin Boyle Production manager Brian Wask brian.wask@haymarketmedia.com Circulation manager Paul Silver

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Oncology Nurse Advisor (ISSN 2154-350X), May/June 2018, Volume 9, Number 3. Published 6 times annually by Haymarket Media Inc, 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, 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.

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EDITORIAL BOARD Eucharia Borden, MSW, LCSW, OSW-C Lankenau Medical Center Wynnewood, Pennsylvania Ann J. Brady, MSN, RN-BC Huntington Cancer Center Pasadena, California Jiajoyce R. Conway, DNP, CRNP, AOCNP 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 Leah A. Scaramuzzo, MSN, RN-BC, AOCN Kalispell Regional Healthcare Kalispell, Montana Lisa A. Thompson, PharmD, BCOP Kaiser Permanente Colorado Rosemarie A. Tucci, RN, MSN, AOCN Lankenau Hospital Wynnewood, Pennsylvania Kara M. L. Yannotti, MMH, BSN, RN, CCRP John Theurer Cancer Center at Hackensack University Medical Center Hackensack, New Jersey

CONTENTS 7

May/June 2018

IN THE NEWS • PANEX Protocol Extends Progression-Free Survival in R/R Multiple Myeloma • FDA Extends Nilotinib Indication to Include Pediatric CML • SEE-ACBT Improves Postsurgical Outcomes of Lung Cancer Resection • Factoring in Breast Density Improves Long-Term Risk Models • Emetogenic Potential of Irinotecan Found to Be High, Not Moderate

• Elderly Patients Underrepresented in Trials for Soft Tissue Sarcoma … and more

NAVIGATOR NOTES Husband-Wife Congruence of Coping Perception Is Supportive Megan Garlapow, PhD

26 18

FEATURES Quality Improvement Project Achieves 0% CLABSI Rate Amy Walton, RN, BSN, CMSRN, OCN; Leah Scaramuzzo, MSN, RN-BC, AOCN

HER2-Positive Breast Cancer: A Review of What We Know Jiajoyce R. Conway, DNP, CRNP, AOCNP

48 FIND US ON

ASK THE EXPERTS Aligning Symptoms With Effective Treatment for Myelofibrosis

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JOURNAL REVIEW Overtreatment a Concern With RAI for Well-Differentiated Thyroid Cancer

CONTENTS

The association between well-differentiated thyroid cancer and risk for AML or CML in patients treated with radioactive iodine.

May/June 2018

John Schieszer, MA

ISSUES IN CANCER SURVIVORSHIP 35

JOURNAL REVIEW Venetoclax Effective in Relapsed/Refractory CLL John Schieszer, MA

STAT CONSULT Osimertinib (Tagrisso)

Cancer Screening Follow-up: Enabling Timely Diagnosis, Treatment

A consensus opinion on timing of diagnostic tests for 4 cancers: breast, cervical, colorectal, and lung. Bette Weinstein Kaplan

THE TOTAL PATIENT 40

RADIATION & YOUR PATIENT Evolving Role of Radiation Therapy in the Treatment of Mesothelioma Bryant Furlow

COMMUNICATION CHALLENGES The Noise of Too Much Information

Letter-Writing Project Communicates Care Wishes to Healthcare Team, Family

What matters most to me, who matters most to me, and what do I want in my last days? Letter-writing project is a tool for patients to communicate their wishes for their last days. Bette Weinstein Kaplan

Ann J. Brady, MSN, RN-BC, CHPN

PUBLISHERS’ ALLIANCE: DOVE PRESS 45

ISSUES IN CANCER SURVIVORSHIP Testicular Cancer Treatment May Increase Risk for Heart Disease in Survivors Bette Weinstein Kaplan

FROM CANCERCARE Challenges of Young Adult Couples Facing Cancer Diagnosis Marlee Kiel, LMSW

ASK A PHARMACIST Capecitabine Tolerance; Sex After Chemo; Pharmacy Regulations Lisa A. Thompson, PharmD, BCOP

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Management of Relapsed/Refractory Marginal Zone Lymphoma: Focus on Ibrutinib

A review of marginal zone lymphomas, a common and varied group of hematologic malignancies, and their treatment, with a focus on the Bruton’s tyrosine kinase ibrutinib. Cancer Management and Research

ON THE

WEB

IN THE NEWS PANEX Protocol Extends Progression-Free Survival in R/R Multiple Myeloma The phase 3 PANORAMA-1 trial demonstrated that the panobinostat plus bortezomib and dexamethasone regimen significantly prolonged progression-free survival (PFS) by 4 months, leading to US FDA approval for the treatment of patients with relapsed/refractory (R/R) multiple myeloma. However, some aspects of the study design were limited as PANORAMA-1 excluded patients who failed previous bortezomib therapy and only allowed for intravenous bortezomib administration, eliciting concerns about tolerability. For this treatment-expansion study, researchers assigned 39 heavily treated patients with relapsed/ refractory multiple myeloma to receive the panobinostat, bortezomib, and dexamethasone (PANEX) Osteolytic lesions protocol; PANEX was designed to provide access to indicating multiple panobinostat and additional data before commercial myeloma availability in the United States. In contrast with the PANORAMA-1 study, investigators were able to administer bortezomib subcutaneously, and patients who failed bortezomib previously were eligible. Overall, 87% of patients received subcutaneous bortezomib. Results showed that of the 39 study participants, 22 achieved a partial response for an overall response rate (ORR) of 56%. Seven patients (18%) had a best response of minimal response, and 9 (23%) patients had a best response of no change. All patients in the study achieved a best response of stable disease or better. The safety profile of PANEX was comparable to those previously reported. The most frequently reported grade 3 or 4 adverse events included thrombocytopenia, fatigue, dehydration, and diarrhea, and key all-grade adverse events associated with treatment included pneumonia, asthenia, vomiting, and peripheral neuropathy. “Overall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen,” concluded the authors. Read more at http://bit.ly/2jLhUqx.

Palliative Sedation an Option for Refractory Symptoms in End-Stage Cancer Palliative sedation (PS), an ethical and monitored procedure to induce unconsciousness in patients with extreme suffering, is an accepted intervention but has been utilized primarily in developed countries with extensive experience with palliative care. For this prospective study, researchers included 66 patients with end-stage cancer who required PS in a palliative care center in Colombia, a country in which palliative care is

still developing. PS was induced with midazolam, and was considered when patients experienced one or more refractory physical, psychosocial, or spiritual symptoms that caused significant suffering. A total of 2890 patients were attended to by the palliative care team, of which 66 required palliative sedation (2.2%); 22% of whom had breast cancer and 82% had metastatic cancer. The primary symptoms that initiated sedation were dyspnea (59.1%), delirium (45.5%), pain (31.8%), and existential suffering (13.6%). Approximately 60% of patients managed with PS had more than 1 refractory symptom.

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IN THE NEWS

Read more at http://bit.ly/2KOu4LH.

Emetogenic Potential of Irinotecan Found to Be High, Not Moderate Chemotherapy-induced nausea and vomiting (CINV) is one of the biggest challenges faced during anticancer treatment. While the introduction of effective antiemetic medication has reduced the incidence of CINV, their unregulated use during oncologic drug development has led to much uncertainty regarding the emetogenic profile of newer medications. For this prospective and retrospective study, researchers evaluated the emetogenic potential of 50 different chemotherapeutic regimens among 157 patients with cancer in the outpatient setting; 27 patients received highly emetogenic chemotherapy (HEC); 93 patients, moderately emetogenic chemotherapy (MEC); 31 patients, low emetogenicpotential treatment; and 6 patients, minimal emetogenic chemotherapy. Results showed that patients who received cisplatin and anthracycline-cyclophosphamide combination therapy, regimens classified as HEC, had CINV incidence of 37.5% and 54.4%, respectively. Regimens classified as MEC had a lower incidence of CINV with the exception of irinotecan; patients who received irinotecan had a CINV incidence of nearly 50%, which was more comparable with HEC regimens. Approximately 70% of patients reported that CINV negatively affected their quality of life, and reported that nausea was the most commonly experienced symptom. “Irinotecan has been associated in this study with an important incidence of nausea and vomiting, which suggests

it is a drug of highly emetogenic potential, regardless of the scheme used,” the authors concluded. “We suggest changing its classification from a moderately to a highly emetogenic drug.” In addition, they noted a need for additional efforts to improve prophylactic therapy for patients receiving HEC regimens. Read more at http://bit.ly/2rz9So9.

Elderly Patients Underrepresented in Trials for Soft Tissue Sarcoma Although approximately half of soft tissue sarcoma (STS) diagnoses involve patients older than 65, the median age of participants in STS studies is 45 to 60; outcomes of elderly patients after first-line chemotherapy require further evaluation. STS studies miss 50% For this study, researchers accessed of affected patients. the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group database to review 12 clinical trials studying the effects of first-line chemotherapy among 2810 patients with STS. Only 12.4% (348) of study participants were 65 years or older, and approximately 90% had a favorable performance status (0 or 1). The most common STS histological subtype was leiomyosarcoma, and 52% (181) and 18% (63) of patients had lung and liver metastases, respectively. First-line therapies studied included doxorubicin, doxorubicin plus ifosfamide, epirubicin, trabectedin, and ifosfamide. The overall response rate among elderly patients was 14.9% (52), median progression-free survival was 3.5 months, and median overall survival was 10.8 months. Among patients younger than 65 years, the overall response rate was 20.3% (501 patients), median progression-free survival was 4.3 months, and median overall survival was 12.4 months. “In light of the aging population, there is an increasing need to design studies that specifically evaluate treatments in elderly patients, not only those with favorable characteristics,” the authors concluded. “The results of this analysis can help in the design of future trials, which should incorporate geriatric tools to stratify patients and assess risk and include health-related quality of life assessments as end points.” Read more at http://bit.ly/2rAbga2.

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the expected number the Tyrer-Cuzick model estimates with and without the addition of breast density. Without breast density, the Tyrer-Cuzick model estimated that 2554 women were at high risk, of whom 147 developed invasive breast cancer. With breast density incorporated, the model estimated that 4645 women were at high risk, of whom 273 developed invasive breast cancer. The top 10% of patients with the highest risk per the Tyrer-Cuzick risk model had a 2.2-fold incidence of breast cancer compared with the middle 80% when not factoring in breast density; when factoring in breast density, there was a 2.5-fold increase. Regardless of whether or not density was factored in, there was little evidence for a decrease in relative risk calibration throughout follow-up.

pouse and partner perception of a breast cancer patient’s ability to cope with treatment and disease can improve the patient’s adjustment and can moderate the connection between functional status and adjustment. SPOUSAL SUPPORT AND ADJUSTMENT TO DISEASE

According to a recent study, in 72 husband-wife couples, congruence of perspectives on efficacy of the wife’s ability to cope with her disease was minimal to modest (R = 0.207); however, additive and multiplicative models assessing the relationship between husbands’ and wives’ perspectives and how it affected adjustment to disease were significant.1 “[H]usbands have a unique perspective on their wives’ coping that contributed to their adjustment to cancer, albeit a small but positive contribution,” the authors noted.1 Researchers administered assessments for marital adjustment, self-efficacy for coping, and adjustment to breast cancer to 72 married, heterosexual couples in which the wife was undergoing treatment for breast cancer. This study used Karnofsky Performance Status (KPS), obtained from the patients’ medical records. Measurements of wives’ perceptions of self-efficacy (WSEC) reflected their own perception at their ability to cope, and measurements of husbands’ perceptions of self-efficacy (HSEC) reflected their perception of their wives’ ability to cope.

Husband-Wife Congruence of Coping Perception Is Supportive Megan Garlapow, PhD

MODELS FOR UNDERSTANDING COPING AND ADJUSTMENT

Researchers then tested 3 different models to better characterize the relationship between WSEC and HSEC. The discrepancy model (WSEC – HSEC), which

is used conventionally to support the idea that spousal congruence improves outcomes, assumes that the larger the difference between spousal perspectives, the more negative the effect on adjustment. The additive model (WSEC + HSEC) assumes a husband’s perspective independently contributes and positively affects adjustment. The multiplicative model (WSEC × HSEC) assumes a synergistic relationship between WSEC and HSEC affecting adjustment. Controlling for age, income, education, marital adjustment, KPS, and stage, no relationship existed between the discrepancy score and wives’ adjustment to cancer (B = 0.089; 95% CI, –0.032 to 0.24); however, the overall regression met statistical significance (R 2 = 0.274; P =.003). With the same controls as in the discrepancy model, a significant relationship existed between the additive model score and wives’ adjustment to cancer (B = 0.206; 95% CI, 0.105-0.325) and the multiplicative model score and wives’ adjustment to cancer (B = 0.001; 95% CI, 0.0001-0.001). Regressions were also signif icant for both the additive (R 2 = 0.397, P <.0001) and multiplicative models (R 2 = 0.385, P <.0001). These results suggest that more perceived coping efficacy from either partner results in improved adjustment. “This study suggests that more efficacious breast cancer patients with respect to coping are better adjusted to their disease than those who report having lower levels of coping efficacy,” wrote the authors. Additionally, research to establish evidence-based approaches to improve

“Future research may benefit from focusing on the sources of coping efficacy judgments made by husbands and wives …” www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 15

NAVIGATOR NOTES

NAVIGATOR NOTES alignment of congruence of perception harbors the potential to improve adjustment to disease, which could affect outcomes. “In order to more clearly understand the husbands’ basis for judging wives’ coping and contributions to their wives’ adjustment, future research may benefit from focusing on the sources of coping efficacy judgments made by husbands and wives and on the couple as the primary unit of study,” the authors concluded. SEXUAL MINORITY POPULATIONS Sexual minority (lesbian, bisexual) female patients with breast cancer face increased distress during treatment and experience inferior clinical outcomes, even when partnered. A 2012 study assessed age-adjusted relative-risk of mortality of female patients (n = 693) cohabiting with female partners vs female patients (n = 136,174) cohabiting with male partners, revealing a 3.2 times relative risk of fatal breast cancer.2 This study assessed data collected from interviews between 1997 and 2003 in the National Health Interview Survey on female patients with breast cancer aged 18 to 80 and cohabiting with a female or male partner. These data were linked to the National Death Index to determine mortality status as of December 31, 2006.

The overall risk of mortality was the same between the 2 patient groups, but the age-adjusted relative risk of mortality was a staggering 3.2 times higher in patients in same-sex relationships. Although the support of a spouse or partner generally improves outcomes in patients with breast cancer, these results point to a discouraging disparity, the nature of which merits further research. “Despite an awareness for more than a decade that lesbian and bisexual women are likely to experience increased risk for breast cancer, the United States currently lacks a public health data strategy to determine if this is so,” the authors concluded.2

The factors affecting this [sexual minority] population remain poorly understood.

2005. These female patients were living with same-sex partners.3 Results indicated same-sex partners were the most important sources of support for patients. However, according the patients’ perspectives, partners also experienced increased distress and burden. Nonetheless, patients often expressed the value of support that comes with “sharing a life beyond cancer.”3 Unfortunately, with a dearth of objective research on how spousal and partner support may affect survivorship and outcomes in sexual minority patients, the factors affecting this patient population remain poorly understood. ■ Megan Garlapow is a medical reporter based in Tempe, Arizona. REFERENCES 1. Merluzzi TV, Martinez Sanchez M. Husbands’ perceptions of their wives’ breast cancer coping efficacy: testing congruence models of adjustment. Cancer Manag Res. 2018;10:297-304.

Indeed, research is lacking into the reasons why sexual minority patients are at increased risk of developing breast cancer and dying from it, and the role a partner plays in affecting outcomes is also poorly understood. A 2012 qualitative study interviewed 15 women with nonmetastatic breast cancer diagnosed between 2000 and

Let us answer your questions! E-mail us at editor.ona@haymarketmedia.com with your general questions for our expert Advisor Forum and your drug-related questions for Ask a Pharmacist!

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2. Cochran SD, Mays VM. Risk of breast cancer mortality among women cohabiting with same sex partners: findings from the National Health Interview Survey, 1997-2003. J Womens Health (Larchmt). 2012;21(5):528-533. 3. White JL, Boehmer U. Long-term breast cancer survivors’ perceptions of support from female partners: an exploratory study. Oncol Nurs Forum. 2012;39(2):210-217.

June 14–16, 2018 | Chicago, Illinois

REVIEW HIGHLIGHTS, TAKEAWAYS, AND EXPERT PERSPECTIVE Browse onsite news and speaker-authored summaries of sessions from the Summit. Topics include: •

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FEATURE | Chemotherapy Administration

Quality Improvement Project Achieves 0% CLABSI Rate A staff survey identified potential practice changes. Implementing those changes resulted in a dramatic improvement in patient outcomes. AMY WALTON, RN, BSN, CMSRN, OCN; LEAH SCARAMUZZO, MSN, RN-BC, AOCN

ot surprisingly, central venous access devices (CVADs) are an important aspect of administering chemotherapy and supportive treatments to oncology patients. But with this comes many risks including, central line-associated bloodstream infections (CLABSIs), and use of these devices is the most common cause of these infections.1 Although there is a large variance in the literature about their cost, some estimate it to be up to $46,000 per infection.2 But the greater impact is mortality. The Centers for Disease Control and Prevention (CDC) estimates the mortality rate to be 12% to 25%.3 Prevention of these infections is paramount. This article will discuss an inpatient oncology unit’s struggles with CLABSI and how significant strides to improve line care reduced the number of infections from 8 CLABSIs in 1 year to 0 in a 367-day period.

BACKGROUND

Consistent adherence to a new nursing protocol and inclusive communications ensured a successful change in patient outcomes.

Located in the Northwest, this 26-bed inpatient medical/surgical oncology unit cares for patients at all phases of cancer treatment. Similar to most oncology units, most of the neutropenic population consists of posttransplant patients and those with hematologic malignancies. Central venous catheters range from implanted ports, tunneled catheters (Groshong®), and peripherally inserted central (PICC) lines. In this hospital, a variety of clinicians place central lines for patients undergoing chemotherapy for cancer including surgeons,

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interventional radiologists, and nurses on the venous access device (VAD) team. Most patients go home with central lines in place to continue treatment and supportive care in the hospital’s outpatient infusion center or in a tertiary setting due to the rural nature of the state. Eight CLABSIs were identified on the inpatient oncology unit in a 9-month period, a significant increase for the unit as well as the hospital. The unit’s leadership team was charged with reducing the CLABSI rate. INTERVENTIONS Through the direction of the unit nurse educator, a team was formed to develop an assessment plan and team approach to resolve this significant issue. The team consisted of staff nurses, oncology educator, leadership team, infection control nurses, members of the VAD team, and a member of the Yellow Belt/Operational Excellence Team to lead the meetings. In addition, all staff were invited to attend the meetings including unit clerks and certified nursing assistants (CNAs). A survey was developed regarding current management of central venous catheters to identify gaps between current unit practices and evidence-based practices. Frequent meetings were held during the development process to keep the team on track. Multiple issues were identified, and an action plan was created.

Bedside shift report was identified as one of the critical factors to the overall communication process about central line management. One of the first issues identified was bathing practices of patients on the unit, specifically the covering over central lines for showering. A literature review supported the use of a water impermeable covering. However, the current practice on the unit was to cover the CVAD with Glad® Press’n Seal® and secure it with tape, or to use Tegaderm dressing, neither were evidence-based practices. In addition, central line dressings got wet after bathing and were not re-dressed immediately. Staff turnover was another problematic issue. Newly hired CNAs lacked acute care experience and knowledge regarding the importance of bathing patients daily. A bathing competency was created to assure bed baths were completed correctly. Current guidelines for care of oncology patients with CVADs recommend washing daily with chlorhexidine gluconate (CHG). This was not the current practice on the unit and was therefore incorporated into the implemented changes.

A sudden increase in CLABSI rates was also previously noted by the hospital’s intensive care unit (ICU) team. After the hospital’s ICU team met with our unit’s leadership team to share their success in reducing line infections, the ICU team also instituted CHG bathing per evidence-based practices described in the literature.4 The nurse survey identified several other variances in central line access device care practices: use of sterile vs clean gloves, frequency of IV tubing changes, and overall frequency of central line dressing changes and changes if nonocclusive or soiled. After the survey was completed, the VAD team presented the questionnaire with the correct answers and the survey results, thus educating the staff about current policy and national recommendations. Central line auditing for each shift ensued to assure all basic measures were being followed, including central line tubing and dressing changes, as well as daily CHG bathing and bed linen changes. Real-time conversations occurred with the staff to identify barriers to optimal line care and opportunities to educate patients about the new bathing process. As part of the bedside report process, staff noted the central line dressing integrity and date change, the IV tubing label, and confirmed the patient bathed with CHG. The leadership team rounded to assure bedside report occurred and addressed any deviations in real time. Bedside shift report was identified as one of the critical factors to the overall communication process about central line management. The team discovered many staff avoided morning bedside shift report in fear of waking the patient. The most influential component of the project was bringing the unit’s CLABSI rate to the forefront. When the issue was first identified, a real patient story and the significant impact the CLABSI had had on the patient, his family, and the unit was shared in a staff meeting. An important factor was to include all float staff in communications to assure that they, too, understood the new processes that were being implemented on the unit. This was accomplished by talking about the number of days since the last CLABSI in the unit huddles held before each shift. Float staff were identified and taught the new bathing process to assure they were with the unit’s implementation of evidence-based standards. A Gemba board was posted next to the unit time clock, showing the number of days since the last CLABSI and current quality data reflecting the evidence and policy-based line care on the unit. Soon, even the patients walking on the unit were drawn to the board and congratulated the staff on the work that was being done to prevent CLABSIs. Continues on page 20

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FEATURE | Chemotherapy Administration Communications with the entire care team helps ensure continued successful outcomes in the prevention of CLABSIs on the unit. DISCUSSION Although several interventions were utilized, a few obstacles were also identified in the course of this huge undertaking. For example, some staff were not open to real-time conversations regarding bathing, CHG usage, and monitoring line care. But this also brought to light the lack of communication between the CNAs and nurses regarding bathing. Once this barrier was addressed, evidence of improved communications was seen in chart audits that demonstrated increases in completed baths and CHG usage. To further support this protocol, bathing, linen change, and CHG checklist were added to the dry-erase boards in each patient room to help communicate care practices and include the patient in the process. A CHG wash handout was developed to assist staff in educating patients and families on the importance of the wash in preventing line infection. The auditing process itself also proved to be a barrier. The charge nurses audited the central venous catheters. Audits included a visual inspection of the dressing and tubing as well as confirmation of daily bathing and linen changes. Some challenges to completing the audits were staff slack, night charges not wanting to wake the patient to view the line, and newer charge nurses forgetting to complete the form — leaving staff report as the means of charge nurse auditing, sometimes with incorrect reports. These barriers were discussed in a charge nurse meeting, and the group agreed on the importance of completing actual line inspections and renewed their dedication to the process. Through coaching and staff support, the auditing process completion rate improved significantly.

Through the staff ’s and leadership’s continued perseverance toward overall patient safety and CLABSI reduction, the unit went 367 days without a documented CLABSI. The CLABSI prevention team continues to identify new interventions to maintain the successful prevention of central line infections on the unit. One new intervention is a computerized power plan to assure that evidence-based interventions continue on all central lines on the unit. These care bundles are recommended and supported by the literature and the CDC to reduce CLABSI rates.1 Staffing constraints and turnover continue to be a challenge for the unit. Continuing up-front and real-time communication about CLABSI monitoring is part of addressing these challenges. Communication with the entire care team helps ensure continued successful outcomes in the prevention of CLABSIs on this inpatient cancer care unit. ■ Amy Walton is a staff nurse on the Inpatient Cancer Care Unit at Billings Clinic, Billings, Montana. Leah Scaramuzzo is RN oncology clinical coordinator, Kalispell Regional Healthcare, Kalispell, Montana. REFERENCES 1. Conley SB. Central line-associated bloodstream infection prevention: standardizing practice focused on evidence-based guidelines. Clin J Oncol Nurs. 2016;20(1):23-26. 2. Haddadin Y, Regunath H. Central line associated blood stream infections (CLABSI). In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; January 2018. https://www.ncbi.nlm.nih.gov/books/NBK430891/. Accessed May 31, 2018. 3. Woodward B, Umberger R. Review of best practices for CLABSI prevention and the impact of recent legislation on CLABSI reporting [published online November 1, 2016]. SAGE Open. doi: 10.1177/2158244016677747 4. Frost SA, Alogso MC, Metcalfe L, et al. Chlorhexidine bathing and health care-associated infections among adult intensive care patients: a systematic review and meta-analysis. Crit Care. 2016;20(1):379.

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FEATURE | Breast Cancer

HER2-Positive Breast Cancer: A Review of What We Know HER2-positive breast cancer presents unique challenges to diagnosis and treatment for clinicians and a daunting prognosis for patients.

FISH test on a biopsy of invasive ductal carcinoma to determine if cells have extra copies of HER2 gene.

JIAJOYCE R. CONWAY, DNP, CRNP, AOCNP

reast cancer is the most common cancer diagnosed among women in the United States, accounting for nearly 1 in 3 cancer cases.1 It is second to lung cancer as a leading cause of cancer death in women. Women living in the United States have a 12.3%, or a 1-in-8 lifetime risk of developing breast cancer.1 Breast cancer is not an isolated uniform entity, but a complex group of diseases that is better understood as a result of greater knowledge of its biologic and genetic subtypes.2,3 The fingerprint of breast cancer is understood in relation to its unique subtypes, each with its own molecular profile, biological behavior, and risk profile.2 Evaluating biomarkers in breast cancer is crucial to diagnosis, prognosis, and treatment decisions. Prognostic and predictive markers are essential to therapeutic decision-making, especially as we aim to individualize treatment plans and outcomes.2 For the patient with breast cancer, a very important component of staging is to determine the status of estrogen, progesterone, and HER2. These are the biomarkers that guide decision-making and patient management, as well as characterize the nature of the breast cancer. TUMOR BIOMARKERS Biomarkers provide clinicians with a more definitive and accurate diagnosis, identification of patients who may achieve a response to treatment and those with a greater likelihood of disease recurrence, and predictive measures

26 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

for those patients most likely to experience toxicity.1 These markers are divided into subcategories: predictive and prognostic. Predictive markers are associated with response or lack of response to a treatment. Prognostic markers — or indicators — provide baseline measurements that project a disease course.2 The role of biomarkers has exceeded that of just being a benchmark for the presence or absence of disease via measurements of serum-based proteins. The paradigm has shifted and the knowledge of biomarker monitoring and analysis has expanded to include assays of circulating factors in the peripheral blood, molecular and genetic assays of the tumor, and tumor/gene profiling via peripheral blood as well. In relation to breast cancer, the American Society of Clinical Oncology (ASCO) guidelines were revised to include that tumor markers were acceptable in the prevention, screening, treatment and surveillance of breast cancer.2 Of these tumor biomarkers, identification of HER2 is recommended for all cases of newly diagnosed breast cancer to identify those patients who may benefit from HER2 monocolonal antibody treatments such as trastuzumab (Herceptin) and/or pertuzumab (Perjeta). MECHANISM OF ACTION HER2 is a transmembrane protein tyrosine kinase receptor that is important to the signal transduction pathways in normal and abnormal cells.2 Breast cancer cells with higherthan-normal levels of HER2 are called HER2-positive.4 Approximately 15% to 30% of human breast tumors express amplification of this protein, and as a biomarker, is an indicator of poor prognosis.2 This subtype of breast cancer has been recognized since the early 1980s when the link between HER2 and cancer cells’ ability to grow rapidly was discovered.3 The metabolic activity of HER2-positive cancer is high; these tumors tend to grow and spread faster than other breast cancer types.4 HER2 receptors signal to the nucleus when bound to their ligand or heregulin, or simply through homodimerization (a chemical reaction that combines 2 identical proteins) or heterodimerization (a chemical reaction that combines 2 non-identical proteins) between HER2 and its partners, HER1, HER3, and HER4. This understanding of the activity of HER2 led to the discovery and development of trastuzumab, a monocolonal antibody that targets HER2 overamplification, meaning that there are too many copies of a normal-appearing gene and that there is an overabundance of the protein that the gene produces.3 Normal cells

have two copies of the HER2 gene, but HER2-positive cancer cells have multiple copies.3 HER2-positive breast cancer is considered to be one of the most dangerous kinds of breast cancer as result of its uncontrolled and aggressive cellular growth.

The metabolic activity of HER2positive cancer is high; these tumors tend to grow and spread faster than other breast cancer types. However, understanding the science behind HER2 mutations has made all the difference in developing therapies that have forever changed the natural history of this disease. HER2 proteins have been noted to be a driver mutation or proto-oncogene. This means that in cancers that are positive for HER2 mutation, the signal can be blocked. If the signal is blocked then the protein is not produced and cellular growth is stopped.3 This knowledge and mechanism of action for HER2positive breast cancer has transformed a disease that was once characterized only with a poor prognosis to one that can be effectively treated if not cured with early diagnosis.3 Yet, we can still aim for prolonged survival benefit and quality of life even in cases of metastatic and advanced disease. Continues on page 28

TABLE 1. FDA-Approved Tests for HER2 Positivity6 Test

What Test Measures

How Results Are Reported

FISH

Number of HER2 gene copies inside each cell

Positive Negative Indeterminate

IHC

How much HER2 protein is present on cancer cell surface

Negative: 0-1+ Borderline: 2+ Positive: 3+

ISH

Number of HER2 gene copies in cancer cells

Positive Negative

SPoT-Light HER2 CISH

Number of HER2 gene copies in cancer cells

Positive Negative Indeterminate

KEY: FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; ISH, in situ hybridization; SPoT-Light HER2 CISH, subtraction probe technology chromogenic in situ hybridization.

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 27

FEATURE | Breast Cancer DIAGNOSTIC TESTS Validating the HER2 status of breast cancer is imperative to treatment outcomes. HER2 positivity is a crucial factor in determining therapies that treat primary disease vs metastatic disease. There are several methods for diagnosing HER2-positive disease. Tests for HER2 status of stage I-III disease are performed on the biopsy specimen at the time of the initial surgery3; whereas HER2 status in stage IV or recurrent disease is confirmed at the site of metastasis when feasible. The FDA has approved 4 methods for HER2 testing: fluorescent in situ hybridization (FISH) assay, immunohistochemistry (IHC), in situ hybridization (ISH), and subtraction probe technology chromogenic in situ hydridization (SPoT-Light HER2 CISH) ( Table 1).3,5 HER2 status, as well as hormone status, should be tested at initial diagnosis and in the setting of recurrent or metastatic disease. The changes in diagnosis from these stages of disease can impact treatment decision planning. WHERE WE ARE TODAY Long-term survival for patients with HER2-positive breast cancer has forever been changed. Treatment options for all stages of disease have grown and expanded, which has proven to be the “good side” of HER2-positive disease.6 Current treatment algorithms for invasive HER2-positive breast cancer has transformed the face of a disease with a death TABLE 2. Chemotherapeutic Regimens for HER2-Positive Breast Cancer5,6 Early Stage ACTH (doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], followed by a taxanea and trastuzumab [Herceptin])

With ongoing clinical trials and studies, the treatment paradigm for patients with HER2-positive breast cancer will continue to evolve. sentence to one with prolonged and overall survival benefit. Management of this disease has shifted from a one-size-fits-all approach to one in which patients are properly categorized by risk (ie, low risk to high risk). A greater understanding of patients’ treatment needs leads to meaningful and durable response to treatment with HER2 therapies. From combination therapies to single-agent monoclonal therapies, the treatment arsenal for HER2-positive breast cancer continues to grow. Both combination therapies and single agents have altered the approach to HER2-positive treatment for clinicians and have been life changing for patients. The therapeutic options for HER2 positive disease are broad and variable ( Table 2). With ongoing clinical trials and studies, the treatment paradigm for patients with HER2-positive breast cancer will continue to evolve. Advances to date have already greatly changed what HER2-positive disease was more than 30 years ago. New approaches to management will extend further to second- and third-line therapies and improved agents that can cross the blood-brain barrier. As a discipline, the commitment to discovering agents for high-risk patients and metastatic disease must continue.6 The discovery of HER2-positive therapies have led to better outcomes and improved survival rates.4 ■ Jiajoyce Conway is an advance practice oncology nurse with Cancer Care Associates of York, in York, Pennsylvania.

TCH (docetaxel, carboplatin, trastuzumab) Trastuzumab as single agent after other therapies Neoadjuvant Any early-stage regimen plus pertuzumab (Perjeta) and trastuzumab Metastatic Taxanea, trastuzumab, pertuzumab Ado-trastuzumab (Kadcyla) Extended Treatment Neratinib (Nerlynx) for 1 year of treatment beyond adjuvant therapy in high-risk patients a

The taxane in these regimens is paclitaxel (Taxol) or docetaxel (Taxotere).

REFERENCES 1. Porter K, Quinn Rosenzweig M. Current and emerging therapies for HER2-positive women with metastatic breast cancer. J Adv Pract Oncol. 2017;8(2):164-168. 2. Bishop CS. Biomarkers in breast cancer. J Adv Pract Oncol. 2011;2(2):101-111. 3. Wilson C. Managing the care of patients with HER2 positive breast cancer: a collaborative practice model. J Adv Pract Oncol. 2016;7(suppl 2):5-20. 4. Breast Cancer HER2 Status. American Cancer Society website. https:// www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancerdiagnosis/breast-cancer-her2-status.html. Accessed May 31, 2018. 5. De Santis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64(1):52-61. 6. Battaglia G. Optimizing HER2-targeted therapy. https://www.onclive.com/ web-exclusives/optimizing-her2targeted-therapy. Accessed May 31, 2018.

28 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

ASK THE EXPERTS | Myelofibrosis

Aligning Symptoms With Effective Treatment for Myelofibrosis Our panel of experts weighs in on risk assessment, treatment options, and symptom burden for patients with myelofibrosis, plus their perspectives on what lies ahead. How is patient risk assessed in myelofibrosis? LYLE: In patients with myelofibrosis risk is assessed based on a variety of clinical and laboratory features. Risk is typically assigned at diagnosis using the International Prognostic Scoring System (IPSS) and throughout the course of the disease with the Dynamic International Prognostic Scoring System (DIPSS or DIPSS+). The IPSS estimates survival at the time of diagnosis and the DIPSS or DIPSS+ adjust risk depending on measurable components of a changing disease. The IPSS assigns 1 point for each of these adverse features: age older than 65, Hgb less than 10g/dL, constitutional symptoms, white blood cell count (WBC) greater than 25,000, and peripheral blasts greater than 1%. Using points, a patient is classified as low risk (0 points), intermediate-1 risk (1-2 points), intermediate-2 (3-4 points), or high risk (5-6 points). Estimated median overall survival for low risk

patients is approximately 11 years compared to approximately 2 years for a high risk patient. More recently, additional clinical features have been identified as having prognostic significance and have been incorporated into the DIPSS+. These include platelets less than 100,000, PRBC transfusion requirements, and complex cytogenetics. Anemia with Hgb less than 10 infers a worse prognosis and counts for 2 points whereas all other components remain at 1 point. The presence or absence of different molecular mutations has become more important as we understand more about the disease biology, and although they are not incorporated into standard prognostic scoring system, they should be taken into account. While this is not a perfect system, assigning risk is important, as treatment can look very different for a low risk patient compared with a high risk patient.1-3 THYNE: Myelofibrosis is a very hetero-

geneous disease. At initial diagnosis,

Lindsey Lyle, MS, PA-C Blood Cancers and Bone Marrow Transplant Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado

risk factors can be evaluated using the International Prognostic Scoring System (IPSS) for myelofibrosis, which looks at age older than 65, hemoglobin less than 10, white blood cell count (WBC) greater than 25,000, the presence of peripheral blasts, and constitutional symptoms (such as unintentional weight loss, fever, or excessive sweating). Based on the number of risk factors, patients are stratified as low, intermediate-1, intermediate-2, or high risk. Similarly, for patients who were previously diagnosed and whose risk needs to be re-assessed, the Dynamic International Prognostic Scoring System (DIPSS) and DIPPSplus can be utilized. What are the goals of treatment of myelofibrosis? LYLE: Patients with myelofibrosis represent a fairly heterogeneous group and goals of treatment can vary depending

Maureen E. Thyne, RPA-C Weill Cornell Leukemia Program at Weill Cornell Medicine and New York-Presbyterian, New York, New York

www.OncologyNurseAdvisor.com â&#x20AC;˘ MAY/JUNE 2018 â&#x20AC;˘ ONCOLOGY NURSE ADVISOR 29

ASK THE EXPERTS | Myelofibrosis on specific clinical needs. For example, if anemia is a patient’s main clinical problem, using therapies to try to increase red blood cell production and reduce transfusion requirements would be a primary goal. Additionally, having a large spleen can cause severe symptoms, which not only significantly affect quality of life but also increase risk for comorbid conditions such as portal hypertension. Therefore, focusing therapy on spleen size reduction is another common target of treatment. The only U.S. Food and Drug Administration (FDA)-approved therapy for myelofibrosis, ruxolitinib, reduces splenomegaly and spleen-related symptoms. In addition to identifying and directing therapy toward specific laboratory or clinical features, assigning risk helps direct goals of treatment. In high-risk patients who have a good performance status, allogeneic stem cell transplant may be indicated, as this is the best chance for a cure. Outside of a stem cell transplant, disease control, spleen size reduction, palliation of symptoms, and improvement of quality of life are the main goals of treatment. Certainly, we hope to prolong the life of these patients with therapy while maintaining as good of quality of life as possible. THYNE: Myelofibrosis is a variable disease, and each patient’s case and care plan are different. We understand that at this time, stem cell transplant is the only opportunity for cure, but there are several medications that can help slow the progression of the disease and/or improve symptoms. Some supportive care measures, like transfusion, may also be utilized. Understanding your patient’s goals, whether that is for aggressive treatment or symptom management or somewhere in between, can help you set a care plan that best suits their specific situation.

What role does ruxolitinib play in the treatment of myelofibrosis? What other treatment options are considered for patients with myelofibrosis? LYLE: Ruxolitinib was FDA approved for patients with intermediate and high risk myelofibrosis based on clinical trials that showed significant reduction in spleen size and improvement in symptoms related to the disease. As previously mentioned, if a patient has symptoms of the disease (eg, significant weight loss, itching, fatigue, getting full easily, pain under left ribs) they are already considered intermediate risk and it would be appropriate to start ruxolitinib therapy. Additionally, ruxolitinib is beneficial for controlling proliferation in patients with elevated or upward trending WBC. Ruxolitinib is a JAK1/2 inhibitor that targets the JAK-STAT pathway that is overactive in myelofibrosis, thus leading to suppressed hematopoiesis (reduction in leukocytosis) and reduction in proinflammatory cytokine production. Due to the suppression of the JAK-STAT pathway, therapy dose-related cytopenias are expected and CBC should be monitored closely. While not FDA approved for myelof ibrosis, other available treatment options outside of a clinical trial are aimed at specific disease features, as mentioned above. For anemia: androgens, prednisone, erythropoietin, immunomodulatory agents (thalidomide, pomalidomide). For the spleen: hydroxyurea, busulfan, cladribine. For symptoms: prednisone.4,5

THYNE: Ruxolitinib is the only medication specifically approved for patients with intermediate or high risk myelofibrosis, and it is used to help improve blood counts, symptoms, and quality of life. Some patients also have an improvement in overall survival. It is an oral medicine, taken twice daily, and requires regular doctor visits to have blood tests and physical exams. Other measures used to treat myelofibrosis include supportive measures, like blood transfusions, or cytoreductive therapies, like hydroxyurea, or even chemotherapy. Stem cell transplant is also an available treatment for certain patients, and at this time is the only treatment that can lead to cure. There are also many clinical trials available for patients in an ongoing effort to improve our treatment algorithm. This is a rare disease, with somewhat limited treatments, so more options are always welcome!

Can you discuss the overall survival data available for the different treatment options? How does this data impact when you initiate treatment? LYLE: Available overall survival data exists for the phase III COMFORT trials with ruxolitinib as overall survival at 144 weeks was a secondary endpoint. The 3-year update from COMFORT-I revealed that survival probability was 70% for patients who were originally randomly assigned to receive ruxolitinib and 61% for those

Often times, especially at diagnosis, patients do not know that the symptoms they are experiencing are due to the underlying MPN. Lindsey Lyle, MS, PA-C

32 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

originally randomly assigned to receive placebo. In COMFORT-II the estimated probability of survival was 81% in the ruxolitinib arm compared with 61% in the best available therapy arm. Most recent updates with 5-year follow-up data in COMFORT-I show that survival was decreased in patients who initially received placebo and then crossed over to ruxolitinib compared with patients who initially started on the ruxolitinib arm. Another important point is that spleen response was maintained for a median of 3 years with many patients still having a durable response at the 5-year follow-up. The data showing a median overall survival benefit suggests that earlier exposure to therapy should be considered in intermediate or high-risk myelofibrosis.4,6-10 How do you assess and manage symptom burden in patients with myelofibrosis? LYLE: Patients can have a wide range

of symptoms that can negatively affect their quality of life. The most common symptoms reported by patients with myeloproliferative neoplasms (MPN) include fatigue, early satiety, night sweats, itching, abdominal discomfort, weight loss, fevers, and bone pain. An MPN symptom assessment tool was developed by Ruben A. Mesa, MD, FACP, Director, UT Health San Antonio Cancer Center, and has been instrumental in the evaluation of presence and severity of symptoms at the initial visit and follow-up visits to help track response to treatment. Practically speaking, providing patients with symptom assessment forms for them to fill out at each visit is a great way to monitor symptoms. Often times, especially at diagnosis, patients do not know that the symptoms they are experiencing are due to the underlying MPN.

We understand that it is meaningful to help improve patients’ symptoms even if it doesn’t ultimately fix the disease entirely. Maureen E. Thyne, RPA-C In these cases, using this tool can help to educate patients and optimize care. Managing symptoms may involve a variety of therapeutic interventions. In my clinical practice the most difficult symptom to treat is fatigue. This often requires collaboration with my internal medicine colleagues and psychology team as we work to identify ways to “save energy” during the day and maximize nighttime sleep behaviors. Controlling the disease with medical therapies, such as ruxolitinib, should also help reduce symptoms. THYNE: Having an open line of communication with your patient is the best way to continually assess their symptom burden. Sometimes asking your patient to keep a symptom journal, or occasionally complete a self-assessment (like the MPN-10, which is available online), can help them remember the symptoms and patterns during your visit. I also welcome the spouse/family member/friends of the patient to weigh in — sometimes they notice new things or changes that the patient doesn’t. Ultimately, encouraging the patient to keep you informed of their symptoms is most important.

What does the future treatment landscape for myelofibrosis look like? LYLE: Clinical trials are a very important part of identifying best treatments for patients with myelofibrosis. Currently there are a variety of trials open with different biological agents that have different targets. For example, sotatercept

is being used in trials with the goal to improve anemia. Trials with other JAK1 and JAK2 inhibitors are also active. One specific JAK2 inhibitor, fedratinib, is on track for potential U.S. Food and Drug Administration approval later this year after the trial was put on hold due to 8 possible cases of Wernicke’s encephalopathy. This therapy may be especially useful in patients who have thrombocytopenia as it is less suppressive to the platelets. Additionally, combination therapies are being used more frequently especially in patients who have high risk disease/blast phase disease who are not eligible for high dose chemotherapy or allogeneic stem cell transplant. Combining therapies with ruxolitinib is also becoming more common as we hope to synergistically improve outcomes. THYNE: Myelofibrosis is a rare disease that remains difficult to treat. Over the past decade or so, however, it has benefitted from increased attention from the medical and scientific communities. We understand that it is meaningful to help improve patients’ symptoms even if it doesn’t ultimately fix the disease entirely. There has also been a steady stream of clinical trials investigating new uses for known medications as well as new compounds, and hopefully we will find a good treatment option for all our patients in the near future. ■ REFERENCES 1. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 33

ASK THE EXPERTS | Myelofibrosis Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901. 2. Passamonti F, Cervantes F, Vannucchi AM, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis.

5. Harrison C, Kiladjian JJ, Al-Ali HK, et al.

8. Verstovsek S, Mesa AR, Gotlib J, et al. Long-term

JAK inhibition with ruxolitinib versus best

outcomes of ruxolitinib therapy in patients

available therapy for myelofibrosis. N Engl

with myelofibrosis: 3-year update from

J Med. 2012;366(9):787-98. doi: 10.1056/

COMFORT-I. Blood. 2013;122(21):abstract 396.

NEJMoa1110556

9. Cervantes F, Vannucchi AM, Kiladjian JJ, et al.

6. Deisseroth A, Kaminskas E, Grillo J, et al. U.S.

Three-year efficacy, safety, and survival find-

Food and Drug Administration approval:

ings from COMFORT-II, a phase 3 study com-

ruxolitinib for the treatment of patients

paring ruxolitinib with best available therapy

effect of driver mutations of JAK2, CALR,

with intermediate and high-risk myelofibro-

for myelofibrosis. Blood. 2013;122(25):4047-53.

or MPL in primary myelofibrosis. Blood.

sis. Clin Cancer Res. 2012;18(12):3212-7. doi:

2014;124(7):1062-1069. doi: 10.1182/

10.1158/1078-0432.CCR-12-0653

Blood. 2010;116(15):2857-2858. 3. Rumi E, Pietra D, Pascutto C, et al. Clinical

blood-2014-05-578435 4. Verstovsek S, Mesa RA, Gotlib J, et al. A

doi: 10.1182/blood-2013-02-485888 10. Verstovsek S, Mesa RA, Gotlib J, et al. Long-

7. Verstovsek S, Mesa RA, Gotlib J, et al.

term treatment with ruxolitinib for patients

Efficacy, safety, and survival with ruxolitinib

with myelofibrosis: 5-year update from

double-blind, placebo-controlled trial

in patients with myelofibrosis: results of a

the randomized, double-blind, placebo-

of ruxolitinib for myelofibrosis. N Engl J

median 3-year follow-up of COMFORT-I.

controlled, phase 3 COMFORT-I trial.

Med. 2012;366(9):799-807. doi: 10.1056/

Haematologica. 2015;100(4):479-88. doi:

J Hematol Oncol. 2017;10(1):55. doi: 10.1186/

NEJMoa1110557

10.3324/haematol.2014.115840

s13045-017-0417-z

MPNs by the Numbers Myeloproliferative neoplasms (MPNs) is a group of diseases characterized by proliferation of red blood cells, white blood cells, and/or platelets. Many patients are asymptomatic for years, and when symptoms do present, they may be nonspecific. Splenomegaly, however, is often present in patients with an MPN at diagnosis.

Essential Thrombocythemia1

Polycythemia Vera2

Primary Myelofibrosis3

What is it: Increased platelets

What is it: Overproduction of blood cells

What is it: Abnormalities in blood cell production

Incidence:

Affects: Women more than men

Affects: Men slightly more than women

Affects: Men and women equally

Average Age of Onset:

<1/100,000

mid-50s

2/100,000

>60

1.5/100,000

>50

References 1. Essential thrombocythemia. NORD National Organization for Rare Disorders website. https://rarediseases.org/rare-diseases/essential-thrombocythemia/. Accessed June 4, 2018. 2. Polycythemia vera. NORD National Organization for Rare Disorders website. https://rarediseases.org/rare-diseases/polycythemia-vera/. Accessed June 4, 2018. 3. Primary myelofibrosis. NORD National Organization for Rare Disorders website. https://rarediseases.org/rare-diseases/primary-myelofibrosis/. Accessed June 4, 2018.

34 ONCOLOGY NURSE ADVISOR â&#x20AC;˘ MAY/JUNE 2018 â&#x20AC;˘ www.OncologyNurseAdvisor.com

JOURNAL REVIEW

esults of a recently published study suggest a change to the standard treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). Australian researchers are reporting that venetoclax plus rituximab may result in significantly higher rates of progression-free survival (PFS) than bendamustine plus rituximab in patients with relapsed or refractory CLL. In their study, published in The New England Journal of Medicine, they report that a substantial rate of clearance of minimal residual disease (MRD) was seen in the venetoclax–rituximab arm, suggesting improved disease control over a longer term even when therapy is discontinued.1 “The consistency of these improvements across all clinical and biological subsets of patients, and the favorable toxicity profile do appear to be sufficient to justify a change in standard therapy, and the regulatory submissions necessary to enable this have been made based on this dataset,” said John F. Seymour, MB, BS, PhD, of the Department of Haematology at the Peter MacCallum Cancer Centre, Melbourne, Australia, and lead author of the study. THE STUDY The team investigated venetoclax because it inhibits BCL2, a pathologically overexpressed protein that is pivotal to the survival of CLL cells. The researchers analyzed the efficacy of venetoclax in combination with

Venetoclax Effective in Relapsed/ Refractory CLL John Schieszer, MA rituximab in the randomized, openlabel, phase 3 MURANO trial. In this study, 389 patients were randomly assigned to receive venetoclax for up to 2 years plus rituximab for the first 6 months (n = 194) or bendamustine plus rituximab for 6 months (n = 195). Patients were enrolled at 109 sites in 20 countries. The median age across the 2 treatment groups was 65 years (range, 22 to 85 years) and 73.8% of the patients were men. WHAT WAS LEARNED The study showed that PFS was significantly higher in the venetoclax–rituximab arm with 32 events of progression or death in 194 patients at a median follow-up period of 23.8 months. In the bendamustine–rituximab arm, there were 114 events in 195 patients. “The major findings of this study were the profound and consistent superiority of the venetoclax combination therapy over the conventional chemo-immunotherapy as shown by the

more than doubling of progression free survival (2 year rates of 85% vs 36%; HR, 0.17),” Dr Seymour told Oncology Nurse Advisor. He said the overall response rate was 93% for the venetoclax–rituximab arm compared with only 68% for the bendamustine-rituximab arm (by investigator). Dr Seymour said attainment of high quality responses as shown by peripheral blood MRDnegativity rate in the peripheral blood were impressive (84% vs 23%). There was a trend for better overall survival (OS) with a rate of 92% for the venetoclax–rituximab arm vs 87% for the bendamustine-rituximab arm. However, the follow-up has only been 2 years. Overall, 379 patients (99.2%) experienced at least one adverse event. The most common adverse event of any grade in both treatment arms was neutropenia, occurring in 60.8% of patients in the venetoclax–rituximab arm and 44.1% of patients in the bendamustine–rituximab arm. However, the rates of grade 3 or 4 febrile neutropenia and infections were lower in the venetoclax-rituximab arm. Grade 3 or 4 tumor lysis syndrome (TLS) developed in 3.1% of the patients in the venetoclax–rituximab arm (6 of 194 patients). IMPLICATIONS FOR NURSES

“The involvement and vigilance of oncology nurses in patient education and safe implementation of the weekly dose ramp up of venetoclax is critical

The results of the MURANO study have the potential to change [the current] paradigm with time-limited therapy after attainment of deep responses, as confirmed by MRD negativity. www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 35

JOURNAL REVIEW

for this safe delivery,” explained Dr Seymour. Oncology nurses should be aware that infection rates were low with venetoclax despite frequent neutropenia. In addition, infections were largely restricted to the first 6 months of treatment and were much lower in the monotherapy phase once CLL disease control was achieved. Despite recent improvements in the treatment of relapsed/refractory CLL, current approaches to targeted therapy achieve low complete remission rates and require continuous therapy indefinitely. The results of the MURANO

study have the potential to change that paradigm with time-limited therapy after attainment of deep responses, as confirmed by MRD negativity. “The vigilance and monitoring of dose ramp up for TLS issues is critical for safe delivery of this highly effective therapy,” Dr Seymour said. “Oncology nurses have a pivotal role in that domain, both in the areas of patient education so they are informed, empowered active partners in their care, as well as the timeliness and vigilance of monitoring and management of emerging TLS signals.”

Hematologic monitoring and education regarding the management of neutropenia are very important. The researchers cautioned that additional follow-up is warranted to determine the durability of these responses. ■ John Schieszer is a medical reporter based in Seattle, Washington. REFERENCE 1. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-20.

Time-saving clinical tools for patient-centered care. OncologyNurseAdvisor.com provides all of the tools you need to better care for your patients. • Cancer treatment regimens • Downloadable patient fact sheets

• Easy-to-use medical calculators • Comprehensive drug slideshows

Visit www.OncologyNurseAdvisor.com today. 36 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

STAT CONSULT Osimertinib (Tagrisso) Drug Type

• Kinase inhibitor

Indication

Stir until tablet is dispersed into small pieces (tablet will not completely dissolve) ■■ Swallow immediately ■■ Rinse container with 4 to 8 oz of water and drink immediately ——For administration via nasogastric tubes ■■ Disperse in 15 mL of noncarbonated water, then use additional 15 mL of water to transfer any residues to syringe ■■ Administer resulting 30 mL of liquid per nasogastric tube instructions with appropriate water flushes (approximately 30 mL) ■■

• First-line treatment of metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test • Metastatic EGFR T790M mutation-positive NSCLC that has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy Mechanism of Action

• Osimertinib is an EGFR kinase inhibitor that binds irreversibly to certain mutant forms of EGFR ——T790M, L858R, and exon 19 deletions • In vitro studies have shown HER2, HER3, HER4, ACK1, and BLK activity inhibition at clinically relevant concentrations Dosage

• 80 mg orally once daily Administration

• One 80-mg tablet daily • Take with or without food • If dose is missed, do not take additional dose; take next prescribed dose as scheduled • May disperse tablet in noncarbonated water for patients who have difficulty swallowing solids ——For patients who have difficulty swallowing ■■ Disperse tablet in 60 mL (2 oz) of noncarbonated water »» Do not crush, heat, or ultrasonicate during preparation

Dose Adjustments

• Cardiac adverse reactions ——QTc interval >500 msec on at least 2 separate ECGs ■■ Withhold until QTc interval <481 msec or recovery to baseline if baseline QTc >481 msec, then resume at 40 mg. ——QTc interval prolongation with signs/symptoms of life-threatening arrhythmia ■■ Permanently discontinue ——Symptomatic congestive heart failure or asymptomatic left ventricular dysfunction that persists ≥4 weeks ■■ Permanently discontinue • Interstitial lung disease (ILD)/pneumonitis ——Permanently discontinue • Other adverse reactions ——Adverse reaction ≥ grade 3 ■■ Withhold up to 3 weeks Continues on page 38

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STAT CONSULT ——If improvement to grade 0 to 2 within 3 weeks ■■ Resume at 80 mg or 40 mg daily ■■ Permanently discontinue if no improvement within 3 weeks • Strong CYP3A4 inducers ——If concurrent use is unavoidable, increase osimertinib dose to 160 mg daily (two 80-mg tablets) ——Resume 80-mg dose 3 weeks after discontinuation of CYP3A4 inducer Specific Populations

• Pregnancy ——No available data in pregnant women ——Osimertinib may cause fetal harm based on findings in animal studies • Nursing mothers ——Do not breastfeed during treatment and for 2 weeks after final dose • Female patients of reproductive potential ——Use effective contraception during treatment and for 6 weeks after final dose • Male patients with female partners of reproductive potential ——Use effective contraception during treatment and for 4 months after final dose • Pediatric ——Safety and efficacy not established • Geriatric ——No clinically relevant differences in safety or efficacy were observed between older and younger patients • Renal impairment ——No dose adjustment recommended for patients with mild to moderate renal impairment ——No recommended dose available for patients with end-stage renal disease • Hepatic impairment ——Mild (total bilirubin less than or at the upper limit of normal (ULN) and AST greather than the ULN or total bilirubin between 1-1.5×ULN and any AST) ■■ No dose adjustment is recommended ——Moderate (total bilirubin 1.5-3×ULN and any AST) ■■ No dose adjustment is recommended ——Severe: No recommended dose Boxed Warnings

• None Contraindications

• None

Cautions

• Cardiomyopathy ——Monitor for cardiac events ——Assess for left ventricular ejection fraction (LVEF) at baseline and during treatment in patients with cardiac risk factors or relevant cardiac signs and symptoms ——Permanently discontinue osimertinib if symptomatic congestive heart failure or persistent, asymptomatic left ventricular (LV) dysfunction does not resolve in 4 weeks • Embryo-fetal toxicity ——Osimertinib may cause fetal harm based on findings in animal studies • Fertility ——Osermitinib may impair fertility in both female and male patients of reproductive potential ■■ In female patients, the effect showed a trend toward reversibility ■■ In male patients, whether the effect is reversible is not known ——Female patients should use effective contraception during treatment and for 6 weeks after their final dose ——Male patients with female partners of reproductive potential should use effective contraception during treatment and for 4 months after their final dose • Interstitial lung disease/pneumonitis ——Withhold and investigate for ILD in patients who develop respiratory symptoms ——Permanently discontinue if ILD confirmed • Keratitis ——Promptly refer patients with signs and symptoms to an ophthalmologist • QTc interval prolongation ——Obtain periodic ECGs and electrolyte measures in patients with ■■ Congenital long QTc syndrome ■■ Congestive heart failure ■■ Electrolyte abnormalities ■■ Patients taking QTc interval-prolonging medicines ——Permanently discontinue if QTc prolongation occurs with signs and/or symptoms of life-threatening arrhythmia Adverse Effects

• Most common adverse reactions (occur in 20% or more of patients) ——Diarrhea ——Dry skin ——Fatigue

38 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

——Nail toxicity ——Rash Drug Interactions

• Strong CYP3A inducers ——If administration with a CYP3A cannot be avoided, increase osimertinib dose ——No adjustment needed for weak/moderate inducers • Effect of osimertinib on other drugs ——Coadministration with breast cancer resistance protein (BCRP) substrates (eg, rosuvastatin, sulfasalazine, topotecan) increases BCRP substrate exposure ——Monitor for BCRP substrate adverse reactions, unless otherwise instructed What to Tell Your Patient

• Osimertinib is a tyrosine kinase inhibitor — a type of anticancer medication — used to treat non-small cell lung cancer (NSCLC) • Osimertinib may be used as a first treatment for NSCLC that has spread and has 1 of these 2 abnormalities in the EGFR gene ——exon 19 deletions ——exon 21 L858R mutations • Osimertinib may also be used if your lung cancer has spread and ——Has an abnormal EGFR gene called T790M ——You have had a previous treatment with an EGFR TKI medicine, and it has stopped working • You should take osimertinib once a day, and you may take it with or without food ——If you miss a dose, take the next dose at its usual time ■■ Do not make up for the missed dose or take an additional dose ——If you cannot swallow osimertinib whole ■■ Dissolve the tablet in 2 oz of noncarbonated water (do not use any other liquids) ■■ Stir until tablet is in pieces (tablet will not fully dissolve) »» Do not crush, heat, or use ultrasound to prepare mixture ■■ Drink mixture right away ■■ Add 4 to 8 oz of noncarbonated water into the container, swish it around, and drink to make sure you take your full dose • You should tell your doctor and nurse if you ——Have lung or breathing problems ——Have heart problems, including a condition called long QTc syndrome

——Have problems with your electrolytes, such as sodium, potassium, calcium, or magnesium ——Have a history of eye problems • You should tell your doctor and nurse if you are taking medication for a heart or blood pressure problem. • You should tell your doctor and nurse about all the medicines you take, including ——Herbal supplements ——Over-the-counter (OTC) medications ——Prescription medications ——Vitamins • Osimertinib may impair your ability to conceive a child ——This effect may be reversible in female patients, but whether it is reversible in male patients is not known ——Ask for information about fertility preservation options before you start treatment ——If you are a male patient with a female partner of reproductive potential ■■ Use effective contraception during treatment and for 4 months after your last dose ——If you are a female patient of reproductive potential ■■ A pregnancy test will be done to make sure you are not pregnant before you start treatment ■■ You should avoid becoming pregnant while receiving osimertinib »» Use effective birth control during treatment and for at least 6 weeks after your last dose • You should not breastfeed during treatment and for 2 weeks after your last dose • You may experience adverse effects while taking osimertinib. ——Call your nurse or doctor if you experience any of these adverse effects or any side effects are severe and cannot be tolerated ■■ Changes in your nails, including »» Brittleness »» Inflammation »» Pain »» Redness »» Separation from nailbed »» Shedding of nails »» Tenderness ■■ Diarrhea ■■ Dry Skin ■■ Rash ■■ Tiredness Prepared by James Nam, PharmD.

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 39

RADIATION & YOUR PATIENT

Radiograph of pleural effusion in mesothelioma

Evolving Role of Radiation Therapy in the Treatment of Mesothelioma Bryant Furlow The optimal palliative, adjuvant, and neoadjuvant roles for radiation therapy in the treatment of malignant mesothelioma are not yet completely established, but the American Society of Clinical Oncology (ASCO) has released an evidence-based clinical guideline that makes several recommendations.

pproximately 3000 new cases of malignant mesothelioma, an aggressive cancer of the lining of internal organs, are diagnosed in the United States each year. The vast majority involve lung pleura and are associated with asbestos inhalation.1

Less frequently, mesothelioma occurs in the peritoneum, testes, or pericardium.1 Most patients are white, male, and older than 65 years.1 Mesothelioma is a dismal diagnosis. There is no known cure.1,2 The FDA last approved a new drug regimen for its treatment — pemetrexed plus cisplatin — back in 2004.3 Diagnosis is usually made after patients begin to experience symptoms such as chest pain or shortness of breath.1 It is often accompanied by pleural effusion, an accumulation of fluid between the pleural layers that encompass the lungs. The diagnostic gold standard is thoracoscopy and endoscopic biopsy for confi rmatory histologic analysis following detection of abnormalities on chest radiography.1 Incidence rates climbed through the 1970s, 1980s, and 1990s; however, following reductions in occupational exposures to asbestos, rates appear to have plateaued.1 Regulatory efforts to reduce workplace exposures began in the 1970s, but overall incidence rates did not decline for several decades because of the long latency period between exposure and carcinogenesis.1 FEW OPTIONS, LIMITED EVIDENCE

Treatment options include surgery, chemotherapy (usually a platinum-based chemotherapy plus pemetrexed), and less frequently, radiotherapy. Cisplatin plus pemetrexed is the first-line standard of care and no validated secondline treatment is available.2 Adding bevacizumab, an anti-VEGF therapy, to cisplatin has been proposed as a new treatment regimen and immunotherapies are under investigation as possible second-line options after disease progression following chemotherapy.2 Evidence-based management of mesothelioma can be challenging

40 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

because patient populations for participation in clinical trials are relatively small. Ashton and colleagues reported in a systematic review of radiotherapy in mesothelioma that of 249 published papers reviewed, only 2 were highquality, randomized clinical trials.4 Evidence that chemotherapy might prolong survival times, perhaps by as much as 7 months, and that a second line of chemotherapy or thalidomide might offer additional, modest survival benefits is limited.1,5 According to a recent analysis of data from 1625 patients in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, the median overall survival time was 1 year among patients who received any chemotherapy for mesothelioma and 4 months for those not receiving chemotherapy (range, 1 to 69 months for both groups).1 Sixteen percent of patients foregoing chemotherapy altogether survived 1 year, compared with 48% of patients undergoing any chemotherapy.1 However, the SEERMedicare study authors cautioned that patient or disease characteristics could have confounded their retrospective database analysis.1 RADIOTHERAPY’S ROLE The goals of radiotherapy in mesothelioma management are prophylaxis and palliation. Treatment is aimed at slowing the spread of disease — thereby prolonging survival — by killing micrometastases and at easing pain and other symptoms.6 “Over the past 15 years, there has been a major shift in the role of radiotherapy for the treatment of mesothelioma,” said Marc de Perrot, MD, Toronto General Hospital, in Ontario, Canada, and coauthors in a 2017 report.6 “Increasing evidence

has supported that mesothelioma is sensitive to radiotherapy treatment.” However, the exact role radiotherapy will eventually play in the treatment paradigm has not yet been determined, they cautioned.6 The complex contours of the lung pleura historically limited the radiation doses that could be attempted for patients with mesothelioma because of toxicities resulting from irradiation of healthy, nontarget lung tissue.4,6 However, with advances in intensitymodulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3DCRT), it became possible to tailor radiation dose delivery to target tissue and to minimize irradiation of radiosensitive nontarget tissues.6 Ashton and colleagues reported an apparent trend in the available prospective data suggesting that high doses of adjuvant radiotherapy can be safely administered following lung-sparing surgery.4 The delivery of high-dose hemithoracic IMRT following surgery might improve survival time for some patients, regardless of response to chemotherapy, according to de Perrot and colleagues.6 Both adjuvant pleural-tumor-targeting IMRT after pleurectomy (partial resection of the pleura) and inductionaccelerated hemithoracic IMRT followed by extrapleural pneumonectomy (resection of a lung and portions of the diaphragm, parietal pleura, and cardiac pericardium) have both been adopted as treatment options.6 However, outcomes from the randomized, controlled, open-label phase 3 SMART clinical study of 203 patients cast doubt on the potential benefits of routine prophylactic postsurgical radiotherapy.7 Prophylactic radiotherapy might benefit a subset of patients who have epithelial disease and tumor volumes smaller than 500 cc3.6

The newly announced randomized phase 2 Symptoms Study of Radiotherapy in Mesothelioma (SYSTEMS)-2 trial will study palliative radiotherapy dose escalation for pain control.8 SYSTEMS-1 was a single-arm, multicenter, prospective phase 2 palliation study of 40 patients who were treated with 20 Gy in 5 dose fractions, planned using CT and PET/CT imaging; its authors reported decreased pain in 47% of patients without improvement to quality of life.3,9 SYSTEMS-2 will compare pain management outcomes for dose-escalated hypofractionation (36 Gy in 6 dose fractions) vs standard radiotherapy palliation (20 Gy in 5 fractions), noted the authors of ASCO’s 2018 clinical practice guideline for malignant pleural mesothelioma.3 GUIDELINE RECOMMENDATIONS Meanwhile, the ASCO guideline makes several recommendations regarding radiotherapy for patients with mesothelioma, including an informal consensus that radiotherapy may be offered to patients with localized recurrence even when recurrence is not symptomatic.3

The goals of RT in mesothelioma are prophylaxis and palliation. Clear communication is key to conveying options and recommendations to patients. The ASCO guideline authors emphasized “increasing information asymmetry between physician and patient” with advances in the field, and the “nearly impenetrable” complexity of relevant information for patients when it is presented using technical

jargon.3 Patients should be told of the limited available clinical-trial evidence base and the goals of different treatment options. (ASCO has separately promulgated a consensus guideline on patient-clinician communication [ J Clin Oncol. 2017;35(31):3618-3632].) The ASCO mesothelioma clinical guideline includes several evidence-based recommendations about radiotherapy. • Adjuvant radiotherapy should be offered to patients with histologically positive resection proceduretract samples.3 (Quality of evidence: Intermediate) • Radiotherapy should be offered for palliation of symptoms. Electrons, IMRT, 2D, and 3DCRT techniques should be selected based on target tissue location.3 (Quality of evidence: Intermediate) • Standard dosing regimens offered to patients should include 8 Gy in a single fraction, 4 Gy in 5 fractions, or 3 Gy in 10 fractions.3 (Quality of evidence: Intermediate) • Neoadjuvant radiotherapy should be avoided with patients undergoing lung-sparing cytoreductive surgery because of the potential for severe pulmonary toxicity. 3 (Quality of evidence: Intermediate) • Adjuvant and neoadjuvant hemothoracic radiotherapy, 3DCRT, or IMRT may be offered but proton beam therapy should be considered only at centers with significant experience, preferably in the context of a clinical trial.3 (Quality of evidence: Intermediate) • Hemithoracic adjuvant radiotherapy may be offered after nonlung-sparing cytoreductive surgery (EPP). Such treatment should be undertaken at centers of excellence. Hemithoracic neoadjuvant radiotherapy or adjuvant IMRT may also be

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 41

RADIATION & YOUR PATIENT offered to these patients, but because of the potential for toxicity, these regimens should be performed only at highly experienced centers of excellent for patients participating in clinical trials.3 (Quality of evidence: Intermediate) CONCLUSION Despite the limited rate of advances over recent decades in treating mesothelioma, there is some reason for hope that radiotherapy might be combined with immuno-oncology treatment to improve patient symptoms and outcomes. Ablative radiotherapy has been tied to immune system stimulation and preclinical lab-animal studies suggest that short-course ablative radiation therapy combined with an immune checkpoint blockade might improve immune system recognition and attack of tumor tissue.6 Clinical trials are now underway for the combination of immunotherapies with chemotherapy, radiotherapy, and/or surgery.6 ■

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

5. Buikhuisen WA, Burgers JA, Vincent AD, et al. Thalidomide versus active supportive care for maintenance in patients with malignant

REFERENCES

mesothelioma after first-line chemotherapy

1. Beebe-Dimmer JL, Fryzek JP, Yee CL, et

(NVALT 5): an open-label, multicentre, ran-

al. Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results

domised phase 3 study. Lancet Oncol. 2013;14(6):543-551.

(SEER)-Medicare investigation of treatment

6. Perrot M, Wu L, Wu M, Cho BCJ. Radiotherapy

patterns and overall survival. Clin Epidemiol.

for the treatment of malignant pleural meso-

2016;8:743-750. 2. Scherpereel A, Wallyn F, Albelda SM,

thelioma. Lancet Oncol. 2017;18(9):e532-e542. 7. Clive AO, Taylor H, Dobson L, et al. Prophylactic

Munck C. Novel therapies for malignant

radiotherapy for the prevention of procedure-

pleural mesothelioma. Lancet Oncol.

tract metastases after surgical and large-bore

2018;19(3):e161-e172.

pleural procedures in malignant pleural meso-

3. Kindler HL, Ismaila N, Armato SG 3rd, et al. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline [published online

thelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial. Lancet Oncol. 2016;17(8):1094-1104. 8. Ashton M, O’Rourke N, Macleod N, et al.

January 18, 2018]. J Clin Oncol. doi:10/1200/

SYSTEMS-2: a randomised phase II study of

JCO.2017.76.6394

radiotherapy dose escalation for pain control

4. Ashton M, O’Rourke N, Currie S, Rimner A, Chalmers A. The role of radical radiotherapy in the management of malignant

in malignant pleural mesothelioma. Clin Transl Radiat Oncol. 2017;8:45-49. 9. MacLeod N, Chalmers A, O’Rourke N, et

pleural mesothelioma: a systematic review.

al. Is radiotherapy useful for treating pain

Radiother Oncol. 2017;125:1-12. doi:10.1016/

in mesothelioma?: a phase II trial. J Thorac

j.radonc.2017.08.003

Oncol. 2015;10(6):944-950.

Cancer Treatment Regimens Review disease-specific treatment regimens from Cancer Therapy Advisor to read about the most up-to-date therapeutic strategies based on guidance from the US FDA and the NCCN for these and other cancers: • Mesothelioma • Breast Cancer • Head and Neck Cancers

• Lung Cancer • Hematologic Cancers • Rare Cancers

Review all regimens at CancerTherapyAdvisor.com/TreatmentRegimens 42 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

COMMUNICATION CHALLENGES

The Noise of Too Much Information Ann J. Brady, MSN, RN-BC, CHPN

helicopter as it lowered itself onto the roof of the building. For the few minutes it took to land and get beyond my vision, I did not look away. Whenever a helicopter arrives it does not seem to matter where you are in the hospital; you can hear it and feel its approach. Like the loud drum of a rock band, it vibrates in your belly. Oddly, it made me think of a recent patient interaction. One that did not go well.

Her attempts to make sense of it were thwarted by changes that we might all consider minor.

had just finished lunch and was enjoying the fresh air on the patio outside the hospital cafeteria. It was a warm spring day, the air crisp, and the patio resonated with the murmur of singing birds. The noise started as a distant yet regular pulse but I wasn’t able to identify it until it got louder and closer: the thump-thump-thump of a helicopter rotor. I work in a large community hospital that is also a trauma center. Tucked against the foothills of the Los Angeles mountains, the sound of an incoming helicopter is both alarming and fascinating. I watched its approach to the helipad. The rotating blades cast oscillating shadows, and the sound echoed from the buildings. I knew transport via a trauma helicopter was a dire prediction for whoever was inside. Something had happened either on the local freeway or in the rugged terrain of the surrounding hills. I was transfixed by the sound as it reverberated through the air and into me. I looked up in awe at the sheer size and noise of the

CASE The diagnosis was bad from the very start. Louisa was going about her daily work routine when she was literally, suddenly, nearly incapacitated by abdominal pain. Dedicated to her work as an office manager of a financial institution, and the type of person not to complain or draw attention to herself, she pulled herself together, finished the task at hand, then called her husband to take her to the ED. The abdominal mass was large. The prognosis was poor. Treatment was not for cure but for palliation of her symptoms. It was one of those “go home and get your affairs in order” kinds of diagnosis. But she was relatively young, still a candidate for some therapy. And willing. Yet her desire for treatment was counterbalanced by her anger over her diagnosis. Cancer had entered her life too swiftly. During any conversation with her about her cancer, she nodded and repeated back information. She seemed to have a handle on things, yet as the days passed her anger and frustration increased. Louisa was distressed by any unexpected changes. A delayed procedure meant she’d been forgotten. When it was explained to her that her procedure was delayed because

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 43

COMMUNICATION CHALLENGES

Maybe one of the most complicated communication challenges is a situation where you never even have a chance to begin a relationship.

the one before lasted longer than expected, she shook her head as if the explanation were an excuse. When the second round of chemo was postponed because her counts were low, that was also taken as mismanagement. Louisa had gone from being the lynchpin of a large organization to a person at the mercy of “hospital time” where everything just took so much longer. By the time we were called in to meet with her for symptom management and a goals-of-care discussion she was dismissive. Surely, we were part of the disorganization to which she was continually subjected. Her husband was rarely present; working, she told us, “and not to be disturbed.” DISCUSSION What is the connection between a helicopter and Louisa? None. And yet many things. The noise of Louisa’s diagnosis was deafening. Her attempts to make sense of it were thwarted by changes that we might all consider minor — a delay going to IR, for instance, that she took as part of the whole mess of her diagnosis and now her life. We knew this and didn’t. Attempts to explain or soothe did neither. She might have been described as angry and in denial but those were facile explanations. She was overwhelmed in an overwhelming way. Yet we were surprised by her. We walked in to the impending negative encounter naïve and open. We were there to help. But she shut us out very quickly. After an explanation of the role of palliative care we reviewed her symptoms and told her of plans to tweak some of her meds. That was acceptable. Then, because we know how confusing a hospital setting is and how daunting it is to have a new and terrible diagnosis, she was asked what her understanding of her disease was. Her answer surprised us because it

skipped over so many steps, a long jump of epic proportions. “Are you telling me I am going to die?” she asked. Her leap to this place took a moment to react to. Very gently the physician member of the team said, “You have a very advanced disease …” Louisa cut her off right then. Her tone was sharp and so were her eyes as she glared at us. “Get out.” We tried to regroup, tried to walk things back, but she turned her head away and said, “Please leave.” We’ve been fired before. We’ve even been fired repeatedly by the same patient only to be asked back in. But with Louisa it was different. It was more than being fired. We were banished. Maybe one of the most complicated communication challenges is a situation where you never even have a chance to begin a relationship. It was more than skepticism on her part, more than a therapeutic relationship that required cultivating; we were the ones to tear off the Band-Aid and expose her vulnerability. And it was too much for her. Our presence was too much. There was no miraculous turnaround. No perfect words that changed the outcome. We were unable to reach her. It happens sometimes. As clinicians with much to offer her, our interaction with Louisa felt like a failure. But was it our failure? Was it something we did? Or was it one more situation beyond her control? One too many. We can’t go back to find out because she doesn’t want us to. I think she was overcome by the wash from the helicopter, by the thundering noise, the thump of the blades, the spinning and cutting movement of shadows. It was just too much. She had to look away. ■ Ann Brady is a symptom management care coordinator at a cancer center in Pasadena, California.

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44 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

Testicular Cancer Treatment May Increase Risk for Heart Disease in Survivors Bette Weinstein Kaplan

ncology nurses can have a significant impact on the lives of patients with testicular cancer, the most common malignancy afflicting men ages 18 to 39 years. Although incidence of testicular cancer has increased over the last 2 decades, the news about this cancer can be heartening: treatment results in a cure for most patients. However, any good news should always be tempered with caution. Testicular cancer is no exception.1 Recent research has found that survivors of testicular cancer have a greater risk of developing metabolic syndrome. The syndrome is characterized by the presence of 3 or more of the following conditions: hypertension, hypertriglyceridemia, abdominal obesity, low high-density lipoprotein (HDL) level, and type 2 diabetes. Presence of any one of these conditions on its own will increase a person’s risk of developing heart disease. Cisplatin-based chemotherapy is the treatment of choice for patients with testicular cancer. Its use has led to a cure rate of 80% for patients with metastatic disease and an overall 5-year survival rate of 95%. The result is that now 1 of every 600 men in the United States is a testicular cancer survivor. Young men who survive the disease can expect to live for approximately 40 more years, comprising a large population ideal for studying the long-term effects of

chemotherapy for this cancer, particularly the metabolic effects. Signs of Metabolic Syndrome

The National Cancer Institute (NCI) funded the Platinum Study for this purpose. It is the largest study to evaluate the numbers of metabolic abnormalities among testicular cancer survivors from North America who were treated with platinum-based chemotherapy. A study population solely from North America provides an advantage over a European-based population for analyzing metabolic syndrome because people in North America tend to be more ethnically and genetically

Now 1 of every 600 men in the United States is a testicular cancer survivor. diverse, noted Mohammad Abu Zaid, MD, assistant professor of medicine, Indiana University School of Medicine and Indiana University Melvin and Bren Simon Cancer Center, both in Indianapolis. “Testicular cancer survivors are all at risk for hypogonadism (low testosterone) which places them at risk for metabolic syndrome and future heart

disease,” Dr Zaid explained to Oncology Nurse Advisor. “In addition, other known risk factors for cardiovascular disease such as obesity — also common among survivors and the US population in general — can add to the risk.” For this study, researchers evaluated 486 testicular cancer survivors, median age 38 years, and selected matched controls from the National Health and Nutrition Examination Survey (NHANES). The control population was men who had no cancer, matched for race, age within 5 years, and level of education. Study results revealed that 43% of the survivors were hypertensive, compared with 31% of controls. The survivors were less likely to have decreased HDL (the “good” cholesterol) levels: 24% vs 35% for the controls. They also had less abdominal obesity (28%) than did the controls (40%). The investigators found that 3 of every 4 testicular cancer survivors were overweight or obese, 43% had hypertension, and a signif icantly higher proportion of survivors had elevated LDL or total cholesteral levels compared with matched controls. Overall, 1 in 5 testicular cancer survivors had metabolic syndrome based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) definition. Continues on page 47

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 45

FROM

THE COUPLE The costs of treatment and caregiving can cause the couple to experience sudden financial instability. This newfound situation may require a reevaluation of career goals, and an assessment of whether those goals are still realistic. There is a chance the patient will no longer be able to work; therefore, the partner will need to assume full

Challenges of Young Adult Couples Facing Cancer Diagnosis Marlee Kiel, LMSW

responsibility for the household income. This can be a very difficult transition for couples of all ages, but is especially difficult for young adults in the early stages of their careers. Young couples have to accelerate their thinking about whether they want children. Unfortunately, infertility is a

common adverse effect of cancer treatment, and YA couples need to speak with their medical team to determine whether childbearing is still a possibility. Although fertility preservation options are available, such concerns can strain a relationship and influence plans for starting a family. Communication between the partners might suffer as a result of fear or differences in coping mechanisms.1 Overall, both the patient and the partner have to reassess their roles and make adjustments based on these new and unforeseen circumstances. THE PATIENT A young adult with cancer experiences challenges unique to their age. Unlike their older counterparts, young adults may struggle to cope with the unexpected disruption of their life, and potentially, death, disease recurrence, or life-long adverse effects.2 Employment can also be a source of worry. The patient may not be fully settled in his or her career or may be physically unable to work while in treatment, and as a result, left with inadequate or no medical insurance. When in a dyadic relationship, patients worry not only about themselves but about their partners’ well-being as well. They have to become more reliant on their partners, which can be challenging for someone who has recently discovered their independence.2 Patients might also require intimate care from their partner; care that they could not have imagined needing until they were significantly older. Feelings of guilt are experienced because patients know that their partner

Knowledge of available support resources for both the patient and the caregiver-partner in a young adult relationship is essential. 46 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com

hen one envisions a couple facing a cancer diagnosis, the image of an older couple well into their marriage comes to mind. Young adult (YA) couples aged 20 to 39 are often overlooked. Young couples with hopes and visions of what their future together will look like rarely include a cancer diagnosis in their visions. Cancer has the ability to shift plans that have been so carefully thought out and eagerly awaited. The couple now not only has to overcome challenges specific to young adult couples, but those that accompany a cancer diagnosis as well. Young adult couples facing a cancer diagnosis are often unable to enjoy the “honeymoon phase” they imagined. The couple spends most of its time going to doctor’s appointments and treatments, rather than happily navigating a life together. This can be taxing on both the patient and the partner, who also often serves as the primary caregiver. Acknowledging the challenges unique to YA couples and remaining informed on ways to support them is important.

now has to fill the enormous role of caregiver. In an attempt to protect their partner from worrying, they might keep their fears and emotions to themselves.2 This can cause them to feel isolated and depressed. Physical changes due to treatment may cause body image issues, in turn, affecting a young couple’s intimacy. The patient will also have to cope with being the cause of a potential loss of the ability to reproduce and its effect on their relationship. THE PARTNER AS A CAREGIVER

The partner in a relationship between young adults experiences a wide array of challenges as a caregiver. He or she may find themselves thinking, “This isn’t what I signed up for,” or “Will I be happy in a relationship if I am unable to have children of my own?”3 Although these types of automatic thoughts are normal, they can cause the caregiver to experience feelings of guilt, anxiety, and depression. Caregivers might feel overwhelmed by their newfound responsibilities of caring for their partners and find that there is little time for themselves and their own health.

Survivorship Continued from page 45

Survivor Risk

This study demonstrated that the metabol ic abnor ma l it ies found among survivors of testicular cancer include increases in blood pressure and LDL and total cholesterol levels. Other metabolic abnormalities include lower rates of decreased HDL levels and abdominal obesity, which the researchers suggest might be the result of shifts in fat metabolism and fat distribution. The researchers also note

Caregivers may have to put their own career on hold to ensure that they are present, physically and emotionally, for their partner. Caregiving can be especially overwhelming if their partner is in treatment for a long period of time or indefinitely. The caregiver may need to share their caregiving duties with their in-laws, which can be helpful but still challenging for a young adult couple starting their lives together. If the patient is given a terminal diagnosis, the partner will have to cope with the loss of a loved one before their lives together have truly begun.

in person, and online are available at CancerCare. Guidance on many YA-specif ic organizations that provide financial, emotional, career, education, and networking advice is available, as well as counseling on sexuality and family planning, which is so important to young adults. ■ Marlee Kiel is an oncology social worker with CancerCare. REFERENCES 1. Paul S. Coping With Cancer as a Young Adult. New York, NY: CancerCare; 012. https://

SUPPORT

www.cancercare.org/publications/164-

Knowledge of available support resources for both the patient and caregiver-partner in a YA relationship is essential. Couples and individual counseling are options for both members of the relationship to process emotions specific to either the patient or the partner. YA patient and caregiver support groups provide the opportunity to connect to others in similar situations. Counseling services with licensed oncology social workers via the phone,

coping_with_cancer_as_a_young_

that hypogonadism and inflammation coexist with these changes. Thus, prevalence of cardiovascular disease risk factors is higher among testicular cancer survivors, even though they might not totally conform to criteria for metabolic syndrome. “Nurses are well suited to address these issues to survivors, as oncologists are usually focused on the risk of cancer recurrence. Nurses can talk about the importance of a healthy lifestyle, diet and exercise. They can screen for obesity, symptoms of low testosterone, and encourage smokers to quit smoking.

adult#!introduction. Accessed May 31, 2018. 2. Zebrack B, Isaacson S. Psychosocial care of adolescent and young adult patients with cancer and survivors. J Clin Oncol. 2012;30(11):1121-1126. 3. Bolte S. Young adults (20-39) with cancer. In: Christ G, Messner C, Behar L, eds. Handbook of Oncology Social Work: Psychosocial Care for People with Cancer. New York, NY: Oxford University Press; 2015:507-513.

They can provide significant assistance to survivors of testicular cancer facing cardiovascular disease risk as time goes on,” Dr Zaid said. ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCE 1. Zaid MA, Gathirua-Mwangi WG, Fung C, et al; Platinum Study Group. Clinical and genetic risk factors for adverse metabolic outcomes in North American testicular cancer survivors. J Natl Compr Canc Netw. 2018;16(3):257-265.

www.OncologyNurseAdvisor.com • MAY/JUNE 2018 • ONCOLOGY NURSE ADVISOR 47

ASK A PHARMACIST

How long after receiving chemotherapy should patients wait to have unprotected sex?

Capecitabine Tolerance; Sex After Chemo; Pharmacy Regulations Why are European patients better able to tolerate high doses of capecitabine than US patients?

This is a really interesting question. One theory relates to folic acid content in food. Capecitabine (Xeloda) is an oral prodrug of fluorouracil (5-FU). 5-FU is frequently given with leucovorin, which is a reduced form of folic acid. This increases the efficacy — and toxicity — of 5-FU. In the United States, many foods are enriched with folic acid. This exposure to more folic acid may explain why patients in the United States experience more adverse effects from capecitabine than their counterparts elsewhere.

Many factors influence when a patient may have unprotected sex during or after their chemotherapy treatment. One important consideration is how long the chemotherapy drug takes to be metabolized and cleared from the body (ie, the pharmacologic half-life). Avoiding unprotected sex until after the drug is expected to be cleared reduces exposing the sexual partner to any chemotherapy that may have penetrated into the patient’s vaginal secretions or semen. Patients receiving therapy that is expected to make them profoundly neutropenic or thrombocytopenic may need to avoid sexual activity until their cytopenia resolves. Female patients who are able to become pregnant and male patients with a female sexual partner who is able to become pregnant should use appropriate contraception methods until after discussion with the patient’s oncology care provider, even if barrier methods are no longer necessary. This is because the chemotherapy’s effects on sperm or egg cells may be longer lasting What impact do the new pharmacy regulations (USP <800>) have on nursing staff?

The United States Pharmacopeia (USP) <800> regulations are related

to the safe handling of hazardous drugs. These standards were developed to protect healthcare workers from hazardous drug exposure and to minimize the risks of these to public health by ensuring a quality healthcare environment. Hazardous drugs are classified as such by the National Institute for Occupational Safety and Health (NIOSH) based on predefined criteria, and include many medications administered by oncology nurses. Some components of USP <800> that may affect oncology nurses include: • Maintaining a facility list of hazardous medications; • Use of personal protective equipment (PPE) by staff involved in every aspect of hazardous drug use, including storage, compounding, administration, spill control, and other aspects of use; • Training and communication for personnel; • Recommendations for staff administering these drugs to reduce exposure; and • Cleaning, decontaminating, and disinfecting. Affected facilities are expected to be compliant with USP <800> by December 2019, so you will likely hear much more on this subject over the next several months if you have not already. ■

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

48 ONCOLOGY NURSE ADVISOR • MAY/JUNE 2018 • www.OncologyNurseAdvisor.com