Clinical Insights: December 2016


CE lesson worth 1.0 contact hour that is intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

Release Date: December 20, 2016Expiration Date: December 20, 2017

This activity is provided free of charge.


This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.


Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may articipate in this CE activity.


Upon completion, participants should be able to:

  • Describe new preventive options and treatments for patients with cancer
  • Identify options for individualizing the treatment for patients with cancer
  • Assess new evidence to facilitate survivorship and supportive care for patientswith cancer


Physicians’ Education Resource®, LLC is approved by the California Board of Registered Nursing,Provider #16669 for 1.0 Contact Hours.


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This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other healthcare provider relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®.

Cervical Cancer

Many Women With Cervical Cancer Not Receiving Recommended Therapy

Laura Panjwani

Fewer than half of women with advanced cervical cancer are receiving all 3 of the treatments that are standard of care (SOC) for the disease: external beam radiation therapy (EBRT), brachytherapy, and chemotherapy, and the presence or absence of brachytherapy was the major difference between patients who did and did not receive SOC, a new study has found.

The research showed that patients who did not receive brachytherapy had a lower chance of survival than those who received all 3 SOC treatments, explained Christine Fisher, MD, a radiation oncologist at the University of Colorado Cancer Center and an investigator on the study.

“Brachytherapy, or internal radiation, is a very, very critical component of the treatment,” said Fisher. “It allows a very high dose of radiation to the tumor, and it is really what allows us to cure these patients, even those who have very large cervical cancers.”

Investigators utilized the National Cancer Database to identify women with locally advanced cervical cancer treated with definitive radiation or chemoradiation therapy, and stratified these patients by treatment received. Of the 15,194 patients in the study, only 44.3% received SOC treatment, and this group had significantly improved overall survival (OS).

Some patients did receive alternatives to brachytherapy, including 23.8% who received an EBRT boost by itself. Nearly 50% of patients received EBRT with brachytherapy and 26.8% of patients received no radiation boost.

Although an EBRT boost was advantageous over no boost at all (HR, 0.72; P <.001), OS was superior in patients who received brachytherapy (HR, 0.55; P <.001).

“Not having that additional radiation, the brachytherapy, leads to a survival detriment that can not be made up in other ways,” said Fisher. “We really find that some people either get no additional treatment or external beam treatment, and none of those are equivalent to using the internal beam radiation.” “With image-guided brachytherapy we now have good data, primarily from Europe, telling us that we can improve survival and also reduce complications for these women with brachytherapy,” she added.

The study found that patients were more likely to receive no radiotherapy boost if they had lower incomes or Medicaid. African-American patients were also less likely to receive SOC.

Unfortunately, this is the same group of women who have very poor access to care and are less likely to receive preventive services for cervical cancer in the first place, said Fisher.

A lack of expertise in brachytherapy at non—comprehensive community cancer centers or centers that don’t regularly see many patients with cervical cancer may also be contributing to the problem, said Fisher.

“In terms of thinking about what might be causing this issue, part of it is the comfort level and expertise with brachytherapy as a technique,” said Fisher.

“It’s been around for a very long time, but it does require procedural skills and comfort with dosing high levels of radiation. It is very time consuming for physicians, it requires a large team of experts, the correct type of machine, and many smaller radiation centers do not have that available.”

Fisher recommends that physicians who did not feel comfortable or are unable to offer patients brachytherapy should refer their patients to a higher volume center, preferably a comprehensive cancer center, instead of doing alternative treatment or skipping the treatment entirely.

For some patients, it may be easier to receive chemotherapy and external beam radiation closer to home, and then travel to a larger center for brachytherapy.

While improving access to SOC treatment for all patients with cervical cancer is essential, the bigger message is to improve and promote cervical cancer screening and prevention, said Fisher.

“Cervical cancer is nearly 100% preventable,” said Fisher. “The ideal goal would be that we wouldn’t have to put patients through this treatment at all anymore, and that we could really prevent this cancer perfectly through vaccination or, next-best option, through routine screening with Pap testing, as well as testing for high-risk HPV DNA.

“Those are always preferred options to having an invasive cancer, which either requires major surgery or radiation.”


Robin TP, Amini A, Schefter TE, et al. Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical cancer. Gynecol Oncol. 2016;143(2):319-325.

Breast Cancer

Randomized Trial Confirms Efficacy of Online Mental Exercises to Combat Chemobrain

Lauren M. Green

Web-based memory and mental processing exercises done over 15 weeks delivered a marked improvement in cognitive function among those who tried the program after experiencing symptoms of cognitive impairment, research published online in the Journal of Clinical Oncology.1

Study author, Victoria J. Bray, MD, said in a statement that these findings are the first from a randomized trial to show a benefit for patients with persistent cognitive symptoms after chemotherapy—also known as “chemobrain”&mdash;a problem that affects up 70% of cancer survivors. Bray is a medical oncologist and PhD candidate at the University of Sidney in Australia where the study was carried out at 18 sites between 2009 and 2014.

The trial enrolled 242 patients with solid tumors: 89% had breast cancer, 5% colorectal cancer, and 95% of the participants were women; the median age of all participants was 53 years. Eligible patients had to have completed at least 3 cycles of adjuvant chemotherapy in the prior 6 months to 5 years and rated their cognitive complaints (changes in concentration and/or memory) “quite a bit” or more along a cognitive function scale. Patients were evaluated at baseline, 15 weeks, and 6 months after the intervention.

For the study, participants were evenly randomized to standard oncology care or cognitive rehabilitation using Insight (brainHQ, Posit Science)2 —a computerized program that employs adaptive exercises targeted at areas of cognition often impacted in patients with cancer, such as divided attention, working memory, and visual processing speed. Those assigned to the intervention arm were asked to do 40 hours of the exercises over 15 weeks, which is equivalent to four, 40-minute sessions each week.

Among the program’s advantages cited by researchers is that it is home-based, relatively inexpensive, and empowers participants to direct their own treatment.

To measure the tool’s effectiveness, researchers used assessments previously validated in the oncology setting. For the primary outcome of perceived cognitive impairment (PCI) after 15 weeks, participants answered the 37-item questionnaire FACT-COG. For the main secondary outcome of neuropsychological function, they completed Cogstate, a battery of 7 tests that can be performed on the computer at home. That assessment takes about 18 minutes and gauges cognition in such areas as processing speed, working memory, decision making, and executive function.

Researchers found that after 15 weeks, patients who did the exercises had a reduction of 7.47 in PCI compared with those in the control arm (95% CI, range: —10.8 to –4.13; P <.001), and this difference persisted after 6 months, when a —6.48 reduction in PCI was observed in the intervention arm (95% CI, –9.85 to –3.11; P <.001).

Perceived cognitive abilities at 15 weeks also significantly improved (3.34; 95% CI, 1.98 to 4.70; P <.001) among those doing the web exercises and continued to be better after 6 months (2.88; 95% CI, 1.50 to 4.25; P <.001). In addition, participants’ quality of life was improved 6 months after participants finished the program.

“Cognitive rehabilitation should be a core part of cancer survivorship care, as cognitive symptoms are very common and have a profound effect on people’s lives,” Patricia Ganz, MD, of UCLA’s Jonsson Comprehensive Cancer Center and ASCO expert in survivorship, noted in a statement. “This study points to a simple tool that may help alleviate mild cognitive problems.”

Objective neuropsychological function test results were not significantly different between the two groups. However, the researchers suggested caution in interpreting this finding, as several participants had difficulty installing and re-accessing Cogstate.

Researchers were also interested to find out what, if any, effect the intervention had on participants’ levels of anxiety/depression, fatigue, and stress, as all have been shown to be associated with patients’ assessments of their cognitive impairment. Each of these symptoms improved among those doing the web-based exercises.

In the intervention arm, reductions in anxiety, depression, and fatigue were reported at 15 weeks, but the differences were not significant at 6 months. On the measure of perceived stress, however, the intervention yielded a significant reduction at both time points.

Study authors note that longer follow-up is needed to determine if the effects of the training are long-lasting. In addition, a number of unanswered questions remain for future research, including how to tailor intervention approaches to specific survivors. For example, a self-directed program such as this one may be suitable for some survivors, whereas a group-based program may work better for others. The ideal length and “dose” of cognitive training also has not yet been determined.

“If we could identify patients who are at risk of cognitive impairment, we could intervene earlier, and possibly achieve even better results. We would also like to explore whether there is added benefit from combining cognitive training with physical exercise,” said Bray.


  • Bray VJ, Dhillon HM, Bell ML, et al. Evaluation of a web-based cognitive rehabilitation program in cancer survivors reporting cognitive symptoms after chemotherapy [published online ahead of print October 28, 2016]. J Clin Oncol.
  • Brain HQ. Brain Training That Works. Accessed October 31, 2016.

Nurse Perspective

Darcy Burbage, RN, MSN, AOCN, CBCN

Darcy Burbage, RN, MSN, AOCN, CBCN

Darcy Burbage, RN, MSN, AOCN, CBCNSurvivorship Nurse NavigatorHelen F. Graham Cancer Center & Research InstituteChristiana Care Health SystemWilmington, DE

Cognitive changes in cancer survivors are a common long-term effect of treatment. Although clinicians relate this concern specifically to chemotherapy, I hear survivors express concerns with their ability to concentrate, multitasking, and planning ability who have not received chemotherapy. Stress, certain medications (ie, targeted therapy including hormonal therapy) or other health problems can also contribute to cognitive changes in survivors.

Results of the recent study by Bray et al are exciting for oncology nurses who work with individuals with cognitive changes, as the number of validated interventions has been limited. Especially encour-aging, is that the intervention described can be used at home, and perceived cognitive abilities as well as quality of life were improved when it was used.

Additional research is needed to determine if the effects of the intervention are permanent or if survivors will need to continue with periodic interventions to maintain the effects of the cognitive rehabilitation program. Further evaluation of the program to determine the appropriate length of this program and if adjustments need to be tailored to the individual survivor are also needed. Although the study size was small, results seem promising.

These findings will help to empower survivors to discuss cognitive changes with their nurses so they can work together to improve cognitive health especially after treatment is completed. Additional findings from this study lend credibility to the importance of ongoing assessment of survivors for cognitive changes throughout the cancer continuum.

In order to provide individualized care, oncology nurses play an important role in advocating for interventions that can improve the quality of life of their patients. I look forward to hearing more about additional research with this intervention and hope to be able to utilize the Insight tool ( with my patients.

Using Genetic Testing to Assess Risk of Venous Thromboembolism

Allie Casey

Genetic testing can help to personalize treatment and predict patients at a higher risk for cancer and can also be used to determine a patient’s potential risk for developing certain complications of cancer treatment. Knowing a patient’s risk is an important factor when deciding whether to take preventive measures that could result in serious side effects.

A recent study found that chemotherapy status and genetic susceptibility could be used to stratify the risk of venous thromboembolism (VTE) in patients receiving chemotherapy for their breast cancer.

Preventive treatment for VTE includes low molecular—weight heparin, but because of the risk of bleeding with the anticoagulant, it is not recommended for patients who are undergoing chemotherapy. Being able to risk-stratify patients to target those who are at highest risk for developing VTE would enable clinicians to be more selective and effective in deciding when to administer thromboprophylaxis.

This study by researchers at the Karolinska Institute in Stockholm, Sweden, examined 4261 women who were diagnosed with primary invasive breast cancer between the years 2001 and 2008 and monitored them through 2012 (Clin Cancer Res. 2016;22(21):5249-5255). Patients were stratified based on potential risk of VTE, taking chemotherapy status and genetic susceptibility into account.

During a median follow-up period of 7.6 years, a total of 276 patients had experienced a VTE event.

To determine genetic susceptibility, researchers used a polygenic risk score (PRS). The PRS considered 9 genetic variants, including factor V Leiden, a mutation in one of the clotting factors in the blood. The researchers classified patients with a PRS in the top 5% to have high genetic susceptibility.

Although the Mayo Clinic reports that most people with factor V Leiden do not develop abnormal blood clots, among those who do, it can create long-term, potentially life-threatening health problems.

Researchers reported that the total cumulative incidence of VTE in 1 year for patients who were both receiving chemotherapy and had high genetic susceptibility was 9.5%, whereas patients who were not receiving chemotherapy and had a lower genetic susceptibility had a 1.3% total cumulative incidence of VTE (P < .001).

The study discovered that both chemotherapy and genetic susceptibility acted independently on the risk of VTE.

Additionally, the impact of a higher PRS was more pronounced in older patients; the cumulative incidence of VTE was 25% in patients who had chemotherapy, a high genetic susceptibility, and were aged 60 years or older.

“Combined with other clinical risk factors and biomarkers, these findings will guide future studies evaluating routine VTE risk assessment in chemotherapy outpatients, and prophylaxis for those at highest risk,” Judith S. Brand, PhD, a postdoctoral researcher and lead author of the study, said in a statement.

“Because older patients demonstrated a stronger genetic effect and higher VTE incidence, this group requires special attention in future risk stratification efforts,” she added.

In the future, Brand suggested studies that are larger scale, with more patients who are older, had chemotherapy, and a high genetic susceptibility. This would allow future researchers to make more precise risk estimates. Brand also recommended further testing of thromboprophylaxis and its risks and benefits in patients with cancer at high-risk for VTE.

Prostate Cancer

Shorter Radiotherapy Course Effective and Safe in Low-Risk Prostate Cancer

Tony Berberabe, MPH

Patient-reported outcomes and quality of life (QOL) measures have demonstrated that hypofractionated radiotherapy (HRT) is a viable, safe, and value-added alternative to patients with low-risk prostate cancer, with HRT offering one-third less treatment time than conventional radiotherapy (CRT) and comparable health-related QOL outcomes, according to findings presented by Deborah Watkins Bruner, PhD, RN, at the 2016 ASTRO Annual Meeting. Abstract PL01

“There is a preponderance of evidence, finally, that shows that HRT is effective,” said Bruner, a nurse researcher at Emory University School of Nursing and the Winship Cancer Institute.

In this study, Bruner assessed the degree, duration, and clinical significance of the differences between men who received HRT or CRT.

The findings are derived from a parent study, led by Lee et al that examined non-inferiority results in which hypofractionation outcomes were shown to be equivalent to outcomes in men who received conventional therapy (J Clin Oncol. 2016;34:2325-2332). Although no differences in early gastrointestinal (GI) or genitourinary (GU) adverse events (AEs) were observed, late grade 2/3 GI-related AEs were about 60% more likely to occur in men who were assigned to treatment with HRT (relative risk 1.55 to 1.59). Late grade 2/3 GU side effects were more likely in men treated with HRT (relative risk, 1.31 to 1.56).

In the study reported here, a total of 962 patients (median age = 67 years) provided health-related QOL data, including 478 men from the CRT group and 448 men from the HRT group. QOL was determined using the Expanded Prostate Index Composite (EPIC), a 50-question instrument that evaluates patient-reported side effects after prostate cancer treatment.

The questionnaire measured side effects in 4 domains—bowel, urinary, sexual, and hormonal. EPIC assesses prostate cancer—specific health-related QOL on a Likert scale that assigns a score of 0-100 to responses; higher scores indicated better QOL. Feedback was collected at baseline, at 6 months, and 1 year posttreatment.

Compared with men without prostate cancer, most patients in both groups reported poor baseline EPIC sexual domain scores, with the CRT group’s score averaging 47.5 and the HRT group’s score averaging 44.2. At baseline, the groups reported only slightly lower-than-average bowel and urinary scores.

Following treatment, patients in the HRT group reported similar health-related QOL as patients in the CRT group. No differences were reported in change scores for either group on any EPIC domain at the 6-month follow-up.

At 12-months of follow-up, hypofractionation resulted in a larger decline in the bowel domain compared with those who received CRT, but the change was not deemed clinically significant to patients.

“In terms of urinary function, there were no significant differences between the 2 arms; in terms of hormonal function, there were no significant differences at any time point,” said Bruner. She noted a decline from baseline for sexual function in both arms that was not significant.

“There’s a huge benefit to patients, and this trial should be practice-changing, because there is now finally enough evidence that HRT is a viable, safe, value-added alternative for patients with low-risk prostate cancer,” Bruner concluded.

Nurse Perspective

Frank delaRama, RN, MSN, AOCNS

Frank delaRama, RN, MSN, AOCNS

Frank delaRama, RN, MSN, AOCNSProstate Cancer Nurse NavigatorPalo Alto Medical FoundationPalo Alto, CA

Given all the effective options available to men with low-risk prostate cancer, making a treatment decision often comes down to potential qualify of life (QOL) issues. For the men in this category that do not select active surveillance, both surgery and radiation offer comparable opportunities to “cure the cancer.” At this critical point, men (and perhaps their significant others) have met with urologic surgeons, radiation oncologists, and even medical oncologists, for a crash course in prostate cancer treatments.

External beam radiotherapy (EBRT) is more often becoming the primary treatment of choice, particularly in men who want to avoid invasive procedures such as surgery or brachytherapy. But, the overall time dedicated to complete the treatment course can be discouraging for those considering EBRT, at over 8 weeks of daily visits. Technology now allows us to give higher daily doses of radiotherapy, better for overall efficacy, but without much difference in the side effect profile, optimizing QOL for men undergoing EBRT. Two weeks less in treatment can be an immense benefit to QOL, as men dealing with cancer strive to fit treatment into daily life for a while.

Measuring QOL, in a study like this, becomes so important in prostate cancer care, not only to help validate a new treatment modality, but also to build a knowledge database to help our future patients make treatment decisions.

Gathering QOL data is never an easy task. Assessment tools, like the EPIC questionnaire, can be daunting to patients. As nurses, we can teach our patients about the impact their input can have. For symptoms that affect the bowel, bladder, and sexual function, there is no better way to get this information than through questionnaires and interviews. Nurses are often in a prime position to help gather this information, and ongoing assessments can benefit one’s care; symptoms can be addressed promptly as soon as identified.

From a broader perspective, as the database of QOL builds for prostate cancer, nurses can use the findings to help newly diagnosed patients understand the potential outcomes of each viable treatment modality: surgery vs brachytherapy vs EBRT (conventional vs hypofractionated).

As a nurse navigator, I have been in many of these discussions with men and their families. Although I am happy to share experiences of previous similar patients, to help the newly diagnosed learn more, QOL studies, like the one presented here, can give us some more concrete data to aid in the shared decision making process.

Oncology Practice

Predictors of Nonadherence to Oral Anticancer Agents

Lauren M. Green

The problem of patients not taking their oral anticancer medications as prescribed continues to vex oncology practitioners. It turns out that a number of risk factors can play a role in nonadherence, including older age, problems with working memory, and feelings of depression, suggesting that current notions of nonadherence may be too narrowly focused. These findings from a pilot study by a team of researchers at the Centre Francois Baclesse in Caen, France, were reported at the recent annual meeting of the European Society of Medical Oncology (ESMO) in Copenhagen. Abstract 1497P

The aim of their study was to prospectively identify profiles of patients who would be less prone to follow their prescribed oral therapies. To do this, they enrolled 126 patients who were beginning their first oral anticancer therapy and had a median age at baseline of 70 years.

Researchers used a neuropsychological battery of tests to assess the patients’ cognitive

function; feelings of autonomy, depression, and anxiety were also captured, along with sociodemographic information. Participants’ adherence was measured 1 and 3 months after their treatment started through self-assessment questionnaires and clinician observations recorded on an observance sheet.

Researchers presented their findings at ESMO after the 1-month follow-up; 111 patients completed the questionnaire, representing a response rate of 88%. Overall adherence was 90%; however, working memory disorders and depression were significantly associated with nonadherence (1.38 [range, 1.03-1.85] and 4.67 [range, 1.11-19.59]), respectively.

The study concluded that both working memory dysfunctions (frequently observed among elderly patients) and depression appear to be predictors of nonadherence.

Study authors noted that these findings highlight that cognitive disorders may be an “underestimated major parameter, notably among elderly patients” and that focusing on cognitive functions before initiation of oral anticancer therapy is relevant to identify the patient profiles more likely to fail self-management of oral anticancer therapy. They added that having this information can help clinical decision making, particularly with elderly patients.

Beyond these factors, do patients actively choose not to take their medicine? Bettina Ryll, MD, PhD, a researcher at Uppsala University in Sweden and chair of the ESMO Patient Advocacy Working Group, explained that they do:

“I believe the current concept of adherence is too narrow, ie, physicians expect patients to take their medication as prescribed and nonadherence is considered a form of disobedience.

“Intentional nonadherence—the patient deciding not to take medication as indicated&mdash;is actually revealing patients’ true preferences, and these might simply be very different from what physicians and other stakeholders consider relevant.”

Instead of enforcing adherence against patients’ preferences, Ryll suggested that clinicians endeavor to understand the factors driving their nonadherence to improve outcomes for patients most at risk.

Lung Cancer

Depression in Lung Cancer Linked to Worse Survival

Allie Casey

Symptoms of depression are common in patients newly diagnosed with lung cancer, and a new study has found that their survival is actually worse when these symptoms emerge or persist after their diagnosis.

Researchers found that when compared with patients with lung cancer who never developed depression, those with new-onset symptoms of depression were 50% more likely to die. And of those whose depression at baseline persisted throughout the study period, 42% were more likely to die. The study was published online ahead of print October 3, 2016 in the Journal of Clinical Oncology.

Using data from the Cancer Care Outcomes Research and Surveillance Consortium, this prospective, observational study looked at 1790 patients from 5 healthcare systems and 15 Veterans Administration medical centers newly diagnosed with lung cancer between 2003 and 2005. Of the study cohort, 57% were aged >65 years, 45% were women, and nearly 30% currently used tobacco.

Patients were given an 8-item depression assessment at diagnosis and then followed up again after 12 months, using the Center for Epidemiologic Studies Depression Scale (CES-D).

Overall, the researchers found that 44% of study participants had depression symptoms at some point over the study period: 38% had depression symptoms at baseline (n = 681), and for 254 of these patients, symptoms persisted during follow-up. Fourteen percent of patients (n = 105) developed new-onset symptoms during treatment.

Depression in patients with cancer is not a new phenomenon, explained Mark Lazenby, PhD, APRN, FAPOS, an associate professor at the Yale School of Nursing and member of the Yale Cancer Center, in a statement.

“We have known since the 1970s that a cancer diagnosis sets off a period of existential plight,” said Lazenby, who was not involved in this research. “Although from this study we cannot say that treating depression would extend survival, previous studies have shown that care aimed at improving psychosocial well-being, which includes but is not limited to detecting and treating depression, does have a survival benefit.”

Notably, in the study reported here, patients who had depressive symptoms when they were diagnosed but who did not have them 1 year later, had a similar risk of death as those patients who were never depressed over the course of the study. That, noted the study authors, suggests a need for better integration of depression treatment into the comprehensive cancer care of these patients.

“Clinicians have to do a better job of treating the whole person and not focusing on the disease only,” said lead author Donald Sullivan, MD, an assistant professor at Oregon Health and Science University.

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