Exploring Chemotherapy-Induced Peripheral Neuropathy Management Practice Patterns Among Oncology Clinicians

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN)—numbness, tingling, or pain in the upper and lower extremities—is a distressing side effect that affects about 60% of cancer survivors receiving neurotoxic agents.¹ Taxanes, platinums, vinca alkaloids, and newer monoclonal antibody drug conjugates such as brentuximab vedotin are common first line treatments for gastrointestinal, breast, gynecologic, lung, lymphoma, and multiple myeloma cancers. Persistent CIPN often limits the dose of mainstay chemotherapy treatments that can be given to treat the cancer and leads to increased risk of falling² and completing daily activities.^3,4

There is only one recommended pharmacological treatment and one modestly beneficial non-pharmacological treatment (exercise) for CIPN.⁵ Duloxetine 60 mg/day (starting with 30 mg/day then progressing to 30 mg twice daily) is the only recommended pharmacological treatment for the management of chronic CIPN pain.⁵ Physical exercise has consistently demonstrated modest and mechanistic benefit in reducing CIPN.^6-8 However, evidence suggests duloxetine and physical exercise are not routinely prescribed for CIPN in practice.^9-11 A survey of 210 oncologists revealed that only 11.8% reported prescribing duloxetine for CIPN. ¹⁰

Studies over the last 10 years have consistently shown a discrepancy between oncology providers’ practices and the national guidelines for CIPN management as well as a self-reported knowledge and skill deficit in CIPN assessment among registered nurses (RNs). Less is known surrounding RN current practices in helping patients prevent and manage CIPN, despite their continual involvement in the patients care and symptom management during and after cancer treatment.

The overall objective of this study was to explore oncology nurses’ and providers’ self-reported practices and perceptions regarding CIPN prevention and management. The results were compared with practices recommended by the national guidelines.

Methods

Design, Sample, and Setting

The study aim was investigated using a cross-sectional, convergent, mixed-methods study design. Seventy-one oncology clinicians were recruited from two National Cancer Institute-designated comprehensive cancer centers and one community cancer center between 5/8/2023 and 8/7/2023. The oncology clinicians were invited to complete an electronic survey and semi-structured interview about their CIPN prevention and management practices. Clinicians were eligible if they were a medical oncologist, advanced practice provider (i.e., physician assistant or nurse practitioner), or chemotherapy-teach RN and had prescribed or taught patients about neurotoxic cancer drugs in the last six months. The University of Michigan IRBMED reviewed the study and determined that the study was exempt from ongoing IRB review. However, participants were still provided with an informed consent page and were told that proceeding with the survey indicated consent to participate in the study. The research procedures were conducted in accordance with the Declaration of Helsinski. The qualitative results are reported in accordance with the Consolidated Criteria for Reporting Qualitative Research Checklist.

Data Collection

Interested clinicians were emailed a link with information about the study and the electronic survey. To aide in identifying duplicate responses, unique participant IDs were generated based on participants’ reported first two letters of their mother’s or friend’s name, last four phone number digits, and professional credentials. The remaining items in the 19-item survey included questions about demographic information (e.g., gender, race/ethnicity, experience with neurotoxic chemotherapy) and perceptions on CIPN prevention and management (e.g., perceived incidence of CIPN and first- and second-line options employed for CIPN prevention and/or management). Survey items were derived from the EVANEURO questionnaire¹⁰ and Theoretical Domains Framework v1.^12,13 The Theoretical Domains Framework Version 2 illuminates the theoretical behavioral domains that should be addressed in implementation research, particularly on improving evidence-based practice uptake among health professionals.¹⁴ The framework consists of 14 domains: knowledge, skills, social/professional role and identity, self-efficacy, optimism, beliefs about consequences, reinforcement, intentions, goals, memory/attention and decision processes, environmental context and resources, social influences, emotion, and behavioral regulation.

Following the survey, participants were prompted to provide their email address to participate in an audio-recorded, semi-structured telephone or video conferencing interview. All interviews were administered by a nurse-scientist or BSN nursing student using an 11-question semi-structured interview. The interview questions prompted clinicians to reflect on their CIPN assessment, prevention, and management practices. The interview guide was derived from an interview guide employed by Knoerl et al.⁹ to interview a separate cohort of clinicians about their CIPN assessment and management practices. All authors reviewed the interview guide before its administration. Table 1 contains the survey questions and interview guide labeled with the Theoretical Domains Framework (TDF) domains that apply to the given questions.

Table 1.

Theoretical Domains Framework operationalization in the study survey (A) and interview guide (B).

A
#	Question	Theoretical Domain
1	Of all your patients, what do you think is the percentage of patients developing troublesome peripheral neuropathy? (0-100 VAS)
2	What first-line medicine/strategy do you recommend to prevent development of peripheral neuropathy? None usually Amitriptyline Duloxetine Gabapentin Opioid Analgesics (morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, tramadol) Pregabalin Physical Exercise Referral to subspecialty (e.g., neurology, pain medicine, physical therapy) Other Prescription Medicines Other Alternative Therapies (e.g., vitamins, herbal remedies, cryotherapy, compression therapy)	Knowledge & Skills
3	What other medicine/strategies do you recommend to prevent peripheral neuropathy?a	Knowledge & Skills
4	What first-line medicine/strategy do you recommend to manage existing peripheral neuropathy?a	Knowledge & Skills
5	What other medicine/strategies do you recommend to manage existing peripheral neuropathy?a	Knowledge & Skills
6	What strategies and supplements do you see your patients using to prevent development of peripheral neuropathy outside of your recommendations?	Social influences (subjective & descriptive norms)
7	What strategies and supplements do you see your patients using to manage their existing peripheral neuropathy outside of your recommendations?	Social influences (subjective & descriptive norms)
Please rate your level of agreement with the following statements:
8	Discussing strategies to prevent and manage peripheral neuropathy with patients is part of my work in my current profession/role. (Strongly Disagree-Strongly Agree)	Professional role and identity
9	If I discuss peripheral neuropathy prevention and management strategies with my patients, I feel like I am making a difference (Never-Always)	Reinforcement (rewards & incentives for the behavior) Beliefs about consequences (attitudes)
B
#	Question	Theoretical Domain
1	Please tell us your current professional role in the Cancer Center.
2	Overall, what are your thoughts about CIPN and its effects on patients? Probe: Such as physical function, quality of life, cancer care?	Beliefs about consequences (attitudes)
3	Think back to your practice for the next several questions: How would you generally assess CIPN? Probe: What is most difficult about assessing CIPN?	Knowledge & skills Beliefs about capabilities (perceived behavioral control)
4	In general, what symptoms do you educate patients about before they begin neurotoxic chemotherapy? Probe: What are the biggest barriers to providing education to patients about the risk of CIPN during a pre-chemotherapy consultation (providers)/education visit (RNs)? Probe: Such as personal knowledge, forgetfulness, thoughts, routines, and systemic, structural and social barriers.	Environmental context and resources (barriers & facilitators) Memory, attention, and decision processes Social influences Emotion (affect & stress) Behavioral regulation (automaticity)
5	In general, how would you generally prevent CIPN? Probe: How effective are these treatments? How acceptable would you say the side effect profile is of these treatments? What is most difficult about preventing CIPN?	Knowledge & skills Beliefs about consequences (attitudes & outcome expectancies) Optimism Beliefs about capabilities (perceived behavioral control)
6	In general, how would you generally manage CIPN? Probe: How effective are these treatments? How acceptable would you say the side effect profile is of these treatments? What is most difficult about managing CIPN?	Knowledge & skills Beliefs about consequences (attitudes & outcome expectancies) Optimism Beliefs about capabilities (perceived behavioral control)
7	Moving forward, what information and resources would be most essential to you when deciding how to assess and manage your patients’ CIPN? Probe: In the future, how would you like to receive this type of information? Would you prefer to receive this all at once or on multiple or repeated occasions?	Environmental context and resources
8	Duloxetine is a treatment recommended as a first line treatment for CIPN, specifically, painful CIPN. What are the biggest barriers to using duloxetine for CIPN? Probe: Such as personal thoughts and routines, and systemic, structural and social barriers.	Environmental context and resources (barriers & facilitators) Memory, attention, and decision processes Social Influences Emotion (affect & stress) Behavioral regulation (automaticity)
9	Physical exercise is recommended as a safe and beneficial therapy during active oncology treatment. What are the biggest barriers to prescribing exercise for CIPN? Probe: Such as personal thoughts and routines, and systemic, structural and social barriers.	Environmental context and resources (barriers & facilitators) Memory, attention, and decision processes Social Influences Emotion (affect & stress) Behavioral regulation (automaticity)
10	(After several interviews): Some people have mentioned […]. What do you think about that?”
11	Are there any final comments or anything that we missed in our discussions regarding CIPN assessment and management?

^aSame response options as for question 2

Abbreviations. CIPN, chemotherapy-induced peripheral neuropathy; VAS, visual analogue scale

Data Analysis

Quantitative data were described using descriptive statistics (i.e., mean, median, SD, Range). All interviews were de-identified and transcribed by a professional transcription company. All transcriptions were verified for accuracy by the study team and inputted into NVivo 12 [QSR International Pty Ltd, Version, Release 1.7.1]. The transcripts were analyzed using inductive content analysis.^15,16 The authors (GKL and RK) read the transcripts in their entirety and collaborated to create an initial list of codes. RK and GKL reviewed three transcripts independently, applied the initial codes, and subsequently met to address any discrepancies in coding and revise the codebook further. After finalizing the codebook, RK and GKL coded the remaining interviews and met to resolve any coding discrepancies. The coded data were summarized and reviewed by the study team to identify themes and subthemes.

Results

Participant Characteristics

Figure 1 summarizes the participant flow through the study. Of the 71 enrollees, 47 oncology clinicians completed the survey (completion rate of 66%); however, three clinicians were removed from analysis because they reported not prescribing/teaching about neurotoxic agents. Thus, a final sample of 44 clinicians were included in the quantitative analysis and nine clinicians participated in the follow-up semi-structured interviews. Overall, participants had a median of 16 years of experience in oncology. Most clinicians specialized in multiple oncologic diseases and prescribed and/or taught patients about the following neurotoxic agents: platinums (91%), taxanes (73%), vinca alkaloids (48%), and/or neurotoxic antibody-drug conjugates (41%) (Table 2). Four main themes regarding clinicians’ CIPN prevention and management practice patterns arose from the quantitative data and semi-structured interviews (Table 3 contains additional specific quote exemplars for each theme).

Figure 1. Study Flow Diagram.

Abbreviations. APP, advanced practice provider; MD, medical oncologist doctors; Ntx, neurotoxic; RN, registered nurse.

Note. All ineligibilities were due to the participant reporting that they did not administer and/or teach patients about neurotoxic chemotherapies or biotherapies. Of the approximately 60-75 neurotoxic chemotherapy-prescribing providers and about 25-30 clinic RNs employed at Site 1, 31 prescribing providers and 14 RNs enrolled in the study (43-53% enrollment rate). External site employment unknown.

Table 2.

Clinician Demographics (N = 44)

Characteristics	N (%) or Median (Range)
Age at consent
Median (Range) (n = 43)	43 (25 – 73)
Gender
Male	14 (31.8%)
Female	30 (67.2%)
Profession
Medical Doctor	25 (56.8%)
Advanced Practice Provider	4 (9.1%)
Registered Nurse	15 (34.1%)
Race
White	33 (75%)
Asian	10 (22.7%)
Missing	1 (2.3%)
Disease Clinic Specialty
Multiple	14 (31.8%)
Colorectal	3 (6.8%)
Breast	5 (11.4%)
Lung	3 (6.8%)
Hematology	9 (20.5%)
Othera	10 (22.7%)
Neurotoxic Cancer Drug Experience b
Bortezomib	14 (31.8%)
Epothilones	8 (18.2%)
Neurotoxic monoclonal antibodies	18 (40.9%)
Platinums	40 (90.9%)
Taxanes	32 (72.7%)
Thalidomide	6 (13.6%)
Vinca Alkaloids	21 (47.8%)
Years of Oncology Experience
Median (Range) (n = 41)	16 (2 – 38)

^aOther practice areas included clinics such as sarcoma, palliative care melanoma, head and neck, urology, and genitourinary.

^bTotal does not equal 100%; participants selected more than one drug.

Table 3.

Themes and Associated Exemplar Quotes from the Semi-Structured Interviews (N = 9)

Themes	Exemplar Quotes
Theme 1: Clinicians primarily recommend gabapentin for CIPN management and often observe cryotherapy used for CIPN prevention, but these interventions are complicated by discomfort, intolerable side effects, and efficacy concerns.	“If there's pain and tingling or burning with it, then our first go-to is gabapentin.” “I've had quite a few patients who were prescribed gabapentin, tried it and did not like the side effects at all. And then the provider will say, well, why don't we try something different? Let's try Lyrica. And at that point, they're just like, I'll just deal with the neuropathy.” “With the cooling therapy, I think, like I said, I'm not really sure about how effective it is long-term, but the side effects in terms of just uncomfortability and maybe some skin issues.”
Subtheme 1a: Clinicians lacked knowledge regarding the CIPN-directed therapeutic effects and side effects of duloxetine.	“Honestly, I would say I haven't had very many patients who have used it [duloxetine] as like a… or who have been prescribed it or recommended it by any of our oncologists. I would assume that a lot of the side effects could be similar to gabapentin or pregabalin in terms of inducing anxiety or depression in patients who might have those issues to begin with. I honestly would have to do more education and more reading on my own before, just to educate myself.”
Subtheme 1b: Clinicians provide education about the general benefits of physical exercise, but do not specifically prescribe exercise for cancer symptom and CIPN reduction	“We tell our patients that for the most part, exercise will keep them feeling normal, especially with fatigue. But again, on the same thing, patients don't want to exercise because they're so fatigued from their therapy that it's hard to get them to want to do the exercise." “I think exercise in general is great. We always tell our patients you should try to walk or whatever it may be…I just don't know if there are certain exercises, like hand exercises, other than moving your feet and your hands or whatever, to keep everything going. I don't know if there's anything in particular that would help. And if so, that would be good information to have too.”
Theme 2: Clinicians perceive CIPN as troublesome and desire additional information and resources regarding CIPN prevention and management.	“I think it can be devastating.” “I've had patients who have been unable to work because of those toxicity, and it can be painful, so it can affect their overall quality of life in that way too.” “Having more education on preventative measures for myself and my colleagues, I think, would be very helpful.”
Theme 3: CIPN-related education provided by clinicians may be limited by patient retention of the amount of education received about cancer treatment and other factors.	“I always like when someone brings someone with them or has someone on the phone, because that's always good to have [someone] extra. It's a lot of information at once. And we'll give teaching sheets to them to say that these are the main things you can expect. And obviously, for the research, the consents have every side effect you could ever have, so they have that too, but we highlight, ‘these are the ones are more likely to happen.’ But just keep educating.” “Sometimes in certain languages, there might not be the exact same word to translate and sometimes patients will have a hard time describing, so we have to play the guessing game, do you mean this?” “A big thing for just education, in general, I know for our clinic is timing. We don't get extra time built into our infusion appointments for education”
Theme 4: Clinicians use subjective CIPN assessment to screen at each visit for common CIPN symptoms (e.g., numbness or tingling) and the impact of symptoms on day-to-day activities.	“It’s such a subjective side effect, it’s not something we can visualize.” “I would ask patients if they're experiencing any pins and needle sensation, if they have any tingling, especially in their hands and feet, if they have trouble getting dressed in the morning with fine motor movements of their fingers, and I try to ask my patients questions like that every chemo cycle so that way I can get an idea of how things have changed over time.” “Well, I feel like sometimes patients are actually worse than what they're telling us because they just want to forge on and finish their treatment and making it not as bad as it really is…And then they'll finally say, ‘Okay, this is really bad and it has been for three months.’" “Sometimes, phrasing in different ways, people will say, especially at the beginning, oh, I did notice that, or I noticed it in these two fingers. And then as treatments progress, if it starts worsening or growing in severity, people start say, I remembered you mentioning buttons on my shirt, and I really started to have trouble with that. So I think giving examples of things where they might recognize it is helpful.”

Abbreviations. CIPN, chemotherapy-induced peripheral neuropathy

Theme 1: Clinicians primarily recommend gabapentin for CIPN management and often observe cryotherapy used for CIPN prevention, but these interventions are complicated by discomfort, intolerable side effects, and efficacy concerns.

Survey results revealed that gabapentin was most recommended as the first line CIPN management strategy, with 80% of RNs and 69% of prescribing providers recommending gabapentin (Table 4). Similarly, most clinicians reported in the interviews that they used gabapentin for painful CIPN (Table 4). However, clinicians frequently reported that gabapentin use is complicated by drowsiness and fatigue. A subset (18%) of clinicians also reported prescribing narcotics for CIPN but not as a first-line therapy. During the interviews, many participants discussed decreasing neurotoxic chemotherapy dosages if CIPN severity was worsening as a key strategy for CIPN prevention or management.

Table 4.

Summary of CIPN Assessment and Management Practices

Question	RN (n = 15)	Providers (n = 29)	Total (n = 44)
Percentage of patients who develop troublesome CIPN
Median (Range)	50 (0 – 80)	33 (3 – 90)	34 (0 – 90)
What first-line medicine/strategy do you recommend to prevent CIPN?
None	4 (26.7%)	19 (65.5%)	23 (52.3%)
Gabapentin	3 (20%)	2 (6.9%)	5 (11.4%)
Physical Exercise	2 (13.3%)	1 (3.4%)	3 (6.8%)
Other Therapiesa	6 (40%)	7 (24.1%)	13 (29.5%)
What other medicine/strategies do you recommend to prevent CIPN? b
None	7 (46.7%)	23 (79.3%)	30 (68.2%)
Duloxetine	3 (20%)	0	3 (6.8%)
Gabapentin	3 (20%)	0	3 (6.8%)
Opioids	3 (20%)	0	3 (6.8%)
Pregabalin	1 (6.7%)	0	1 (2.3%)
Physical Exercise	3 (20%)	3 (10.3%)	6 (13.6%)
Referral to Subspecialty	1 (6.7%)	0	1 (2.3%)
Other Therapiesc	1 (6.7%)	3 (10.3%)	4 (9.1%)
What first-line medicine/strategy do you recommend to manage existing CIPN?
None	2 (13.3%)	0	2 (4.5%)
Duloxetine	1 (6.7%)	5 (17.2%)	6 (13.6%)
Gabapentin	12 (80%)	20 (69%)	32 (72.7%)
Referral to subspecialty	0	1 (3.4%)	1 (2.3%)
Other Therapiesd	1 (6.7%)	2 (6.9%)	3 (6.8%)
Missing	0	1 (3.4%)	1 (2.3%)
What other medicine/strategies do you recommend to manage existing CIPN? b
None	3 (20%)	0	3 (6.8%)
Amitriptyline	2 (13.3%)	3 (10.3%)	5 (11.4%)
Duloxetine	4 (26.7%)	15 (51.7%)	19 (43.2%)
Gabapentin	5 (33.3%)	14 (48.3%)	19 (43.2%)
Opioid Analgesics	3 (20%)	5 (17.2%)	8 (18.2%)
Pregabalin	5 (33.3%)	15 (51.7%)	20 (45.5%)
Physical Exercise	6 (40%)	8 (27.6%)	14 (31.8%)
Referral to subspecialtye	4 (26.7%)	12 (41.4%)	16 (36.4%)
Other Therapiesf	2 (13.3%)	9 (31%)	11 (25%)
What medicine/strategies do you observe your patients using to prevent CIPN outside of your recommendations?
None	4 (26.7%)	8 (27.6%)	12 (27.3%)
Vitamin B	1 (6.7%)	4 (13.8%)	5 (11.4%)
Icing/Cold Therapy	4 (26.7%)	1 (3.4%)	5 (11.4%)
CBD	1 (6.7%)	1 (3.4%)	2 (4.5%)
Otherg	1 (6.7%)	3 (10.3%)	4 (9.1%)
Missing	4 (26.7%)	12 (41.4%)	16 (36.4%)
What medicine/strategies do you observe your patients using to manage existing CIPN outside of your recommendations? b
None	5 (33.3%)	7 (24.1%)	12 (27.3%)
Vitamins/Supplements	0	5 (17.2%)	5 (11.4%)
Acupuncture	1 (6.7%)	2 (6.9%)	3 (6.8%)
CBD	1 (6.7%)	5 (17.2%)	6 (13.6%)
Physical Therapy	1 (6.7%)	1 (3.4%)	2 (4.5%)
Otherh	1 (6.7%)	3 (10.3%)	6 (13.6%)
Missing	7 (46.7%)	9 (31%)	15 (34.1%)
Discussing strategies to prevent and manage peripheral neuropathy with patients is part of my work in my current profession/role.
Strongly Disagree	1 (6.7%)	1 (3.4%)	2 (4.5%)
Somewhat disagree	1 (6.7%)	0	1 (2.3%)
Neither agree nor disagree	2 (13.3%)	2 (6.9%)	4 (9.1%)
Somewhat agree	8 (53.3%)	6 (21%)	14 (31.8%)
Strongly agree	3 (20%)	20 (69%)	23 (52.3%)
If I discuss peripheral neuropathy prevention and management strategies with my patients, I feel like I am making a difference
Never	1 (6.7%)	0	1 (2.3%)
Rarely	1 (6.7%)	1 (3.4%)	2 (4.5%)
Sometimes	5 (33.3%)	12 (41.4%)	17 (38.6%)
Often	3 (20%)	12 (41.4%)	15 (34.1%)
Always	4 (26.7%)	4 (13.8%)	8 (18.2%)

Abbreviations. CIPN, chemotherapy-induced peripheral neuropathy; RN, registered nurse.

Notes. Percentages reflect the number who selected a particular response out of the sample size for each column heading.

^aOther first-line prevention recommendations included alpha lipoic acid, alpha lineic acid, cryotherapy, vitamin B, and massage

^bTotal does not equal 100% as participants’ selected more than one option

^cOther second-line prevention recommendations included givosiran, vitamin B, or alpha lipoic acid

^dOther first-line management recommendations included givosiran, massage, and acupuncture

^eReferral to subspecialty included referrals to symptom management, neurology, physical therapy, physical medicine and rehabilitation, and palliative care

^fOther second-line management recommendations included givosiran, massage, and acupuncture

^gOther prevention strategies used by patients included fasting, massage, hydration, “as seen on TV”

^hOther management strategies used by patients included lidocaine, “as seen on TV,” water therapy

As for prevention, the survey findings revealed that most (73%) RNs and some (34%) providers recommended a first-line strategy to prevent CIPN: primarily alternative therapies (36%) including physical exercise, supplements, cryotherapy, and massage. Even though only four (14%) providers and one (7%) RN recommended cryotherapy as a strategy to prevent CIPN, seven (78%) participants in the interviews mentioned cryotherapy for CIPN prevention. However, the clinicians were not convinced of the efficacy of cryotherapy and noticed that it is uncomfortable for patients. Some (36%-38%) clinicians also observed patients using various alternative modalities to prevent and manage CIPN without their recommendation, such as vitamins, cannabis, cryotherapy, and acupuncture.

For the last two (TDF-derived) questions of the survey, most (84%) clinicians (73% of RNs and 89% of providers) agreed that discussing strategies to prevent and manage CIPN with patients is part of their work in their current professional role. However, the responses to both TDF-derived questions covered the full range (1-5) of the Likert scale. About half the clinicians (46.7% of RNs; 55.2% of providers) felt like they often or always were making a difference if they discussed CIPN prevention and management strategies with their patients. All six RNs who had high scores (rated >= 4) on the TDF-derived questions also reported giving CIPN prevention and management recommendations. The two RNs who gave no recommendations for CIPN management also had low scores on both TDF-derived questions.

Clinicians lacked knowledge regarding the CIPN-directed therapeutic effects and side effects of duloxetine.

Duloxetine was recommended by three RNs (7% of clinicians) for later-line prevention, 14% of clinicians for first-line management, and 43% of clinicians for later-line management of CIPN. However, among providers who reported that they felt like they were making an important difference when discussing CIPN management (TDF questions ratings >= 4), 14 (93%) prescribed duloxetine as a first- or second-line treatment.

Some interviewees reported that duloxetine “can be effective with minimal side effects” but most others shared comments such as “I guess we just don't typically use it. We have more experience with the gabapentin…”; “I don't remember seeing it prescribed and knowing that it was for neuropathy”; and “I would assume that a lot of the side effects could be similar to Gabapentin or Lyrica in terms of inducing anxiety or depression…I honestly would have to do more education and more reading on my own before, just to educate myself.” A few clinicians also suggested the stigma of duloxetine being an antidepressant and lack of patients’ access to it may be barriers to duloxetine use for CIPN.

Clinicians provide education about the general benefits of physical exercise, but do not specifically prescribe exercise for cancer symptom and CIPN reduction.

Physical exercise was recommended by 7% of clinicians for first-line prevention, 14% of clinicians for later-line prevention, no clinicians for first-line management, and 32% of clinicians for later-line management of CIPN. Five of the seven providers who chose physical exercise as a line of CIPN management also had high scores (rated >= 4) on the TDF-derived questions.

In the interviews, participants shared that “we do try to educate patients that, if you get out and you move around, it's going to help…get your blood flowing; it'll help you feel better.” However, many participants also commented on fatigue and one RN commented on gastrointestinal issues (inability to be too far from a bathroom) being a demotivator and barrier to patients engaging in physical exercise. One NP said, “I think that for patients to really buy into that, it has to be like a prescription where we say, ‘We need you to do this three times a day…three times a week’…so it's kind of more prescription so that they're more apt to do.”

Theme 2: Clinicians perceive CIPN as troublesome and desire additional information and resources regarding CIPN prevention and management.

Nurses (n = 15) estimated that 50% (Range = 0%-80%) of patients experience troublesome CIPN. Whereas prescribing providers (n = 29) estimated that 33% (Range = 3%-90%) of patients experience troublesome CIPN. The 19 clinicians who perceived that at least 50% of patients have troublesome CIPN mostly specialized in gastrointestinal, breast, lung, and hematological cancers. The 15 clinicians who perceived that less than 50% of patients have troublesome CIPN mostly specialized in “other” cancers, such as genitourinary cancers and sarcoma.

During the interviews, some clinicians expressed a sense of discouragement, saying “Most difficult is that there is not a way to fix it. And that's hard to say, but there's no way to fix it.” Additionally, several clinicians reported frustration with the lack of CIPN treatments and desired additional information regarding CIPN prevention and management for themselves and on an educational pamphlet or in a series of educational videos to provide to patients. When receiving education, some participants preferred the education emailed on multiple occasions, contained in a PowerPoint or tip sheet, linked on the University website, or presented during a nursing huddle or half-hour in-service. Some participants preferred information to be distributed via regular research emails with a link to the article. One clinician highlighted the importance of using their own and colleagues’ experiences as evidence to direct their future practice, saying “if people have significant experience and success in treating it, then [I] would want to know what their tips and tricks [are].”

Additionally, a few participants commented on the potential usefulness or drawbacks of distributing a pre-visit CIPN questionnaire to patients. One RN suggested it would be helpful if patients were given a CIPN questionnaire to complete during online check-in before their appointment. One oncologist suggested patient reported outcome measures can be beneficial if there is evidence supporting their use in practice, but shared concerns about a) interpreting patient’s survey responses if untrained on cutoff levels for the measure and b) the survey burden for patients who already must complete many pre-visit questionnaires/forms.

Theme 3: CIPN-related education provided by clinicians may be limited by patient retention of the amount of education received about cancer treatment and other factors.

All the interviewed clinicians reported educating their patients about CIPN: primarily what it feels like, how it can impact daily activities, and how often people develop it on their type of treatment. Education is provided verbally and in teaching sheets during initial consent/education about the chemotherapy and “all [its] pertinent toxicities” (e.g., nausea, diarrhea, constipation, skin changes) as well as at each visit when monitoring for CIPN. Clinicians commented that sometimes “they [patients] are not quite grasping what we’re saying,” “We usually try to tell people, at least at their first treatment, to bring a friend or a family member with them to have a second set of ears hearing the education. Obviously, it's such an overwhelming process for any patient to go through…” Clinicians also commented on education barriers such as patient language difficulty, varying health literacy, emotions and ill state associated with recent cancer diagnosis as well as inadequate time built in the appointment for RNs to reinforce education.

Theme 4: Clinicians use subjective CIPN assessment to screen at each visit for common CIPN symptoms (e.g., numbness or tingling) and the impact of symptoms on day-to-day activities.

Per the interviews, education about CIPN was often intertwined with assessment of CIPN and other symptoms at each chemotherapy cycle. No clinicians reported using objective forms of CIPN assessment during the interviews. Instead, CIPN was assessed using various questions. Some clinicians simply asked “How’s the neuropathy?” Other clinicians used descriptors such as numbness, tingling, pain in the extremities, pins and needles, burning, and feeling like your foot is falling asleep. Further, many clinicians assessed if patients had any trouble buttoning or zipping a shirt, putting on earrings, grabbing or holding things, writing, walking, feeling the floor under their feet, or balancing/being stable on their feet.

In general, clinicians perceived CIPN as “such a subjective side effect” that can be challenging to assess, because “you just have to depend on your patients to be truthful and honest about it.” Further, clinicians expressed difficulty interpreting and acting upon the subjective assessment due to CIPN’s potential temporary nature and unclear etiology: whether mostly due to comorbidities (e.g., diabetes or spinal lesions) or the chemotherapy.

Discussion

The results of this convergent, mixed-methods study identified discrepancies between evidence-based guidelines on CIPN management and current oncology clinician practices. Clinicians consistently reported using gabapentin first line over duloxetine to treat CIPN. Consistent with prior literature,^9,10,17 under 20% of clinicians recommended opioids (and only as later line treatment) for painful CIPN. Clinicians’ recommendation of gabapentinoids as first line treatment for CIPN is consistent with other quantitative and qualitative reports^9,10,17 and may be due to clinicians’ superseding familiarity with gabapentinoids and knowledge deficit regarding duloxetine’s therapeutic and side effects. This study highlighted a new barrier: the stigma surrounding duloxetine being a medicine for depression. Other studies have also suggested barriers to duloxetine prescription may include unawareness of the national guidelines for CIPN management,¹⁷ risk of duloxetine drug-drug interactions,⁹ and insurance requirements for Prior Authorization and failure of “preferred” agents before prescribing duloxetine.⁹ Clinicians have expressed concerns regarding duloxetine’s moderate CYP2D6 inhibiting effects.^9,18 Concomitant administration of duloxetine with CYP1A2 inhibitors (e.g., ciprofloxacin) can result in higher duloxetine blood concentrations.¹⁹ Combining duloxetine with monoamine oxidase inhibitors and drugs such as doxorubicin is contraindicated;^19,20 however, systematic reviews have also demonstrated duloxetine’s safety (i.e., no significant difference in adverse events compared to placebo) during various stages of cancer treatment.^5,21 Additionally, many insurance companies now cover duloxetine for neuropathic pain conditions without prior authorization requirements.

Consistent with prior studies, clinicians often recommended non-pharmacological interventions for CIPN such as vitamin B and supplements, ^9,10 cryotherapy, massage, and acupuncture, despite perceiving their efficacy to be low or variable. Further, nurses often recommended physical exercise during cancer treatment; however, it was seldom prescribed to reduce CIPN. Based on its safety and multivariate benefits including modest benefit in reducing CIPN, the national guidelines recommend physical exercise even during active cancer treatment.^6,8,22,23 Prior studies also suggest that oncology clinicians often discuss exercise with their patients but rarely prescribe physical exercise due to barriers including patient resistance to exercise and lack of provider knowledge, time, and appropriate programs for referral.^24,25 Studies suggest that patients desire and benefit from receiving recommendations from their oncologist and care team for exercise^25-29 and additional benefit from concurrent motivational supports to sustain physical exercise behaviors during the taxing cancer treatment period.²⁷ Clinicians suggested that nonpharmacological interventions, particularly physical exercise, may be more successful if patients are provided with a formal prescription and the process is streamlined utilizing the electronic medical record.^29,30

Evidence suggests both appropriate and suboptimal CIPN assessment practices have been exhibited by clinicians.^9,10,30,31 All participants in this study reported integrating CIPN assessment with patient education about various cancer treatment side effects and solely using subjective assessment. Yet, participants also expressed challenges with patient retention of information and frustration with the unpredictability and subjective nature of CIPN. For example, clinicians perceived that some patients may write-off and underreport their symptoms and clinicians may interpret the patients’ reports differently. Other barriers to comprehensive CIPN assessment suggested in prior studies have included patient and clinician difficulty with CIPN descriptors, low perceived priority of CIPN compared to other life-threatening symptoms, and lack of clinician time, tools, standardized processes, and skills/training.^9,10,30-33

Overall, clinicians generally perceived CIPN as problematic, with GI,¹⁰ breast, lung, and hematological oncology clinicians perceiving the highest rates of problematic CIPN. Frontline treatments for these cancers include platinums, taxanes, vinca alkaloids, and brentuximab vedotin, which are also known to induce the highest rates of high-grade CIPN.^34,35 For example, it is estimated that nearly all GI patients experience acute CIPN after receiving oxaliplatin, and a third of GI patients experience Grades 2-4 CIPN years after completing chemotherapy.³⁶ Hence, clinicians also expressed a desire for additional education and resources about CIPN assessment and management through a variety of different mediums, including via printed quick-sheets, repeated emails, PowerPoint slides, distribution of the research articles themselves, 30-minute in-services, and sharing of success stories and tips among colleagues.³³

Application of the TDF domains may help improve the implementation and efficacy of interventions for improving CIPN assessment and management practices. Prior studies of interventions (e.g., clinical guideline distribution and clinical decision support tools) have highlighted barriers to implementation and efficacy including lack of clinician perceived value of utilizing the intervention, time to implement the tool recommendations, and compatibility between the intervention and clinic flow.^17,37-39 The current study suggests intervention implementation could be improved by applying the following TDF domains: behavioral regulation (habit breaking), professional role and identity, beliefs about consequences, reinforcement, and environmental context and resources. Specifically, interventions should first promote clinicians’ perceived value of utilizing evidence based CIPN assessment and management practices, by enhancing their a) sense of personal role in CIPN management, b) perceived importance of CIPN and hopelessness optimism regarding CIPN treatments, c) observation of positive outcomes from evidence-based practice, and d) assurance of patient access to duloxetine and physical exercise environments. Second, interventionists need to seamlessly integrate the intervention into the clinical workflow, utilizing the EMR and considering clinicians’ time and priorities, patient mental energy and information retention.^31,33

Limitations

A limitation to the generalizability of this analysis was the homogeneity in the cancer site demographics and low response rate (potentially leading to a biased sample and response set). Few participants volunteered for the interviews, which may have prevented attainment of full data saturation. Further, the co-investigators led some of the interviews, which may have introduced bias.

Implications for Nursing Practice

Additional training, resources, and practice changes are needed to make evidence based CIPN assessment and management a norm in cancer centers. Oncology RNs (particularly those practicing in GI, breast, lung, and hematological cancer specialties) can serve crucial roles in developing and championing interventions to address the longstanding gaps in clinical CIPN assessment and management practices. For example, RNs could give input on how to best disseminate the evidence and identify what aspects of comprehensive CIPN assessment can be integrated into the clinic workflow. They could also help build in patient questionnaires (e.g., the brief and clinician highly rated patient neurotoxicity questionnaire)⁴⁰ in the patient portal and medical record to better assess CIPN and a process of ordering referrals and nonpharmacological interventions in the electronic medical record. This would meet the needs of clinicians who previously requested a prioritized list of evidence-based nonpharmacological interventions for CIPN.⁹ Finally, nurses could help lead peer discussions about personal CIPN management practices and successes and the state of the science.

Independently, RNs can continue to educate themselves and evaluate their personal values and priorities when caring for patients with or at risk for CIPN. They may choose to reflect on the importance of prioritizing CIPN physical assessment to address their concerns of the unpredictable and subjective nature of a problem that currently causes impaired quality of life and chemotherapy dose reduction in a significant number of patients. Further, RNs may choose to reflect on a) the utility of patient questionnaires to reduce the reporting bias from patients who have difficulty expressing the extent of their symptoms to their care team compared to b) the potential survey burden on patients and information overload for clinicians.⁹ Finally, RNs could reflect on what resources might help them make the best decisions when choosing how to guide their patients and change their practice according to the evidence to maximize positive outcomes for patients with or at-risk for CIPN.

Conclusion

Study results revealed several gaps in CIPN assessment and management among nurses and providers, including exclusive use of subjective CIPN assessment approaches and recommending CIPN prevention and management modalities with little evidence supporting their efficacy (e.g., gabapentin, cryotherapy, vitamin B). In addition, clinicians desired additional CIPN education for their patients and themselves. Theoretically (e.g., TDF) based and stakeholder driven approaches are needed to address the long-standing barriers to evidence based and national guideline compliant clinical practices. Ultimately, further rigorous research is needed to discover effective CIPN interventions and strategies to increase patient and provider knowledge regarding evidence based CIPN assessment and management strategies.