Evaluating the caregiver experience during neoadjuvant therapy for pancreatic ductal adenocarcinoma

Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden that patients experience during NT, but caregiver well‐being during NT is poorly understood.


| INTRODUCTION
Neoadjuvant therapy (NT) is increasingly used for patients with localized pancreatic ductal adenocarcinoma (PDAC). 1,2Since all patients with PDAC benefit from systemic chemotherapy and a large proportion are unable to receive it following pancreatic surgery due to complications or prolonged recovery, NT ensures its delivery and improves receipt of multimodality therapy. 310] Caregivers serve an important role by providing emotional and physical support to patients throughout cancer treatment. 11These individuals often take on the role of coordinating healthcare appointments, transporting patients to appointments, helping with activities of daily living (e.g., showering and cooking), and are the main point of contact for the wider support network of family members and friends. 12,13The interruption to their own daily routine combined with the stress of an uncertain prognosis for their loved one can impact caregivers' own quality of life.In addition, given the aggressive nature of PDAC, NT can be uniquely distressing given the uncertainty of future surgery and overall prognosis. 114][15][16] Therefore, the purpose of this study was to characterize the caregiver experience and quality of life during NT for PDAC, which may highlight opportunities to tailor supportive care strategies aimed at improving outcomes for both patients and caregivers.

| Study design and population
The study was approved by The Ohio State University Wexner Medical Center institutional review board (IRB# 2019C0155).
Caregivers of patients with PDAC currently undergoing NT with the intention of proceeding to curative-intent surgical resection were recruited to participate in this study.Patients were asked to identify their primary family/friend caregiver and for permission to contact them.Eligible participants were contacted by phone, and informed consent was obtained.Participants completed the Caregiver Quality of Life Index-Cancer survey (CQOLC), which was delivered through an emailed link to the REDCap survey.Participants were then contacted by trained research staff for semi-structured interviews with open-ended questions at a time convenient for them and completed by phone.Interviews were audio-recorded and later transcribed using transcription software.

| Data analysis
All interviews were conducted over the phone, audio recorded, and then transcribed using Landmark, a professional transcription service for qualitative research.Transcripts were uploaded to NVivo20 (QSR International, Australia) for data extraction, synthesis, and analysis.Data extraction followed an integrated approach, including both an inductive and deductive coding methodology.Two researchers independently coded the transcripts for subthemes in an iterative fashion until thematic saturation was achieved. 17Interviews were rereviewed and coded using the final codebook.Assessment of thematic saturation can be found in Supporting Information: Table S1. 18All discrepancies were discussed at team meetings until a consensus was reached.
The Caregiver Quality of Life Index-Cancer (CQOLC) survey is a 35-item questionnaire that evaluates the physical, emotional, social, financial, and spiritual quality of life (QOL) of caregivers.Questions are scored on a 5-point Likert scale from 0 ("not at all") to 4 ("very much") with scores ranging from 0 to 140.A higher score indicates better QOL.Scores from "negative" questions (e.g., My sleep is less restful) were inverted so that a higher rating always correlates with better QOL.This survey has been validated in both the inpatient and outpatient oncology settings.It has strong test-retest reliability (0.95) and internal consistency (Cronbach's α = 0.91). 19,200][21] The quantitative data were reported as mean with standard deviation (SD).

| Patient and participant demographics
A total of 28 patients and their caregivers were included in this study.
The mean treatment duration of NT at the time of caregiver participation was 2.9 ± 1.9 months.The majority did not experience severe complications during NT (n = 17, 61%) (Table 1).Of the 28 caregivers included in the study, 26 completed the CQOLC survey, and 15 participated in the semi-structured interviews.The mean age of participating caregivers was 60.1 ± 13.5 years old, and most were female (n = 21, 75%), Caucasian (n = 24, 85.7%), married (n = 21, 75%), and a spouse or significant other of the patient (n = 20, 71.4%).None of the caregivers reported a personal history of cancer (Table 2).
The mean overall score on the CQOLC was 83.0 ± 21.1, and the median score was 86.5 (range: 43-119) on a scale of 0-140, consistent with an overall moderate QOL.Items rated lowest (i.e., least distressing) on well-being included "the need to protect my loved one bothers me" (mean 3.65 ± 1.0), "it bothers me that I need to be available to chauffeur my loved one to appointments" (mean 3.57 ± 0.9), and "I am glad that my focus is on getting my loved one well" (mean 3.42 ± 0.9).Items rated highest (i.e., most distressing) were "it upsets me to see my loved one deteriorate" (mean 0.84 ± 0.8), "I have more of a positive outlook on life since my loved one's illness" (mean 1.12 ± 1.1), and "my level of stress and worries has increased" (mean 1.19 ± 1.0).Complete results from CQOLC are reported in Figure 1.When analyzed by the CQOLC subsection, "emotional burden" (mean 47.3 ± 20.9) and "positive adaptation" (mean 57.3 ± 13.9) were rated the worst, whereas "financial concerns" (mean 67.6 ± 28.5) and "disruption to daily life" (mean 72.7 ± 20.6) were less impactful on caregiver well-being (Figure 2).

| Qualitative results
Several themes were identified from the qualitative analysis of the semi-structured interviews.First, caregivers' perspectives on the patient's treatment decision-making and experience with NT were noted.Second, caregiver emotional symptoms, impact on their daily life, and coping strategies were commonly discussed.Finally, caregiver needs were frequently mentioned, as well as realistic goals and expectations for the patient and themselves.

| Caregiver perspective of treatment and patient experience
Almost all caregivers (93%) reported initial unfamiliarity with the concept of NT, felt that NT was presented to them as the only option and that NT was the physician's decision.Similarly, nearly all participants (93%) reported that the primary justification for selecting NT was to improve the chance of resectability.A few caregivers (27%) reported that, while patients understood the rationale for NT, they were more hopeful about surgery than NT since it would ultimately remove the cancer ("he was really hoping to have surgery right away and just get it out of there and be done").Approximately half of the caregivers (47%) in the study expressed that they were fully involved in the decision-making for their loved one's treatment, while others (53%) felt they took a more tangible supportive role in the form of attending appointments, helping coordinate care, and reaching out to the medical team.
Most caregivers (80%) believed that their loved ones received adequate emotional and psychosocial support from family members, friends, and religious groups.Others expressed encouraging their loved ones to utilize counseling services (20%).Several caregivers (27%) also mentioned the positive impact of receiving practical and decision-making support from different family members and colleagues with healthcare backgrounds (e.g., "I've got a daughter-in-law who is a nurse so she was able to come to the house and [help].") According to most caregivers (67%), patients were worried and felt guilty about the impact of their cancer diagnosis on family and friends' well-being.Some caregivers (13%) expressed that the patient felt worried about leaving their family behind and exhausting resources and finances.One caregiver stated: "she apologizes profusely for one thing or another…" In addition, some patients (33%) felt discouraged by no longer being able to support their loved ones, both financially and practically.Participants (40%) also discussed the major side effects and uncertainty their loved ones felt about tolerating NT ("He hates it.He hates chemo.He, at several different times, said he wasn't going to have it no more.").Caregivers (87%) expressed that the patients felt weak after NT and experienced a significant impact (53%) on their everyday life ("she doesn't have the strength and stamina to stand in front of the stove and cook…").

| Caregiver emotional symptoms
Caregivers described feeling fearful about how the patient would respond to different treatment options and the unknown nature of prognosis (73%).One caregiver stated: "you always have fear of the unknown, you don't know what's gonna happen."Other emotional symptoms included stress and anxiety (53%), feeling sorry for their loved ones (33%), sadness and grief (33%), frustration (13%), and shock (13%).On the other hand, caregivers also felt a desire to be strong for their loved ones (33%), and thankful for the immense support (13%).Representative quotes can be found in Table 3.

| Caregiver coping
The most common coping strategy employed by patients was maintaining hope in regard to the patient's prognosis (73%).They also frequently chose to focus on the present (67%); treating it as the new normal made them feel less overwhelmed.One caregiver explained: "we're just taking it 1 day at a time, one chemotherapy at a time."Participants also shared that facing reality (i.e., acceptance or rationalization, 47%) felt like the only way to move forward.As one caregiver shared, "I guess there's no way around that.Just kind of suck it up and face it."Several caregivers mentioned that having access to relevant, thorough, and timely information about their loved one's prognosis and treatment options provided comfort (53%).
Other coping strategies included end-of-life planning (33%), putting faith in the medical team (27%), and religion (20%).While some caregivers (27%) found having a positive outlook on their loved one's condition helped their ability to cope, others (13%) downplayed both the treatment severity and their emotional response.Additional caregiver quotes can be found in Table 5.

| Caregiver goals, needs, and recommendations
Regarding caregivers' goals, some were optimistic that NT could improve their loved one's likelihood of undergoing surgical resection (40%), whereas others remained uncertain about the patient's prognosis during NT, but their goal was to provide their loved one with comfort and good quality of life (20%).Many caregivers highlighted the need for information on symptom management and what is normal versus abnormal during NT (40%).A few caregivers (13%) shared that they may benefit from support

| DISCUSSION
While surgical resection remains necessary for curative-intent treatment for PDAC, patients with localized cancers are increasingly receiving chemotherapy with or without radiation therapy before surgery. 2,22The neoadjuvant period is unique in that not only may patients experience potentially toxic side effects of aggressive treatment, but they also must live with their cancer in situ along with uncertainty about their prognosis and likelihood of undergoing surgery.How this experience impacts patients and their loved ones is poorly understood.Previously published studies have highlighted the patient experience during NT for PDAC, as well as the caregiver experience in the setting of unresectable cancer, but little has been written about the caregiver experience during NT for PDAC. 8,23,24In this cross-sectional mixed-methods analysis of caregivers' experiences and QOL during NT for PDAC, we found that caregivers' well-being is often characterized by emotional stress and anxiety, T A B L E 4 Representative quotes describing neoadjuvant therapy impact on different facets of the caregiver's daily life.

Impact Frequency Representative quote
Impact on home life 15 "I come home and that's a job in itself taking care of him, he's independent still, but still just the emotional support.And then also just doing my day-to-day things that still need done around the house…" "I find it very hard for me to get up and I don't have the energy like I used to.I mean I can get up and go to work to do an 8-h shift, come home, do a load of laundry, vacuum, make dinner, walk to the store, walk for a walk.And now it's like I'm worn out faster." "…little chores around the house that kind of were his thing to take care of, I'm having to do all of that and you know when the kids call and they need something, it falls on me to make sure that, you know, they get the help they need…" Self-care, sleeping, eating, exercising "And then we throw in the travel because of where we live.There's no surgeon and then the dates that we've tried to always finagle around with getting in for chemo and into hotel rooms and with the type of treatment, it's taken, it's a toll.""So, we've just learned every other week, we have a day we have to just dedicate solely to being down there and I take my work along and work from there actually.But that's been the biggest barrier.It's just kind of getting there and then just having to put everything on hold that day." Impact on work 9 "I've missed a lot of work and I'm actually switching jobs because of this to make it easier for me to be able to do things with her." "I was self-employed, I'm an attorney, I had my own office.I was stressed out about it anyway, but then once this happened.I can't work 50-60 h.I can't do that now so I'm literally closing my practice.""I wouldn't be able to really mentally be into my job, because I'd be there worrying." Financial concerns 9 "Financially is the biggest struggle trying to downsize things and get rid of some bills.So, I'm not gonna have to be responsible for multiple car payments and all that…" "I can't lie, money's tight right now with me not working." Social life or support 8 "I have a very good minister who checks in with us and I have a really strong Christian friend who talks to me quite often.""All the kids, we've got five kids and like she said, I think all of them have been supportive and are willing to help out.We've got other family members who have offered too.And she has a friend down the street here that helps too.So, we've got a lot of support.She has a lot of support."Patience 3 "…as long as you have patience.We're not the only person with an issue, there's other people out there too, and it all worked out.I mean, it worked out fine." "… I just have to gulp down an extra dose of patience and just be there for him." Physical symptoms 2 "I find it very hard for me to get up and I don't have the energy like I used to.I mean I can get up and go to work to do an 8-h shift, come home, do a load of laundry, vacuum, make dinner, walk to the store, walk for a walk.And now it's like I'm worn out faster." "I was self-employed, I'm an attorney, I had my own office.I was stressed out about it anyway but then once this happened, I can't take my full responsibility of what I usually work 50-60 h.I can't do that now so I'm literally closing my practice." | 781 disruption of their daily life, increasing financial burden, and a reluctance to engage in self-care activities.
An important finding from our study was that nearly all caregivers were unfamiliar with the concept of NT before meeting with their oncology providers.Previous studies have found a similar lack of awareness among patients as well as an inherent preference for upfront surgery, especially for those with anatomically resectable cancers. 8,25ereas most caregivers eventually understood the rationale for NT, many reported hoping for upfront surgery to "just get the cancer out."Indeed, because not all patients who initiate NT will be able to undergo surgical resection, this decision carries uncertainty and fear among patients and caregivers alike. 26Patients and caregivers often have difficulty recalling information from office visits, and information found online is only of moderate quality/reliability. [27][28][29] Our study suggests that caregivers value transparency and honesty from providers.As such, clearly discussing treatment options and providing expectations for NT, symptom management, and expected treatment effects is critical.
The current study is the first to characterize the impact of NT on the caregiver experience.Our findings are consistent with existing literature on the caregiver experience during palliative chemotherapy.Caregivers are faced with the challenge of taking on new roles at home conflicting emotions as they watch their loved ones undergo treatment.Multiple studies demonstrate a disconnect between patient and caregiver perceptions.1][32][33][34] These studies suggest that this experience can be improved through open communication between the caregiver, patient, and family.Comparably in this study, caregivers expressed similar concerns in the semi-structured interviews.Among all caregiver participants, it was the emotional burden subcategory of the CQOLC surveys that most heavily impacted their QOL.These findings suggest that caregivers experience significant emotional T A B L E 5 Representative quotes describing caregiver coping during neoadjuvant therapy.symptoms during NT for PDAC and highlight the need for specific supportive care strategies.
In our study, caregivers coped with these challenges in several ways: adjusting their perspective, end-of-life planning, and by placing faith in the medical team and/or religion.Caregivers who use these active coping strategies are more likely to have positive expectations and feel hopeful for the future. 35While mainly conducted in the palliative care setting, these studies also support that early incorporation of the palliative care team to establish a long-term relationship and provide additional support can be effective ways to improve caregiver coping.Interestingly, "positive adaptation" was one of the lowest-rated CQOLC subscales in our study, suggesting that assistance with developing coping strategies could help caregivers of patients undergoing NT.Additional information may be learned from the ongoing PAN-CARER study, an exhaustive analysis of 300 caregivers of patients with PDAC across different regions, socioeconomic groups, and ethnic groups throughout the UK. 368][39][40][41][42][43] The results of this study highlight opportunities to improve the well-being of caregivers of patients with PDAC receiving NT.Unfortunately, there is a lack of practical tools for screening caregivers and identifying how to best support them. 44Incorporating a therapist into the multidisciplinary team to provide coping mechanisms and communication tools for families, repeated education sessions during appointments about symptom management and care at home, and ensuring the caregiver has access to accurate resources and a support network can all be useful interventions. 45Additionally, many caregivers are not aware of preexisting resources at their disposal, like employee assistance programs or benefits of the Family and Medical Leave Act (FMLA).Highlighting these under-utilized resources at clinic appointments is crucial.
Despite the novelty of this study, several limitations exist.First, the study was performed at a single academic medical center in a large metropolitan area with a relatively homogenous patient population.
Therefore, these findings may not be generalizable to patients and caregivers in other settings and should be confirmed in other clinical scenarios.Second, the study was cross-sectional in design, so the caregiver experience could be influenced by the timing of the interview or changes over time during NT.Future research should evaluate the longitudinal outcomes of caregivers prospectively.Finally, the relatively small sample size precluded comparisons between cohort types (e.g., anatomic stage, caregiver relationship, etc.).
In conclusion, in this mixed-method analysis of caregiver quality of life and experiences during NT for PDAC, we found that caregivers have unique experiences and challenges highlighted by emotional symptoms, disruption of their daily life responsibilities, increasing financial burden, and a reluctance/inability to participate in self-care.
Assessing caregiver needs and providing supportive care resources should be done during NT.

T A B L E 1
Patient demographics for the study cohort.

T A B L E 3
Caregiver emotional symptoms during neoadjuvant therapy.then with the chemo making him weak, it scares me for him to get up, and try to walk upstairs to the bathroom.""You always have fear of the unknown, you don't know what's gonna happen."Stress and anxiety 8 "I'm nervous…I have anxiety anyway, my anxiety just has been through the roof, pretty much out of control.I have panic attacks.My anxiety is just doubled or tripled I think which makes everything more difficult […] Sometimes I'm just kind of collapsing and just emotionally I'm just frozen […] I sleep instead of getting stuff done sometimes.If I have time I'll nap and stuff instead of accomplishing something.""[their recent medical experience] was really terrifying and stressful."Courage 6 "I think I felt like I needed to be the strong one and just really kind of , and I was just crying all the time at the drop of a hat.It all happened so fast.""I don't have to let him see me cry, or my family members to see me cry.That's my time alone in between the time I leave the house and time I get to school or time I leave the school to get to the house.
" Frustration 3 "I get tired of hearing people say, oh, well my mother had skin cancer, she survived.Well, skin cancer and pancreatic cancer are not the same thing […] Don't even tell me about it.Pancreatic cancer is not survivable […] I just don't like the comparison.It's not fair to him to hear it and it's not fair to me either.And so, I guess I get a little frustrated at that." "She said until they get in there to actually do the surgery she could not tell us the exact stage.And I got kind of aggravated with that.But it just seemed like at first they did not want to communicate with us very well until I got upset with them."Hope or gratitude 2 "At first it was very difficult, given the first meeting we had locally with somebody.It soundedpretty gloomy, pretty sad, and then we sought a second opinion.After talking and meeting with everybody over there, it's like we did a complete 180 turn from what we had first heard.You have no idea how uplifting and encouraging it was meeting with your groups over there.It was very, very encouraging.""I told you about the big outpouring of support, but it's hard to just accept that.You know people just start bringing food in and it's very, very kind."Shock 2 "I was just shocked at the whole diagnosis.Not so much what was happening.""It is always a shock because she's a very healthy seventy-year-old that lived a clean life, so to speak, didn't drink much, never smoked.Always watched what she ate and exercised all the time." 15"I have no time for self-care, that's completely gone.Yeah absolutely, no self-care.Just my whole routine is different, everything just kind of is different now, it's like being in crisis mode for months.""I don't get to do anything that I used to do and enjoy doing." Hope for the future 11 "I guess the whole notion that this is in preparation for surgery is what makes us so optimistic.""And the concern was what would life be afterwards.And we were assured that nothing is guaranteed, but she could return to normal life.So, that helped us out a lot with that worry."Focus on the present 10 " I guess, honestly, I haven't really thought about [the future] because where we are right now is literally like our new normal.So,I haven't really given it any different thought.Obviously, once she has her surgery and we find out what her life may be like after that, then we'll adjust with that.""…whatwe've been thinking about a lot is just if things don't go well, making sure that what time she has is spent well and that we can be happy and do things that are enjoyable to [her]… we're just hoping to fit in as much of the things that she's enjoyed in life as we can."We felt pretty confident moving forward.I felt like she's an exception to what most people go through, but that was due to who she was and how early they caught the tumor.""I'mhaving confidence that if anyone can do it, she can because of the individual she is and they caught it early, that's the key to all of it."Faith(spiritual and in doctor) 7 "I just wish they could have went in and took it out and have been done with, but the doctors knows what to do.They know better than me.So, we left it up to the doctors about the chemo first.""We have faith, we trust in God, and we are praying that God will take care of us, take care of him, and all this situation.
" Acceptance 7 "…it's inevitable and we both know it.So, we just make the best of it and go on.""…when you don't have the option or the choice you just have to take the risk.That's what's gonna cure the problem […], I think I'm a little more accepting of how things are.It's not me that it's happening to, it's him.""…given the circumstances, we are not negative, we really can't see any other way but surviving this and in putting this kind ofbehind us.""I guess you just have to do it.I want her to live, so I have to do what I have to do." Plan for the worst 5 "I guess what I'm doing is planning for the worst.""I don't want to think the worst, but I need to be realistic.And if he doesn't get better […] if it does get worse, if it shortens our time together […] what if he gets down and really can't do anything.Will I need equipment in the house.Will I need help?[…] I think about all those possibilities."Gratitude and positivity 4 "And honestly, we were so fortunate that who he was enabled him to be rushed through the system."Downplaying 2 "My emotions are in supporting her and what needs to be done.So, yeah it hasn't affected me, no."