Emerging From the Haze™: Pilot Feasibility Study Comparing Two Virtual Formats of a Cognitive Rehabilitation Intervention.

OBJECTIVES: To gather feasibility and preliminary data comparing two virtual delivery methods for providing Emerging From the Haze™ (Haze) to cancer survivors compared to waitlist control (WLC). SAMPLE & SETTING: Eligible participants (N = 93) reported cancer-related cognitive impairment following chemotherapy for stage I-III solid tumors, Hodgkin lymphoma, or non-Hodgkin lymphoma. METHODS & VARIABLES: A three-arm randomized design was used to compare virtual live group presentation of Haze sessions, virtual prerecorded Haze group sessions, and WLC. Data were collected at baseline, week 10, and week 14. RESULTS: Feasibility was demonstrated. Significant cognitive function improvement at week 10 versus WLC was reported for the live group, and clinical improvement was reported for the prerecorded group. The prerecorded group reported significant improvement at week 14 versus WLC in physical activity, sleep, and health-related quality of life. IMPLICATIONS FOR NURSING: Additional pilot and feasibility evidence for cognitive rehabilitation interventions was demonstrated. Prerecorded Haze delivery shows potential for clinical effectiveness and scalability. Future multisite research is warranted.

Type I interferons, inflammation, and fatigue in a longitudinal RNA study of women with breast cancer.

BACKGROUND: Fatigue is a common side effect of cancer and its treatment and is thought to be driven in part by activation of the proinflammatory cytokine network. However, the cellular and molecular underpinnings of cancer-related fatigue (CRF) have not been determined, nor have immune pathways beyond inflammation been carefully investigated. The goal of this study was to examine the association between CRF and activation of canonical proinflammatory gene regulation pathways and Type I interferon (IFN) signaling pathways in breast cancer patients during and after treatment. METHODS: Women diagnosed with early-stage breast cancer (n = 181) completed assessments before and after treatment with radiation and/or chemotherapy and at 6, 12, and 18-month post-treatment follow-ups. Assessments included self-reported fatigue (Multidimensional Fatigue Symptom Inventory - Short Form) and expression of pre-specified sets of Type I IFN and pro-inflammatory immune response genes determined from mRNA sequencing of PBMCs. Mixed effect linear models examined changes in fatigue and immune gene expression over time and tested the hypothesis that fatigue would be associated with increased expression of Type I IFN and inflammatory response genes. RESULTS: There were significant changes in fatigue and immune gene expression across the assessment period; all measures increased from pre- to post-treatment but showed diverging patterns over the follow-up, with declines in fatigue and persistent elevations in Type I IFN and proinflammatory gene expression. In mixed effect linear models, expression of Type I IFN response genes was elevated in association with fatigue across the assessment period, from pre-treatment to 18-month follow-up. In contrast, pro-inflammatory gene expression was associated with fatigue only at 6, 12, and 18-month follow-ups. Analyses controlling for changes in leukocyte subsets continued to show a significant association between fatigue and Type I IFN gene expression but reduced the time-dependent association with pro-inflammatory gene expression to non-significant. CONCLUSIONS: Results revealed unexpected complexity in the immune underpinnings of CRF and identify a novel role for IFN signaling as a robust contributor to this symptom before, during, and after treatment. Pro-inflammatory gene expression emerged as a predictor of fatigue later in the cancer trajectory, and that effect was primarily accounted for by a concurrent increase in monocyte prevalence.

Post-traumatic stress symptoms, post-traumatic stress disorder, and post-traumatic growth among cancer survivors: a systematic scoping review of interventions.

The detrimental effects of Post-Traumatic Stress Symptoms (PTSS) and Post-Traumatic Stress Disorder (PTSD) and the benefits of Post-Traumatic Growth (PTG) are well established for cancer survivors. Increased cancer survival rates necessitate an understanding of how these two paradoxical outcomes, PTSS/PTSD and PTG, are targeted through interventions. This systematic scoping review aims to (a) examine existing evidence on interventions targeting PTSS/PTSD and/or PTG among cancer survivors and (b) identify knowledge gaps to inform future research. Following the six steps of a scoping review, 76 articles met the inclusion criteria. Quantitative articles were examined using descriptive analysis. Frequency counts of the collated data were tabulated into summary tables. Qualitative articles were reviewed using meta-synthesis. Most articles were quantitative (n = 52) and targeted PTG (n = 68) through promising intervention approaches such as psychotherapy, mindfulness, physical activity, and psilocybin-assisted therapy. Three key implications for future research and practice were synthesized: (1) mechanistic considerations for intervention design that provide a roadmap for rigorous and theoretically-grounded research; (2) the need for improved representation of cancer survivors in trials; and (3) potential facilitators of intervention efficacy. Together, these findings can direct future research to optimize interventions to reduce PTSS/PTSD and promote PTG achievement among cancer survivors.

Palliative Care Education in US Physical Medicine and Rehabilitation Residency Programs: Current Practices, Perceived Needs, and Barriers.

Background: Physical medicine and rehabilitation (PM&R) clinicians commonly care for patients with serious illness/injury and would benefit from primary palliative care (PC) training. Objective: To assess current practices, attitudes, and barriers toward PC education among U.S. PM&R residencies. Design: This is a cross-sectional study utilizing an electronic 23-question survey. Setting/Subjects: Subjects were program leaders from U.S. PM&R residency programs. Results: Twenty-one programs responded (23% response). Only 14 (67%) offered PC education through lectures, elective rotations, or self-directed reading. Pain management, communication, and nonpain symptom management were identified as the most important PC domains for residents. Nineteen respondents (91%) felt residents would benefit from more PC education, but only five (24%) reported undergoing curricular change. Lack of faculty availability/expertise and teaching time were the most endorsed barriers. Conclusion: PC education is heterogeneous across PM&R programs despite its perceived value. PC and PM&R educators can collaborate to build faculty expertise and integrate PC principles into existing curricula.

Benefits of nature-based walking for breast cancer survivors.

INTRODUCTION: Physical activity (PA) promotes significant physical and psychosocial benefits for breast cancer survivors. While evidence exists regarding recommendations for the frequency, duration and intensity of exercise that optimise PA benefits for cancer survivors, the role of the environment in achieving optimal outcomes has yet to be determined. This paper presents a protocol for a clinical trial to evaluate the feasibility of a 3-month nature-based walking programme for breast cancer survivors. Secondary outcomes assessed include the impact of the intervention on fitness, quality of life outcomes, and biomarkers of ageing and inflammation. METHODS AND ANALYSIS: The trial is a 12-week single-arm pilot study. Twenty female breast cancer survivors will engage in a supervised moderate intensity walking intervention in small groups in a nature reserve for 50 minutes three times per week. Data will be collected at baseline and end of study, and include assessment of inflammatory cytokines and anti-inflammatory myokines (TNF-α, IL-1ß, IL-6, CRP, TGF-ß, IL-10, IL-13), as well as ageing (DNA methylation, ageing genes) biomarkers; surveys (Patient-Reported Outcomes Measurement Information System-29, Functional Assessment of Cancer Therapy-General, Post-Traumatic Growth Inventory); and fitness assessments (6 min Walk Test, Grip-Strength, One Repetition-Maximum Leg Press). Participants will also complete weekly surveys assessing social support and participate in an exit interview. This is an important first step for future research on the influence of exercise environment on cancer survivor PA outcomes. ETHICS AND DISSEMINATION: This study was approved by the Cedars Sinai Medical Center Institutional Review Board (IIT2020-20). Findings will be disseminated through academic manuscripts, conferences, and community presentations. TRIAL REGISTRATION NUMBER: NCT04896580.

Fatigue as an Understudied Barrier to Participation in Life Roles.

Fatigue is one of the most burdensome and disabling symptoms in numerous acute and chronic conditions and is associated with reduced participation in all aspects of daily life, for example, parenting, employment, and socialization. Historically, occupational practitioners played key roles in fatigue management by creating and implementing interventions. The American Occupational Therapy Foundation convened a Planning Grant Collective workshop with the goal to develop collaborative research ideas and proposals to advance the understanding and management of fatigue. Participants from occupational therapy and other disciplines, with expertise with fatigue or who were conducting research on fatigue, participated in a 3-day virtual workshop. Four main topics emerged: implementation science, treatment taxonomy, trial design and comparative effectiveness, and phenotyping. This white paper describes the proceedings, summarizes the discussions, and outlines recommendations from the PGC workshop on fatigue.

A perspective on a precision approach to pain in cancer; moving beyond opioid therapy.

PURPOSE: Cancer-related pain is primarily treated with opioids which while effective can add significant patient burden due to side effects, associated stigma, and timely access. The purpose of this perspective discussion is to argue for a precision approach to pain in cancer based on a biopsychosocial and spiritual model which we argue can offer a higher quality of life while limiting opioid use. CONCLUSIONS: Pain in cancer represents a heterogenous process with multiple contributing and modulating factors. Specific characterization of pain as either nociceptive, neuropathic, nociplastic, or mixed can allow for targeted treatments. Additional assessment of biopsychosocial and spiritual issues can elucidate further points of targeted intervention which can lead to overall greater pain control.Implications for RehabilitationPrecision Pain Management in CancerPain in cancer is complex and heterogeneous with multiple contributing etiologies.A comprehensive assessment addressing the biopsychosocial and spiritual aspects of pain may lead to better control.Utilizing multiple targeted treatment strategies may help to curb opioid use.

The Streaming Web-Based Exercise at Home Study for Breast and Prostate Cancer Survivors: A Feasibility Study Protocol.

BACKGROUND: Despite the known benefits of physical activity in cancer survivors, adherence to exercise guidelines remains low. Known barriers to adhering to guidelines include a lack of time and an unwillingness to return to treatment facilities. Virtual exercise programming could assist in mitigating these barriers. This protocol presents a single arm pilot study exploring the feasibility of personalized Zoom-delivered exercise training for breast and prostate cancer survivors. A secondary objective is to determine the preliminary efficacy of participation on body composition, estimated VO2max, hand grip, one repetition maximum leg press, resting heart rate, resting blood pressure, exercise self-efficacy, and intentions to remain active. METHODS: Breast (n = 10) and prostate (n = 10) cancer survivors will participate in a 24-week feasibility study, including (1) 12 weeks of one-on-one virtual personal training with an exercise physiologist (EP) via Zoom, and (2) individual exercise for a 12-week follow-up period using recordings of Zoom sessions for guidance. Physical assessments and surveys will be implemented at baseline, 12 weeks, and at the end of the study (24 weeks from baseline). CONCLUSIONS: While virtual exercise programming became popularized during the pandemic, evidence is still required to understand whether it can successfully address barriers and promote participation.

A 6-Week Program to Strengthen Resiliency Among Women With Metastatic Cancer: A Randomized Clinical Trial.

PURPOSE: The objective of this study was to evaluate the effect of an intervention (Growing Resilience And CouragE; GRACE) on spiritual well-being, quality of life, and general well-being in women with metastatic cancers reporting existential or spiritual distress. PATIENTS AND METHODS: Prospective, randomized, wait-list control clinical trial. Women with metastatic cancer experiencing existential or spiritual concerns were randomized to GRACE or waitlist control. Survey data were collected at baseline, end of program, and 1-month follow-up. Participants included English-speaking women, 18 or older, with metastatic cancer, existential or spiritual concerns, and reasonable medical stability. Eighty-one women were assessed for eligibility; 10 were excluded (not meeting exclusion criteria, refusal to participate, and death). The primary outcome was spiritual well-being measured pre- and post-program. Secondary measures assessed quality of life, anxiety, depression, hopelessness, and loneliness. RESULTS: Seventy-one women (aged 47-72) were enrolled (GRACE n = 37, waitlist control n = 34). GRACE participants demonstrated significant improvements in spiritual well-being compared to control at end of program (parameter estimate (PE), 16.67, 95% CI, 13.17, 20.16) and 1-month follow-up (PE, 10.31, 95% CI, 6.73, 13.89). Additionally, significant improvements were demonstrated in quality of life at the end of program (PE, 8.51, 95% CI, 4.26, 12.76) and 1-month follow-up (PE, 6.17, 95% CI, 1.75, 10.58). GRACE participants also demonstrated improved depression and hopelessness at follow-up, as well as improved anxiety. CONCLUSIONS: Findings suggest the value of evidence-based psychoeducational and experiential interventions for improving the well-being and quality of life of women with advanced cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02707510.

The 24-Hour Movement Paradigm: An integrated approach to the measurement and promotion of daily activity in cancer clinical trials.

Increased physical activity (PA), improved sleep, and decreased sedentary behavior (SB) are essential components of supportive care for cancer survivors. However, researchers and health care professionals have achieved limited success in improving these behaviors among cancer survivors. One potential reasoning is that, over the past two decades, guidelines for promoting and measuring PA, sleep, and SB have been largely siloed. With greater understanding of these three behaviors, health behavior researchers have recently developed a new paradigm: the 24-Hour movement approach. This approach considers PA, SB, and sleep as movement behaviors along a continuum that represent low through vigorous intensity activity. Together these three behaviors form the sum of an individual's movement across a 24-hour day. While this paradigm has been studied in the general population, its usage is still limited in cancer populations. Here, we seek to highlight (a) the potential benefits of this new paradigm for clinical trial design in oncology; (b) how this approach can allow for greater integration of wearable technology as a means of assessing and monitoring patient health outside the clinical setting, improving patient autonomy through self-monitoring of movement behavior. Ultimately, implementation of the 24-Hour movement paradigm will allow health behavior research in oncology to better promote and assess critical health behaviors to support the long-term well-being for cancer patients and survivors.

Loneliness as a risk factor for cancer-related cognitive impairment: a secondary data analysis from the Haze study.

PURPOSE: The purpose of this study was to investigate the association between loneliness and cancer-related cognitive impairment (CRCI) in a cohort of breast cancer survivors. METHODS: Female breast cancer survivors (stage I-III) reporting cognitive impairments 2 months to 5 years after chemotherapy (n = 61) participated in a prospective, nonblinded, waitlist-controlled pilot study. The intervention was a tailored cognitive rehabilitation program. Data were collected pre-/post-intervention. Loneliness was measured using the UCLA Loneliness Scale. Perceived cognitive function was measured using two subscales of the FACT-Cog and two PROMIS - Applied Cognition short forms. Spearman correlation coefficients were calculated to determine the relationship between loneliness and perceived cognitive function (PCF). RESULTS: Participants' loneliness severity was correlated with diminished PCF across all cognitive measures (Spearman r= -0.63 FACT-Cog Perceived Cognitive Impairment, p < 0.0001; r= -0.6 FACT-Cog Perceived Cognitive Abilities, p < 0.0001; r= -0.49 PROMIS Cognitive Ability, p = 0.0002; r = 0.50 PROMIS General Concerns, p = 0.0002). Loneliness scores significantly decreased following participation in the cognitive rehabilitation program in intervention participants as compared to wait-list controls [-5.0 ± 7.24, 95% CI (-8.06, -1.94), p = 0.0025]. CONCLUSIONS: Perceived loneliness was significantly and consistently correlated with PCF. The intervention may have served a dual purpose in both addressing cognitive deficits and loneliness. Additional research dedicated to understanding the association between loneliness and cognitive function, as well as screening for and addressing loneliness in clinical oncology settings, may be warranted. IMPLICATIONS FOR REHABILITATIONScreening for and addressing loneliness in oncology rehabilitation settings is warranted.Rehabilitation professionals are well-positioned to screen for and address loneliness during clinic visits as part of routine cancer rehabilitation care.Group settings may be appropriate for addressing cancer-related cognitive impairment in rehabilitation, as these groups may serve the dual purpose of addressing cognitive impairment and loneliness simultaneously.

Palliative Rehabilitation in Acute Inpatient Rehabilitation: Prognostic Factors and Functional Outcomes in Patients with Cancer.

BACKGROUND: Prognosis has a vital role for patients with cancer undergoing palliative rehabilitation in acute inpatient rehabilitation. This study aimed to identify the proportion of patients who survived <2 months after discharge and the associated prognostic factors. MATERIALS AND METHODS: This was a secondary analysis of a retrospective study of 163 consecutive patients admitted to acute inpatient rehabilitation from September 1, 2017, to February 28, 2018 at a cancer center. Baseline demographics, clinical characteristics, and putative prognostic factors, including Activity Measure for Post-Acute Care (AM-PAC) functional scores, were analyzed. RESULTS: Of 163 patients, 27 (17%; 95% CI, 11-23) died within 60 days of discharge. These patients were more likely to be male (OR = 2.83; 95% CI, 1.16-6.92; P = .017); have longer hospital stays (OR = 1.02; 95% CI, 1-1.04; P = .015); receive ≥ weekly packed red blood cell (OR = 5.31; 95% CI, 1.86-15.1; P = .003) or platelet (OR = 4.57; 95% CI, 1.44-14.5; P = .014) transfusions; have lower AM-PAC daily activity scores upon discharge (OR = 0.90; 95% CI, 0.83-0.97; P = .006); and have lower AM-PAC basic mobility scores upon admission (OR = 0.91; 95% CI, 0.85-0.98; P = .018) and discharge (OR = 0.88; 95% CI, 0.82-0.94; P = <.001). Multivariate analysis showed that the male sex (OR = 2.71; 95% CI, 1.03-7.15; P = .037) was independently associated with ≤2 months survival, whereas AM-PAC basic mobility score at admission of >33 (OR = 0.24, 95% CI, 0.07-0.79; P = .022) was less likely. CONCLUSION: Approximately 1 in 6 patients who completed acute inpatient rehabilitation died within 2 months of discharge, had poorer baseline functional status, and were less likely to regain function than those who lived longer.

Acute health-related quality of life outcomes and systemic inflammatory markers following contemporary breast cancer surgery.

Contemporary breast cancer surgical procedures vary greatly by the amount of tissue removed, anesthesia time, and reconstruction. Despite historical literature comparing the health-related quality of life (HRQOL) after lumpectomy and mastectomy, HRQOL data are limited regarding contemporary surgical procedures. Further, biological processes (e.g., inflammation) associated with HRQOL outcomes have not been described. We conducted two studies to examine differences in post-operative physical and mental functioning, pain, fatigue, and systemic inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) in women with early-stage breast cancer. Study 1 assessed women before and after surgery (n = 27) and Study 2 used a large cross-sectional sample (n = 240) to confirm findings from Study 1 and included a no-surgery comparison group. In Study 1, women who received mastectomy had lower physical functioning than lumpectomy (ps < 0.05), and those who received bilateral mastectomy had worse pain (p < 0.01) and fatigue (p = 0.029) than lumpectomy. Results were replicated in Study 2: mastectomy groups exhibited poorer physical functioning (ps < 0.01) and greater pain (ps < 0.001) than lumpectomy, and bilateral mastectomy was associated with worse fatigue (p < 0.05). Women who received bilateral mastectomy had higher levels of CRP than lumpectomy (p < 0.01) and higher TNF-α than the no-surgery group (p < 0.05). All surgery groups exhibited higher IL-6 than no-surgery (ps < 0.05). More extensive surgery is associated with poorer postoperative HRQOL. As compared to lumpectomy and no-surgery, mastectomy is associated with higher concentrations of systemic inflammatory markers.

Acute and Chronic Effects of Adjuvant Therapy on Inflammatory Markers in Breast Cancer Patients.

BACKGROUND: Inflammation contributes to poor behavioral, functional, and clinical outcomes in cancer survivors. We examined whether standard cancer treatments-radiation and chemotherapy-led to acute and persistent changes in circulating markers of inflammation in breast cancer patients. METHODS: A total of 192 women diagnosed with early stage breast cancer provided blood samples before and after completion of radiation and/or chemotherapy and at 6-, 12-, and 18-month posttreatment follow-ups. Samples were assayed for circulating inflammatory markers, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, downstream markers of their activity (soluble TNF receptor type II [sTNF-RII], C reactive protein), and other inflammatory mediators (IL-8, interferon-γ [IFN-γ]). Analyses evaluated within-group changes in inflammatory markers in 4 treatment groups: no radiation or chemotherapy (n = 39), radiation only (n = 77), chemotherapy only (n = 18), and chemotherapy with radiation (n = 58). RESULTS: Patients treated with chemotherapy showed statistically significant increases in circulating concentrations of TNF-α, sTNF-RII, IL-6, and IFN-γ from pre- to posttreatment, with parameter estimates in standard deviation units ranging from 0.55 to 1.20. Those who received chemotherapy with radiation also showed statistically significant increases in IL-8 over this period. Statistically significant increases in TNF-α, sTNF-RII, IL-6, IFN-γ, and IL-8 persisted at 6, 12, and 18 months posttreatment among patients treated with chemotherapy and radiation (all P < .05). Patients treated with radiation only showed a statistically significant increase in IL-8 at 18 months posttreatment; no increases in any markers were observed in patients treated with surgery only. CONCLUSIONS: Chemotherapy is associated with acute increases in systemic inflammation that persist for months after treatment completion in patients who also receive radiation therapy. These increases may contribute to common behavioral symptoms and other comorbidities in cancer survivors.

Feasibility Pilot Study of a Virtual Intervention for Survivors With Decreased Perceived Cognitive Function After Cancer Treatment.

OBJECTIVES: Many cancer survivors report issues with cognitive function following diagnosis and treatment. The purpose of this single-arm pilot study was to test the feasibility and acceptability of virtual delivery of a cognitive rehabilitation intervention for participants in virtual groups. SAMPLE & SETTING: 37 adult cancer survivors reporting impaired cognitive function following primary treatment were enrolled from Cedars-Sinai Medical Center and affiliates, the University of Kansas Cancer Center, and the Masonic Cancer Alliance. METHODS & VARIABLES: Two cohorts attended six weekly virtual sessions and completed pre- and postintervention patient-reported outcome questionnaires designed to measure perceived cognitive function, loneliness, and determinants of behavior change for exercise, sleep, and mindfulness. RESULTS: Postintervention scores for perceived cognitive function, determinants of behavior change, and loneliness ratings significantly improved. IMPLICATIONS FOR NURSING: Evidence continues to build in support of cognitive rehabilitation interventions for cancer survivors. Nurses play an important role in terms of patient identification, participation, and facilitation.

A Targeted Approach to Post-Mastectomy Pain and Persistent Pain following Breast Cancer Treatment.

Persistent pain following treatment for breast cancer is common and often imprecisely labeled as post-mastectomy pain syndrome (PMPS). PMPS is a disorder with multiple potential underlying causes including intercostobrachial nerve injury, intercostal neuromas, phantom breast pain, and pectoralis minor syndrome. Adding further complexity to the issue are various musculoskeletal pain syndromes including cervical radiculopathy, shoulder impingement syndrome, frozen shoulder, and myofascial pain that may occur concurrently and at times overlap with PMPS. These overlapping pain syndromes may be difficult to separate from one another, but precise diagnosis is essential, as treatment for each pain generator may be distinct. The purpose of this review is to clearly outline different pain sources based on anatomic location that commonly occur following treatment for breast cancer, and to provide tailored and evidence-based recommendations for the evaluation and treatment of each disorder.

Cancer Telerehabilitation.

Telemedicine has clear benefits to the cancer population, including reducing the risk of contracting communicable disease, reaching remote populations, and added convenience. With adequate preparation, cancer rehabilitation telemedicine can serve as a suitable substitute for in-person encounters in several situations. There are limits with technologic deficits, reimbursement questions, and the inability to conduct hands-on physical examinations. It is important to appropriately triage patients to the most suitable visit type, whether telemedicine or in person, with aims of reducing unnecessary risks, monitoring for potential complications, and having productive encounters.