A Positive Psychology Intervention in Allogeneic Hematopoietic Stem Cell Transplantation Survivors (PATH): A Pilot Randomized Clinical Trial.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience significant psychological distress and low levels of positive psychological well-being, which can undermine patient-reported outcomes (PROs), such as quality of life (QoL). Hence, we conducted a pilot randomized clinical trial to assess the feasibility and preliminary efficacy of a telephone-delivered positive psychology intervention (Positive Affect for the Transplantation of Hematopoietic stem cells intervention [PATH]) for improving well-being in HSCT survivors. METHODS: HSCT survivors who were 100 days post-HSCT for hematologic malignancy at an academic institution were randomly assigned to either PATH or usual care. PATH, delivered by a behavioral health expert, entailed 9 weekly phone sessions on gratitude, personal strengths, and meaning. We defined feasibility a priori as >60% of eligible participants enrolling in the study and >75% of PATH participants completing ≥6 of 9 sessions. At baseline and 9 and 18 weeks, patients self-reported gratitude, positive affect, life satisfaction, optimism, anxiety, depression, posttraumatic stress disorder (PTSD), QoL, physical function, and fatigue. We used repeated measures regression models and estimates of effect size (Cohen's d) to explore the preliminary effects of PATH on outcomes. RESULTS: We enrolled 68.6% (72/105) of eligible patients (mean age, 57 years; 50% female). Of those randomized to PATH, 91% completed all sessions and reported positive psychology exercises as easy to complete and subjectively useful. Compared with usual care, PATH participants reported greater improvements in gratitude (ß = 1.38; d = 0.32), anxiety (ß = -1.43; d = -0.40), and physical function (ß = 2.15; d = 0.23) at 9 weeks and gratitude (ß = 0.97; d = 0.22), positive affect (ß = 2.02; d = 0.27), life satisfaction (ß = 1.82; d = 0.24), optimism (ß = 2.70; d = 0.49), anxiety (ß = -1.62; d = -0.46), depression (ß = -1.04; d = -0.33), PTSD (ß = -2.50; d = -0.29), QoL (ß = 7.70; d = 0.41), physical function (ß = 5.21; d = 0.56), and fatigue (ß = -2.54; d = -0.33) at 18 weeks. CONCLUSIONS: PATH is feasible, with promising signals for improving psychological well-being, QoL, physical function, and fatigue in HSCT survivors. Future multisite trials that investigate PATH's efficacy are needed to establish its effects on PROs in this population.

Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update.

PURPOSE: To update the ASCO guideline on the management of cancer-related fatigue (CRF) in adult survivors of cancer. METHODS: A multidisciplinary panel of medical oncology, geriatric oncology, internal medicine, psychology, psychiatry, exercise oncology, integrative medicine, behavioral oncology, nursing, and advocacy experts was convened. Guideline development involved a systematic literature review of randomized controlled trials (RCTs) published in 2013-2023. RESULTS: The evidence base consisted of 113 RCTs. Exercise, cognitive behavioral therapy (CBT), and mindfulness-based programs led to improvements in CRF both during and after the completion of cancer treatment. Tai chi, qigong, and American ginseng showed benefits during treatment, whereas yoga, acupressure, and moxibustion helped to manage CRF after completion of treatment. Use of other dietary supplements did not improve CRF during or after cancer treatment. In patients at the end of life, CBT and corticosteroids showed benefits. Certainty and quality of evidence were low to moderate for CRF management interventions. RECOMMENDATIONS: Clinicians should recommend exercise, CBT, mindfulness-based programs, and tai chi or qigong to reduce the severity of fatigue during cancer treatment. Psychoeducation and American ginseng may be recommended in adults undergoing cancer treatment. For survivors after completion of treatment, clinicians should recommend exercise, CBT, and mindfulness-based programs; in particular, CBT and mindfulness-based programs have shown efficacy for managing moderate to severe fatigue after treatment. Yoga, acupressure, and moxibustion may also be recommended. Patients at the end of life may be offered CBT and corticosteroids. Clinicians should not recommend L-carnitine, antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of CRF. There is insufficient evidence to make recommendations for or against other psychosocial, integrative, or pharmacological interventions for the management of fatigue.Additional information is available at www.asco.org/survivorship-guidelines.

Patient reported outcomes and patient experiences of immune checkpoint modulators for advanced or recurrent melanoma: a mixed methods study.

PURPOSE: Little is known about late and long-term patient-reported outcomes (PROs) of immune checkpoint modulators (ICMs) outside clinical trials. We conducted a cross-sectional, mixed-methods study to describe long-term PROs among advanced melanoma patients who began standard of care treatment with ICMs at least 1 year previously. METHODS: All participants completed the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM), assessing 46 immune-related side effects on a 5-point Likert scale, and a subset completed individual interviews. Descriptive statistics were computed for quantitative data and applied thematic analysis was used to examine qualitative data. RESULTS: Participants (N = 80) had a mean age of 67 years, and the majority were male (66%), non-Hispanic White (96%), and college graduates (61%). Single-agent nivolumab was the most common first (47%) and current/recent ICM (64%). On the FACT-ICM, 98% of participants reported at least one side effect, and 78% reported moderate or severe side effects. The most common moderate or severe side effects were aching joints (43%) and fatigue (38%). In interviews (n = 20), we identified five themes regarding patients' longer-term experiences after ICMs: lasting fatigue or decline in functioning, minimal side effects, manageable thyroid and pituitary dysfunction, skin conditions can be difficult to manage, and treating the cancer is worth the side effects. CONCLUSIONS: Nearly all patients reported side effects of ICMs at least 1 year after starting treatment. Our findings suggest that ICM side effect screening and management-especially for aching joints and fatigue-are indicated during long-term care of people living with advanced melanoma.

Alzheimer's disease-related biomarkers and cancer-related cognitive decline: the thinking and living with cancer study.

PURPOSE: We evaluated whether plasma Alzheimer's Disease (AD)-related biomarkers were associated with cancer-related cognitive decline (CRCD) among older breast cancer survivors. METHODS: We included survivors 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched non-cancer controls (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (pre-systemic therapy) and annually for up to 60-months. Cognition was measured using tests of attention, processing speed and executive function (APE) and learning and memory (LM); perceived cognition was measured by the FACT-Cog PCI. Baseline plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), beta-amyloid 42/40 (Aß42/40) and phosphorylated tau (p-tau181) were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD-biomarkers, time, group (survivor vs control) and their two- and three-way interactions, controlling for age, race, WRAT4 Word Reading score, comorbidity and BMI; two-sided 0.05 p-values were considered statistically significant. RESULTS: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline NfL levels than controls (p = .013). Survivors had lower adjusted longitudinal APE than controls starting from baseline and continuing over time (p = <0.002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except controls had lower APE scores with higher GFAP levels (p = .008). CONCLUSION: The results do not support a relationship between baseline AD-related biomarkers and CRCD. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers and examine other mechanisms and factors affecting cognition pre-systemic therapy.

Need for Behavioral Interventions for Young Adults Living with Advanced Cancer in the U.S.

The population of young adults (YAs) aged 18-39 living with advanced cancer is growing and faces a compounded set of challenges at the intersection of age and disease. Despite these substantial challenges, behavioral interventions tailored to YAs living with advanced cancer remain scarce. This commentary aims to (1) discuss the unmet psychological, social, and behavioral needs of YAs living with advanced cancer; (2) highlight the paucity of behavioral interventions tailored to this growing population; (3) offer recommendations for the development of behavioral interventions targeting the unique needs of YAs living with advanced cancer; and (4) describe potential far-reaching public health benefits of these targeted behavioral interventions.

Novel Virtual Reality App for Training Patients on MRI-guided Radiation Therapy.

Purpose: Patients receiving respiratory gated magnetic resonance imaging-guided radiation therapy (MRIgRT) for abdominal targets must hold their breath for ≥25 seconds at a time. Virtual reality (VR) has shown promise for improving patient education and experience for diagnostic MRI scan acquisition. We aimed to develop and pilot-test the first VR app to educate, train, and reduce anxiety and discomfort in patients preparing to receive MRIgRT. Methods and Materials: A multidisciplinary team iteratively developed a new VR app with patient input. The app begins with minigames to help orient patients to using the VR device and to train patients on breath-holding. Next, app users are introduced to the MRI linear accelerator vault and practice breath-holding during MRIgRT. In this quality improvement project, clinic personnel and MRIgRT-eligible patients with pancreatic cancer tested the VR app for feasibility, acceptability, and potential efficacy for training patients on using breath-holding during MRIgRT. Results: The new VR app experience was tested by 19 patients and 67 clinic personnel. The experience was completed on average in 18.6 minutes (SD = 5.4) by patients and in 14.9 (SD = 3.5) minutes by clinic personnel. Patients reported the app was "extremely helpful" (58%) or "very helpful" (32%) for learning breath-holding used in MRIgRT and "extremely helpful" (28%) or "very helpful (50%) for reducing anxiety. Patients and clinic personnel also provided qualitative feedback on improving future versions of the VR app. Conclusion: The VR app was feasible and acceptable for training patients on breath-holding for MRIgRT. Patients eligible for MRIgRT for pancreatic cancer and clinic personnel reported on future improvements to the app to enhance its usability and efficacy.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.

Barriers to endocrine therapy adherence: perspectives of Black breast cancer survivors and their providers.

PURPOSE: Adherence to oral endocrine therapy (ET) remains an issue for up to half of women prescribed these medications. There is emerging data that Black breast cancer survivors (BCS) have lower rates of ET adherence. Given the disparities in breast cancer recurrence and survival for Black BCS compared to their White counterparts, the goal of this study is to better understand barriers to ET adherence among Black BCS from the patient and provider perspectives. METHODS: In this qualitative study, we conducted semi-structured interviews between October 29, 2021, and March 1, 2023. Interviews were recorded and transcribed, and coded data were organized into primary and secondary themes. Participants were recruited from a single academic cancer center. A convenience sample of 24 Black BCS and 9 medical oncology providers was included. Eligible BCS were 18 years or older, English-speaking, diagnosed with stage I-III hormone receptor-positive breast cancer, who had initiated ET. RESULTS: Mean age of the BCS was 55 years (interquartile range, IQR 17 years). About one-fourth had a high school diploma or less (26.1%) and 47% completed a college education or higher. Approximately one-third of participants had annual household incomes of $40,000 or less (30.4%) or more than $100,000 (30.4%). Forty-three percent of the patient participants had private insurance; 11% were insured through Medicaid or the federal healthcare exchange; 26.1% had Medicare; and 13% were uninsured. Of the 9 medical oncology providers interviewed, 2 were advanced practice providers, and 7 were medical oncologists. We found 3 major themes: (1) Black BCS often had concerns about ET before initiation; (2) after initiation, both BCS and providers reported side effects as the most impactful barrier to ET adherence; and (3) survivors experienced challenges with managing ET side effects. CONCLUSIONS: Our results suggest that multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black women and may reduce disparities in outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black breast cancer survivors.

Psychosocial consequences of head and neck cancer symptom burden after chemoradiation: a mixed-method study.

PURPOSE: Patients with head and neck cancer (HNC) experience significant symptom burden from combination chemotherapy and radiation (chemoradiation) that affects acute and long-term health-related quality of life (HRQOL). However, psychosocial impacts of HNC symptom burden are not well understood. This study examined psychosocial consequences of treatment-related symptom burden from the perspectives of survivors of HNC and HNC healthcare providers. METHODS: This was a cross-sectional, mixed-method study conducted at an NCI-designated comprehensive cancer center. Participants (N = 33) were survivors of HNC who completed a full course of chemoradiation (n = 20) and HNC healthcare providers (n = 13). Participants completed electronic surveys and semi-structured interviews. RESULTS: Survivors were M = 61 years old (SD = 9) and predominantly male (75%), White (90%), non-Hispanic (100%), and diagnosed with oropharynx cancer (70%). Providers were mostly female (62%), White (46%) or Asian (31%), and non-Hispanic (85%) and included physicians, registered nurses, an advanced practice nurse practitioner, a registered dietician, and a speech-language pathologist. Three qualitative themes emerged: (1) shock, shame, and self-consciousness, (2) diminished relationship satisfaction, and (3) lack of confidence at work. A subset of survivors (20%) reported clinically low social wellbeing, and more than one-third of survivors (35%) reported clinically significant fatigue, depression, anxiety, and cognitive dysfunction. CONCLUSION: Survivors of HNC and HNC providers described how treatment-related symptom burden impacts psychosocial identity processes related to body image, patient-caregiver relationships, and professional work. Results can inform the development of supportive interventions to assist survivors and caregivers with navigating the psychosocial challenges of HNC treatment and survivorship.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Feasibility and acceptability of C-PRIME: A health promotion intervention for family caregivers of patients with colorectal cancer.

PURPOSE: This study aimed to test the feasibility and acceptability of a digital health promotion intervention for family caregivers of patients with advanced colorectal cancer and explore the intervention's preliminary efficacy for mitigating the impact of caregiving on health and well-being. METHODS: We conducted a single-arm pilot feasibility trial of C-PRIME (Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life), an 8-week digital health-promotion behavioral intervention involving monitoring and visualizing health-promoting behaviors (e.g., objective sleep and physical activity data) and health coaching (NCT05379933). A priori benchmarks were established for feasibility (≥ 50% recruitment and objective data collection; ≥ 75% session engagement, measure completion, and retention) and patient satisfaction (> 3 on a 1-5 scale). Preliminary efficacy was explored with pre- to post-intervention changes in quality of life (QOL), sleep quality, social engagement, and self-efficacy. RESULTS: Participants (N = 13) were M = 52 years old (SD = 14). Rates of recruitment (72%), session attendance (87%), assessment completion (87%), objective data collection (80%), and retention (100%) all indicated feasibility. All participants rated the intervention as acceptable (M = 4.7; SD = 0.8). Most participants showed improvement or maintenance of QOL (15% and 62%), sleep quality (23% and 62%), social engagement (23% and 69%), and general self-efficacy (23% and 62%). CONCLUSION: The C-PRIME digital health promotion intervention demonstrated feasibility and acceptability among family caregivers of patients with advanced colorectal cancer. A fully powered randomized controlled trial is needed to test C-PRIME efficacy, mechanisms, and implementation outcomes, barriers, and facilitators in a divserse sample of family caregivers. TRIAL REGISTRATION: The Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life (C-PRIME) study was registered on clinicaltrials.gov, NCT05379933, in May 2022.

Acute cancer-related symptoms and concerns among patients receiving chemotherapy: current state of the science.

PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.

"I couldn't connect the wires in my brain." Young adult cancer survivors' experience with cognitive functioning.

OBJECTIVE: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors. METHODS: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.e., affected cognitive abilities, risk and protective factors influencing the impact of CRCI, and strategies for coping with CRCI). RESULTS: YA cancer survivors (N = 20) were, on average, 23 years old at diagnosis and 26 years old when interviewed. Diverse cancer types and treatments were represented; most participants (85%) had completed cancer treatment. Participants described experiences across three qualitative topics: (1) affected cognitive abilities (i.e., concentration and attention, prospective memory, and long-term memory), (2) Risk factors (i.e., fatigue, sleep problems, mood, stress/distractions, and social isolation) and protective factors (i.e., social support), and (3) coping strategies, including practical strategies that helped build self-efficacy (e.g., writing things down, reducing distractions), beneficial emotion-focused coping strategies (e.g., focus on health, faith/religion), strategies with mixed effects (i.e., apps/games, medications/supplements, and yoga), and "powering through" strategies that exacerbated stress. CONCLUSIONS: YA cancer survivors experience enduring cognitive difficulties after treatment. Specific concerns highlight the importance of attention and executive functioning impairments, long-term memory recall, and sensitivity to distractions. Future work is needed to improve assessment and treatment of CRCI among YA cancer survivors.

Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies. This timely minireview provides researchers and clinicians with an overview of challenges and opportunities for improving disaster preparedness and response for cancer survivors.

15 years of patient-reported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis.

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9-25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6-15), RCC (11.86, range: 6-15), UC (11.50, range: 9-14), and PC (10.56, range: 6-15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

The efficacy and safety of ketamine for depression in patients with cancer: A systematic review.

Background: Management of depression in the oncology population includes supportive psychotherapeutic interventions with or without psychotropic medication, which take time to demonstrate effectiveness. Fast-acting interventions, like ketamine, can provide a rapid antidepressant effect; however, there has been limited research on effects of ketamine among cancer patients. The objective of this review is to provide an overview of research on the efficacy and safety of ketamine on depression in patients with cancer. Methods: We reviewed the published literature in MEDLINE® (via PubMed®), EMBASE, and Scopus from 1 January 1982 to 20 October 2022. We screened the retrieved abstracts against inclusion criteria and conducted a full-text review of eligible studies. Following extraction of data from included studies, we used a framework analysis approach to summarize the evidence on using ketamine in patients with cancer. Results: All 5 included studies were randomized clinical trials conducted in inpatient settings in China. In all included studies ketamine was administered intravenously. Three studies used only racemic ketamine, and two studies used both S-ketamine and racemic ketamine. All included studies reported ketamine a tolerable and effective drug to control depression symptoms. Conclusion: Included studies showed administration of sub-anesthesia ketamine significantly improves postoperative depression among patients with cancer.

Relationships Among Physical Activity, Sleep, and Cancer-related Fatigue: Results From the International ColoCare Study.

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.

Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

PURPOSE: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. METHODS: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. RESULTS: Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms. CONCLUSIONS: Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

Patient-Reported Outcomes among Multiple Myeloma Patients Treated with Standard of Care Idecabtagene Vicleucel.

Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality of life (HRQOL) and symptoms from pre-infusion (baseline) through day (D)90 post-infusion. Baseline PRO associations with patient characteristics, mean PRO changes, and time to stable change were evaluated with t-tests, linear mixed-effects models, and Kaplan-Meier analyses, respectively. Within-person change scores and minimally important difference thresholds determined clinical and meaningful significance. Participants (n = 42) were a median of 66 years old (range: 43-81). At baseline, extramedullary disease was associated with worse physical well-being (p = 0.008), global pain (p < 0.001), performance status (p = 0.002), and overall symptom burden (p < 0.001). Fatigue (p < 0.001) and functional well-being (p = 0.003) worsened by D7 before returning to baseline levels. Overall HRQOL (p = 0.008) and physical well-being (p < 0.001) improved by D60. Most participants reported PRO improvement (10-57%) or maintenance (23-69%) by D90. The median time it took to stabile deterioration in functional well-being was 14 days. The median time it took to stabile improvement in physical and emotional well-being was 60 days. Overall, RRMM patients reported improvements or maintenance of HRQOL and symptom burden after SOC ide-cel.

Associations of Germline Genetic Variants With Depression and Fatigue Among Hematologic Cancer Patients Treated With Allogeneic Hematopoietic Cell Transplantation.

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT). METHODS: Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05. RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ). CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.