CaRE@ELLICSR: Effects of a clinically integrated, group-based, multidimensional cancer rehabilitation program.

BACKGROUND: Although oncology clinical practice guidelines recognize the need and benefits of exercise, the implementation of these services into cancer care delivery remains limited. We developed and evaluated the impact of a clinically integrated 8-week exercise and education program (CaRE@ELLICSR). METHODS: We conducted a mixed methods, prospective cohort study to examine the effects of the program. Each week, participants attended a 1-h exercise class, followed by a 1.5-h education session. Questionnaires, 6-min walk tests (6MWT), and grip strength were completed at baseline (T0), 8 weeks (T1), and 20 weeks (T2). Semi-structured interviews were conducted with a sub-sample of participants about their experience with the program. RESULTS: Between September 2017 and February 2020, 277 patients enrolled in the program and 210 consented to participate in the research study. The mean age of participants was 55 years. Participants were mostly female (78%), white/Caucasian (55%) and half had breast cancer (50%). Participants experienced statistical and clinically meaninful improvements from T0 to T1 in disability, 6MWT, grip strength, physical activity, and several cancer-related symptoms. These outcomes were maintained 3 months after program completion (T2). Qualitative interviews supported these findings and three themes emerged from the interviews: (1) empowerment and control, (2) supervision and internal program support, and (3) external program support. CONCLUSIONS: This study demonstrates the impact of overcoming common organizational barriers to deliver exercise and rehabilitation as part of routine care. CaRE@ELLICSR demonstrated clinically meaningful improvements in patient-reported and functional outcomes and was considered beneficial and important by participants for their recovery and wellbeing.

A Feasibility Randomized Controlled Trial of Prehabilitation During Neoadjuvant Chemotherapy for Women with Breast Cancer: A Mixed Methods Study.

BACKGROUND: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed. PATIENTS AND METHODS: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation. RESULTS: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience. CONCLUSIONS: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted.

Neural alpha oscillations index context-driven perception of ambiguous vowel sequences.

Perception of bistable stimuli is influenced by prior context. In some cases, the interpretation matches with how the preceding stimulus was perceived; in others, it tends to be the opposite of the previous stimulus percept. We measured high-density electroencephalography (EEG) while participants were presented with a sequence of vowels that varied in formant transition, promoting the perception of one or two auditory streams followed by an ambiguous bistable sequence. For the bistable sequence, participants were more likely to report hearing the opposite percept of the one heard immediately before. This auditory contrast effect coincided with changes in alpha power localized in the left angular gyrus and left sensorimotor and right sensorimotor/supramarginal areas. The latter correlated with participants' perception. These results suggest that the contrast effect for a bistable sequence of vowels may be related to neural adaptation in posterior auditory areas, which influences participants' perceptual construal level of ambiguous stimuli.

A longitudinal multidimensional rehabilitation program for patients undergoing allogeneic blood and marrow transplantation (CaRE-4-alloBMT): Protocol for a phase II feasibility pilot randomized controlled trial.

BACKGROUND: Allogeneic blood and marrow transplantation (alloBMT) is a curative treatment for blood cancers associated with various treatment-related adverse events and morbidities. Current rehabilitation programs are limited for patients undergoing alloBMT and research is urgently needed to test the acceptability and effectiveness of these programs. In response, we developed a 6-month multidimensional longitudinal rehabilitation program that spans from pre transplant to 3 months post transplant discharge (CaRE-4-alloBMT). METHODS: This study is a phase II randomized controlled trial (RCT) conducted at the Princess Margaret Cancer Centre in patients undergoing alloBMT. A total of 80 patients stratified by frailty score will be randomized to receive usual care (n = 40) or CaRE-4-alloBMT plus usual care (n = 40). The CaRE-4-alloBMT program includes individualized exercise prescriptions, access to online education through a dedicated self-management platform, wearable technology for remote monitoring, and remote tailored clinical support. Feasibility will be assessed by examining the recruitment and retention rates and adherence to the intervention. Safety events will be monitored. Acceptability of the intervention will be assessed through qualitative interviews. Secondary clinical outcomes will be collected through questionnaires and physiological assessments at baseline (T0, 2-6 weeks pre-transplant), transplant hospital admission (T1), hospital discharge (T2), and 3 months post-discharge (T3). CONCLUSION: This pilot RCT study will determine the feasibility and acceptability of the intervention and study design and will inform full-scale RCT planning.

Fear of cancer recurrence therapy (FORT): A randomized controlled trial.

OBJECTIVE: Most fear of cancer recurrence (FCR) interventions have small effects, and few target FCR. This randomized controlled trial (RCT) with breast and gynecological cancer survivors evaluated the efficacy of a cognitive-existential fear of recurrence therapy (FORT) compared to an attention placebo control group (living well with cancer [LWWC]) on FCR. METHOD: One hundred and sixty-four women with clinical levels of FCR and cancer distress were randomly assigned to 6-weekly, 120 min FORT (n = 80) or LWWC (n = 84) group sessions. They completed questionnaires at baseline (T1), posttreatment (T2; primary endpoint), 3 (T3), and 6 months (T4) posttreatment. Generalized linear models were used to compare group differences in the fear of cancer recurrence inventory (FCRI) total score and secondary outcomes. RESULTS: FORT participants experienced greater reductions from T1 to T2 on FCRI total with a between-group difference of -9.48 points (p = .0393), resulting in a medium effect of -0.530, with a maintained effect at T3 (p = .0330) but not at T4. For the secondary outcomes, improvements were in favor of FORT, including FCRI triggers (p = .0208), FCRI coping (p = .0351), cognitive avoidance (p = .0155), need for reassurance from physicians (p = .0117), and quality of life (mental health; p = .0147). CONCLUSIONS: This RCT demonstrated that FORT, compared to an attention placebo control group, resulted in a greater reduction in FCR posttreatment and at 3 months posttreatment in women with breast and gynecological cancer, indicating its potential as a new treatment strategy. We recommend a booster session to sustain gains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in patients with newly diagnosed glioblastoma.

Background: In addition to poor survival rates, individuals with glioblastoma (GBM) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients; and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance. Methods: This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4 weeks; ie, baseline) and 3, 6, 12, and 18 months later, or until tumor progression. Here, we present baseline data. Forty-five GBM patients (mean age = 55 years) completed objective neurocognitive tests, and self-report measures of neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms. Results: Compared to normative samples, GBM patients scored significantly lower on all neurocognitive tests, with 34 (76%) patients exhibiting neurocognitive impairment. Specifically, 53% exhibited impairment in memory retention, 51% in executive function, 42% in immediate recall, 41% in verbal fluency, and 24% in attention. There were high rates of clinically elevated sleep disturbance (70%), fatigue (57%), depressive symptoms (16%), and neurobehavioral symptoms (27%). A multivariate regression analysis revealed that depressive symptoms are significantly associated with neurocognitive impairment. Conclusions: GBM patients are vulnerable to adverse outcomes including neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms shortly after diagnosis, prior to completing chemoradiation. Those with increased depressive symptoms are more likely to demonstrate neurocognitive impairment, highlighting the need for early identification and treatment of depression in this population.

Neurocognitive Performance in Adults Treated With Radiation for a Primary Brain Tumor.

Purpose: The contributory effects of radiation dose to different brain regions on neurocognitive performance after radiation therapy (RT) for primary brain tumors is not well known. Methods and Materials: In this retrospective cohort study, 30 patients with brain tumors treated with photon RT were identified, and radiation dosimetric parameters across brain regions were calculated. All patients had longitudinal neurocognitive evaluations at baseline and after treatment. Generalized estimating equations were used to model each neurocognitive endpoint over time in a multivariable analysis, while adjusted for multiple comparisons of brain regions. Results: Median follow-up from RT to last assessment was 4.1 years. Fewer years of formal education and older age at the time of RT were associated with lower scores in language, verbal memory, and working memory, after adjustment for baseline scores in multivariable analyses. Higher radiation dose to specific brain regions was not associated with declines in any of the evaluated cognitive domains. On average, there was no clinically significant decline (magnitude of z score change >1) between first and last neurocognitive evaluation. Across each individual cognitive domain, fewer than 15% of patients were impaired at most recent follow-up. Conclusions: In this small study of 30 patients treated with RT for a primary brain tumor, brain region dosimetry was not associated with decline in cognitive performance. Older age at time of RT and fewer years of formal education were associated with declines in cognitive performance, suggesting that effects of nondosimetric factors on cognitive performance should be considered alongside treatment factors and dosimetry in neuro-oncology research.

Neural correlates of concurrent sound perception: A review and guidelines for future research.

The perception of concurrent sound sources depends on processes (i.e., auditory scene analysis) that fuse and segregate acoustic features according to harmonic relations, temporal coherence, and binaural cues (encompass dichotic pitch, location difference, simulated echo). The object-related negativity (ORN) and P400 are electrophysiological indices of concurrent sound perception. Here, we review the different paradigms used to study concurrent sound perception and the brain responses obtained from these paradigms. Recommendations regarding the design and recording parameters of the ORN and P400 are made, and their clinical applications in assessing central auditory processing ability in different populations are discussed.

Brain Fog in Hypothyroidism: What Is It, How Is It Measured, and What Can Be Done About It.

Background: Some levothyroxine (LT4)-treated hypothyroid patients report a constellation of persistent and distressing cognitive symptoms that has been termed brain fog. This narrative review focuses on attempts to define and measure hypothyroid-associated brain fog, summarize possible etiologies and contributing factors, present treatment options, and propose avenues for future research. Methods: Published literature was reviewed to summarize available information on patient-reported symptoms associated with brain fog in hypothyroidism, as well as objective evidence of impairment based on neurocognitive testing and functional imaging studies. Given the limited information specific for hypothyroid-associated brain fog, relevant data from other medical conditions associated with brain fog were also reviewed and incorporated into recommendations for clinical care and future research areas. Results: Hypothyroid-associated brain fog has not been well defined or quantitated, and the underlying pathophysiology is unclear. Symptoms vary among patients but commonly include fatigue, depressed mood, and cognitive difficulties in the areas of memory and executive function. Symptoms often predate the diagnosis of hypothyroidism, and the magnitude of cognitive impairment can range from mild to severe. Regardless of severity, these symptoms are associated with impaired quality of life and cause dissatisfaction with treatment, so often lead to requests for alternate therapies. Disease-specific and psychological factors impact the experience of brain fog in complex ways, including potential limitations in LT4 monotherapy, self-knowledge of a disease state, and expectations for therapeutic effects. Conclusions: Brain fog is a variable symptom complex in people with hypothyroidism, causing significant distress and diminished quality of life. In the absence of proven therapies, individualized treatment plans are recommended, which incorporate thyroid-specific, general medical, and psychosocial approaches. In particular, cognitive rehabilitation is an underutilized technique that is beneficial in other medical conditions associated with brain fog and could improve symptoms in hypothyroid people. The limitations in our current knowledge and questions presented throughout this review highlight a major need for clinical research in this understudied area. Future research should include attention to standardization of survey instruments to quantitate brain fog in hypothyroid people, as well as rigorously designed intervention studies.

The Development and Evaluation of a Patient Educational Resource for Cancer-Related Cognitive Dysfunction.

Cancer patients and survivors frequently experience cognitive deficits, including problems with attention and memory. These symptoms, referred to as cancer-related cognitive dysfunction (CRCD), are associated with distress. Learning about CRCD and self-management strategies may improve functioning and quality of life in cancer survivors. This study describes the development and evaluation of a CRCD resource for cancer patients. An educational booklet was developed in accordance with multiple evidence-based guidelines for cancer patient education. Cancer patients on chemotherapy (N = 113; 34% men; median age 55, range 19-85) reviewed the booklet and self-reported CRCD knowledge before and after reading the booklet. They also gave ratings on general impressions of the booklet. Seventy-five percent of participants reported that the resource increased their self-reported CRCD knowledge. A Wilcoxon signed-rank test demonstrated that exposure to the booklet elicited a statistically significant change in self-reported knowledge (Z = - 7.13, p < 0.001). A repeated-measures ANCOVA determined that the means of self-reported CRCD knowledge were significantly different between pre- and post-exposure (F(1, 92) = 7.96, p = 0.006, η2 = 0.08). Exploratory analyses revealed that self-reported CRCD knowledge increased across all educational attainment levels from pre- to post-exposure. Ninety-one percent of participants reported that all patients undergoing cancer treatment would find this booklet helpful. Cancer patients at risk for cognitive challenges gained self-reported CRCD knowledge from the booklet, and they think this knowledge would be helpful to others. A resource that makes CRCD understandable and manageable can bridge the gap in self-rated knowledge across education levels.

Evaluation of Usability and Satisfaction of Two Online Tools to Guide Return to Work for Cancer Survivors on the Cancer and Work Website.

Prompt services and work-focused support systems are needed to aid cancer survivors returning to work or finding work. Purpose This knowledge translation and implementation project focused on the knowledge users' experience and need for refinement of three work-focused tools to support return to work and maintain work following cancer through their participation in a hands-on workshop. The tools assessed for their utility are a Job Analysis Tool (JAT), a Return to Work (RTW) tool, and a bilingual Canadian website on Cancer and Work. Methods Four workshops took place in three Canadian cities. Participants included cancer survivors, healthcare professionals, and employer representatives. Following an overview of the website and tools, workshop participants (N = 28) completed qualitative and quantitative satisfaction and usability questionnaires using the System Usability Scale and open-ended questions. Qualitative data was analyzed using content analyses from the think-aloud data and from the four open-ended questions collected during the users' use of the tools and website. Results Overall, most study participants reported high satisfaction with the JAT and RTW tools, the Cancer and work website and the workshop. Good usability scores were reported for the RTW planner (73.65 ± 12.61) and the website (74.83 ± 12.36), and only acceptable usability scores for the JAT (68.53 ± 11.90). Conclusion Overall, the study documented the value of the tools and the website to support the RTW process as assessed by several key knowledge user groups. The JAT is considered a helpful procedure to identify job demands in order to guide job accommodations. Given participants' responses that the tool is useful, the next steps are to implement the recommendations for improvement and knowledge dissemination to increase its uptake and the use of job analysis overall.

Chemo-brain: An activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

Adults with non-central nervous system (CNS) cancers frequently report problems in attention, memory and executive function during or after chemotherapy, referred to as cancer-related cognitive dysfunction (CRCD). Despite numerous studies investigating CRCD, there is no consensus regarding the brain areas implicated. We sought to determine if there are brain areas that consistently show either hyper- or hypo-activation in people treated with chemotherapy for non-CNS cancer (Chemo+). Using activation likelihood estimation on brain coordinates from 14 fMRI studies yielding 25 contrasts from 375 Chemo+ and 429 chemotherapy-naive controls while they performed cognitive tasks, the meta-analysis yielded two significant clusters which are part of the frontoparietal attention network, both showing lower activation in Chemo+. One cluster peaked in the left superior parietal cortex, extending into precuneus, inferior parietal lobule, and angular gyrus. The other peaked in the right superior prefrontal areas, extending into inferior prefrontal cortex. We propose that these observed lower activations reflect a dysfunction in mobilizing and/or sustaining attention due to depletion of cognitive resources. This could explain higher level of mental fatigue reported by Chemo+ and why cancer survivors report problems in a wide variety of cognitive domains.

CaRE @ Home: Pilot Study of an Online Multidimensional Cancer Rehabilitation and Exercise Program for Cancer Survivors.

BACKGROUND: Although facility-based cancer rehabilitation and exercise programs exist, patients are often unable to attend due to distance, cost, and other competing obligations. There is a need for scalable remote interventions that can reach and serve a larger population. METHODS: We conducted a mixed methods pilot study to assess the feasibility, acceptability and impact of CaRE@Home: an 8-week online multidimensional cancer rehabilitation and exercise program. Feasibility and acceptability data were captured by attendance and adherence metrics and through qualitative interviews. Preliminary estimates of the effects of CaRE@Home on patient-reported and physically measured outcomes were calculated. RESULTS: A total of n = 35 participated in the study. Recruitment (64%), retention (83%), and adherence (80%) rates, along with qualitative findings, support the feasibility of the CaRE@Home intervention. Acceptability was also high, and participants provided useful feedback for program improvements. Disability (WHODAS 2.0) scores significantly decreased from baseline (T1) to immediately post-intervention (T2) and three months post-intervention (T3) (p = 0.03 and p = 0.008). Physical activity (GSLTPAQ) levels significantly increased for both Total LSI (p = 0.007 and p = 0.0002) and moderate to strenuous LSI (p = 0.003 and p = 0.002) from baseline to T2 and T3. Work productivity (iPCQ) increased from T1 to T3 (p = 0.026). There was a significant increase in six minute walk distance from baseline to T2 and T3 (p < 0.001 and p = 0.010) and in grip strength from baseline to T2 and T3 (p = 0.003 and p < 0.001). CONCLUSIONS: Results indicate that the CaRE@Home program is a feasible and acceptable cancer rehabilitation program that may help cancer survivors regain functional ability and decrease disability. In order to confirm these findings, a controlled trial is required.

Sexual satisfaction in nasopharyngeal carcinoma survivors: Rates and determinants.

OBJECTIVES: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC). MATERIALS AND METHODS: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction. RESULTS: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant. CONCLUSIONS: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required.

The Prevalence and Determinants of Return to Work in Nasopharyngeal Carcinoma Survivors.

PURPOSE: To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW). METHODS AND MATERIALS: This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status. RESULTS: Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW. CONCLUSIONS: The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.

Cognitive functioning in thyroid cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Some thyroid cancer (TC) survivors experience cognitive symptoms. PURPOSE: The purpose of this study is to perform a systematic literature review and meta-analysis comparing cognitive performance in TC survivors to controls. METHODS: We performed a seven-database electronic search and hand-search. We performed duplicate independent reviews and data abstraction. Random effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), where a negative value implies worse performance in the TC group. RESULTS: We reviewed 1174 unique citations and 10 full-text papers. We included seven studies of 241 treated TC survivors and 273 controls. Cognitive function was statistically significantly worse in TC survivors in the following domains: Attention and Concentration (Digit Span Forwards) SMD - 0.37 (95% CI - 0.62, - 0.13, p = 0.003, four studies), Speed of Processing (Trail Making A) SMD - 0.36 (95% CI - 0.66, - 0.05, p = 0.022, four studies), and Language (Controlled Oral Word Association [COWAT]-Categories) SMD - 0.97 (95% - 1.31, - 0.64, p < 0.001, two studies). Executive Function results varied: COWAT-Letters SMD - 0.60 (95% CI - 0.94, - 0.27, p < 0.001, two studies), Digit Span Backwards SMD - 0.40 (95% CI - 0.64, - 0.15, p = 0.002, four studies), and Trail Making B test SMD - 0.20 (95% CI - 0.51, 0.10, p = 0.191, four studies). Statistical heterogeneity limited the COWAT-Categories and Digit Span Backwards meta-analyses. CONCLUSIONS: Cognitive function was worse in TC survivors in multiple domains. Limitations included few studies, potential confounding, and lack of prospective data. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors may experience impairments in cognitive function and should report cognitive concerns to healthcare practitioners.

Cognitive rehabilitation for executive dysfunction in brain tumor patients: a pilot randomized controlled trial.

PURPOSE: Patients with brain tumors face unique quality of life challenges. Executive dysfunction is common and functionally limiting, with no established treatments as standard care. This pilot study evaluated the efficacy of Goal Management Training (GMT), a behavioral intervention combining mindfulness and strategy training, for improving executive and real-life functioning in this population. METHODS: Twenty-five primary brain tumor survivors were randomized to GMT, an active control (Brain Health Program, BHP), or a wait-list (WAIT) control group. The BHP was a supportive care intervention offering education and activities to promote general brain health, without cognitive strategy training. Participants in GMT and BHP completed eight individual sessions and homework between sessions; those in WAIT received usual care. Assessments at baseline, immediately post-training, and 4-month follow-up used a battery of objective and subjective measures, including functional goal attainment. RESULTS: Adherence (% sessions completed) was high for both GMT (98.9%) and BHP (84.4%). Executive functions improved with GMT but not BHP or WAIT (repeated measures analysis of variance, time-by-group interaction, post-training P = 0.077, follow-up P = 0.046). Both intervention groups reported fewer cognitive concerns at post-training (P = 0.049) and follow-up (P < 0.001). Functional goal attainment was greatest with GMT (post-training P = 0.027, follow-up P = 0.064). CONCLUSIONS: GMT improved executive and real-life functioning in brain tumor survivors, with gains maintained at 4-month follow-up. Clinical implementation of this adaptable program merits consideration for clinically stable patients with cognitive dysfunction. Further development and larger prospective cognitive rehabilitation trials appear warranted.

A cross sectional study in cognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors treated with intensity-modulated radiotherapy.

PURPOSE/OBJECTIVES: To determine neurocognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS/METHODS: A cross-sectional cohort of NPC ≥4 years (y) following IMRT was assessed. Objective cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and patient-reported memory was assessed with the MDASI-HN problems remembering item. Patient and family ratings of patients' neurobehavioral symptoms of apathy, disinhibition and executive dysfunction were assessed with the Frontal Systems Behavior Scale (FrSBe). Other patient-reported symptoms (MDASI-HN), mood (HADS), and quality of life (FACT-H&N) were also collected. RESULTS: Among 102 participants: M:F = 66:36; median age 56y (32-77); median time since IMRT 7.5y (4.2-11.1). Impaired MoCA scores (<23) were observed in 33 (32%). Patient and family ratings of pre-illness neurobehavioral symptoms were in the normal range (total FrSBe T-scores 53.3 and 59.0 respectively). In contrast, post-treatment patient and family T-scores were clinically impaired (64.7, 71.3 respectively), with apathy, disinhibition and executive dysfunction post-treatment ratings all significantly worse than pre-treatment (p < 0.001). Prevalence of clinically significant post-treatment disturbance was high by patient and family ratings (48%/66% apathy, 35%/53% disinhibition, 39%/56% executive dysfunction). Post-treatment neurobehavioral symptoms strongly correlated with lower quality of life (r = -0.62) and higher anxiety (r = 0.62) and depression scores (r = 0.67, all p < 0.001). Total MoCA scores did not correlate with RT dose. However, greater declines in apathy, disinhibition and executive dysfunction were associated with receiving >75 Gy to temporal lobes. CONCLUSION: NPC treated with IMRT had moderate to high rates of neurocognitive impairment and clinically significant apathy, disinhibition, and executive dysfunction.

Long-Term Late Toxicity, Quality of Life, and Emotional Distress in Patients With Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: To report long-term (>4 years) toxicity and quality of life (QoL) among patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) in a nonendemic center. METHODS AND MATERIALS: A cross-sectional cohort study enrolled patients with NPC who were disease-free and ≥4 years after IMRT ± chemotherapy. Physician-reported adverse events (Common Terminology Criteria for Adverse Events, version 4.03) and patient-reported QoL (Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue), utilities (EuroQOL-5D), head and neck symptoms (MD Anderson Symptom Inventory-Head and Neck), and emotional distress (Hospital Anxiety and Depression Scale) were collected. Consenting patients also underwent endocrine screening and audiometry. RESULTS: Among 107 patients enrolled, median age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2-11.1), respectively. Most patients (99%) received 70 Gy in 35 fractions; the majority (93%) received concurrent chemotherapy. Mean scores for the Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue, and EuroQOL-5D were 105.0 (46-148), 116.6 (44-160), and 0.85 (0.29-1.00), respectively. Dry mouth, mucus, swallowing/chewing, memory, and teeth/gum problems were scored highest on the MD Anderson Symptom Inventory-Head and Neck; mean symptom severity and symptom interference scores were 2.3 and 2.4, respectively. Grade 3 or higher physician-reported adverse events were noted in 50 patients (47%), most frequently hearing problems (46, 43%). Audiometry revealed significant bilateral hearing loss (grade ≥3) in 68 patients (72%). Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly correlated with QoL. Most patients (69%) developed hypothyroidism; 1 patient (1%) developed pituitary dysfunction requiring hormone replacement. V50 >90 and V45 >99 to the thyroid correlated with significantly higher rates of hypothyroidism. CONCLUSIONS: Despite the implementation of IMRT, survivors of NPC still experience many physical symptoms that affect long-term QoL many years after treatment. Depression, anxiety, and fatigue remain common in long-term survivors and are highly correlated with QoL.

Towards the validation of a new, blended theoretical model of fear of cancer recurrence.

OBJECTIVE: Fear of cancer recurrence (FCR) is defined as "fear, worry, or concern about cancer returning or progressing". To date, only the seminal model proposed by Lee-Jones and colleagues has been partially validated, so additional model testing is critical to inform intervention efforts. The purpose of this study is to examine the validity of a blended model of FCR that integrates Leventhal's Common Sense Model, Mishel's Uncertainty in Illness Theory, and cognitive theories of worry. METHODS: Participants (n = 106) were women diagnosed with stage I to III breast or gynecological cancer who were enrolled in a Randomized Controlled Trial of a group cognitive-existential intervention for FCR. We report data from standardized questionnaires (Fear of Cancer Recurrence Inventory-Severity and Triggers subscales; Illness Uncertainty Scale; perceived risk of recurrence; Intolerance of Uncertainty Scale; Why do people Worry about Health questionnaire; Reassurance-seeking Behaviors subscale of the Health Anxiety Questionnaire, and the Reassurance Questionnaire) that participants completed before randomization. Path analyses were used to test the model. RESULTS: Following the addition of four paths, the model showed an excellent fit (χ2 = 13.39, P = 0.20; comparative fit index = 0.99; root mean square error of approximation = 0.06). Triggers, perceived risk of recurrence, and illness uncertainty predicted FCR. FCR was associated with maladaptive coping. Positive beliefs about worrying and intolerance of uncertainty did not predict FCR but led to more maladaptive coping. CONCLUSIONS: These results provide support for a blended FCR model.