Advances in precision oncology and cancer therapies have improved survival for Canadians with advanced cancer, resulting in a growing population living long-term while receiving ongoing treatment. However, little is known about their supportive care needs or how they differ from those treated with curative intent, limiting the relevance of existing resources. As such, this study aimed to explore the lived experiences and challenges faced by Canadians receiving ongoing treatment for advanced cancer. A qualitative study was conducted involving semi-structured virtual interviews with 22 Canadians receiving ongoing treatment for advanced cancer. Interviews were audio-recorded, transcribed verbatim, and analysed thematically using descriptive techniques. Two overarching themes were identified. First, participants described challenges unique to living long-term with advanced cancer, including persistent treatment-related symptoms, uncertainty about the future, and disruptions to daily routines, responsibilities, and identity. Second, participants described barriers and facilitators influencing their ability to live well with advanced cancer, including capacity for self-management and self-advocacy, support from family and friends, financial considerations, and support from healthcare providers. Participants reported difficulty navigating available resources and limited guidance from providers and felt that existing supports and resources were insufficient to address the challenges they experienced. Individuals living with advanced cancer face physical, emotional, practical, and adjustment-related challenges that are distinct from those with earlier stage cancers. Existing supports are rarely effective at addressing these challenges, leaving patients to grapple with unmet needs. Future research should include the development and adaptation of supports that are accessible and tailored to this population.

Purpose: Prostate cancer survivors frequently lack access to comprehensive survivorship care, particularly in rural settings. We evaluated whether a digitally delivered, multicomponent survivorship program demonstrated equitable implementation and comparable longitudinal psychosocial outcomes across rural and urban contexts in an international Phase 4 implementation trial. Materials and Methods: This ongoing Phase 4, single-arm, prospective international implementation study evaluated the Prostate Cancer Patient Empowerment Program (PC-PEP), a 6-month, home-based digital intervention. Participants with prostate cancer completed assessments at baseline and 6, 12, and 24 months. Rural vs urban participants were compared on demographics, follow-up, and evaluation metrics. Exploratory longitudinal generalized estimating equation (GEE) models assessed change in psychological distress (K10) and health-related quality of life (SF-12 Mental Component Summary [MCS]), adjusting for covariates, and tested for differential trajectories by rurality. Results: Among 689 participants (urban n = 483; rural n = 206), follow-up completion was similar between groups at 6 months (82.1% vs 77.5%), 12 months (66.5% vs 68.5%), and 24 months (59.9% vs 56.6%). Baseline psychosocial, functional, and symptom outcomes were comparable. Program acceptability was high with ≥ 92% of participants recommending PC-PEP and endorsing that it should be standard care. Rural participants rated pelvic floor muscle training and dietary guidance more favorably. Psychological distress decreased and SF-12 MCS improved over time, with no difference by rurality. Conclusions: PC-PEP demonstrated equitable reach, follow-up, and perceived usefulness across rural and urban settings, alongside sustained improvements in mental health outcomes. These findings support scalable, equity-oriented digital survivorship care for men with prostate cancer.

Androgen deprivation therapy (ADT) is regularly used to treat locally advanced and metastatic prostate cancer (PCa) with toxicities, including metabolic syndrome (MS) and associated adverse hormonal changes. This study evaluated whether metformin mitigates changes in laboratory biomarkers associated with MS and type II diabetes mellitus (T2DM) in PCa patients receiving ADT. PRIME is a phase III double-blind, randomized controlled trial in which 166 normoglycemic patients with PCa receiving ADT were randomized to receive metformin or placebo. For this study, 47 patients from the metformin arm and 32 patients from the placebo arm underwent serum collection and analysis of the following analytes at baseline, 9, and 12 months: IGF-1, IGFBP1, IGFBP2, IGFBP3, IGFBP7, leptin, adiponectin, GDF15, insulin, C-peptide, GIP, GLP-1, and IL-6. Independent t-tests were used to determine whether significant changes in analytes were evident in patients receiving metformin vs placebo and to evaluate analyte changes from baseline for the metformin and placebo groups separately. Mean leptin values increased markedly in the placebo group and significantly less in the metformin group across all time points. Significant improvements were also observed in IGFBP1, IL-6, C-peptide, and GLP-1 with metformin compared with placebo. GDF15 and IGFBP3 significantly increased compared with baseline with ADT alone. This study demonstrates that metformin can mitigate biomarker changes induced by ADT associated with an increased risk of T2DM and MS. In addition, the attenuated increase in leptin signals a potential for improved PCa outcomes, as high leptin values have been correlated with aggressive disease and worse prognosis.

Study Objectives: Cancer-related fatigue is one of the most common symptoms in cancer survivors. Cognitive behavioral therapy for insomnia (CBT-I) can improve fatigue, but mechanisms are unclear. This secondary analysis of a randomized controlled trial evaluated whether CBT-I led to a significant improvement in fatigue, accounting for change in comorbid symptoms of insomnia, perceived cognitive impairment (PCI), anxiety, and depression. The parent study evaluated the impacts of CBT-I on PCI and insomnia. Methods: Cancer survivors with insomnia and PCI were randomized to CBT-I or sleep-self-monitoring waitlist control. Fatigue was measured using the Multidimensional Fatigue Symptom Inventory-Short Form at pre-, mid-, and post-treatment. Significant improvement in fatigue was defined as a reduction of >10.79 points. Insomnia, PCI, anxiety, and depression symptoms were assessed. A linear mixed model evaluated whether CBT-I improved fatigue after adjusting for comorbidities. Mediation analyses examined whether change in comorbidities accounted for the effect of CBT-I on fatigue. Results: The sample consisted of 132 cancer survivors (77% female, M-age = 60.12 years, 41% breast cancer). There was a significant group-by-time interaction on fatigue, p < .001, with the CBT-I group experiencing a 20.6-point reduction in fatigue compared to 3.7 points in the control. Improvements in fatigue were fully accounted for by improvements in the comorbidities with change in insomnia accounting for 45.3% of the effect observed in fatigue. Conclusions: CBT-I resulted in significant improvement in fatigue, and these effects were largely accounted for by changes in insomnia. CBT-I is a robust intervention with efficacy for improving fatigue among cancer survivors. Clinical Trial Information: Online Treatment of Cognitive Impairment and Insomnia in Cancer Survivors, https://clinicaltrials.gov/study/NCT04026048?term=NCT04026048&rank=1, ClinicalTrials.gov ID: NCT04026048

PurposeThis secondary analysis of a randomized clinical trial aimed to understand the cost-effectiveness of cognitive behavioral therapy for insomnia (CBT-I) in improving absenteeism (i.e., time away from work) and presenteeism (i.e., unproductivity while at work) among cancer survivors.MethodsA total of 55 currently employed mixed cancer survivors who met DSM-5 criteria for insomnia disorder and self-reported cognitive impairments were randomized to receive seven weekly, individual CBT-I sessions immediately or after a waiting period. Participants completed the Work Productivity and Activity Impairment Questionnaire (WPAI). Information from participants and the Labour Force Survey (LFS) were used to calculate costs. Education-adjusted mixed-effects models using intention-to-treat principles assessed immediate and longer-term effects of treatment on work productivity.ResultsWhile CBT-I was not associated with significant improvements in absenteeism, the treatment group reported a 23.5-point reduction in presenteeism post-treatment, compared to a 0.45-point decrease in the waitlist control group. Improvements in presenteeism were maintained at 6-month follow-up. The mean cost of total work productivity loss was CAD627.59 per person per week before beginning CBT-I. Treatment resulted in a 48.4%, 44.6%, and 30.5% reduction in lost productivity immediately, 3 and 6 months post-treatment, respectively. Total cost savings for the first year after treatment, adjusting for treatment costs, were estimated at CAD 9478.82.ConclusionsIntervening upon late and long-term effects of cancer treatment (e.g., sleep, fatigue, cognitive impairment) through CBT-I produces meaningful and durable improvements in work productivity, particularly presenteeism.Implications for Cancer SurvivorsWith appropriate treatment, survivors can address side effects and increase productivity, but additional work is needed to improve access to and coverage for evidence-based interventions.

Objectives Cognitive Behavioral Therapy for Insomnia (CBT-I) can effectively improve insomnia among cancer survivors. This secondary analysis explored what factors were associated with higher beliefs about credibility and expectancy and examined the impact of perceived treatment credibility and expectancy on outcomes. Methods As part of a randomized waitlist-controlled trial, cancer survivors (N = 132) with insomnia received 7 weekly virtual sessions of CBT-I. Credibility and expectancy beliefs were assessed at baseline for insomnia and perceived cognitive impairment (PCI) using the Credibility Expectancy Questionnaire. We examined which factors were associated with greater credibility and expectancy beliefs and whether credibility and expectancy moderated change in symptoms. Semi-structured interviews explored patient perceptions. Results Only younger age was associated with higher pre-treatment expectations for both insomnia and PCI (p = 0.009; p = 0.008). The magnitude of expectancy for insomnia and cognitive functioning were similar. Neither beliefs about credibility nor expectancy acted as moderators of change in symptoms of insomnia (p = 0.972; p = 0.502) or PCI (p = 0.143; p = 0.283), respectively. Qualitative results suggest credibility and expectancy can be optimized by: 1) promoting an understanding of sleep; 2) setting appropriate pre-treatment beliefs that foster optimism and mitigate skepticism; 3) promoting consistent engagement with treatment; and 4) fostering positive therapeutic relationships. Conclusion/implications CBT-I is effective regardless of pre-existing beliefs and expectations. While these factors may play a role in the decision to pursue CBT-I, our results suggest that clients are likely to see benefits if they engage in the therapy.

Cancer-related fatigue (CRF) can be a persistent and severe consequence of cancer treatment. Cognitive behavioral therapy for insomnia (CBT-I) can improve CRF in those with insomnia comorbid with cancer. This secondary analysis of a randomized controlled trial investigated what proportion of participants benefit and the factors associated with an improvement in CRF following CBT-I. Atlantic Canadian cancer survivors (N = 121) with insomnia disorder and perceived cognitive impairment symptoms were recruited to participate in a randomized controlled trial of CBT-I. Fatigue was measured using the Multidimensional Fatigue Symptom Inventory–Short Form. Univariable and multivariable binary logistic regressions were used to assess clinical, symptom, and demographic factors associated with a significant improvement in CRF after CBT-I. The majority (75

PURPOSE Comorbid insomnia and cancer-related cognitive impairment (CRCI) are experienced by up to 26% of individuals diagnosed with cancer. This study examined the efficacy and durability of cognitive behavioral therapy for insomnia (CBT-I) on perceived CRCI in cancer survivors. METHODS Atlantic Canadian cancer survivors with insomnia and CRCI were randomly assigned to receive seven weekly virtual CBT-I sessions (n = 63) or placed in a waitlist control group (n = 69) to receive treatment after the waiting period. Participants completed assessments at baseline, 1 month (mid-treatment), and 2 months (post-treatment). Age- and education-adjusted mixed-effects models using intention-to-treat principles assessed change at post-treatment. Data from both groups were then pooled to assess the durability of effects at 3 and 6 months. A mediation analysis examined whether change in insomnia symptoms mediated the effect of CBT-I on cognitive outcomes. RESULTS The mean age of the sample was 60 years, 77% were women, and breast cancer was the most common diagnosis (41%). The treatment group reported an 11.35-point reduction in insomnia severity, compared with a 2.67-point reduction in the waitlist control group ( P < .001). The treatment group had a greater overall improvement than the waitlist control on perceived cognitive impairment ( P < .001; d = 0.75), cognitive abilities ( P < .001; d = 0.92), and impact on quality of life ( P < .001; d = 1.01). These improvements were maintained at follow-up. Change in insomnia symptoms fully mediated the effect of CBT-I on subjective cognitive outcomes. CONCLUSION Treating insomnia with CBT-I produces clinically meaningful and durable improvements in CRCI. There is an urgent need increase access to evidence-based treatment for insomnia in cancer centers and the community.

Abstract Introduction Comorbid insomnia and perceived cognitive impairments (PCI) affect up to 26% of individuals diagnosed with cancer. Given the association between sleep and cognition, and the lack of interventions to improve PCI, the present study examined the impact of cognitive behavioral therapy for insomnia (CBT-I) on PCI among cancer survivors with insomnia disorder and cognitive complaints (clinicaltrials.gov:NCT04026048). Methods Cancer survivors (N=122) with insomnia and PCI were randomized to 7 weekly virtual CBT-I treatment sessions (n=56) or waitlist control (WLC: n=66). Participants completed the Insomnia Severity Index and the Functional Assessment of Cancer Therapy – Cognitive Function upon entering the study (baseline; T0), and then again at 4 (T1), and 8 (T2) weeks. A series of 2 (treatment group: CBT-I and WLC) by 3 (time: T0, T1, T2) mixed ANOVAs were performed to assess changes in insomnia symptoms, PCI, perceived cognitive abilities (PCA), and impact of cognitive function on quality of life (QOL). Results Participants were, on average, aged 60 years, had 16 years of education, and 79% were female. Breast cancer was the most reported cancer type (46%). No significant differences were observed between groups at T0 for demographic or clinical variables (p>.05). There was a significant group by time interaction for insomnia [p=<.001, partial eta squared (pes)=.36]. Individuals randomized to CBT-I reported significant decreases in insomnia symptoms post treatment compared to WLC (CBT-I: -11.5; WLC: -2.7). Significant interactions were also observed for PCI (p=<.001, pes=.11), PCA (p=<.001, pes=.16), and impact on QOL (p=<.001, pes=.15). Participants randomized to CBT-I reported significantly less PCI (CBT-I: 14.7; WLC: 4.1), better PCA (CBT-I: 5.8; WLC: 1.1), and less impact on QOL (CBT-I: 4.9; WLC: 1.1) than participants in the WLC. Conclusion In addition to improving insomnia, CBT-I significantly improve perceived cognitive functioning and quality of life among cancer survivors. Further research is needed to understand the mechanisms underlying improvements in cognition following CBT-I. Support (if any) Dr. Sheila Garland is supported by a Canadian Cancer Society Emerging Scholar Award (Survivorship) (grant #707146). This project was funded through a grant from the Canadian Institutes of Health Research (CIHR) (grant number: PJT 162428) and the Beatrice Hunter Cancer Research Institute.

PDF file - 41K, Univariate Kaplan-Meir plot of biochemical relapse-free rate of survival versus time to recurrence for patients who underwent IGRT with differential Prostate Stem Cell Antigen (PSCA) status is displayed. PSCA appears to be a significant prognosticator (Kaplan-Meier estimate bRFR 79% vs. 49%, p=0.0024).

Penile cancer is a rare genitourinary malignancy for which limited treatment options exist beyond primary surgical resection. Metastatic lymphadenopathy represents a particularly poor prognosis with a lack of literature to suggest the effectiveness of radiation or systemic therapies. Our case documents an inguinal recurrence of penile squamous cell carcinoma not amenable to surgical intervention demonstrating complete response to salvage radiotherapy in the palliative setting. These observations propose the need for further research around the utility of radiotherapy in the management of metastatic penile malignancies.

Supplementary Table 1 from β1-Integrin Circumvents the Antiproliferative Effects of Trastuzumab in Human Epidermal Growth Factor Receptor-2–Positive Breast Cancer

Supplementary Figure Legends 1-2, Tables 1-6 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

PDF file - 41K, Percentage genome alteration (PGA) levels are displayed for patient biopsies categorized as per their NKX3.1/T-category status (a), NKX3.1/PSA status (b), NKX3.1/Gleason-score status (c), NKX3.1/c-MYC/T-category status (d) and NKX3.1/c-MYC/PSA status (e). The median PGA for each group is represented by the black line. (GS=Gleason-score, *=significantly different). Patients with NKX3.1 allelic loss have a significant increase in PGA as compared to patients with a normal status of NKX3.1 in T-category groups pT1=0.00045 and pT2<0.0001 (a). Patients with NKX3.1 allelic loss have a significant increase in PGA as compared to patients with a normal status of NKX3.1 in PSA p<=10<0.0001 and p>10=0.0012 (b). Patients with NKX3.1 allelic loss have a significant increase in PGA as compared to patients with a normal status of NKX3.1 in Gleason-scores pGS6=0.0015 and pGS7<0.0001 (c). Patients with NKX3.1 allelic loss and c-MYC allelic gain have a significant increase in PGA as compared to patients with a normal status of NKX3.1 and c-MYC in T-category groups pT1=0.00029 and pT2<0.0001 (d). Patients with NKX3.1 allelic loss and c-MYC allelic gain have a significant increase in PGA as compared to patients with a normal status of NKX3.1 and c-MYC in PSA p<=10<0.0001 and p>10=0.001 (e).

Objectives This paper (1) sought to compare sleep, mood and physical symptom profiles of men with prostate cancer (PCa) who experienced subjective and objective cancer-related cognitive impairment (CRCI) during the first year of treatment and (2) examine if fluctuations in mood and physical symptoms are associated with change in subjective or objective CRCI. Methods This prospective observational cohort study examined 24 new patients with PCa receiving androgen deprivation therapy (ADT) and radiation therapy (RT) during the first 12 months of treatment. Participants completed subjective and objective assessments of cognition, sleep continuity and self-report measures of insomnia, fatigue, depression and anxiety. Independent sample t-tests, correlations and hierarchical regressions were used to compare groups, explore associations, and assess change over time. Effects are reported as corrected Cohen’s d (d c ). Results Men with objective CRCI reported worse subjective time asleep (d c =0.47) and more depression (d c =0.55). Men with subjective CRCI reported worse insomnia (d c =0.99), hot flashes (d c =0.76), sleep quality (d c =0.54), subjective total sleep time (d c =0.41), wake after sleep onset (d c =0.71), sleep efficiency (d c =0.49), fatigue (d c =0.67) and objectively estimated sleep latency (d c =0.72) than men without subjective CRCI. Declines in perceived cognition was associated with higher anxiety (p=0.05), fatigue (p≤0.01) and symptoms of insomnia (p=0.01). Finally, subjective time awake during the night (p=0.03) and fatigue (p=0.02) were associated with subjective cognitive decline, controlling for objective change. Conclusions Subjective concerns of CRCI appear more critical to patient experience than objective measurements in men with PCa who have received RT and ADT. Interventions to improve sleep may result in an improved perception of cognition.

Perceived cognitive impairment (PCI) and sleep disturbances (such as insomnia) are commonly reported barriers preventing cancer survivors from resuming normal functioning. Cognitive-behaviour therapy for insomnia (CBTI) is the treatment of choice for insomnia among cancer survivors. Literature suggests that treatment with CBT-I may lead to an improvement in PCI, but this needs to be tested in a sample of patients with PCI at study entry with cognitive impairments as the primary study outcome. Here we describe the design of a clinical trial to evaluate the efficacy of videoconference-delivered CBT-I for the improvement of PCI among cancer survivors. This project is a randomized waitlist-controlled trial with a recruitment target of 124 adult cancer survivors (solid tumors and hematological malignancies) who have completed primary treatment at least 6 months prior, report PCI and meet criteria for insomnia disorder. Participants will complete assessments at baseline, 4 weeks (mid-treatment), 8 weeks (post treatment), and 3 and 6 months post-treatment. The primary outcome is the Functional Assessment of Cancer Therapy ? Cognitive Function (FACT-Cog). Treatment of PCI in cancer patients is a priority for clinicians, researchers, and patients. This research will increase our understanding of the mechanisms of cognitive impairment associated with cancer, and potentially expand currently available treatment options.

Background Androgen deprivation therapy (ADT) may affect cognitive function in men with prostate cancer (PCa). This study examined whether insomnia symptoms mediate the relationship between ADT and perceived cognitive function and whether depressive symptoms, fatigue severity, and physical activity moderate the strength of this relationship. Methods This was a prospective study of ADT recipients (n = 83) who were matched with control patients with PCa who were not on ADT (n = 92) and with controls with no history of cancer (n = 112) over a 2-year follow-up period. Perceived cognitive function and satisfaction were assessed with the Everyday Cognition Scale. Insomnia was assessed with the Insomnia Severity Index. Multilevel mediation analyses were conducted to estimate the indirect effect of ADT on perceived cognitive function through insomnia symptoms. Exploratory moderated mediation analyses assessed whether the indirect effect of ADT on perceived cognitive function through insomnia symptoms was dependent on levels of fatigue, depression, or physical activity. Results Insomnia symptoms significantly mediated the relationship between receipt of ADT and perceived cognitive function (P < .001) and satisfaction with cognition (P < .001) after controlling for comorbidities. Men with greater fatigue had a more pronounced association of ADT with insomnia severity. Men with greater depressive symptoms had a stronger association between insomnia severity and worse perceived cognitive function. Physical activity was not a significant moderator of the relationship between ADT and perceived cognitive function. Conclusions Insomnia influenced the relationship between ADT and perceived cognitive abilities. Interventions to address insomnia, fatigue, and depression may improve perceived cognitive function.

INTRODUCTION:Studies that use objective assessments often only recruit individuals in the geographic region in which the study is being conducted, because the assessments require that the researcher and participant be face to face. This limits the number and variety of individuals who can participate. Telehealth is one approach that could be used to increase sample size and representativeness. The present analysis aims to evaluate the experience of individuals diagnosed with breast or prostate cancer, who participated by telehealth in studies investigating the effects of cancer treatment on sleep and cognition. Specifically, this study aimed to highlight potential benefits of using telehealth and identify ways to improve the process for future studies and assessments.METHODS:Telephone interviews were conducted with 20 individuals with cancer who participated via telehealth in a larger study investigating the effects of cancer treatment on sleep and cognition; 12 individuals had breast cancer and 8 individuals had prostate cancer. Participants were organized into the four regional health authorities of Newfoundland and Labrador: Eastern, Western, Central, and Grenfell-Labrador. Participants of varying ages and communities were purposively selected. Participants were interviewed about their experience participating in the study via telehealth and invited to offer suggestions for how to improve the process. Interview transcripts were coded using a thematic analysis approach. Demographic information was used to characterize the sample.RESULTS:Including telehealth as an option in the overall study allowed for a 55% sample size increase for participants with breast cancer, and a 45% sample size increase for participants with prostate cancer. Participants reported an overall positive experience (70% reported the experience as good and/or great), with telehealth allowing for greater convenience, more personable interactions, increased access, and an otherwise unavailable opportunity to help others and themselves. Identified areas for improvement were sound quality, and better access for those who still face barriers of commuting to telehealth locations. Inter-rater reliability yielded a 92% agreement.CONCLUSIONS:For studies and assessments requiring face-to-face contact, telehealth is clearly a feasible option for improving research representativeness and access for individuals residing in rural areas. Future research should make use of telehealth services, to give a voice to rural individuals who are too often left out.