Jamie M. Jacobs

Mobile Application to Promote Adherence to Oral Chemotherapy and Symptom Management: A Protocol for Design and Development

Background Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer. While oral chemotherapy includes benefits such as ease of administration, convenience, and minimization of invasive infusions, patients receive less oversight, support, and symptom monitoring from clinicians. Additionally, adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens. With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology, we created a mobile health intervention for medication and symptom management. Objective The objective of this study was to develop and evaluate the usability and acceptability of a smartphone app to support adherence to oral chemotherapy and symptom management in patients with cancer. Methods We used a 5-step development model to create a comprehensive mobile app with theoretically informed content. The research and technical development team worked together to develop and iteratively test the app. In addition to the research team, key stakeholders including patients and family members, oncology clinicians, health care representatives, and practice administrators contributed to the content refinement of the intervention. Patient and family members also participated in alpha and beta testing of the final prototype to assess usability and acceptability before we began the randomized controlled trial. Results We incorporated app components based on the stakeholder feedback we received in focus groups and alpha and beta testing. App components included medication reminders, self-reporting of medication adherence and symptoms, an education library including nutritional information, Fitbit integration, social networking resources, and individually tailored symptom management feedback. We are conducting a randomized controlled trial to determine the effectiveness of the app in improving adherence to oral chemotherapy, quality of life, and burden of symptoms and side effects. At every stage in this trial, we are engaging stakeholders to solicit feedback on our progress and next steps. Conclusions To our knowledge, we are the first to describe the development of an app designed for people taking oral chemotherapy. The app addresses many concerns with oral chemotherapy, such as medication adherence and symptom management. Soliciting feedback from stakeholders with broad perspectives and expertise ensured that the app was acceptable and potentially beneficial for patients, caregivers, and clinicians. In our development process, we instantiated 7 of the 8 best practices proposed in a recent review of mobile health app development. Our process demonstrated the importance of effective communication between research groups and technical teams, as well as meticulous planning of technical specifications before development begins. Future efforts should consider incorporating other proven strategies in software, such as gamification, to bolster the impact of mobile health apps. Forthcoming results from our randomized controlled trial will provide key data on the effectiveness of this app in improving medication adherence and symptom management. Trial Registration ClinicalTrials.gov NCT02157519; https://clinicaltrials.gov/ct2/show/NCT02157519 (Archived by WebCite at http://www.webcitation.org/6prj3xfKA)

Stress management, leukocyte transcriptional changes and breast cancer recurrence in a randomized trial: An exploratory analysis

PURPOSE Cognitive behavioral stress management (CBSM) is an empirically-validated group-based psychosocial intervention. CBSM is related to decreased self-reported indicators of psychological adversity during breast cancer treatment and greater disease-free survival (DFS) vs. a control condition. This study examined relationships between CBSM, DFS, and a potential biobehavioral pathway linking these variables in breast cancer patients through a gene expression composite representing the leukocyte conserved transcriptional response to adversity (CTRA). DESIGN Women with stage 0-IIIb breast cancer completed questionnaires and provided blood samples post-surgery. Participants were randomized to 10-week group-based CBSM or a psychoeducation control group and followed at 6 months, 12 months, and median 11 years. In total, 51 participants provided blood data for longitudinal analyses (CBSM n=28; Control n=23). Mixed model analyses examined CBSM effects on 6-12 month changes in CTRA expression (53 indicator genes representing pro-inflammatory, anti-viral and antibody production signaling). Cox regression models assessed the relationship between 6 and 12 month changes in CTRA expression and 11-year DFS. RESULTS Patients randomized to CBSM showed attenuated 6-12 month change in CTRA gene expression, whereas patients randomized to control showed increased CTRA expression (p=0.014). Average DFS was 5.92 years (SD=3.90). Greater 6-12 month CTRA increases predicted shorter 11-year DFS controlling for covariates (p=0.007). CONCLUSIONS CBSM attenuated CTRA gene expression during the initial year of breast cancer treatment. In turn, greater increases in CTRA gene expression predicted shorter long-term DFS. These findings identify a biobehavioral oncology pathway to examine in future work.

Mindfulness and Coping Are Inversely Related to Psychiatric Symptoms in Patients and Informal Caregivers in the Neuroscience ICU: Implications for Clinical Care.

Objective:To assess the correlation of psychosocial resiliency factors (mindfulness and coping) with symptoms of posttraumatic stress, anxiety, and depression in patients recently admitted to the neuroscience ICU and their primary informal caregivers. Design:A descriptive, cross-sectional correlational study. Setting:Neuroscience ICU in a major medical center. Participants:A total of 78 dyads of patients (total n = 81) and their primary caregivers (total n = 92) from June to December 2015. Study enrollment occurred within the first 2 weeks of patient admission to the neuroscience ICU. Intervention:None. Measurements and Main Results:Dyads completed self-report measures of mindfulness (Cognitive and Affective Mindfulness Scale-Revised), coping (Measure of Coping Status-A), posttraumatic stress (Posttraumatic Checklist–Specific Stressor), anxiety (Hospital Anxiety and Depression Scale-A), and depression (Hospital Anxiety and Depression Scale-D). Rates of clinically significant posttraumatic stress, anxiety, and depressive symptoms were high and comparable between patient and caregiver samples. Own psychological resilience factors and psychiatric symptoms were strongly correlated for both patients and caregivers. Depressive symptoms were interdependent between patients and their caregivers, and one’s own mindfulness was independently related to one’s partner’s depressive symptoms. Conclusions:Rates of clinically significant psychiatric symptoms were high, equally prevalent in patients and caregivers, and interdependent between patients and their caregivers. For both patients and caregivers, psychological resiliency factors were associated with both self and partner psychiatric symptoms. Findings suggest that attending to the psychiatric health of both patients and caregivers in the neuroscience ICU is a priority and that patients and their caregivers must be considered together in a system to fully address either individual’s psychiatric symptoms.

Treatment Satisfaction and Adherence to Oral Chemotherapy in Patients With Cancer

PURPOSE Although patients with cancer overwhelming prefer oral to intravenous chemotherapy, little is known about adherence to oral agents. We aimed to identify the rates and correlates of adherence in patients with diverse malignancies. MATERIALS AND METHODS Ninety patients with chronic myeloid leukemia or metastatic renal cell carcinoma, non-small-cell lung cancer, or breast cancer enrolled in this prospective, single-group, observational study of medication-taking behaviors. Adherence was measured via self-report and with an electronic pill cap (Medication Event Monitoring System cap). Patients completed surveys regarding symptom distress, mood, quality of life, cancer-specific distress, and satisfaction with clinician communication and treatment at baseline and 12-week follow-up. RESULTS As measured by the Medication Event Monitoring System, patients took, on average, 89.3% of their prescribed oral chemotherapy over the 12 weeks. One quarter of the sample was less than 90% adherent, and women were more adherent than men (mean difference, 9.59%; SE difference, 4.50%; 95% CI, -18.65 to -0.52; P = .039). Improvements in patient symptom distress (B = -0.79; 95% CI, -1.41 to -0.18), depressive symptoms (B = -1.57; 95% CI, -2.86 to -0.29), quality of life (B = 0.38; 95% CI ,0.07 to 0.68), satisfaction with clinician communication and treatment (B = 0.73; 95% CI, 0.49 to 0.98), and perceived burden to others (B = -1.28; 95% CI, -2.20 to -0.37) were associated with better adherence. In a multivariate model, improved treatment satisfaction (B = 0.71; 95% CI, 0.48 to 0.94) and reduced perceived burden (B = -0.92; 95% CI, -1.76 to -0.09) were the strongest indicators of better adherence. CONCLUSION Women and patients who reported increased treatment satisfaction and reduced burden to others were more adherent to oral chemotherapy. Interventions that help patients improve communication with clinicians and reduce burden may optimize oral chemotherapy adherence.

Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up

BACKGROUND Mild to moderate depressive symptoms are common during treatment for non-metastatic breast cancer. The goal of this secondary analysis was to determine if depressive symptoms predict clinical outcomes at long-term follow-up. METHODS From 1998 to 2005, we interviewed 231 women with the Hamilton Rating Scale for Depression who were participating in a psychosocial study 2-10weeks post-surgery for non-metastatic breast cancer (Stage 0-IIIb). We conducted Kaplan Meier (K-M) curves and Cox proportional hazards (PH) models to examine associations between depressive symptoms, overall survival, and disease-free survival at 8-15-year follow-up. RESULTS A total of 95 women (41.1%) scored in the mild-moderately depressed range. Non-depressed women had longer overall survival (M=13.56years; SE=0.26) than those in the mild/moderate depressed group (M=11.45years; SE=0.40), Log-rank χ2(1)=4.41, p=0.036. Cox PH models, adjusting for covariates, showed comparable results: mild/moderate depressive symptoms hazard ratio=2.56, [95% CI, 1.11 to 5.91], p=0.027. Similar results were observed in a subsample with invasive disease (n=191). Depression category did not predict disease-free survival in the overall or invasive sample. CONCLUSIONS Screening and referrals for treatment of depressive symptoms, even at subclinical levels, is important early in treatment. A randomized trial is warranted to determine effects of depressive symptoms on clinical outcomes.

Differential effects of early palliative care based on the age and sex of patients with advanced cancer from a randomized controlled trial

Background: Early palliative care interventions enhance patient outcomes, including quality of life, mood, and coping, but it remains unclear whether certain subgroups of patients are more likely to benefit from early palliative care. We explored whether age and sex moderate the improved outcomes seen with early palliative care. Methods: We performed a secondary analysis of data from a randomized trial of 350 patients with advanced lung and non-colorectal gastrointestinal cancer. Patients received an early palliative care intervention integrated with oncology care or usual oncology care alone. We used linear regression to determine if age (older or younger than 65) and sex moderated the effects of the intervention on quality of life (Functional Assessment of Cancer Therapy–General (FACT-G)), depression symptoms (Patient Health Questionnaire 9 (PHQ-9)), and coping (Brief COPE) within lung and gastrointestinal subgroups. Results: At 24 weeks, younger patients with lung cancer receiving early palliative care reported increased use of active coping (B = 1.74; p = 0.02) and decreased use of avoidant coping (B = –0.97; p = 0.02), but the effects of early palliative care on these outcomes were not significant for older patients. Male patients with lung cancer assigned to early palliative care reported better quality of life (FACT-G: B = 9.31; p = 0.01) and lower depression scores (PHQ-9: B = –2.82; p = 0.02), but the effects of early palliative care on these outcomes were not significant for female patients. At 24 weeks, we found no age or sex moderation effects within the gastrointestinal cancer subgroup. Conclusion: Age and sex moderate the effects of early palliative care for patients with advanced lung cancer. Early palliative care may need to be tailored to individuals’ unique sociodemographic and clinical characteristics.

How changes in physical activity relate to fatigue interference, mood, and quality of life during treatment for non-metastatic breast cancer

OBJECTIVE Physical activity (PA) following surgery for breast cancer may improve depressive symptoms and quality of life (QoL) via reduction in fatigue-related daily interference (FRDI). Less is known about how change in PA may relate to these psychosocial factors throughout the course of treatment. In a secondary analysis of a previous psychosocial intervention trial, we examined relationships between change in PA, depressive symptoms, and functional QoL, as mediated by change in FRDI, and whether naturally occurring change in PA provided benefit independent of the intervention. METHOD Women (N=240) with non-metastatic stage 0-III breast cancer were randomized to cognitive-behavioral stress management (CBSM) or a control 2-10weeks post-surgery. PA, FRDI, clinician-rated depressive symptoms, self-reported depressed mood, and functional QoL were assessed at baseline and three months post-intervention. RESULTS Increased PA was associated with reductions in clinician-rated depressive symptoms, depressed mood, and improved QoL, mediated by a reduction in FRDI. This was above and beyond the effect of CBSM. CONCLUSIONS Increased PA may mitigate FRDI and improve depressive symptoms and functional QoL for women undergoing breast cancer treatment, beyond effects of a psychosocial intervention. Benefits of an integrated PA and psychosocial approach should be investigated further.

Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia

BACKGROUND Patients with schizophrenia experience markedly increased breast cancer mortality, yet reasons for this disparity are poorly understood. We sought to characterize disruptions in breast cancer care for patients with schizophrenia and identify modifiable predictors of those disruptions. MATERIALS AND METHODS We performed a medical record review of 95 patients with schizophrenia and breast cancer treated at an academic cancer center between 1993 and 2015. We defined cancer care disruptions as processes that interfere with guideline-concordant cancer care, including delays to diagnosis or treatment, deviations from stage-appropriate treatment, and interruptions in treatment. We hypothesized that lack of psychiatric treatment at cancer diagnosis would be associated with care disruptions. RESULTS Half of patients with schizophrenia experienced at least one breast cancer care disruption. Deviations in stage-appropriate treatment were associated with breast cancer recurrence at 5 years (p = .045). Patients without a documented psychiatrist experienced more delays (p = .016), without documented antipsychotic medication experienced more deviations (p = .007), and with psychiatric hospitalizations after cancer diagnosis experienced more interruptions (p < .0001). Independent of stage, age, and documented primary care physician, lack of documented antipsychotic medication (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 1.90, 12.98) and psychiatric care (OR = 4.56, 95% CI = 1.37, 15.15) predicted cancer care disruptions. CONCLUSION Disruptions in breast cancer care are common for patients with schizophrenia and are associated with adverse outcomes, including cancer recurrence. Access to psychiatric treatment at cancer diagnosis may protect against critical disruptions in cancer care for this underserved population. IMPLICATIONS FOR PRACTICE Disruptions in breast cancer care are common for patients with schizophrenia, yet access to mental health treatment is rarely integrated into cancer care. When oncologists documented a treating psychiatrist and antipsychotic medication, patients had fewer disruptions in breast cancer care after adjusting for age, cancer stage, and access to primary care. Addressing psychiatric comorbidity at breast cancer diagnosis may increase the likelihood that patients with schizophrenia receive timely, stage-appropriate cancer treatment. Comanagement of schizophrenia and breast cancer at cancer diagnosis may be one key strategy to decrease inequities in cancer treatment and improve cancer survival in this underserved population.

Differential psychological effects of cognitive-behavioral stress management among breast cancer patients with high and low initial cancer-specific distress

OBJECTIVE Cognitive-behavioral stress management (CBSM) improves adaptation to primary treatment for breast cancer (BCa), evidenced as reductions in distress and increases in positive affect. Because not all BCa patients may need psychosocial intervention, identifying those most likely to benefit is important. A secondary analysis of a previous randomized trial tested whether baseline level of cancer-specific distress moderated CBSM effects on adaptation over 12 months. We hypothesized that patients experiencing the greatest cancer-specific distress in the weeks after surgery would show the greatest CBSM-related effects on distress and affect. METHODS Stages 0-III BCa patients (N = 240) were enrolled 2-8 weeks after surgery and randomized to either a 10-week group CBSM intervention or a 1-day psychoeducational (PE) control group. They completed the Impact of Event Scale (IES) and Affect Balance Scale (ABS) at study entry, and at 6- and 12- month follow-ups. RESULTS Latent Growth Curve Modeling across the 12-month interval showed that CBSM interacted with initial cancer-related distress to influence distress and affect. Follow-up analyses showed that those with higher initial distress were significantly improved by CBSM compared to control treatment. No differential improvement in affect or intrusive thoughts occurred among low-distress women. CONCLUSION CBSM decreased negative affect and intrusive thoughts and increases positive affect among post-surgical BCa patients presenting with elevated cancer-specific distress after surgery, but did not show similar effects in women with low levels of cancer-specific distress. Identifying patients most in need of intervention in the period after surgery may optimize cost-effective cancer care.

Depression, inflammation, and epidermal growth factor receptor (EGFR) status in metastatic non-small cell lung cancer: A pilot study☆

OBJECTIVE Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression. METHODS Fifty-five patients with newly diagnosed stage IV NSCLC completed self-report and clinician-administered depression assessments prior to receiving results of tumor genotyping. We measured serum levels of circulating biological markers of inflammation: IL-1β, IL-6, TGF-α, and TNF-α. We examined differences in depression severity, MDD, and inflammatory biomarkers in patients with and without EGFR mutations. RESULTS Patients with EGFR mutations (n=10) had lower depression severity (t[43]=2.38, p=0.03) than those without EGFR mutations (n=38) and fewer patients with EGFR mutations had concurrent MDD (2.08%) relative to those without mutations (27.08%). Patients with MDD had higher levels of TNF-α than those without MDD (t[40]=2.95, p=0.005). Those with EGFR mutations exhibited higher levels of TNF-α relative to those without EGFR mutations (t[35]=2.17, p=0.04). CONCLUSIONS Patients with stage IV NSCLC harboring an EGFR mutation exhibited elevated proinflammatory marker TNF-α, yet had lower depression severity than patients without EGFR mutations. More work is warranted to examine the interaction between tumor genotyping and inflammatory cytokines in the context of depression.