Journal Article Annotations
2017, 4th Quarter
Psycho-Oncology & Palliative Care
Annotations by Elie Isenberg-Grzeda, MD, and Carlos Fernandez-Robles, MD
- Chemotherapy and post-traumatic stress in the causation of cognitive dysfunction in breastcancer patients
- Massage therapy decreases cancer-related fatigue: results from a randomized early phase trial
- The role of a palliative care intervention in moderating the relationship between depression and survival among individuals with advanced cancer
PUBLICATION #1 — Psycho-Oncology & Palliative Care
Chemotherapy and post-traumatic stress in the causation of cognitive dysfunction in breast cancer patients
Hermelink K, Bühner M, Sckopke P, et al
Abstract: J Natl Cancer Inst 2017; 109(10)
Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress.
Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided.
Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02).
Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.
On PubMed: J Natl Cancer Inst 2017; 109(10)
Type of study: Prospective cohort study
The finding: The authors tried to address the knowledge gap of why cancer patients are known to have cognitive dysfunction even prior to starting chemotherapy. They tested the possibility that PTSD may be a contributor to cancer-related cognitive impairment, by comparing cognitive performance among (a) breast cancer patients (stage 0-III) who received chemotherapy; (b) breast cancer patients who did not receive chemotherapy; and (c) healthy controls. They also used structured clinical interviews to measure the incidence of PTSD at various time points. They found that PTSD partially accounted for the greater degree of cognitive dysfunction noted among both cancer groups compared to healthy controls.
Strength and weaknesses: They had a relatively large sample size (n=150 cancer patients; n=56 controls), low attrition rates, the use of gold standard methods of neuropsychological testing, and the use of structured clinical interviews to diagnose PTSD. The main limitation is generalizability to other patient populations.
Relevance: Much attention has been paid to trying to elucidate the mechanism behind cognitive dysfunction among cancer patients even prior to starting treatment. Various mechanisms have been proposed, including the possibility that inflammatory processes caused by the tumor are responsible for early cognitive dysfunction seen prior to initiating treatment. The authors study PTSD and propose a possible link between cancer-related PTSD and cognitive dysfunction, which is becoming increasingly substantiated by their research. It thus behoves clinicians to evaluate for PTSD and treat as necessary among patients with cancer.
PUBLICATION #2 — Psycho-Oncology & Palliative Care
Massage therapy decreases cancer-related fatigue: results from a randomized early phase trial
Kinkead B, Schettler PJ, Larson ER, et al
Abstract: Cancer 2017 Oct 17 (Epub ahead of print)
Background: Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors.
Methods: This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue scale secondary.
Results: Mean baseline MFI scores for 57 evaluable subjects were 62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard deviation) 6-week reduction in MFI total scores of -16.50 (6.37) (n = 20) versus -8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n = 17) (treatment-by-time P < .0001). The mean baseline PROMIS Fatigue scores were SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in PROMIS Fatigue scores was -5.49 (2.53) points for SMT versus -3.24 (2.57) points for LT and -0.06 (1.88) points for WLC (treatment-by-time P = .0008). Higher credibility, expectancy, and preference for SMT than for LT did not account for these results.
Conclusion: SMT produced clinically significant relief of CRF. This finding suggests that 6 weeks of a safe, widely accepted manual intervention causes a significant reduction in fatigue, a debilitating sequela for cancer survivors.
On PubMed: Cancer 2017 Oct 17 (Epub ahead of print)
Type of study: Randomized controlled trial (RCT)
The finding: The authors studied the early (6-week) impact of Swedish massage versus (a) an active control (light touch) and (b) waitlist control on cancer-related fatigue among a sample of stage 0-III breast cancer survivors. They found that the treatment arm (Swedish massage) yielded clinically-significant improvements in cancer-related fatigue compared to both control groups.
Strength and weaknesses: The main limitations are the single-blind design (though the intervention prevents a double-blind design), small sample size (n=22 per group), and homogenous patient population (breast cancer survivors). The strength include the credibility, expectancy, and preference analysis that the authors conducted, as a way of ensuring that the results found were not attributable to differences in expectations between groups.
Relevance: Cancer-related fatigue can be a disabling outcome of cancer treatment, and one that affects survivors as well as their families. The mainstay of treatment has been pharmacologic (stimulants), albeit with limited efficacy. More recently, nonpharmacologic treatments have been proposed and studied, mostly in the realm of physical activity. This study reports on yet another nonpharmacologic treatment with efficacy in reducing cancer-related fatigue, which is a much needed addition to the literature and a welcomed addition to a relatively limited toolbox.
PUBLICATION #3 — Psycho-Oncology & Palliative Care
The role of a palliative care intervention in moderating the relationship between depression and survival among individuals with advanced cancer
Prescott AT, Hull JG, Dionne-Odom JN, et al
Abstract: Health Psychol 2017; 36(12):1140-1146
Objective: Randomized controlled trials (RCTs) of early palliative care interventions in advanced cancer have positively impacted patient survival, yet the mechanisms remain unknown. This secondary analysis of 2 RCTs assessed whether an early palliative care intervention moderates the relationship between depressive symptoms and survival.
Method: The relationships among mood, survival, and early palliative care intervention were studied among 529 advanced cancer patients who participated in 2 RCTs. The first (N = 322) compared intervention versus usual care. The second (N = 207) compared early versus delayed intervention (12 weeks after enrollment). The interventions included an in-person consultation, weekly nurse coach-facilitated phone sessions, and monthly follow-up. Mood was measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. Cox proportional hazard analyses were used to examine the effects of baseline CES-D scores, the intervention, and their interaction on mortality risk while controlling for demographic variables, cancer site, and illness severity.
Results: The combined sample was 56% male (M = 64.7 years). Higher baseline CES-D scores were significantly associated with greater mortality risk (hazard ratio [HR] = 1.042, 95% confidence interval [CI] [1.017, 1.067], p = .001). However, participants with higher CES-D scores who received the intervention had a lower mortality risk (HR = .963, CI [0.933, 0.993], p = .018) even when controlling for demographics, cancer site, and illness-related variables.
Conclusion: This study is the first to demonstrate that patients with advanced cancer who also have depressive symptoms benefit the most from early palliative care. Future research should be devoted to exploring the mechanisms responsible for these relationships. (PsycINFO Database Record
On PubMed: Health Psychol 2017; 36(12):1140-1146
Type of study: A pooled, secondary analysis of two previous RCTs.
The finding: Among advanced cancer patients randomized to receive (a) palliative care intervention versus usual care, or (b) early palliative care versus delayed intervention, the authors found that early palliative care intervention prolonged survival the most among the subset of patients with clinically-relevant depressive symptoms.
Strength and weaknesses: This study was a reanalysis of two RCTs which had previously been conducted, which was both a strength and a weakness of the study. As a post hoc analysis, the authors were unable to control for possible confounding variables. As with all pooled analyses, the larger sample size also allowed for findings which may not have been possible with each of the two smaller studies.
Relevance: It is well understood that early palliative care intervention prolongs survival among patients with advanced cancer. It is also well known, from large meta-analyses, that depression seems to negatively impact survival among cancer patients. The authors aimed to study whether early palliative care interventions moderate the impact that depression has on survival, and they conclude that it may mediate this relationship by helping depressed cancer patients engage in health-promoting behaviors when they otherwise wouldn’t. The fact that depressed patients have a greater survival benefit from early palliative care compared to non-depressed patients may also guide the allocation of resources when early palliative care is being considered.