Journal Article Annotations
2018, 2nd Quarter

Psycho-Oncology & Palliative Care

Annotations by Elie Isenberg-Grzeda, MD, and Carlos Fernandez-Robles, MD
July 2018

Does stress increase risk of breast cancer? A 15-year prospective study
Prevalence of cognitive impairment and association with survival among older patients with hematologic cancers
Does depression treatment improve the survival of depressed patients with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials

PUBLICATION #1 — Psycho-Oncology & Palliative Care

Does stress increase risk of breast cancer? A 15-year prospective study

Butow P, Price M, Coll J, et al

Abstract: Psychooncology 2018 Apr 20 (Epub ahead of print)

OBJECTIVE: The possible impact of stress on cancer incidence remains controversial. We prospectively evaluated associations between life event stressors, social support, personality characteristics (optimism, anger control, antiemotionality), and risk of developing primary breast cancer (BCa), in women at increased familial risk of BCa.

METHODS: A prospective cohort, repeated measures design was used. Recruitment was through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, which collects genetic, epidemiological, and clinical data from Australasian families with multiple BCa cases. Acute and chronic stressors for the prior 3 years and psychosocial, clinical, and epidemiological variables were measured at cohort entry and at 3-yearly intervals. Cox proportional hazard regression analysis controlling for BCa risk factors and familial clustering was undertaken. The primary outcome was histopathologically confirmed BCa (invasive or ductal carcinoma in situ, including occult cases diagnosed during risk-reducing mastectomy).

RESULTS: Of 3595 consecutive women invited to participate, 3054 (85.0%) consented. Of these, 2739 (89.7%) from 990 families (range 1-16 per family) completed at least 1 assessment point. During the study, 103 women were diagnosed with BCa. No stressor or psychosocial variable or interaction between them was significantly associated with BCa in unadjusted or adjusted models (total acute stressors HR = 1.03 [0.99-1.08], P = .19; total chronic stressors HR = 1.0 [0.90-1.11], P = .98).

CONCLUSIONS: This study did not demonstrate an association between acute and chronic stressors, social support, optimism, antiemotionality or anger control, and BCa risk. Women should focus on proven methods of BCa risk reduction.

On PubMed: Psychooncology 2018 Apr 20 (Epub ahead of print)

Annotation

Type of study: Cohort study

The finding: In a prospective cohort study sample of 2,739 Australasian women at increased familial risk for breast cancer, the authors found no statistically significant associations between psychosocial stress and breast cancer incidence.

Strength and weaknesses: The main strength of this study is that the authors addressed methodological issues of prior studies, which have included inadequate power and control of potential confounders, as well as failing to consider stressor severity and chronicity, social support and personality. In addition, the authors reported a very high response rate of 85%. The limitations include the fact that the authors did not evaluate for coping style, which may have been a confounding variable. In addition, the study may have been underpowered to detect a statistically significant relationship between chronic severe stress and breast cancer risk. Finally, the results may not necessarily be generalizable to non-breast cancer patients, or even those not at risk of familial breast cancer.

Relevance: Decades worth of messages aimed at cancer patients have emphasized the role of optimism, positive attitude, and stress reduction in the treatment or prevention of cancer, without a strong evidence base to substantiate the message. This, of course, can add to the guilt and self-blame of those diagnosed with cancer, having felt that they failed in some way. The results of this study are reassuring to healthcare providers treating breast cancer patients, since they add to the mounting evidence that the burden of stressors in the lives of breast cancer patients do not appear to increase the incidence of breast cancer. The authors note the importance of treating anxiety for other reasons.

PUBLICATION #2 — Psycho-Oncology & Palliative Care

Prevalence of cognitive impairment and association with survival among older patients with hematologic cancers

Hshieh TT, Jung WF, Grande LJ, et al

Abstract: JAMA Oncol 2018; 4(5):686-693

Importance: As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers.

Objective: To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer.

Design, Setting, and Participants: This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival.

Exposures: The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail.

Results: Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03).

Conclusions and Relevance: These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

On PubMed: JAMA Oncol 2018; 4(5):686-693

Annotation

Type of study: Prospective cohort study

The finding: Cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival.

Strengths: Adequate sample size, and use of Frailty scales. Homogeneity of the sample.

Weaknesses: Use of only two cognitive screening tools, in domains that can be particularly challenging to test. Despite the high prevalence, it may be underestimated given the skills required to reach a center the size of the one where the study was conducted. The characteristics of the patients and the intensity of the treatment may be higher given the center where the study was conducted, resulting in higher mortality than in community non-complicated cancer patients. Authors also highlight the probability of a self-selection bias.

Relevance: This study looked at the prevalence of cognitive impairment measured by Clock-in-a-Box test and five-word recall test, and correlation with frailty, in patients presenting for first-time evaluation of hematological malignancies at a large university affiliated cancer center. Additionally, it correlated scores with survival. The finding of high prevalence of cognitive disorders and association with frailty and poorer prognosis can help C-L psychiatrists look for these deficits early in treatment, and also advocate for routine screening proceedings, and implement early interventions geared at supporting these patients, that otherwise could be missed.

PUBLICATION #3 — Psycho-Oncology & Palliative Care

Does depression treatment improve the survival of depressed patients with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials

Mulick A, Walker J, Puntis S, et al

Abstract: Lancet Psychiatry 2018; 5(4):321-326

BACKGROUND: Comorbid major depression has been associated with worse survival in patients with cancer. However, we do not know if treating depression improves survival. In the SMaRT Oncology-2 (good prognosis cancers) and SMaRT Oncology-3 (lung cancer, a poor prognosis cancer) trials, we found that a depression treatment programme, Depression Care for People with Cancer (DCPC), was effective in reducing comorbid major depression. In this analysis, we aimed to identify whether DCPC also had an effect on survival.

METHODS: The trials were conducted in three cancer centres and their associated clinics in Scotland, UK. In SMaRT Oncology-2, outpatients with good prognosis cancers and major depression were randomly assigned in a 1:1 ratio to DCPC or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. In SMaRT Oncology-3, outpatients with lung cancer and major depression were randomly assigned (1:1 ratio) to DCPC or usual care with stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. For this analysis, we obtained long-term data on deaths (all causes) in the SMaRT Oncology-2 and 3 trial participants, censored at July 31, 2015, and analyzed survival as a trial outcome. We estimated unadjusted hazard ratios (HRs) for each trial using Cox regression, and pooled the log HRs in a fixed-effects meta-analysis.

FINDINGS: We recruited 642 participants; between May 12, 2008, and May 13, 2011, 500 participants were recruited to the SMaRT Oncology-2 trial and between Jan 5, 2009, and Sept 9, 2011, 142 participants were recruited to the SMaRT Oncology-3 trial. We followed up SMaRT Oncology-2 and SMaRT Oncology-3 participants for a median of 5 years and 1 year, respectively. 135 (27%) of 500 SMaRT Oncology-2 participants and 114 (80%) of 142 SMaRT Oncology-3 participants died within this period. We found no significant effect of DCPC on survival in the total follow-up period for either SMaRT Oncology 2 (HR 1·02, 95% CI 0·72-1·42, p=0·93) or SMaRT Oncology-3 (HR 0·82, 95% CI 0·56-1·18, p=0·28; pooled HR 0·92, 95% CI 0·72-1·18, p=0·51).

INTERPRETATION: DCPC is highly effective in improving depression and quality of life in depressed patients with cancer, but there was no evidence for a significant effect on survival. Despite the absence of an effect on length of life, the management of depression remains important for its beneficial effect on quality of life.

On PubMed: Lancet Psychiatry 2018; 5(4):321-326

Annotation

Type of study: Randomized controlled trial

The finding: Depression treatment in cancer patients improved quality of life, but there is no evidence that it has an impact on survival.

Strengths and duration: Sample size 642 patients, followed up to 5 years. The study design was adequate.

Weakness: Despite the large sample size it was estimated that small positive impact on survival could be missed. Given the limited nature of the study, participants could not be followed beyond the study conclusion, and long-term impact on survival could also be missed. Finally, the heterogenic nature of the sample does not allow to study disease-specific impact.

Relevance: This article presents the results of a randomized controlled study looking at the impact of SMaRT protocol for depression compared to usual care, and finds that while it helps improve quality of life, it does not have any impact on survival. This study will help consultation-liaison psychiatrists have more informed discussions with their patients about the importance and the role of depression treatment during cancer care.