In Regard to Ding et al. 2020: “Managing Cancer and Living Meaningfully (CALM) Intervention on Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors”

To Dr. Block and the editorial board of Integrative Cancer Therapies,

We have read with great interest a study by Ding et al investigating the feasibility and acceptability of Managing Cancer and Living Meaningfully (CALM) and its effect on reducing chemotherapy-related cognitive impairment (CRCI) in Chinese breast cancer survivors (BCs). ¹ Thirty-four BCs were randomly assigned to receive CALM and 40 were assigned to care as usual (CAU). After the intervention, both the CALM and CAU groups experienced significant gains in objective and subjective cognitive functioning as measured by the Mini-Mental Status Exam (MMSE; objective cognition) and the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog; subjective cognition). Compared to the CAU group, the CALM group had significant reduction on questionnaires of subjective prospective memory (PM) and retrospective memory (RM). These findings point to the importance of identifying cognitive changes following non-central nervous system (CNS) cancer diagnosis. Further, it is essential to continue investigating cost-effective and evidence-based interventions to address cognitive difficulties in non-CNS cancer survivors.

CALM is a brief, one-on-one, semi-structured psychotherapeutic intervention designed to reduce distress in patients with advanced cancer. ² It aims to help patients adapt to the challenges of their disease and its treatment while remaining engaged in life as they simultaneously face mortality. ² However, the rationale for applying this existential psychotherapy to BCs with cognitive concerns is unclear. In all prior research on CALM, this psychotherapy was applied to patients with high levels of depressive symptoms and/or death distress, in the context of advanced cancer. In regard to the study by Ding et al, what is the rationale for applying CALM outside of this context and in the absence of high levels of psychiatric distress? Moreover, what is the theoretical or empirical basis for the mechanisms by which an existential psychotherapy could impact cognition, objective or subjective? The authors suggest that CALM is used to reduce CRCI, however; current CALM trials have not been tested in this capacity or adapted to support this claim. At its core, CALM is a supportive talk therapy and does not include any component of cognitive rehabilitation, brain training, or compensatory strategies that may affect cognitive symptoms associated with chemotherapy.

CRCI is defined as a decline in a patient’s objective cognitive function relative to a pre-cancer baseline and attributable to the cancer and its treatments. ³ Subjective, or self-reported, measures of cognition are not validated as sufficient means to assess cognitive function alone. ⁴ The authors interpret their results as evidence that CALM greatly improved “cognition”; but results suggest that CALM only had a differential effect on measures of subjective cognitive function; in fact, both groups demonstrated an improvement on a cognitive screener, the MMSE—the only objective neurocognitive test administered in this study. Importantly, the MMSE is not validated to detect CRCI and has been criticized for its poor sensitivity in identifying mild neurocognitive decline, such as CRCI. ⁵ The International Cancer and Cognition Task Force (ICCTF) recommends a set battery of neuropsychological tests to identify the neurocognitive effects of chemotherapy which has been widely implemented within other CRCI research studies. ⁴ What may explain the change on the cognitive screener in both groups? Could these changes be due to practice effects, the passage of time, or some other unidentified variable? It is unclear what the CAU group entails, and this information may help interpret these results. Lastly, a reliable change index could be calculated to determine whether a clinically meaningful change was observed on the MMSE across time to aid in interpretation and potentially rule-out practice effects as a concern.

It is important to accurately define, detect, and treat CRCI in patients with cancer. It is equally important to enhance the psychosocial support services for distress in patients with cancer. In pursuit of these goals, it is vital that the field commits to an evidence-based definition of CRCI (outlined above) and seeks to measure CRCI using both ICCTF and neuropsychological recommendations. Additionally, to ensure resources are properly allocated to those in need, providing CALM in its evidence-based context—for those with high psychological distress and advanced cancer—will contribute to improved psychosocial support for our patients. We commend the authors for investigating and implementing CALM and hope that future work can build on our recommendations.