The Cancer-Related Symptoms Puzzle: Piecing Cancer-Related Cognitive Impairment to Cancer Care Research

As a palliative care and cancer nursing researcher, I have dedicated my entire career to developing interventions for cancer-related symptoms, including single symptoms such as pain, fatigue, and sleep disturbance, as well as symptom clusters. These symptoms have a negative impact on the functional performance, quality of life, and even quality of death of patients with cancer.

The worldwide cancer burden is predicted to reach 28.4 million cases by 2040, a 47% increase from 2020, showing that more people are expected to suffer from cancer and its related symptoms.1 Cancer-related symptoms are well recognized as risk factors for a decreased overall quality of life, and numerous strategies have been developed to alleviate them.2–4 As cancer care researchers, we are very familiar with symptoms such as pain, fatigue, nausea and vomiting, mental health issues, and so on. With the development of new cancer treatments, patients may experience additional symptoms that have not been as thoroughly researched. For example, reports of cognitive difficulties related to cancer treatment have started to appear in the literature for the last 2 decades. The evolving body of research on this subject has led to a renaming of these cognitive difficulties to cancer-related cognitive impairment (CRCI). However, a surprising fact is that research papers studying the mechanisms, prevalence, and risk factors of CRCI and its management are still limited.

Cognitive impairment is commonly observed in patients with cancer through symptoms such as memory loss, drowsiness, and inattention, which the researchers and clinicians may identify CRCI by some commonly used tools or surveys. For example, the MD Anderson Symptom Inventory5 and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire6 are widely known in cancer care research. We also adopted these reliable, validated tools as outcome measures to examine the effects of the cancer care intervention in our study. Unfortunately, we were unable to test specific cognitive skills (ie, attention, verbal learning, executive functions and decision making, and language comprehension and orientation) using only part of the items in these measurements, as cognitive skills are complex and require the integration of abilities to think, read, learn, remember, reason, and pay attention. More detailed and comprehensive tools for measuring the perceived, self-reported cognitive function in patients with cancer, such as the Functional Assessment of Cancer Therapy-Cognitive Function or the Brief Perceived Cognitive Impairment Scale,7 should be used in future research. So as the objective cognitive performance, a specific tool for assessing the actual cognitive performance in patients with CRCI is needed, which would contribute to the synthesis of evidence in this aspect.

The potentially negative consequences of cancer and its associated therapies on cognitive functioning are emerging as a key focus of cancer care research. Not only does the cancer progression affect cognitive function, the treatments themselves also take part in cognitive deterioration. For example, the chemotherapy-related cognitive impairment, which has been introduced as a Medical Subject Headings term in 2021, shows that detrimental effects of chemotherapy on the brain and cognitive function are receiving more attention.8 Studies have also revealed that almost every type of chemotherapeutic agent has been linked to adverse neurological consequences, and the chemotherapy-related cognitive impairment may occur during or after the chemotherapy.8

The development of CRCI affects quality of life and can result in diminished functional independence. Not surprisingly, cognitive impairment is a significant burden not only on individual patient outcomes but also on future care and medical treatment plans that involve decision-making processes between patients, their families, and clinicians. Given the facts of the CRCI from current evidence and an increased number of cancer patients in the global, CRCI is a relatively new and less explored area, whereas insufficient studies in cancer care research are focused on cognitive performance as a primary outcome. Future research using appropriate CRCI measurement tools recommended by the Cancer Neuroscience Initiative Working Group,9 as well as developing strategies to improve cognitive decline, are warranted.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. 2. Wong WM, Chan DNS, He X, So WKW. Effectiveness of pharmacological and nonpharmacological interventions for managing the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients undergoing chemotherapy: a systematic review. Cancer Nurs. 2022. doi:10.1097/NCC.0000000000001048. 3. Chung MH, Wang SY, Lin CC. Symptom clusters and impact of fatigue and sleep disturbance on symptom experiences of hepatoma patients in Taiwan. Cancer Nurs. 2017;40(5):403–411. 4. Sun JL, Lin CC. Relationships among daytime napping and fatigue, sleep quality, and quality of life in cancer patients. Cancer Nurs. 2016;39(5):383–392. 5. Cleeland CS, Mendoza TR, Wang XS, et al. Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer. 2000;89(7):1634–1646. 6. EORTC Quality of Life Group. Item Library. https://qol.eortc.org/item-library/. Accessed March 7, 2022. 7. Kim HJ, Barsevick AM. The Brief Perceived Cognitive Impairment Scale–Korean: a validation study. Cancer Nurs. 2019;42(2):148–155. 8. Williams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol. 2016;174(6):835–846. 9. Henneghan AM, Van Dyk K, Kaufmann T, et al. Measuring self-reported cancer-related cognitive impairment: recommendations from the cancer neuroscience initiative working group. J Natl Cancer Inst. 2021;113(12):1625–1633.

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