Symptom burdens related to chemotherapy-induced anemia in stage IV cancer

Discussion

In this study, we described the number and type of symptoms documented in the medical record notes among stage IV NHL, breast cancer, and lung cancer patients who did or did not develop CIA during chemotherapy. Patients who developed CIA had significantly greater numbers of different symptoms documented during chemotherapy than those who did not develop CIA (6.8 vs 4.1). This difference is clinically significant because most symptoms described in this study can be expected to have a negative impact on a patient’s quality of life. In patients who developed CIA, fatigue was the most commonly documented symptom, noted for 90% of the study population. In addition to fatigue, many other symptoms were noted in a large proportion of patients. In contrast, in patients who did not develop CIA, only a few symptoms (including fatigue) were more commonly noted in this sample. We observed more symptoms in chemotherapy cycles with higher grades of anemia. Of the symptoms examined, abdominal pain, depression, diarrhea, dizziness/lightheadedness, dyspnea, edema, fatigue, heart failure, headache, hypotension, insomnia, leg pain, loss of appetite, nausea/vomiting, pale skin, pectoral angina, sweating, and syncope particularly demonstrated a clearly increasing prevalence with declining Hb level. We also reported that patients who developed severe anemia (grades 3 and 4) experienced an average of 5 to 6 different symptoms at the time of the anemia episode. These data demonstrated a significant symptom burden in cancer patients with CIA seen in community-based oncology practices. Findings on the types of symptoms most commonly noted in various grades of CIA episodes provided some guidance for supportive care planning. As previous studies have shown a reduction in symptom burden after anemia treatment in patients with CIA,^14-16 our results support the idea of early lab draws and active management of CIA in maintaining quality of life in cancer patients undergoing chemotherapy.

Our findings on the prevalence of fatigue are in line with other studies in the literature. Maxwell reported that the prevalence of fatigue was 80% to 96% in cancer patients.¹⁷ Cella and colleagues found that using FACT-General questionnaire, 75% of cancer patients reported fatigue.¹¹ The comparability of our estimate and those found in studies based on patient self-report offered some assurance of the validity of assessing symptom prevalence through physician record notes. In addition to fatigue, we described prevalence of 23 additional symptoms, most of which have not been extensively studied in the literature. Gabrilove and colleagues found that a substantial proportion of patients with CIA had moderate to severe score for lack of appetite (36%) and disturbed sleep (41%) using the MDASI.¹⁰ The prevalence of loss of appetite and insomnia was around 50% and 25%, respectively, in our study samples. A 2013 systematic review of 21 multinational studies reported the pooled prevalence of several nonfatigue symptoms in cancer patients including headache (23%), sleep disturbance/insomnia (49%), appetite changes (45%), nausea/vomiting (26%), diarrhea (15%), depression (34%), dyspnea (44%), dizziness (26%), numbness/tingling (42%), edema (14%), and sweating (28%).¹⁸ Our prevalence estimates in patients with CIA for most of these symptoms were higher, likely because Reilly and colleagues used source studies that included any cancer patients undergoing treatment and not just those with CIA. Our findings on the increased symptom burden in patients who experienced episodes of advanced anemia compared with patients with mild anemia were also consistent with the literature. To this end, several studies using MDASI or the FACT-An reported differential symptom burdens by Hb level based on patient self-report,^10,11,19 including data on improvement in symptom burden and quality of life after anemia was amended with the use of ESA.^20,21

We found that the number of pre-existing symptoms was significantly higher in patients who went on to develop CIA than in patients who did not develop CIA. Specifically, fatigue, loss of appetite, and pale skin before chemotherapy seemed to be significantly more common in patients who went on to develop CIA. This finding suggested that presentation of these symptoms before chemotherapy initiation may be a predictor for developing moderate or severe anemia during treatment. This is a novel hypothesis, as no studies have evaluated the relationship between pretreatment symptom and risk of CIA. However, our study was not designed to address this specific question. Additional investigation is needed to further shed light on whether the occurrence of anemia-related symptoms in nonanemic patients can be used to effectively risk-stratify patients for subsequent CIA.

Contrary to our expectation, the prevalence of most symptoms did not clearly increase as chemotherapy progressed. There are several possible explanations to this phenomenon, with the most likely being related to reporting of anemia-related symptoms. For example, patients might stop reporting the same symptom repeatedly or become adjusted to the new Hb levels, leading to less symptom manifestation. Clinicians may also be less likely to ask about symptoms in later treatment cycles and/or to document chronic symptoms. Several symptoms were rarely documented altogether, such as cold intolerance, heat intolerance, heart failure, and vertigo. Symptoms reported in earlier cycles could also be managed successfully. Another possible explanation is differential loss of follow-up. Patients who experienced severe adverse events or symptoms may terminate treatment prematurely. Thus, symptom burden found toward later cycles may not represent the true symptom burden should everyone who initiated the chemotherapy treatment complete all planned cycles.