Changes in Quality-of-Life Parameters in Patients Receiving Therapeutic Interventions for Cancer-Associated Anemia: A Systematic Review
Authors: Marivada Snigdha , Panch Sandhya R. , Pirouz Kamyab , Kamwal Chhaya , Dreyzin Alexandra , Livinski Alicia , Stroncek David F. , Li Xiaobai , Bryant Barbara 
Published: November 2021

Abstract
Introduction: Cancer-associated anemia (CAA) is multifactorial in etiology and can occur due to the malignancy itself or as a side effect of the treatment. The prevalence of CAA can exceed 90%. Several studies have reported positive correlations between increased hemoglobin (Hb) and improved health-related quality of life (HR-QoL) measures including fatigue scores and scores for physical, mental and social well-being. However, Hb increases and extent of improvement in HR-QoL measures varied by therapeutic interventions (Oral/intravenous iron, erythropoietin stimulating agents (ESAs), transfusions, and/or others), as did HR-QoL tools used in these studies. We conducted a systematic review to identify final target Hb levels as well as changes in Hb from baseline that resulted in significant improvement in HR-QoL parameters following interventions for CAA. We also sought to identify HR-QoL tools that effectively and comprehensively captured symptomatic improvement following Hb increases in patients with CAA.
Methods: Randomized Controlled Trials (RCTs) and prospective studies which evaluated HR-QoL changes following drug interventions for CAA were identified through searches of the CINAHL Plus, Embase, PubMed, and Web of Science for articles in English from 1997-2021. Inclusion criteria were: RCT or prospective study; patients with CAA; a HR-QoL was used. Two reviewers independently screened abstracts. A third reviewer resolved disagreements. Bias assessment was performed using Joanna Briggs checklist.
Results: Of the 8243 studies identified of which 1718 were duplicates and 6525 records were screened at the title and abstract level. Of the 59 full text articles reviewed, 38 articles met our eligibility criteria (Figure 1). A total of 19 RCTs and 19 prospective studies were identified. On average, studies were conducted over 14.2 ± 5.5 weeks, with a mean of 546 ± 693 study participants in each study. 23 studies provided information on the number of enrolled participants completing study. Mean study completion rates among participants was 70 ± 1 (%). A summary of HR-QoL measures utilized in the various studies is presented in Table 1.
Hb changes and HR-QoL score changes were reported consistently in 30 studies and are presented in Table 2. Therapeutic interventions for CAA included ESAs (n=19; 65.5%), Oral/IV iron (n=1; 3.4%); transfusions (n=2; 6.9%), other agents used in specific conditions (luspatercept (MDS)) n=1; 3.3%, or combinations of these (n=7; 24.1%). Overall, 78% of studies that reported an Hb increase following drug interventions for CAA also reported an improvement in HR-QoL measures. Mean Hb increases was 1.9 g/dL. Median change in the most frequently used HR-QoL (FACT-An, FACT-F) was +3 points (Range: 0-4).
Studies utilizing transfusions as the intervention for CAA reported the lowest final Hb (8.8 gm/dL) as well as the lowest change in Hb (Δ Hb= 1gm/dL) levels from study onset to completion. These studies also reported the least improvements in HR-QoL scores. HR-QoL tools used in transfusion-based studies were variable. With regard to other outcomes measured in the various studies, raising Hb levels by various interventions did not significantly impact bleeding scores, infections, hospitalizations, or mortality.
Conclusions: Our data suggest the need to identify optimum Hb thresholds (final target Hb levels as well as changes in Hb levels from baseline) that result in meaningful improvements in HR-QoL parameters following the use of any therapeutic intervention for CAA. Specifically, studies utilizing transfusions alone as intervention for CAA may not reach the optimum threshold (&gt;11gm/dL or a Δ Hb of greater than 2 gm/dL) to result in meaningful improvements in HR-QoL measures as has been shown in studies utilizing ESAs or iron or a combination of these agents. Further, it is imperative for studies in transfusion medicine to identify appropriate HR-QoL tool/s that comprehensively capture all aspects of well-being related to CAA. As such, studies may need to utilize more than one HR-QoL tool that gathers information on physical, social and emotional well-being before and after transfusions, while balancing the risk of questionnaire fatigue. A meta-analysis of our systematic review is ongoing and will provide additional information on data gathered thus far.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.