Introduction:
Oncology patients are generally transfused to maintain a hemoglobin (Hb) above 7 g/dL (Holst et. al. BMJ 2015). Some centers use higher Hb thresholds before radiation therapy (RT) because pre-clinical data suggest that oncology patients with low hemoglobin levels may respond sub-optimally to radiation therapy due to hypoxia-induced radio-resistance (Pitson et. al. Int J Radiat Oncol Biol Phys 2001; Tatum et. al. Int J Radiat Biol 2006). It is hypothesized that higher hemoglobin levels improve tissue oxygenation, which facilitates formation of reactive oxygen species that optimize cancer cell death. No standard red blood cell transfusion thresholds have been established using interventional study data for patients with malignancies treated with radiation. This systematic review aimed to investigate the role of red blood cell (RBC) transfusion in radiation oncology patients and whether maintaining a higher Hb leads to improved overall survival, efficacy of RT on disease control and transfusion-related morbidity.
Methods:
We performed a literature search of PubMed, EMBASE and the Cochrane Library for randomized controlled trials, cohort studies and large case series comparing RBC transfusion thresholds in radiation oncology patients. We hand-searched references of identified articles. Eligibility criteria were studies that assessed patients receiving any RT modality for malignancy of any diagnosis and stage. Exclusion criteria were studies that did not evaluate hemoglobin or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional tumor control, number of transfusions and adverse events associated with either radiation or transfusion. Screening and data extraction were done in duplicate. A meta-analysis was planned with outcomes presented as odds ratios with 95% confidence intervals.
Results:
Our search yielded 6172 titles. After exclusions, 39 articles underwent full text review (Figure 1). Only one study met the pre-specified inclusion criteria; therefore, a meta-analysis was not performed. The identified study pooled results from two Danish randomized controlled trials (DAHANCA 5 and 7) that stratified patients with head and neck squamous cell carcinoma with low pre-radiation hemoglobin levels (females <13 g/dL and males <14.5 g/dL) to RBC transfusion (235 patients) versus no transfusion (230 patients) (Hoff et. al. Acta Oncol 2011). The study found no significant differences between groups in locoregional disease control or overall survival after five years of follow up, despite increased hemoglobin levels in the transfused group. Given the search results, we expanded the review to extract data from other relevant trials not meeting inclusion criteria to conduct a narrative review of the available literature. The extracted studies involved a variety of malignancies and were primarily single-center retrospective studies assessing outcomes of local transfusion policies. Some studies featured univariate and multivariate analyses, but had conflicting results on the effects of transfusion on disease control and mortality. A major criticism of these studies was the lack of comparison between different transfusion thresholds in anemic patients.
Conclusions:
This systematic review illustrates the lack of data on the effect of RBC transfusion strategies in oncology patients undergoing radiation. Well-designed prospective studies are urgently needed in this area due to variability in practice.
No relevant conflicts of interest to declare.
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