Does transfusion improve the outcome for HNSCC patients treated with radiotherapy? – Results from the randomized DAHANCA 5 and 7 trials

Abstract

Background. Patients with head and neck squamous cell carcinoma (HNSCC) and a low level of hemoglobin often have a poor response to radiation that may be related to hypoxia-induced radioresistance. We have previously published the importance of hemoglobin level and the effect of transfusion by the results from the randomized DAHANCA 5 trial, including 414 patients in the analysis. Aim of the current analysis was to gain additional power by adding patients from the continued subrandomization in the DAHANCA 7 trial, now including a total of almost 1200 patients. Material and methods. Patients were randomized to treatment in the DAHANCA 5 and 7 study (nimorazole vs. placebo and five fx/week vs. six fx/week), and in addition, patients with “low” pre-irradiation hemoglobin values (females <13 g/dl; males <14.5 g/dl) were subrandomized to plus or minus transfusion. Transfusion was given with packed red blood cells with the aim to achieve a hemoglobin level in the “high” value range. Results. A total of 1166 patients were included, 701 patients had high hemoglobin levels and 465 had low hemoglobin levels. Among the low hemoglobin patients, 235 were randomized to receive transfusion. Patient characteristics and treatment arms were well balanced. In the majority of patients, transfusion resulted in increased hemoglobin levels although this decreased slightly throughout treatment as in the non-transfused patients. Overall, the patients with low hemoglobin level had a significant reduced probability of locoregional control, disease-specific and overall survival. In the low hemoglobin group, transfusion did not improve the outcome in locoregional control, disease-specific or overall survival. In multivariate analyses, HPV/p16 status, T and N classification were significant factors for all outcome measures, whereas there was no significant influence of transfusion or hemoglobin level on endpoints. Conclusion. Transfusion prior to and during radiation treatment did not improve the outcome in patients with HNSCC and low hemoglobin values, but may have a negative impact on survival.

Acknowledgements

Supported by CIRRO – The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, the Danish Council for Strategic Research and The Danish Cancer Society. No conflicts of interest declared by the authors.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online at http://www.informahealthcare.com/doi/abs/10.3109/0284186X.2011.592650.

Appendix 1. Units of blood.

Appendix 2. Hemoglobin level during RT treatment

Blue = males

Red = females

Showing median Hb level during radiotherapy as a function of hemoglobin group.

Appendix 3. Subgroup analysis by treatment group in the original DAHANCA 5 and 7 trials.

Appendix 4. Multivariate model including transfusion during RT variable.