Transfusion Use Challenged For HNSCC Chemo-Radiotherapy

Research suggests that packed red cell transfusion does not combat head and neck tumour hypoxia during treatment or improve patient outcome

medwireNews: Patients undergoing radical chemoradiotherapy for stage III– IV head and neck squamous cell carcinoma (HNSCC) may not benefit from packed red cell transfusion (PRCT), research suggests.

The results challenge the belief that PRCT “increases tumour oxygenation and overcomes hypoxia-induced radio-resistance”, explain Shreerang Bhide, from The Royal Marsden Hospital in London, UK, and colleagues in the British Journal of Cancer.

The study included 20 patients, 17 of whom developed low haemoglobin (<11.5 g/dL) during induction chemotherapy, cisplatin chemotherapy and 65 Gy of radiation in 30 fractions over 6 weeks to the primary tumour and involved nodes, plus 54 Gy prophylactic therapy in 30 fractions to nodal regions.

The researchers note that their study has only a small number of patients but did include a “spectrum” of HNSCC profiles, including human papillomavirus-positive and -negative oropharyngeal tumours and laryngeal and hypopharyngeal cancers.

The patients were transfused with a median of two units of PRCs after a median of 11 fractions of chemoradiation; haemoglobin levels rose from a pretransfusion median of 10.0 g/dL to a post-transfusion 12.3 g/dL.

Magnetic resonance imaging taken before and after transfusion showed that PRCT significantly improved primary tumour oxygenation in just four patients, and these patients did not experience an oxygenation boost to their lymph nodes.

Two patients experienced an oxygenation increase only to their lymph nodes with PRCT and no change in primary tumour oxygenation was detected in 11 patients. One patient showed a reduction in tumour oxygenation after PRCT.

Transfusion was not associated with a significant change in levels of 12 cytokines measured from blood samples taken before and after PRCT, and cytokine levels did not significantly correlate with tumour oxygenation.

“Therefore, neither the radiation delivered between pre- and post-PRCT scans nor the cytokines present in the transfusate altered perfusion or vascular permeability in the tumour to a degree sufficient to affect tissue oxygenation”, the authors summarise.

At 3 months, 55% of the 20 patients had achieved a complete clinical and radiological response to chemoradiotherapy, while 45% had evidence of persistent or progressive disease. Of the four patients who experienced improved tumour oxygenation after transfusion, three experienced disease progression and one achieved complete remission.

The researchers emphasize that “the observed magnitude of improved tumour oxygenation following PRCT did not translate into improved treatment outcomes in these patients.”

They conclude: “This study suggests that PRCT during radical [chemoradiotherapy] for HNSCC does not improve tumour oxygenation.

“Therefore, oncologists should consider changing practice according to [UK National Institute for Health and Care Excellence] and American Association of Blood Banks guidelines on PRCT for anaemia.”

Nevertheless, the authors add: “Hypoxia-induced treatment resistance is still a problem in HNSCC management and alternative strategies such as hypoxic sensitisers such as nimorazole or vascular-targeting agents should be explored using a personalised targeted strategy based on molecular hypoxic signatures.”

References

Welsh L, Panek R, Riddell A, et al. Blood transfusion during radical chemo-radiotherapy does not reduce tumour hypoxia in squamous cell cancer of the head and neck. Br J Cancer; Advance online publication 24 November 2016. doi: 10.1038/bjc.2016.386

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