Session Item

RTT track: Treatment planning and dose calculation / QC and QA
9345
Poster
RTT
11:18 - 11:26
Reactivation of HCMV during RT of the brain results in critical illness and early mortality
PH-0361

Abstract

Reactivation of HCMV during RT of the brain results in critical illness and early mortality
Authors: Frey|, Benjamin(1)*[benjamin.frey@uk-erlangen.de];Goerig|, Nicole(1);Ina|, Becker(1);Anna-Jasmina|, Donaubauer(1);Klaus|, Korn(2);Klaus|, Überla(2);Manuel|, Schmidt(3);Arnd|, Dörfler(3);Tobias|, Engelhorn(3);Ilker|, Eyüpoglu(4);Florian|, Putz(1);Sabine|, Semrau(1);Udo S.|, Gaipl(1);Rainer|, Fietkau(1);
(1)Universitätsklinikum Erlangen- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Radiation Oncology, Erlangen, Germany;(2)Universitätsklinikum Erlangen- Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of Clinical and Molecular Virology, Erlangen, Germany;(3)Universitätsklinikum Erlangen- Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of Neuroradiology, Erlangen, Germany;(4)Universitätsklinikum Erlangen- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Neurosurgery, Erlangen, Germany;
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Purpose or Objective

Neurological deterioration and early death of patients suffering from brain tumours or brain metastases are mostly attributed to tumour growth and/or therapeutic side effects. Encephalopathy caused by human-cytomegalovirus-(HCMV)-reactivation remains undetected due to an inconclusive routine diagnosis. We therefore prospectively analysed HCMV-reactivation as a prominent condition leading to neurological decline and worse clinical outcome after the start of radiochemotherapy in brain cancer patients.

Material and Methods

Brain tumour patients who are irradiated at the brain have been included in the GLIO-CMV01 trial (NCT02600065). HCMV-analyses and immunophenotyping of peripheral blood as well as extended MRI-studies including additional independent retrospective neuroradiological evaluation are performed. Up to now, 118 adult patients (63 histologically proven high-grade gliomas, 55 with brain metastases) were included in the study and had a follow up of up to 600 days. The Department of Virology is analysing virus load according to standard procedures, while immune phenotyping of whole blood is performed according to established in-house procedures.  Study endpoints are symptomatic viremia and overall survival (OS).

Results

An amount of 24% (28/118) of all included patients (12/44 glioblastoma, 3/13 anaplastic astrocytoma; 8/31 non-small-cell lung cancer (NSCLC), 13/24 other brain metastases) were diagnosed with HCMV-viremia during or within 4 weeks after radio(chemo)therapy. All patients who developed HCMV-viremia were CMV-IgG positive, meaning, that they had a prior infection with HCMV during their lifetime. Moreover, 21/28 of the patients showing HCMV-viremia suffered from significant neurological decline, which was effectively reversed during and after antiviral treatment. The patients who suffered from the HCMV-viremia displayed a pre-therapeutically significantly reduced basophil count (glioblastoma: P=0.002, NSCLC: P=0.02). While all patients with HCMV reactivation did not show any MRI-signs of tumour progression, the median OS was significantly reduced; after HCMV-associated encephalopathy symptoms patients with glioblastoma had a calculated 1-year OS of 22% vs 69% (P=0.01) and patients with metastases from NSCLC showed an 1-year OS of 0% vs 32% (P=0.02).

Conclusion

The HCMV-reactivation of brain cancer patients after the start of radio(chemo)therapy is a significant risk for cognitively detrimental, but treatable encephalopathy and premature death. Due to inconclusive routine diagnostic, the HCMV reactivation is mostly missed. We urge routinely performed HCMV-diagnostics in combination with basophil count assessment and study-based anti-viral regimens for brain cancer patients treated with radio(chemo)therapy.