Biomarkers of gut microbial transfer and their association with cognitive impairment in long-term survivors of testicular germ cell tumors.

Authors

null

Michal Chovanec

Department of Oncology, Comenius University and National Cancer Institute, Bratislava, Slovakia

Michal Chovanec , Katarina Kalavska , Jana Obertova , Patrik Palacka , Katarina Rejlekova , Zuzana Sycova-Mila , Valentina De Angelis , Zuzana Orszaghova , Peter Lesko , Daniela Svetlovska , Beata Mladosievicova , Jozef Mardiak , Michal Pastorek , Barbora Vlkova , Peter Celec , Michal Mego

Organizations

Department of Oncology, Comenius University and National Cancer Institute, Bratislava, Slovakia, Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia, 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia, National Oncological Institute, Bratislava, Slovakia, National Cancer Institute, Bratislava, Slovakia, 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia, Translation Research Unit, Comenius University, National Cancer Institute, Bratislava, Slovakia, Comenius University, Bratislava, Slovakia, Faculty of Medicine, Comenius University, Bratislava, Slovakia, Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia, Institute of Molecular Biomedicine, Facultz of Medicine, Comenius University, Bratislava, Slovakia

Research Funding

Other

Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis. Methods: GCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial transfer and dysbiosis (GMT) high mobility group box-1 (HMGB-1), lipopolysaccharide (LPS), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers of GMT. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6). Results: GCT survivors with higher sCD14 had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overal cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and LPS. Survivors treated with ≥ 400mg/m2 of cisplatin based chemotherapy had higher LPS (567.8 ± 42.7 vs 462.9 ± 51.9, P = 0.03). Survivors treated with chemotherapy + radiotherapy vs orchiectomy only had non-significantly higher sCD14 (7279.9 ± 810.1 vs 5851.0 ± 481.7, P = 0.09). Conclusions: sCD14 may serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors.

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Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer,Urethral Cancer

Sub Track

Translational Research, Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr 426)

DOI

10.1200/JCO.2022.40.6_suppl.426

Abstract #

426

Poster Bd #

K10

Abstract Disclosures

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