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. 2021 Oct;197(10):926-934.
doi: 10.1007/s00066-021-01802-4. Epub 2021 Jun 29.

Dose-dependence of radiotherapy-induced changes in serum levels of choline-containing phospholipids; the importance of lower doses delivered to large volumes of normal tissues

Karol Jelonek  1 , Aleksandra Krzywon  2 , Katarzyna Papaj  3 , Pawel Polanowski  2 , Krzysztof Szczepanik  2 , Krzysztof Skladowski  2 , Piotr Widlak  2
Affiliations

Dose-dependence of radiotherapy-induced changes in serum levels of choline-containing phospholipids; the importance of lower doses delivered to large volumes of normal tissues

Karol Jelonek et al. Strahlenther Onkol. 2021 Oct.

Abstract

Background: Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established.

Methods: Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The liquid chromatography-mass spectrometry (LC-MS) approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins.

Results: No statistically significant differences were found in the pretreatment samples from patients with different locations and stages of cancer. To compensate for potential differences between schemes of radiotherapy, the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient's body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Furthermore, we observed several phospholipids whose serum levels correlated with the degree of acute radiation toxicity.

Conclusion: Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient's organism to intensity-modulated radiotherapy (IMRT).

Keywords: Head and neck cancer; Ionizing radiation; Lipidomics; Mass spectrometry; Radiation response.

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Conflict of interest statement

K. Jelonek, A. Krzywon, K. Papaj, P. Polanowski, K. Szczepanik, K. Skladowski and P. Widlak declare that they have no competing interests. The funders had no role in the following: design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Fig. 1
Fig. 1
Numbers of lipids which serum levels were significantly correlated with maximum GTV dose, a total absorbed radiation energy, and volumes of tissues irradiated at different BED (10 Gy intervals in the 10 to 100 Gy range). Different classes of lipids (LPC, PC, and SM) are color-coded; positive (r > 0.3) and negative (r < −0.3) correlations are presented above and below the zero line, accordingly. ARS acute radiation sequel, GTV gross tumor volume, BED biologically effective doses, LPC lysophosphatidylcholine, PC phosphatidylcholine, SM sphingomyelin
Fig. 2
Fig. 2
Correlations between serum levels of selected lipids and maximum GTV dose (a), the total absorbed radiation energy (b), and volume of tissues irradiated at 20 Gy BED (c). Illustrated are three compounds: LPC(18:0), SM(36:1), and PC(38:2). Grey zone represents 95% confidence intervals for the correlation coefficient. Max GTV maximum gross tumor volume, BED biologically effective doses, V20 volumes irradiated with at least 20 Gy of BED, LPC lysophosphatidylcholine, PC phosphatidylcholine, SM sphingomyelin
Fig. 3
Fig. 3
Correlations between serum levels of selected lipids and acute radiation toxicity. Illustrated are three compounds: LPC(16:1), SM(36:0), and PC(38:2). ARS acute radiation sequel, LPC lysophosphatidylcholine, PC phosphatidylcholine, SM sphingomyelin
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References

    1. Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: a continuing challenge. Oncology. 2016;91(1):13–23. doi: 10.1159/000446117. - DOI - PubMed
    1. Cmelak AJ. Current issues in combined modality therapy in locally advanced head and neck cancer. Crit Rev Oncol Hematol. 2012;84(2):261–273. doi: 10.1016/j.critrevonc.2012.04.004. - DOI - PubMed
    1. Lin C, Donaldson SS, Meza JL, Anderson JR, Lyden ER, Brown CK, Morano K, Laurie F, Arndt CA, Enke CA, Breneman JC. Effect of radiotherapy techniques (IMRT vs. 3D-CRT) on outcome in patients with intermediate-risk rhabdomyosarcoma enrolled in COG D9803—a report from the Children’s Oncology Group. Int J Radiat Oncol Biol Phys. 2012;82(5):1764–1770. doi: 10.1016/j.ijrobp.2011.01.036. - DOI - PMC - PubMed
    1. Abel E, Silander E, Nyman J, Björk-Eriksson T, Hammerlid E. Long-term aspects of quality of life in head and neck cancer patients treated with intensity modulated radiation therapy: a 5-year longitudinal follow-up and comparison with a normal population cohort. Adv Radiat Oncol. 2020;5(1):101–110. doi: 10.1016/j.adro.2019.07.015. - DOI - PMC - PubMed
    1. González Ferreira JA, Jaén Olasolo J, Azinovic I, Jeremic B. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: review of the literature. Rep Pract Oncol Radiother. 2015;20(5):328–339. doi: 10.1016/j.rpor.2015.05.010. - DOI - PMC - PubMed

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