ESTRO 2024 - Abstract Book

S5374

Radiobiology - Tumour biology

ESTRO 2024

The primary objective of this study was to explore the association of plasma ceramides with biochemical cure rate of PCa patients treated with EBRT and high dose-rate brachytherapy boost (HDRb). The secondary objectives were to assess the association of plasma ceramides with treatment-related toxicities and to examine the impact of ADT on ceramide levels.

Material/Methods:

30 intermediate- to high-risk PCa patients were recruited between 2018 and 2020. Blood samples were taken at the time of consent, after the last EBRT fraction, after the HDRb treatment, and then at 3-, 6-, 12-, and 18-months post treatment. Lipids were extracted and purified from plasma samples, and sphingolipid content was analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry. Patients were categorized based on every analyzed ceramide level change during or after treatments: increased or decreased/unchanged compared to baseline. Treatment outcome was analyzed by the PSA value closest to 4 years after treatment or at the time of biochemical failure if it happened before. Toxicities were assessed using the maximum International Prostate Symptoms Score (IPSS) obtained at early (≤ 6 months) and late (7-24 months) time points.

Results:

The 30 patients had a mean age of 70.8 ± 7.7 years, and the median follow-up was 44.5 months (IQR 41-48 months). Seventeen patients (56.7%) had an intermediate-risk disease according to the NCCN classification, and thirteen (43.3%) had a high-risk disease. Nineteen (63.3%) patients received ADT as part of their treatment regimen. One patient died of an unrelated cause after 28 months of follow-up. Of the 29 remaining, 22 (75.9%) have achieved biochemical cure, as defined by a 4-year PSA value ≤ 0.2 ng/ml. Increases in ceramide C16 (92.9 vs. 60%, p=0.039) and C24:1 (100 vs 63.2%, p=0.028) during follow-up compared to baseline were significantly associated with better biochemical cure rate. Patients who experienced an increase in C18 ceramide during treatments were found to have a higher maximal IPSS in the first six months after treatments than those for which C18 decreased or did not change (mean of 14.5 vs 9.9, p=0.018). For late toxicities, patients with increased C22:1 ceramide during treatment had a lower maximal IPSS from 6 to 24 months after treatments (mean of 6.9 vs 13.8, p=0.003). Patients not receiving ADT were more likely to have decreased levels of total ceramides and C16, C20, C22, and C24 in the follow-up period (OR 3.49 to 7.65, p= 0.007 to 0.049). Their level of C22 (OR=5.0, p=0.049) and C24:1 (OR 3.94, p=0.026) were also at greater risk of being diminished during treatments. Despite these results, ADT use was not significantly associated with biochemical cure rate.

Conclusion:

This study suggested that increased levels of ceramide C16 and C24:1 after EBRT + HDRb treatment were associated with a higher rate of biochemical cure. Moreover, some ceramide subspecies were significantly associated with higher early IPSS (C18) and lower late IPSS (C22:1). ADT use seemed to impact plasmatic ceramides concentration changes in these patients but did not affect biochemical cure rate. Because of the small sample size, these results are hypothesis-generating and can serve as a cornerstone for planning a more extensive study.