Labor Pachmann

Abstract Background: Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide. Emerging evidence suggests that a subpopulation of circulating tumor cells—circulating cancer stem cells (cCSCs)—plays a pivotal role in metastasis, therapy resistance, and disease relapse. However, functional assessment of these cells in a minimally invasive manner poses a significant clinical challenge. Tumorsphere assays offer a unique in vitro platform to enrich and evaluate the self-renewal capacity of cCSCs, potentially reflecting the biological aggressiveness of the tumor. Establishing a reliable method for cultivating tumorspheres from peripheral blood may provide a novel biomarker for monitoring tumor progression and facilitating patient stratification. Materials and Methods: A total of 98 breast cancer patients, representing stages I to IV, were enrolled in this study. Peripheral blood samples were collected from each patient to detect cCSCs using the stemtrac® method, followed by a standardized tumorsphere-forming assay. Results: Tumorsphere count showed a significant correlation with disease stage and metastatic status. Patients with stage IV disease exhibited a higher median tumorsphere count compared to those with stage I (30 vs. 10; p < 0.002). Metastatic patients had more tumorspheres than non-metastatic patients (30 vs. 15; p < 0.005), with the highest counts observed in cases with multiple metastases (median 61; p < 0.001). Additionally, higher tumorsphere counts were associated with features of tumor aggressiveness, including HER2/neu positivity (35 vs. 10; p < 0.05), increased Ki-67 index, and higher histological grade Conclusion: These findings underscore the clinical relevance of tumorsphere assays as a minimally invasive method for monitoring tumor biology. The number of tumorspheres derived from peripheral blood may serve as a surrogate biomarker for disease progression, metastatic potential, and tumor aggressiveness, offering promising implications for real-time patient stratification and personalized treatment planning in breast cancer. Citation Format: M. PizonD. SchottK. Pachmann. Tumorsphere Formation as a Liquid Biopsy Biomarker of Tumor Aggressiveness and Metastatic Burden in Breast [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-01.

Abstract Background: Radiotherapy (RT) is an essential component of multimodality therapy in the primary or postoperative treatment of prostate cancer with curative intent by preventing local recurrence and distant metastases, indicating its impact on residual occult tumor, such as circulating tumor cells. Immunogenic changes in cancer cells induced by RT can lead to adaptive up-regulation of PD-L1 expression. As immune checkpoint inhibition plays an increasingly important role in prostate cancer, radiogenic PD-L1 upregulation may be of therapeutic importance. The aim of this study was to determine PD-L1 status on CETCs before and during RT. Methods: Peripheral blood samples were collected from 52 primary non-metastatic prostate cancer patients. CETCs were enumerated and analyzed for PDL-L1 expression prior to (baseline), 3 and 6 weeks after the start of RT using fluorescence scanning microscopy. Results: PD-L1 expression was detectable in CETCs and localized in the membrane and/or cytoplasm. We found a correlation between PD-L1 status in CETCs and aggressiveness of cancer disease prior to RT. The frequency of PD-L1 positive CETCs depended on the grading and Gleason score of the primary tumor. Patients with a high Gleason score and G3 tumors had significantly more PD-L1 positive CETCs compared to patients with a low Gleason Score and G1 tumors. Moreover, patients in stage I/II had significantly less PD-L1 positive CETCs compared to patients in stage III/IV (mean 54.25 vs. mean 69.65; p<0.05). A higher number of PD-L1 positive CETCs were detected in patients who had radical prostatectomy before start of RT than in those who had no surgical intervention (mean 66.24 vs. mean 47.46; p<0.01). Interestingly, the fraction of PD-L1 positive CETCs decreased significantly during RT only in patients with G3 tumors and a high Gleason Score. Conclusion: Our results indicated that PD-L1 in CETCs is closely related to the aggressiveness of the primary tumor and may be a co-factor associated with the progression of prostate cancer. PD-1/PD-L1 blockade combined with RT represents a novel and promising treatment strategy that could contribute to improve the treatment efficacy of prostate cancer. Citation Format: Dorothea Schott, Monika Pizon, Ulrich Pachmann, Katharina Pachmann, Matthias Mäurer. Sequential tracking of PD-L1 expression on circulating epithelial tumor cells (CETCs) in men with primary non-metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2745.

INTRODUCTION AND AIMS: Diabetes is also in Switzerland the leading cause for end stage renal disease and initiation of dialysis. Various studies have shown diabetes to be a significant predictor for mortality in dialysis patients. There is little information available in Swiss dialysis patients with diabetes about their mortality early after initiation of dialysis. METHODS: All medical establishments in Switzerland (both public and private; N88) providing chronic treatment by either hemo-and/or peritoneal dialysis, had to provide relevant data. Incident dialysis patients (hemo-or peritoneal dialysis; N895) from the Swiss dialysis registry were followed up from 2014 on until December 31, 2016 (mean follow up days751). Deaths occurred during this time (N189) were recorded and mortality risk was assessed with Cox-proportional hazard models. Patients were stratified according their status regarding systemic diabetes mellitus, type either 1 or 2, regardless of renal involvement with diabetic nephropathy. RESULTS: Characteristics of the dialysis population are provided in the Table . Dialysis patients with diabetes are significantly older, have a higher body mass index (p0.068) and have been longer on dialysis. The comorbidity score and count were slightly different between the two groups, however not significant. After removing the counts attributed to diabetes, the difference between these two groups disappeared.Cox regression analysis, adjusted for age and coronary artery disease, does not show a higher mortality for diabetic patients on dialysis, as shown previously. However, in the first year, dialysis patients without diabetes have a 86% higher risk to die than patients with diabetes (p0.019). This effect disappears in the follow up, with a tendency to reduced mortality in diabetics ! odds ratio0.845, p0.269, 95th percentile: 0.628-1.138. CONCLUSIONS: Unlike for many other countries, who have found diabetes to be a clear mortality risk factor in dialysis patients, this is not observed for Switzerland. To the contrary, diabetics in our country show a tendency to slightly better survival, at least in the first two years after initiation of dialysis therapy. The reason for this finding is unclear. Possible explanations are earlier start of dialysis therapy and/or better medical management. The latter is supported by a higher proportion of hypertensive diabetic patients on dialysis being treated with antihypertensive medication (vs. non-diabetics). Also, the prevalence of catheters among diabetics is lower.