Trans-arterial radioembolization (TARE) is established as a treatment for colorectal liver metastases and may also be beneficial in other tumour entities. This prospective analysis aimed to evaluate the safety and effectiveness of TARE in patients with liver metastases of non-colorectal origin. Data were extracted from the prospective, multicentre, observational CIRSE Registry for SIR-Spheres Therapy (CIRT). Adult patients with liver metastases of non-colorectal origin, including neuroendocrine tumours (NET), breast cancer, pancreatic cancer and melanoma treated with TARE Yttrium-90 resin microspheres, were included. Safety and survival analyses were conducted. Assessment for independent prognostic factors was conducted using Cox proportional hazards models. Adverse events were defined according to the CTCAE 4.03. A total of 169 patients underwent TARE: NET (n = 58), breast cancer (n = 47), pancreatic cancer (n = 32), and melanoma (n = 32) with median follow-up of 19.3, 9.6, 5.6 and 14.8 months, respectively. Median overall survival (OS) was 33.3 (22.4-NA), 10.7 (7.7–16.3), 5.6 (4.9–10.1), 14.7 (8.7–27) months, for the NET, breast cancer, pancreatic cancer and melanoma cohorts, respectively. Overall, severe adverse events (grade ≥ 3) occurred in 10
To describe Undifferentiated Pleomorphic Sarcoma of Bone (UPSB) treated in Germany, Austria, or Switzerland and using the same treatment-approach as for osteosarcoma. The database of the Cooperative Osteosarcoma Study Group (COSS) was screened for UPSB. Eligible patients were evaluated for patient, tumor, and treatment related variables, and outcomes. One-hundred thirty-two eligible patients were identified (median age 41.7 (range: 10.3–74.6) years; males 58
Triple-negative breast cancer (TNBC) is a heterogeneous disease with the lowest survival rate of all clinical subtypes of breast cancer, but patients who achieve a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have a good prognosis. Results from the phase III KEYNOTE-522 trial established a new standard of care (SOC) for stage II-III TNBC, leading to US Food and Drug Administration approval in 2022 for the addition of carboplatin and pembrolizumab to NACT. Although the addition of carboplatin had previously been shown to increase pCR rates to NACT, it was not widely adopted as part of SOC NACT until its incorporation into both arms of KEYNOTE-522. Given the toxicities associated with carboplatin, there remains a need to better define its therapeutic benefit and to identify prognostic and predictive biomarkers of patient response and survival. We performed a pooled analysis of three randomized early-stage TNBC clinical trials that investigated the addition of carboplatin to NACT: BrighTNess (NCT02032277, n = 471), CALGB 40603 (NCT00861705, n = 351), and GeparSixto (NCT01426880, n = 262). We evaluated its impact on pCR, event-free survival (EFS), and overall survival (OS), and we explored germline BRCA1 and BRCA2 (gBRCA) mutation status as a potential biomarker. Additionally, we examined the prognostic and predictive value of eight published gene expression signatures (IgG, CD4, CD8, B-cell T-cell cooperativity, CD274, Immune1, Hypoxia core, VEGF). To analyze associations with pCR, we fit logistic mixed-effects regression models with study as a random effect. Associations with EFS and OS were evaluated using Cox proportional hazards models stratified by study. Multivariate models included age, tumor size, nodal status, gBRCA mutation status, and tumor grade as covariates. For the pooled dataset (n = 1084), in multivariate models, the addition of neoadjuvant carboplatin was significantly associated with increased pCR rate (odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.41-2.55, p < 0.001) and EFS (hazard ratio [HR] = 0.71, 95% CI = 0.54-0.93, p = 0.01), but not OS (HR = 0.93, 95% CI = 0.65-1.31, p = 0.66). When considering only gBRCA mutant samples (n = 137), we found that the addition of carboplatin conveys a significant EFS benefit (HR = 0.50, 95% CI = 0.25-1.00, p = 0.05) but had no significant impact on pCR rate or OS. Among the eight gene expression signatures tested, all six immune signatures were associated with a higher pCR rate in multivariate models, with Benjamini-Hochberg (B-H) adjusted p < 0.05. Four signatures (IgG, CD8, CD274, and Immune1) were associated with improved EFS and OS (B-H adjusted p < 0.05). However, no interaction between carboplatin and any tested signature was significantly predictive of pCR, EFS, or OS. Whole transcriptome analyses are ongoing to identify gene expression features that may predict response to neoadjuvant carboplatin. Within a pooled analysis of the BrighTNess, CALGB 40603, and GeparSixto clinical trials, we found that neoadjuvant carboplatin was associated with a significant improvement in pCR rate and EFS, but not OS. The addition of carboplatin significantly improved EFS in patients with gBRCA mutations despite not significantly improving pCR rate or OS. While many immune-related gene expression signatures were prognostic, none were predictive for benefit from neoadjuvant carboplatin. These findings support the inclusion of neoadjuvant carboplatin in SOC treatment of stage II-III TNBC and further emphasize the prognostic importance of the TNBC immune microenvironment. P50-CA058223; https://acknowledgments.alliancefound.org. BrighTNess was funded by AbbVie and GeparSixto was funded by GSK. B. M. Felsheim, V. Nekljudova, L. A. Carey, J. Huober, A. Schneeweiss, S. M. Tolaney, M. Untch, C. S. Kuzma, A. Fernandez-Martinez, S. Rachakonda, R. Suresh, D. G. Stover, P. Rastogi, M. Darsow, D. E. Lake, H. S. Rugo, J. O’Shaughnessy, M. Golshan, A. D. Pfefferle, W. M. Sikov, O. Metzger, C. Denkert, C. E. Geyer Jr., C. M. Perou, S. Loibl. Pooled analysis of the BrighTNess, CALGB 40603 (Alliance), and GeparSixto clinical trials identifies the impact of neoadjuvant carboplatin on pCR and survival in early-stage triple-negative breast cancer [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 RF2-02.
Accurate assessment of Ki67, a marker of cellular proliferation, is critical for breast cancer diagnostics and treatment decision-making. This study evaluates an automated Ki67-area identification approach, combined with digital image analysis (DIA) for exact Ki67 quantification. A total of 61 tissue samples from breast cancer patients from two clinical trials (GeparSixto and GeparSepto) were analyzed. The supervised DIA workflow employed automated Ki67-stained tumor area identification, followed by automated Ki67 scoring and was quality-controlled by trained pathologists. Comparisons with manual assessments were conducted to evaluate concordance and scoring precision. The DIA approach identified 232 tumor areas across 61 whole slide images (WSIs). The supervised system demonstrated a high correlation with manual scores (r = 0.78), and improved precision (standard deviation between evaluated tumor areas) was noted in therapy-naïve samples (p < 0.001). While manual assessments predominantly employed stepwise increments (5
We report correlative circulating tumor DNA (ctDNA) analyses from TRANSFORM (ClinicalTrials.gov identifier: NCT03575351) evaluating lisocabtagene maraleucel (liso-cel) versus standard of care (salvage immunochemotherapy, high-dose chemotherapy, autologous stem cell transplantation [ASCT]) in second-line large B-cell lymphoma (LBCL). ctDNA association with efficacy was investigated at predefined time points (random assignment, day 43, day 64, and day 126 [3 months after liso-cel, approximately 2 months after ASCT]) for 136 patients using ultrasensitive PhasED-Seq. ctDNA clearance (measurable residual disease [MRD]neg) predicted longer event-free survival (EFS) at all time points in both arms, with significantly more liso-cel-treated patients achieving MRDneg. Liso-cel demonstrated superior outcomes versus ASCT, including longer EFS, progression-free survival (PFS), and duration of response among patients in complete response (CR) and MRDneg. ctDNA re-emergence in patients with CR after ASCT confirmed its potential in predicting relapse. MRDneg remained significantly associated with EFS after adjusting for positron emission tomography (PET) response, while interaction testing revealed a significant interaction between PET status and treatment arm for EFS. Liso-cel achieved deeper, more durable molecular clearance by ctDNA, consistent with superior EFS and PFS versus ASCT for second-line LBCL treatment. ctDNA-MRD provided prognostic value beyond PET, supporting its role as a complementary biomarker for treatment response and relapse prediction.
