Citations

ABSTRACTLung transplantation is indicated for selected patients with advanced pulmonary arterial hypertension (PAH). We used a modified Delphi process to develop recommendations on care of patients with PAH undergoing lung transplantation. This Delphi panel was recruited from the Pulmonary Vascular Research Institute's Innovative Drug Discovery Initiative ‐ Lung Transplantation Workstream, consisting of clinical and research experts in PAH and lung transplantation. In this process, 29 panelists were given open‐ended questions, querying topics related to lung transplantation in PAH. A steering group converted the responses into discrete statements. Panelists then rated agreement using a Likert scale in two further survey rounds: −5 (strongly disagree) to 5 (strongly agree). Consensus was defined as mean ≥ 2.5 or ≤ −2.5, with a standard deviation not crossing zero. Consensus was reached on 141 of 223 statements. Notable areas of consensus were for early discussions about transplantation, and agreement with previously published referral and listing criteria. There was agreement that lung transplantation could be offered in sick candidates, including those with concurrent renal or hepatic insufficiency. Bilateral lung transplantation was considered the procedure of choice for most patients, with rare indications for heart‐lung transplantation. Consensus on bridging strategies included use of veno‐arterial extracorporeal membrane oxygenation and preemptive awake cannulation in those with severe right ventricular dysfunction. Consensus was also achieved on intraoperative use of invasive hemodynamic monitoring, and prolonged postoperative circulatory support guided by hemodynamic response and echocardiography. Patients with PAH undergoing transplantation require specialized management, which differs somewhat from other candidates.

Abstract Background: Chromosomal instability (CIN) is frequent in patients with metastatic castration-resistant prostate cancer (mCRPC) and determines taxane resistance. A circulating tumor cell (CTC) assay which morphologically identifies CTCs with CIN (CTC-CIN) from a single tube of whole blood could predict clinical outcomes in this population. We tested this hypothesis as a pre-planned, secondary outcome of the CARD trial, where patients with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate + prednisolone/prednisone) were randomized to treatment with cabazitaxel or the alternative ARPI. Methods: CTCs were isolated from blood samples obtained at baseline; cycle two, and end of treatment. The associations of baseline CTC and counts with imaging-based progression free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate (PRR) were assessed. Results: Of 255 patients randomized, CTC counts were acquired from 237 patients at screening, 213 patients at C2D1, and 166 patients at EOT. High baseline CTC counts were significantly associated with worse OS (median OS, 14.9 vs 9.8 months; univariate HR, 1.81; 95% CI, 1.30 - 2.51; p < 0.001). High baseline CTC-CIN counts were significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs 8.9 months; univariate HR, 2.16; 95% CI, 1.52 - 3.06; p < 0.001; multivariate HR, 1.56; 95% CI, 1.01 - 2.43; p = 0.047). Low CTC-CIN at baseline predicted ibPFS, ORR, and PRR benefit with cabazitaxel; conversely, high at baseline predicted no different ibPFS or OS outcomes with cabazitaxel or a second ARPI. Conclusions: This preplanned biomarker analysis of CARD confirmed that CTC-CIN counts are prognostic for OS and may be predictive of cabazitaxel benefit. (Funded by Sanofi and Epic Sciences; CARD ClinicalTrials.gov number, NCT02485691.) Citation Format: Ossian Longoria, Jan Rekowski, Santosh Gupta, Nick Beije, Klaus Pantel, Eleni Efstathiou, Cora Sternberg, Daniel Castellano, Karim Fizazi, Bertrand Tombal, Adam Sharp, Oliver Sartor, Sandrine Mace, Christine Geffriaud-Ricouard, Richard Wenstrup, Ronald de Wit, Johann de Bono. Morphological evaluation of chromosomal instability in circulating tumor cells and prediction of taxane resistance in metastatic prostate cancer: a prespecified sub-analysis of the CARD trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1145

Abstract Background Recently, a model to predict 5-year recurrence-free survival (RFS) and melanoma-specific survival (MSS) after sentinel lymph node biopsy (SLNB) was published. The aim of this study was to validate that model in a large independent international cohort. Methods The database of the Sentinel Lymph Node Working Group (SLNWG) was analysed for patients with malignant melanoma who underwent SLNB. Patients with clinical stage III melanoma, a history of other malignancies, or receiving concomitant systemic therapies during follow-up were excluded. The model’s predictive performance was evaluated using discrimination and calibration metrics in the eligible cohort. Decision curve analysis was performed to assess the clinical value of the model. Results The external validation cohort consisted of 6174 patients of the SLNWG from the USA, Europe, and Israel. A positive sentinel node was found in 788 patients (12.8%). The area under the time-dependent receiver operating characteristic (ROC) curve of the external validation was 0.76 (95% c.i. 0.74 to 0.77) for RFS and 0.79 (95% c.i. 0.76 to 0.81) for MSS. The model was well calibrated, as the observed 5-year survival rates aligned closely with the predicted survival rates (calibration slope of 0.98 for RFS and calibration slope of 0.99 for MSS). The model provided a net benefit versus the ‘treat all’ and ‘treat none’ strategies at the predetermined probability threshold for recurrence of 45%. Conclusion The model demonstrated good performance in a large heterogeneous independent cohort, emphasizing its robustness. Decision curve analysis revealed a clear net benefit of the model over a treat all strategy, highlighting its potential for clinical use.

Abstract Purpose: The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings. Experimental Design: In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types. Results: Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P < 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44–0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity. Conclusions: Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.

Study Design Narrative Review. Objectives To summarize the work of the AO Spine Knowledge Forum Tumor, specifically studies from the Epidemiology, Process and Outcomes in Spine Oncology (EPOSO) study. Methods A narrative review of all published manuscripts from the EPOSO study was undertaken. EPOSO represents a multicenter, prospective registry effort across 10 North American and European sites to enroll patients with metastatic disease of the spine. Results The current review summarized all studies from the EPOSO network, divided into the following five sections: (1) quality of life and satisfaction, (2) overall survival, (3) spinal instability, (4) neurologic outcome in patients with metastatic epidural spinal cord compression or radicular pain, and (5) patient and tumor-specific factors. Several important findings were elucidated. Patient evaluation should include SINS, nutritional status, severity and duration of neurologic deficit, extent of metastatic tumor burden, and differentiation of axial from radicular pain. Moreover, SOSGOQ2.0 serves as a useful and validated instrument for patient-reported outcome instrument. Despite the palliative nature of metastatic spine surgery, clear improvement in quality-of-life is seen. Even in patients with short-survival, the remaining weeks and months of life result in improved quality-of-life. Metastatic spine surgery often improves neurologic function, potentially enhancing survival through increased performance status. Conclusions Several noteworthy results have come from the EPOSO network, highlighting important trends in metastatic spine care. The AO Spine Knowledge Forum Tumor has helped advancing metastatic spine tumor research as well as ensure these new findings reach and benefit clinicians and their patients.