RESUMO
BACKGROUND: The TNM (tumor-node-metastasis) Evaluation Committee of Union for International Cancer Control (UICC) and College of American Pathologists (CAP) recommended to prospectively validate the cost-effective and robust tumor-stroma ratio (TSR) as an independent prognostic parameter, since high intratumor stromal percentages have previously predicted poor patient-related outcomes. PATIENTS AND METHODS: The 'Uniform Noting for International application of Tumor-stroma ratio as Easy Diagnostic tool' (UNITED) study enrolled patients in 27 participating centers in 12 countries worldwide. The TSR, categorized as stroma-high (>50%) or stroma-low (≤50%), was scored through standardized microscopic assessment by certified pathologists, and effect on disease-free survival (DFS) was evaluated with 3-year median follow-up. Secondary endpoints were benefit assessment of adjuvant chemotherapy (ACT) and overall survival (OS). RESULTS: A total of 1537 patients were included, with 1388 eligible stage II/III patients curatively operated between 2015 and 2021. DFS was significantly shorter in stroma-high (n = 428) than in stroma-low patients (n = 960) (3-year rates 70% versus 83%; P < 0.001). In multivariate analysis, TSR remained an independent prognosticator for DFS (P < 0.001, hazard ratio 1.49, 95% confidence interval 1.17-1.90). As secondary outcome, DFS was also worse in stage II and III stroma-high patients despite adjuvant treatment (3-year rates stage II 73% versus 92% and stage III 66% versus 80%; P = 0.008 and P = 0.011, respectively). In stage II patients not receiving ACT (n = 322), the TSR outperformed the American Society of Clinical Oncology (ASCO) criteria in identifying patients at risk of events (event rate 21% versus 9%), with a higher discriminatory 3-year DFS rate (stroma-high 80% versus ASCO high risk 91%). A trend toward worse 5-year OS in stroma-high was noticeable (74% versus 83% stroma-low; P = 0.102). CONCLUSION: The multicenter UNITED study unequivocally validates the TSR as an independent prognosticator, confirming worse outcomes in stroma-high patients. The TSR improved current selection criteria for patients at risk of events, and stroma-high patients potentially experienced chemotherapy resistance. TSR implementation in pathology diagnostics and international guidelines is highly recommended as aid in personalized treatment.
RESUMO
This retrospective study explores the utility of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in enhancing the intraoperative identification and guidance for the resection of abdominal paragangliomas. They can be challenging to detect during minimally invasive surgery, due to their anatomical location, varying size and similar appearance in regard to their surrounding tissue. Patients with suspected abdominal paragangliomas planned for a minimally-invasive resection were included. As part of standard of care they received single intravenous dose of 5 mg ICG after abdominal exploration. NIR fluorescence imaging of the anatomical region of the suspected lesion was performed immediately following intravenous administration, to assess fluorescence signals, intraoperative identification, and histopathological correlation. Out of five resected suspicious lesions, four were imaged with NIR fluorescence, pathology confirming four as paragangliomas, the latter turned out to be an adrenal adenoma. NIR fluorescence identified all four lesions, surpassing the limitations of white-light visualization. Homogeneous fluorescence signals appeared 30-60 s post-ICG administration, which lasted up to 30 min. The study demonstrates the feasibility and potential clinical value of fluorescence-guided minimally-invasive resections of abdominal paragangliomas using a single intravenous ICG dose. These findings support the scientific basis for routine use of ICG-fluorescence-guided surgery in challenging anatomical cases, providing valuable assistance in lesion detection and resection.
