Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor-stroma ratio in colon cancer.

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.

Grading of follicular lymphoma in cytological samples.

OBJECTIVE: The treatment of follicular lymphoma (FL) depends on its grade. The current World Health Organization (WHO) 2008 Classification of Tumours of Haematopoietic and Lymphoid Tissues recommends the grading of FL on histological samples according to the Mann and Berard method, taking into consideration the number of centroblasts. There is no generally accepted method for the grading of FL in fine needle aspiration biopsy (FNAB) samples. The aim of the present study was to devise a grading system for FL in cytological samples. METHODS: Flow cytometry (FC) was performed on 60 FNAB samples of patients with primary FL. We assumed that FL cells larger than reactive T lymphocytes on FC histograms corresponded to centroblasts. The percentage of large cells was calculated and compared with histological grade, proliferative activity and number of centroblasts per high-power field (HPF) on histological slides, and with survival. RESULTS: The histological analysis of lymph nodes revealed 20 patients with high-grade and 40 patients with low-grade FL. The percentage of large cells in FNAB samples correlated significantly with histological grade (P = 0.02), MIB1 status (P < 0.001) and the number of centroblasts per HPF (P < 0.001). An age over 60 years and a percentage of large cells over 50% in FNAB samples were found to have a statistically significant impact on survival by univariate analysis (P = 0.001 and P = 0.006, respectively). CONCLUSIONS: The percentage of large lymphoma cells in FNAB samples of FL determined by FC can be used as a reliable method for FL grading, as it is comparable with the histological grading system.

Electrochemotherapy: a new technological approach in treatment of metastases in the liver.

Electrochemotherapy is now in development for treatment of deep-seated tumors, like in bones and internal organs, such as liver. The technology is available with a newly developed electric pulse generator and long needle electrodes; however the procedures for the treatment are not standardized yet. In order to describe the treatment procedure, including treatment planning, within the ongoing clinical study, a case of successful treatment of a solitary metastasis in the liver of colorectal cancer is presented. The procedure was performed intraoperatively by inserting long needle electrodes, two in the center of the tumor and four around the tumor into the normal tissue. The insertion of electrodes proved to be feasible and was done according to the treatment plan, prepared by numerical modeling. After intravenous bolus injection of bleomycin the tumor was exposed to electric pulses. The delivery of the electric pulses did not interfere with functioning of the heart, since the pulses were synchronized with electrocardiogram in order to be delivered outside the vulnerable period of the ventricles. Also the post treatment period was uneventful without side effects. Re-operation of the treated metastasis demonstrated feasibility of the reoperation, without secondary effects of electrochemotherapy on normal tissue. Good antitumor effectiveness with complete tumor destruction was confirmed with histological analysis. The patient is disease-free 16 months after the procedure. In conclusion, treatment procedure for electrochemotherapy proved to be a feasible technological approach for treatment of liver metastasis. Due to the absence of the side effects and the first complete destruction of the treated tumor, treatment procedure for electrochemotherapy seems to be a safe method for treatment of liver metastases with good treatment effectiveness even in difficult-to-reach locations.