Prognostic features were evaluated in 92 patients with follicular center cell (FCC) lymphomas. Cleaved‐cell lymphomas (N = 73) were associated with significantly better survival than transformed cell lymphomas, 58 months vs. 6 months (p < .001). Among the cleaved‐cell group neither age, sex, heavy or light chain surface immunoglobulin, nor bone marrow involvement was a statistically significant prognostic indicator of survival. With stratification by cell of origin, survival in patients with cleaved‐cell lymphoma having a nodular histologic pattern was statistically equivalent to survival in patients having a diffuse histologic pattern (p = .22). FCC lymphomas of small cleaved cells had a better median survival than lymphomas of large cleaved cells (61 months vs. 33 months) but this only approached statistical significance (p = .08). Patients with symptoms had a median survival of 40 months as compared to 72 months in patients asymptomatic at presentation (p = .07). Involvement of lungs, pleura, or gastrointestinal tract, or extensive hepatic involvement was associated with a median survival of 16 months as compared to 63 months in patients in whom these features were absent (p < .001). Classification of lymphomas with respect to imune origin has clinical significance as it allows the identification of patients with B‐cell neoplasms who may have a clinical course similar to that usually associated with nodular lymphomas despite having a diffuse histologic pattern. Although in cleaved FCC lymphomas marrow involvement apparently has no prognostic value, involvement of other stage IV sites has grave prognostic implications; therefore, use of the term stage IV without specification of involved site may be of limited meaning in patients with these lymphomas.
Ataxia-telangiectasia mutated (ATM), a key activator of DNA damage response mechanisms, represents a potential biomarker for targeted gastric carcinoma therapies. A phase II study (Study 39; NCT01063517) designed to investigate the combination olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer did not meet its primary endpoint of progression-free survival; however, an improvement in the secondary endpoint of overall survival was recorded with a greater overall survival benefit noted in patients with ATM-negative tumors. An ATM immunohistochemical (IHC) diagnostic assay was developed to identify patients who may respond favorably to targeted therapies and deployed in the confirmatory phase III GOLD trial (NCT01924533). The VENTANA ATM (Y170) assay was developed for investigational use in formalin-fixed, paraffin-embedded gastric carcinoma samples using an anti-ATM rabbit monoclonal antibody (clone Y170) and was optimized with OptiView DAB IHC Detection Kit on a BenchMark ULTRA instrument. The assay was deployed in studies assessing sensitivity, specificity, robustness, precision, and determining optimal ATM staining cutoff to define ATM-deficiency (ATM-low). The ATM (Y170) assay met all predefined product development acceptance criteria. Multiple parameters were characterized, including repeatability, reproducibility, analytical sensitivity, specificity, robustness, and product stability. The scoring algorithm was defined; gastric carcinoma samples were considered ATM-negative or ATM-positive when <25% or ≥25%, respectively, of tumor cell nuclei expressed ATM at any IHC stain intensity and nuclei of immune and/or endothelial cells expressed ATM at a moderate stain intensity (internal positive control). Results highlight reproducibility of the assay, supporting suitability for investigational use for evaluation of gastric carcinoma samples using tumor cell staining cutoff of <25% to define ATM-deficiency. Using this ATM assay, phase III GOLD trial (NCT01924533) clinical trial did not meet its primary endpoint, only suggesting, but not demonstrating, that assessment of ATM levels by IHC could possibly be useful in assessing the degree of benefit that may be achieved by adding olaparib to paxitaxel when treating gastric carcinoma. The utility of ATM (Y170) assay as a companion diagnostic requires further clinical validation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.