Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies.
Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies.
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DOI：
10.1200/po.23.00349
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发表时间：
2024-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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晚期癌症患者预后不良，通常有效治疗的选择有限，基于基因组学的治疗指导仍然仅使一小部分患者受益。下一代离体方法，如基于细胞质量的反应测试（MRT），为更广泛的癌症患者群体提供了一种替代的精确医学方法，但仍需要验证临床可行性和潜在影响。我们评估了使用活细胞MRT预测患者药物敏感性的临床可行性和准确性。使用具有48小时结果周转时间的统一测量工作流程，样品在体外用一组药物处理后进行MRT。疗程结束后，临床反应数据与基于MRT的结局预测相关。从104例实体（n = 69）和血液（n = 35）恶性肿瘤患者中采集标本，使用的组织形式包括针吸活检、恶性液体、骨髓穿刺液和血液样本。在81例（78%）符合MRT要求的标本中，41例（51%）接受医生选择治疗的患者接受了与MRT匹配的治疗。MRT与临床反应高度一致，比值比（OR）为14.80（P =.0003 [95%CI，2.83 - 102.9]）。实体瘤和血液系统恶性肿瘤的OR分别为20.67（P = 0.0128 [95%CI，1.45 - 1，375.57]）和8.20（P = 0.045 [95%CI，0.77 - 133.56]）。总体而言，这些结果的预测准确性为80%（P = 0.0026 [95% CI，65 - 91]）。MRT与临床疗效有高度相关性。常规临床使用在技术上是可行的，广泛适用于各种样本和恶性肿瘤类型，支持未来验证研究的需求。MRT预测癌症患者的药物敏感性的准确率为80%，有望用于肿瘤和药物机制的临床应用。
Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary. We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity. Using a unified measurement workflow with a 48-hour result turnaround time, samples were subjected to MRT after treatment with a panel of drugs in vitro. After completion of therapeutic course, clinical response data were correlated with MRT-based predictions of outcome. Specimens were collected from 104 patients with solid (n = 69) and hematologic (n = 35) malignancies, using tissue formats including needle biopsies, malignant fluids, bone marrow aspirates, and blood samples. Of the 81 (78%) specimens qualified for MRT, 41 (51%) patients receiving physician-selected therapies had treatments matched to MRT. MRT demonstrated high concordance with clinical responses with an odds ratio (OR) of 14.80 (P = .0003 [95% CI, 2.83 to 102.9]). This performance held for both solid and hematologic malignances with ORs of 20.67 (P = .0128 [95% CI, 1.45 to 1,375.57]) and 8.20 (P = .045 [95% CI, 0.77 to 133.56]), respectively. Overall, these results had a predictive accuracy of 80% (P = .0026 [95% CI, 65 to 91]). MRT showed highly significant correlation with clinical response to therapy. Routine clinical use is technically feasible and broadly applicable to a wide range of samples and malignancy types, supporting the need for future validation studies. MRT predicts cancer patients' drug sensitivity with 80% accuracy, holding promise for clinical use across tumors & drug mechanisms.
影响因子：
16.6
作者：
Cetin AE;Stevens MM;Calistri NL;Fulciniti M;Olcum S;Kimmerling RJ;Munshi NC;Manalis SR
通讯作者：
Manalis SR