Naqvi Mohammad Faraz, Vo Henry Hiep, Vining David, Tsimberidou Apostolia-Maria
Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ther Adv Med Oncol. 2021 Mar 24;13:17588359211001538. doi: 10.1177/17588359211001538. eCollection 2021.
Patients with advanced and/or metastatic solid tumors have limited treatment options. Mutations that serve as biomarkers of carcinogenesis can be found in cell-free DNA of patients' plasma. Analysis of circulating tumor DNA (ctDNA) was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is not technically feasible or it is associated with high risk for complications. The role of ctDNA in precision oncology is promising but its clinical significance across tumor types remains to be validated. We report a case series of three heavily pretreated patients with advanced solid tumors who received matched targeted therapy based on ctDNA analysis and/or tumor molecular profiling.
Three patients with advanced, metastatic cancer and the following characteristics are presented: a 71-year-old woman with ovarian cancer and mutation identified in ctDNA and tumor tissue was treated with a PARP inhibitor and achieved partial response by RECIST (Response Evaluation Criteria in Solid Tumors) for 22.6+ months; a 40-year-old woman with adenoid cystic carcinoma of the parotid gland was treated with a MEK/RAF pathway inhibitor on the basis of amplification on ctDNA analysis and had stable disease for 20.2 months; and a 56-year-old woman with breast cancer and a mutation identified by ctDNA analysis was treated with a PARP inhibitor and achieved stable disease for 9.1 months. All three patients are alive at the time of this report.
These results suggest that ctDNA analysis can contribute to selection of targeted therapy in patients with advanced, metastatic cancer. Prospective clinical trials to evaluate and optimize ctDNA biomarkers, as well as the integration of novel and/or alternative targeted therapies, are warranted to fully assess the role of ctDNA analysis in cancer therapy.
www.clinicaltrials.gov (NCT02152254). Registered May 28, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02152254. MD Anderson protocol # PA12-1161 (approval ID IRB1 FWA00000121) and # PA11-0377 (approval ID IRB4 FWA00005015).
晚期和/或转移性实体瘤患者的治疗选择有限。致癌作用的生物标志物突变可在患者血浆的游离DNA中发现。当肿瘤活检在技术上不可行或与高并发症风险相关时，循环肿瘤DNA（ctDNA）分析作为一种非侵入性、成本效益高的肿瘤活检替代方法而被开发出来。ctDNA在精准肿瘤学中的作用很有前景，但其在不同肿瘤类型中的临床意义仍有待验证。我们报告了一个病例系列，包括三名接受过大量治疗的晚期实体瘤患者，他们根据ctDNA分析和/或肿瘤分子谱分析接受了匹配的靶向治疗。
介绍了三名具有以下特征的晚期转移性癌症患者：一名71岁的卵巢癌女性，其ctDNA和肿瘤组织中检测到 突变，接受PARP抑制剂治疗，根据实体瘤疗效评价标准（RECIST）达到部分缓解，持续22.6 + 个月；一名40岁的腮腺腺样囊性癌女性，基于ctDNA分析中的 扩增，接受MEK/RAF通路抑制剂治疗，病情稳定20.2个月；一名56岁的乳腺癌女性，通过ctDNA分析检测到 突变，接受PARP抑制剂治疗，病情稳定9.1个月。在本报告发布时，所有三名患者均存活。
这些结果表明，ctDNA分析有助于晚期转移性癌症患者靶向治疗的选择。有必要进行前瞻性临床试验，以评估和优化ctDNA生物标志物，以及整合新的和/或替代的靶向治疗方法，以全面评估ctDNA分析在癌症治疗中的作用。
www.clinicaltrials.gov（NCT02152254）。2014年5月28日注册。https://www.clinicaltrials.gov/ct2/show/NCT02152254。MD安德森方案#PA12 - 1161（批准ID IRB1 FWA00000121）和#PA11 - 0377（批准ID IRB4 FWA00005015）。
