Radigan Rachel, Sangal Ashish, Zhang Dong, Weber Jonathan, Schmalzle Megha, Finkelstein Alexa, Duggal Vaibhav, Kao Johnny
Department of Radiation Oncology, Good Samaritan University Hospital, West Islip, New York, United States of America.
Center for Cancer Research, New York Institute of Technology College of Osteopathic Medicine, Greenvale, New York, United States of America.
PLoS One. 2025 Jun 11;20(6):e0325769. doi: 10.1371/journal.pone.0325769. eCollection 2025.
Despite significant progress in solid tumor oncology, including widespread genomic testing, metastatic cancer remains largely incurable and results in approximately 90% of cancer deaths. In the context of systems biology, RNA transcriptome-based (RNA-seq) testing is utilized to identify master regulator proteins that are putative drivers of tumor progression. After extensive preclinical testing and validation, Darwin OncoTarget and OncoTreat has been developed as a commercially available next generation precision oncology test with preliminary evidence of efficacy in treatment-refractory advanced cancers. We designed this pilot trial to assess the feasibility of integrating Darwin OncoTarget and OncoTreat testing in patients with oligometastases receiving comprehensive involved site radiotherapy. Eligible patients are adults with solid tumor oligometastases with up to 10 discrete tumors amenable to radiation therapy following prior first-line systemic therapy. Tumor biopsy is required to allow for precision medicine testing to supplement standard clinical management. Formalin fixed paraffin embedded tissue with >50% tumor will be sent to the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center for Darwin OncoTarget and OncoTreat testing. Patients will either continue standard of care systemic therapy or proceed with an alternative FDA approved treatment informed by Darwin testing. This trial evaluates the feasibility and utility of integrating novel precision oncology testing in a community hospital setting. This study will utilize precision oncology testing in the population of induced, recurrent or persistent oligometastases that currently have limited or largely ineffective systemic treatment options. This trial represents an early attempt at integrating next generation precision medicine testing and systems biology in the context of radiation therapy.
尽管实体肿瘤肿瘤学取得了重大进展，包括广泛的基因组检测，但转移性癌症在很大程度上仍然无法治愈，约90%的癌症死亡由其导致。在系统生物学背景下，基于RNA转录组的（RNA测序）检测被用于识别作为肿瘤进展推定驱动因素的主调控蛋白。经过广泛的临床前测试和验证，达尔文肿瘤靶点与肿瘤治疗检测已作为一种可商购的下一代精准肿瘤学检测方法开发出来，并有初步证据表明其对难治性晚期癌症有效。我们设计了这项试点试验，以评估在接受综合受累部位放疗的寡转移患者中整合达尔文肿瘤靶点与肿瘤治疗检测的可行性。符合条件的患者为患有实体肿瘤寡转移的成年人，在接受一线全身治疗后，有多达10个可接受放射治疗的离散肿瘤。需要进行肿瘤活检，以便进行精准医学检测，以补充标准临床管理。将含有>50%肿瘤的福尔马林固定石蜡包埋组织送往哥伦比亚大学医学中心的个性化基因组医学实验室进行达尔文肿瘤靶点与肿瘤治疗检测。患者将继续接受标准的全身治疗或根据达尔文检测结果进行另一种FDA批准的治疗。该试验评估了在社区医院环境中整合新型精准肿瘤学检测的可行性和实用性。本研究将在目前全身治疗选择有限或基本无效的诱导性、复发性或持续性寡转移人群中利用精准肿瘤学检测。该试验代表了在放射治疗背景下整合下一代精准医学检测和系统生物学的早期尝试。
