Department of Radiooncology and Radiotherapy, Translational Radiation Oncology Research Laboratory, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Department of Radiooncology and Radiotherapy, Translational Radiation Oncology Research Laboratory, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Cancer Research Center (DKFZ), Heidelberg, and German Cancer Consortium (DKTK), partner site Berlin, Germany.
Eur J Cancer. 2024 Dec;213:115100. doi: 10.1016/j.ejca.2024.115100. Epub 2024 Oct 28.
Current treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40-60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework.
Fresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays.
In total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens.
Our findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening.
目前对头颈鳞状细胞癌（HNSCC）的治疗包括手术、放疗和化疗。尽管采用了积极的多模式方法，但仍有 40-60%的病例发生肿瘤复发，导致生存结局不佳。HNSCC 缺乏针对特定疗法的常见遗传驱动因素，且缺乏可靠的治疗选择生物标志物。我们研究了在临床试验框架内将药物和放射敏感性筛选纳入患者来源的类器官（PDO）中的程序要求。
纳入了 186 例 HNSCC 患者的 198 个新鲜肿瘤样本。类器官建立成功率与临床和程序参数相关。确定了建立 PDO 培养物的时间框架，并通过连续传代评估其长期生长潜力。此外，我们对匹配的肿瘤-类器官对进行了全外显子测序。我们采用了三种 PDO 模型来建立放射敏感性测定。
总共成功建立了 35%的患者肿瘤的 PDO 模型，这些模型显示出与亲本肿瘤相似的组织形态特征和基因组改变。对于肿瘤细胞含量为 30%或更高的样本，成功率上升至 77%。高龄、既往放疗和组织处理延迟被确定为植入的负面预测因素。预计筛选所需的时间间隔与 PDO 指导选择根治性放疗方案兼容。
我们的研究结果表明，在高质量样本和高效的组织处理条件下，77%的 HNSCC 患者可以成功进行 PDO 筛选。鉴于涉及的程序挑战，未来旨在将 PDO 用于指导治疗决策的临床试验应考虑实施集中 PDO 筛选。
