Witjes Vera M, de Hullu Joanne A, Hermkens Dorien M A, Smolders Yvonne H C M, Swillens Julie E M, Slob Sarah-Lotte, Bosse Tjalling, Mourits Marian J E, Ausems Margreet G E M, Ligtenberg Marjolijn J L, Hoogerbrugge Nicoline
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
Int J Cancer. 2025 Aug 1;157(3):504-512. doi: 10.1002/ijc.35440. Epub 2025 Apr 16.
Despite international agreement on the importance of tumor DNA testing and germline testing for determining PARP inhibitor treatment eligibility in patients with ovarian carcinoma (OC) and for cancer prevention in their relatives, the optimal strategy remains under debate. In the Netherlands, the "Tumor-First workflow" was initiated and implemented nationwide: a well-validated tumor DNA test is the primary test for detecting tumor pathogenic variants (PVs) in OC risk genes (BRCA1/2, RAD51C/D, BRIP1, PALB2). The detection of tumor PVs is subsequently used to stratify germline testing and determine treatment eligibility. The Tumor-First workflow is efficient and saves costs. The aim of this study was to evaluate the nationwide implementation of the Tumor-First workflow. We analyzed real-time genetic testing practices, including tumor DNA and germline testing, in patients diagnosed with OC from 2019 to 2023, as identified through the Dutch Pathology Registry (Palga). Testing data were collected from diagnostic pathology and genetic reports. Out of the 3926 OC patients, 2778 (71%) received OC tumor DNA testing as the primary test. Between 2019 and 2023, this percentage increased from 50% to 85%. Of these tumor DNA tests, 2703 (97%) were successful, with 398 (15%) resulting in the identification of a PV in an OC risk gene. Most of these patients (291; 73%) underwent germline testing, and 147 (51%) were found to have a germline PV. We conclude that the nationwide implementation of the Tumor-First workflow for OC was effective. Multidisciplinary efforts contributed to a more efficient detection of germline and somatic PVs in OC risk genes.
尽管国际上就肿瘤DNA检测和种系检测对于确定卵巢癌（OC）患者使用PARP抑制剂的治疗资格以及对其亲属进行癌症预防的重要性已达成共识，但最佳策略仍存在争议。在荷兰，“肿瘤优先工作流程”已在全国启动并实施：一项经过充分验证的肿瘤DNA检测是检测OC风险基因（BRCA1/2、RAD51C/D、BRIP1、PALB2）中肿瘤致病变异（PV）的主要检测方法。随后，利用检测到的肿瘤PV对种系检测进行分层并确定治疗资格。肿瘤优先工作流程高效且节省成本。本研究的目的是评估肿瘤优先工作流程在全国范围内的实施情况。我们分析了2019年至2023年通过荷兰病理登记处（Palga）确诊为OC的患者的实时基因检测实践，包括肿瘤DNA检测和种系检测。检测数据来自诊断病理报告和基因报告。在3926例OC患者中，2778例（71%）接受了OC肿瘤DNA检测作为主要检测。在2019年至2023年期间，这一比例从50%增至85%。在这些肿瘤DNA检测中，2703例（97%）检测成功，其中398例（15%）在OC风险基因中检测到PV。这些患者中的大多数（291例；73%）接受了种系检测，其中147例（51%）被发现存在种系PV。我们得出结论，OC的肿瘤优先工作流程在全国范围内的实施是有效的。多学科努力有助于更有效地检测OC风险基因中的种系和体细胞PV。
