Principe Miguel Alfonso V, Gokgoz Nalan, Prochazka Patrick, Coward Victoria S, Saini Sidharth, MacParland Sonya, Gladdy Rebecca, Ferguson Peter, Wunder Jay S, Andrulis Irene L, Chung Peter, Griffin Anthony M, White Lawrence M, Dickson Brendan C, Tsoi Kim M
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Ann Surg Oncol. 2025 Mar;32(3):1511-1521. doi: 10.1245/s10434-024-16521-0. Epub 2024 Nov 18.
Peritumoral edema on staging magnetic resonance imaging (MRI) is associated with higher local recurrence in soft tissue sarcoma (STS). This may relate to the presence of satellite malignant cells that are difficult to distinguish from benign atypia, leading to over- or undertreatment. This study evaluated a novel targeted molecular approach to identify malignancy in STS peritumoral planes as a means to improve personalized care.
In the targeted molecular approach, whole-exome sequencing was employed to identify tumor-specific variants (TSVs), and peritumoral planes were assayed for malignancy, defined as two or more TSVs/plane, using droplet digital polymerase chain reaction (PCR). Feasibility was evaluated using a retrospective cohort (n = 8) in which planes with cellular atypia were tested. A prospective cohort (n = 8) then assayed all peritumoral planes with radiologic edema.
The targeted molecular approach identified malignancy in three of eight cases with cellular atypia of unknown significance (37.5%) and five of eight cases with peritumoral edema on staging MRI (62.5%). Peritumoral regions were heterogeneous; in none of the malignant cases did all sampled planes have evidence of tumor. Malignancy was also identified in regions without cellular atypia. Both cases with a local recurrence had molecular evidence of malignancy outside the main mass despite R0 margins.
This study describes a novel personalized approach to detect malignancy in peritumoral regions in STS and is the first to identify molecular evidence of tumor outside the main mass. While development of a clinical tool is underway, these findings support the current approach of treating all peritumoral edema as malignant.
分期磁共振成像（MRI）显示的肿瘤周围水肿与软组织肉瘤（STS）的局部复发率较高相关。这可能与难以与良性异型性区分的卫星恶性细胞的存在有关，从而导致治疗过度或不足。本研究评估了一种新型靶向分子方法，以识别STS肿瘤周围平面中的恶性肿瘤，作为改善个性化治疗的一种手段。
在靶向分子方法中，采用全外显子测序来识别肿瘤特异性变异（TSV），并使用液滴数字聚合酶链反应（PCR）检测肿瘤周围平面是否存在恶性肿瘤，定义为每个平面有两个或更多TSV。使用回顾性队列（n = 8）评估可行性，其中对具有细胞异型性的平面进行检测。然后，前瞻性队列（n = 8）对所有具有放射性水肿的肿瘤周围平面进行检测。
靶向分子方法在8例意义不明的细胞异型性病例中的3例（37.5%）以及8例分期MRI显示肿瘤周围水肿的病例中的5例（62.5%）中识别出恶性肿瘤。肿瘤周围区域是异质性的；在所有恶性病例中，并非所有采样平面都有肿瘤证据。在没有细胞异型性的区域也发现了恶性肿瘤。尽管切缘为R0，但两例局部复发的病例在主肿块外均有恶性肿瘤的分子证据。
本研究描述了一种检测STS肿瘤周围区域恶性肿瘤的新型个性化方法，并且首次识别出主肿块外肿瘤的分子证据。虽然正在开发一种临床工具，但这些发现支持将所有肿瘤周围水肿视为恶性肿瘤的当前治疗方法。
