Gofrit Ofer N, Gofrit Ben, Popovtzer Aron, Sosna Jacob, Goldberg S Nahum
Department of Urology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
School of Engineering and Computer Science, Hebrew University of Jerusalem, Jerusalem, Israel.
Cancer Rep (Hoboken). 2025 May;8(5):e70228. doi: 10.1002/cnr2.70228.
Metastatic spread can follow either the linear route-dissemination of fully malignant cells from the primary tumor, or the parallel route-dissemination of immature tumor cells and independent maturation to metastases in target organs. The linear/parallel ratio (LPR) is a model that uses metastases diameter comparisons to decipher dissemination route. LPR of +1 suggests pure linear and -1 pure parallel spread.
To examine the metastases trajectory in pancreatic duct adenocarcinoma (PDAC).
A total of 133 patients with PDAC, including 97 patients (72.9%) with synchronous and 36 (27.1%) with metachronous metastases with a total of 1054 lung and 2898 liver metastases, were evaluated. We found that metastatic spread to both liver and lungs is almost exclusively via the linear route (lungs median LPR + 1, interquartile range [IQR] 0.97,1. Liver median LPR + 0.98, IQR 0.83,1). Calculated from the primary diagnosis, overall survival (OS) of patients with metachronous metastases was significantly better compared to patients with synchronous disease (14 months, IQR 10,26, vs. 7 months, IQR 6,9, p < 0.0001). However, calculated from the time of metastases diagnosis, OS of both groups was similar (4 months, IQR 3,8, vs. 7 months, IQR 6,9, p = 0.235).
These two observations suggest that metastatic spread of PDAC is almost exclusively via the linear route, that is, directly from the primary tumor. Therefore, liver or lung metastases are already present in most patients with PDAC at the time of initial diagnosis. This suggests that local treatment in patients with seemingly localized disease does not decrease their risk of developing metastases and that systemic treatment must follow.
转移扩散可以遵循线性途径——完全恶性细胞从原发肿瘤的播散，或者平行途径——未成熟肿瘤细胞的播散并在靶器官中独立成熟为转移灶。线性/平行比（LPR）是一种利用转移灶直径比较来解读播散途径的模型。LPR为 +1 提示纯线性播散，-1 提示纯平行播散。
研究胰腺导管腺癌（PDAC）的转移轨迹。
共评估了133例PDAC患者，其中97例（72.9%）为同时性转移，36例（27.1%）为异时性转移，共有1054个肺转移灶和2898个肝转移灶。我们发现，肝和肺的转移扩散几乎均通过线性途径（肺的LPR中位数为 +1，四分位数间距[IQR]为0.97,1；肝的LPR中位数为 +0.98，IQR为0.83,1）。从初次诊断计算，异时性转移患者的总生存期（OS）明显优于同时性转移患者（14个月，IQR为10,26，对比7个月，IQR为6,9，p < 0.0001）。然而，从转移灶诊断时间计算，两组的OS相似（4个月，IQR为3,8，对比7个月，IQR为6,9，p = 0.235）。
这两项观察结果表明，PDAC的转移扩散几乎均通过线性途径，即直接从原发肿瘤转移。因此，大多数PDAC患者在初次诊断时肝脏或肺部已经存在转移灶。这表明，看似局限性疾病患者的局部治疗并不能降低其发生转移的风险，必须进行全身治疗。
