Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway; Institute for Clinical Medicine, University of Oslo, POB 1171 Blindern, N-0318, Oslo, Norway.
K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway.
Eur J Surg Oncol. 2019 Dec;45(12):2340-2346. doi: 10.1016/j.ejso.2019.07.017. Epub 2019 Jul 17.
Surgery combined with perioperative chemotherapy has become standard of care in patients with resectable colorectal liver metastases. However, poor outcome is expected for a significant subgroup. The clinical implications of inter-metastatic heterogeneity remain largely unknown. In a prospective, population-based series of patients undergoing resection of multiple colorectal liver metastases, the aim was to investigate the prevalence and prognostic impact of heterogeneous response to neoadjuvant chemotherapy.
Radiological response to treatment was evaluated in a lesion-specific manner in 2-5 metastases per patient. Change of lesion diameter was evaluated and response/progression was classified according to three different size thresholds; 3, 4 and 5 mm. A heterogeneous response was defined as progression and response of different metastases in the same patient.
In total, 142 patients with 585 liver metastases were examined with the same radiological method (MRI or CT) before and after neoadjuvant treatment. Heterogeneous response to treatment was seen in 16 patients (11%) using the 3 mm size change threshold, and this group had a 5-year cancer-specific survival of 19% compared to 49% for patients with response in all lesions (p = 0.003). Cut-off values of 4-5 mm were less sensitive for detecting a heterogeneous response, but the survival difference was similar and significant.
A subgroup of patients with multiple colorectal liver metastases had heterogeneous radiological response to neoadjuvant chemotherapy and poor prognosis. The evaluation of response pattern is easy to perform, feasible in clinical practice and, if validated, a promising biomarker for treatment decisions.
手术联合围手术期化疗已成为可切除结直肠癌肝转移患者的标准治疗方法。然而，对于相当一部分患者，其预后仍然较差。转移灶间异质性的临床意义在很大程度上尚不清楚。本研究旨在通过对接受结直肠癌肝多发转移灶切除术的患者进行前瞻性、基于人群的系列研究，调查新辅助化疗中异质性反应的发生率及其对预后的影响。
采用病变特异性方法对每位患者的 2-5 个转移灶进行治疗反应的影像学评估。评估病灶直径的变化，并根据三种不同的大小阈值（3、4 和 5mm）对反应/进展进行分类。将不同转移灶的异质性反应定义为同一患者中不同转移灶的进展和反应。
共 142 例患者的 585 个肝转移灶接受了新辅助治疗前后相同的影像学方法（MRI 或 CT）检查。采用 3mm 大小变化阈值，16 例（11%）患者出现治疗异质性反应，其 5 年癌症特异性生存率为 19%，而所有病灶均有反应的患者为 49%（p=0.003）。4-5mm 的截止值检测异质性反应的敏感性较低，但生存差异相似且有统计学意义。
结直肠癌肝多发转移灶患者中存在亚组患者对新辅助化疗的影像学反应存在异质性，且预后较差。反应模式的评估易于实施，在临床实践中可行，如果得到验证，将是一种有前途的治疗决策的生物标志物。
